At the end of every month, the International Myeloma Foundation Newsroom will feature a wrap-up of some of the most fascinating studies about multiple myeloma from medical journals. Here is the May 2026 edition.

The IMF team of medical editors has provided overviews of key studies. Yet, we encourage you to visit the actual articles in the journals for full details and to increase your understanding. Check the IMF Newsroom monthly for updates like this one.

In the Journals (Key Myeloma Research in May 2026)

"Clinical Development of Bispecific Antibodies: Review, Advances, and Challenges in Hematological Malignancies"

Source

Saitoh, A. (2026). Clinical Development of Bispecific Antibodies: Review, Advances, and Challenges in Hematological Malignancies. In: Yasunaga, M. (eds) Bispecific Antibodies. Methods in Molecular Biology, vol 2997. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-5037-0_17 May 1, 2026.  

Overview

Bispecific antibodies (bsAbs) are a type of precision cancer treatment designed to attack tumors by binding to two different targets on cancer cells simultaneously. Unlike standard monoclonal antibodies, they are engineered to recruit your own T cells — a core component of your immune system — directly to myeloma cells, triggering their destruction. This approach helps overcome one of myeloma's key survival strategies: hiding from immune detection.

Several bsAbs have already received regulatory approval in the US, Europe, and Japan for blood cancers, with most working by redirecting T cells through a protein called CD3. Researchers are also testing additional mechanisms beyond CD3 targeting to broaden how these therapies activate the immune system.

This review covers bsAbs currently in clinical development for blood cancers, including how they are structured, how they work, and what early trial results show about their effectiveness and side effect profiles — with a focus on the most advanced candidates currently under investigation.

"MDM2 Drives Proteasome Inhibitor Resistance and Represents a TP53-Independent Therapeutic Vulnerability in Multiple Myeloma"

Source

Labrador M, Cozzubbo S, Porro M, Cumerlato M, Bandini C, Mereu E, Paradzik T, Donati B, Manicardi V, Ronchetti D, et al. MDM2 Drives Proteasome Inhibitor Resistance and Represents a TP53-Independent Therapeutic Vulnerability in Multiple Myeloma. Cells. 2026; 15(9):831. https://doi.org/10.3390/cells15090831 May 1, 2026. 

Overview

Proteasome inhibitors like carfilzomib are a standard part of myeloma treatment, but resistance — particularly in relapsed or refractory disease — limits how long they remain effective. This study set out to find what drives that resistance.

Using two independent screening methods, researchers identified a protein called MDM2 as a key factor that helps myeloma cells survive carfilzomib exposure. When MDM2 activity was high, myeloma cells recovered faster after treatment. Blocking MDM2 with an experimental drug called NVP-CGM097 restored carfilzomib sensitivity across multiple cell lines, including those already resistant to proteasome inhibitors. This held true regardless of TP53 status — relevant because TP53 mutations, including the deletion del(17p), are associated with poorer prognosis in myeloma.

The combination worked by stalling the cell cycle and reducing activity of a cancer-driving protein called c-MYC, while leaving normal blood cells unaffected. Results held up in models that mimic the bone marrow environment, and in samples taken directly from people with myeloma.

The findings position MDM2 inhibition as a potential strategy to overcome proteasome inhibitor resistance, including in genetically high-risk disease.

"CD161⁺ NKT Cell Proportion as a Predictive Biomarker for Bortezomib Treatment Response in Newly Diagnosed Multiple Myeloma Patients"

Source

Zhou S, Xu X, Cuo J, Sun C, Hou Y, Wang X, Nana D, Weixun S. CD161⁺ NKT Cell Proportion as a Predictive Biomarker for Bortezomib Treatment Response in Newly Diagnosed Multiple Myeloma Patients. Clin Lab. 2026 May 1;72(5). doi: 10.7754/Clin.Lab.2025.250744.  

Overview

Natural killer T (NKT) cells are immune cells that normally help the body identify and attack cancer. In myeloma, their function is often impaired, which may allow the disease to evade immune detection. This study examined whether measuring a specific subset of NKT cells — identified by the markers CD3, CD56, and CD161 — in a standard blood draw could predict how well newly diagnosed people with myeloma would respond to bortezomib plus dexamethasone.

Across 72 newly diagnosed participants, those with lower baseline levels of these cells responded worse to treatment and tended to have higher disease burden, including more advanced ISS stage and elevated LDH and beta-2 microglobulin. Those with higher baseline levels were significantly more likely to respond. A cutoff level of 1.85% identified likely non-responders with 88% sensitivity and 72% specificity. After treatment, CD161-positive NKT cell levels rose in those who responded.

The findings suggest this cell population could serve as a routine blood-based marker to flag, before treatment begins, who is less likely to respond to bortezomib-based therapy — potentially informing earlier decisions about alternative approaches.

"Extracellular Enolase-1 Promotes CAF-Associated Stromal Reprogramming via the Plasmin/TGF-β Axis in Multiple Myeloma"

Source

Chung I-C, Chuang T-Y, Ko Y-T, Chen M-L, Hsu P-Y, Huang W-C, Yuan T-T. Extracellular Enolase-1 Promotes CAF-Associated Stromal Reprogramming via the Plasmin/TGF-β Axis in Multiple Myeloma. Cancers. 2026; 18(9):1467. https://doi.org/10.3390/cancers18091467 May 1, 2026.  

Overview

The bone marrow environment plays an active role in myeloma progression. Certain cells within it — called cancer-associated fibroblasts (CAFs) — can be reprogrammed to support tumor growth and shield myeloma cells from treatment. This study investigated whether a protein called enolase-1 (ENO1), found on cell surfaces and in the space between cells, drives that reprogramming.

In laboratory models combining myeloma cells with bone marrow stromal cells, extracellular ENO1 triggered a chain reaction: it activated a protein called plasmin, which in turn activated TGF-β, a signaling molecule that converted normal stromal cells into CAFs. These reprogrammed cells became more metabolically active and secreted higher levels of cytokines that promote tumor growth.

Blocking ENO1 with an experimental antibody called HuL001 reversed these effects. Stromal cells pre-treated with HuL001 were less capable of supporting tumor growth in bortezomib-resistant myeloma models. When combined with lenalidomide, HuL001 also overcame bortezomib resistance directly.

The results point to extracellular ENO1 as a driver of the tumor-supportive bone marrow environment in myeloma, and suggest that targeting it could disrupt both stromal reprogramming and drug resistance simultaneously.

"The Role of CD56 as an Immunophenotypic Marker in the Clinical Course of Multiple Myeloma"

Source

Karabekov A, Kemaikin V, Burkitbayev Z, Zhakhina G, Sipenova A, Berger I, Orumbayeva U, Iskakova Z, Ibragimova R, Temir N, et al. The Role of CD56 as an Immunophenotypic Marker in the Clinical Course of Multiple Myeloma. Journal of Clinical Medicine. 2026; 15(9):3492. https://doi.org/10.3390/jcm15093492 May 1, 2026.   

Overview

CD56 is a protein found on the surface of myeloma cells in most — but not all — cases. Whether its presence or absence meaningfully predicts outcomes has been debated, particularly as treatment has evolved. This study examined CD56 status in 88 newly diagnosed people with myeloma, all treated with modern induction therapy followed by autologous stem cell transplantation (ASCT).

CD56-negative cases, which made up 23% of the group, showed higher rates of extramedullary disease — myeloma growing outside the bone marrow — and responded less well to induction therapy (65% vs. 85% response rate). This suggests CD56 negativity reflects a more aggressive disease biology at diagnosis.

Despite these differences, CD56 status did not translate into differences in progression-free or overall survival. Those who received more CD34+ stem cells at transplant and achieved stronger post-transplant responses fared better regardless of CD56 status.
The results suggest that while CD56 negativity is a marker of higher disease burden and poorer initial treatment response, intensive therapy with ASCT may offset that disadvantage. CD56 status may be more useful for understanding disease biology at diagnosis than for predicting long-term outcomes in people proceeding to transplant.

"BCMA-directed CAR-T cell therapy in relapsed/refractory multiple myeloma: efficacy, safety, survival, and future directions – A systematic review and meta-analysis"

Source

Muhammad Shaheer Mannan, Adeena Musheer, Muhammad Waqas Khan, Hur Abbas, Sheikh Abdul Qadir Jillani, Ali Shan Hafeez, BCMA-directed CAR-T cell therapy in relapsed/refractory multiple myeloma: efficacy, safety, survival, and future directions – A systematic review and meta-analysis, Current Problems in Cancer, 2026, 101301, ISSN 0147-0272, https://doi.org/10.1016/j.currproblcancer.2026.101301. May 1, 2026.    

Overview

This meta-analysis pooled data from 14 clinical trials — covering 1,278 people with relapsed or refractory myeloma who had received a median of three to eight prior lines of therapy — to produce a consolidated picture of how BCMA-directed CAR-T cell therapy performs across studies.

The overall response rate was 86%, a figure that held up across sensitivity analyses. Severe neurotoxicity (a side effect called ICANS) was uncommon, occurring in 3% of cases. However, the safety profile was not uniformly reassuring: treatment-related mortality reached 5%, and severe hematologic toxicities — effects on blood cell counts — were frequent, though the analysis assessed these separately.

Around 4% of participants stopped treatment due to toxicity, and there was meaningful variation across trials in several of the safety outcomes, suggesting that results differ depending on the specific CAR-T product, patient population, and trial design.
Taken together, the data confirm that BCMA-directed CAR-T therapy produces high response rates even in heavily pre-treated myeloma, but the risk of serious complications — particularly blood count-related toxicities and treatment-related death — means patient selection and toxicity management remain areas where current practice needs refinement.

"Feasibility of decentralized real-world monitoring of SARS-CoV-2 booster vaccines and COVID-19 outcomes in myeloma"

Source

William A. Wood, Shaji K. Kumar, Emily A. Semmel, Shandra James, Mark A. Schroeder, David J. Chung, Aaron Rosenberg, Jeffrey Zonder, Samuel Rubinstein, Anita D’Souza, Thomas Martin, Ajai Chari, Ravi Vij, Ajay K. Nooka, Kenneth C. Anderson, Donna S. Neuberg, Shambavi Richard, Kathleen Torres, Brendan M. Weiss, Levi Pederson, Andriy Derkach, Susan Geyer, Saad Z. Usmani; Feasibility of decentralized real-world monitoring of SARS-CoV-2 booster vaccines and COVID-19 outcomes in myeloma. Blood Adv 2026; 10 (9): 3094–3102. doi: https://doi.org/10.1182/bloodadvances.2025018963 May 1, 2026.    

Overview

Myeloma and its treatments suppress the immune system, making COVID-19 infection a particular concern.Myeloma and its treatments suppress the immune system, making COVID-19 infection a particular concern. The COSMIC study was designed to track COVID-19 outcomes and vaccine impact in people with myeloma, while also testing whether a decentralized, patient-reported data model could work at speed across multiple treatment centers.

201 participants enrolled across 8 sites in just four months. The group ranged in age from 30 to 93 (median 67), was 46% female, and included 17% non-Hispanic Black and 8% Hispanic/Latino participants — demographic representation that is often limited in myeloma research. At enrollment, 55% had already had COVID-19 and had received a median of four SARS-CoV-2 vaccines. Over the six-month follow-up, 18 additional infections and 57 further vaccinations were recorded across the group.

Patient-reported outcome completion was 97% at baseline, dropping to around 80% at one and six months — solid retention for a decentralized study. No meaningful differences in health-related quality of life emerged over time or based on COVID-19 history.
Beyond the clinical findings, the study's primary contribution is methodological: it shows that a provider network can rapidly build an evidence base around an emerging threat using patient-reported data, electronic health records, and remote consent — a model with applications beyond COVID-19.

"Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma"

Source

Lorea Jordana-Urriza, Guillermo Serrano, Sergio Camara-Peña, Maria E. Calleja-Cervantes, Patxi San Martin-Uriz, Aintzane Zabaleta, Aina Oliver-Caldes, Marta Español-Rego, Diego Alignani, Teresa Lozano, Saray Rodriguez-Diaz, Elena Iglesias, Valentin Cabañas, Juan L. Reguera, Veronica Gonzalez-Calle, Maria V. Mateos, Fermin Sanchez-Guijo, Bruno Paiva, Juan J. Lasarte, Susana Inoges, Ascension Lopez-Diaz de Cerio, Azucena Gonzalez-Navarro, Manel Juan, Carlos Fernandez de Larrea, Esteban Tamariz, Ana Alfonso-Pierola, Paula Rodriguez-Otero, Jesus F. San-Miguel, Mikel Hernaez, Juan R. Rodriguez-Madoz, Felipe Prosper; Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma. Blood Neoplasia 2026; 3 (2): 100203. doi: https://doi.org/10.1016/j.bneo.2026.100203  May 1, 2026.   

Overview

One of the central challenges with CAR-T therapy in myeloma is that the infused cells often lose effectiveness over time. This study used single-cell multiomics — a technique that simultaneously measures gene activity and other molecular features at the level of individual cells — to examine why BCMA-targeted CAR-T cells behave differently depending on where they are in the body and how they evolve after infusion.

CAR-T cells collected from bone marrow showed more signs of activation but also greater exhaustion compared to those circulating in the blood. A breakdown in the normal transition from effector to memory T cells meant more cells reached a terminally differentiated state — essentially burned out and unable to persist — which correlated with worse durability of response.

In one participant with a partial response, researchers identified a single CAR-T cell clone that had expanded extensively in the bone marrow. These cells produced high levels of interleukin-10 (IL-10), a signaling molecule that, when elevated, appeared to suppress CAR-T cell proliferation. Further analysis showed that activation of the T cell's own native receptor — separate from the CAR construct — drove IL-10 production, pointing to an unintended mechanism undermining therapy.

The findings identify specific molecular checkpoints that limit CAR-T durability in myeloma, and suggest that targeting the effector-to-memory transition or IL-10 signaling could be avenues for improving how long CAR-T therapy remains effective.

"Leveraging AI to Evaluate Minimal Residual Disease Endpoint Surrogacy in Multiple Myeloma"

Source

Zexin Ren, Zixuan Zhao, Andrew J. Cowan, Will Ma, En Xie, Qian Shi; Leveraging AI to Evaluate Minimal Residual Disease Endpoint Surrogacy in Multiple Myeloma. Cancer Research Communications 2026; https://doi.org/10.1158/2767-9764.CRC-25-0393 May 1, 2026.   

Overview

Minimal residual disease (MRD) testing measures whether any myeloma cells remain detectable after treatment — even at very low levels. Achieving MRD negativity, particularly alongside a complete response (MRD-CR), has been linked to better long-term outcomes, and the FDA has been evaluating it as a potential endpoint for approving new myeloma treatments more quickly. This study set out to strengthen that evidence base using a novel AI-assisted approach to synthesizing data across trials.

Nineteen randomized clinical trials (20 treatment comparisons) were analyzed. At the trial level, MRD-CR rates explained 71% of the variation in survival outcomes across studies — a moderate but meaningful association. At the individual level, the picture was stronger: people who achieved MRD-CR were 7.28 times more likely to have better progression-free survival than those who did not.

The methodological contribution here is notable. Rather than waiting for raw patient data — which is rarely shared across trials — the researchers used AI tools to reconstruct synthetic individual-level data from published Kaplan-Meier curves and subgroup analyses. This allowed a more granular analysis than trial-level statistics alone permit.

The results add to the case that MRD-CR is a reliable surrogate for survival in myeloma, and that AI-assisted data synthesis could keep regulatory evidence bases current as new trial data emerges.

"A differentiated effector T cell repertoire defines a functionally high-risk group of smoldering myeloma patients"

Source

Firestone, R.S., Simhal, A.K., Akhlaghi, T. et al. A differentiated effector T cell repertoire defines a functionally high-risk group of smoldering myeloma patients. Blood Cancer J. 16, 67 (2026). https://doi.org/10.1038/s41408-026-01486-y May 1, 2026.    

Overview

Smoldering multiple myeloma (SMM) sits between MGUS and active myeloma — detectable disease, but without the organ damage that triggers treatment. The central clinical question is identifying which people with SMM will progress quickly and which will not, since many never develop active myeloma in their lifetimes. Current risk models, including the Mayo 2/20/20 score, rely on tumor burden measurements. This study asked whether immune system features in a standard blood draw could add predictive information independent of tumor burden.

Researchers compared peripheral blood T cell profiles from nine SMM patients who progressed to active myeloma within a median of 2.1 years against nine who had not progressed after a median follow-up of 8.6 years, matched by Mayo risk score at diagnosis. Using high-dimensional immune profiling and machine learning, they found that early progressors had higher levels of exhausted, terminally differentiated T cells — a pattern resembling the immune dysfunction seen in active myeloma. Four markers (Granzyme B, Granzyme K, CD272, and CD45RA) carried the most predictive weight, and a random forest model distinguished progressors from non-progressors with 75% accuracy.

Elevated IL-18 in plasma, a marker linked to immunosuppression in active myeloma, was also enriched in early progressors. Because the two groups were matched by conventional risk scores, these immune signatures appear to capture something tumor burden measurements miss. The sample size is small and findings require prospective validation, but the four-marker profile is simple enough for standard clinical flow cytometry.

"Targeting the immunological synapse in multiple myeloma"

Source

Sumei, L., Bahmani, F. Targeting the immunological synapse in multiple myeloma. Discov Onc (2026). https://doi.org/10.1007/s12672-026-05125-7 May 2, 2026.     

Overview

When a T cell recognys and kills a cancer cell, it does so through a highly structured contact point called the immunological synapse — essentially the physical interface through which the T cell delivers its lethal signal. In myeloma, this process breaks down. The bone marrow environment disrupts synapse formation, and myeloma cells exploit that disruption, along with metabolic changes and clonal evolution, to evade immune attack.

This review uses the immunological synapse as an organizing framework for understanding both why current T cell-based therapies sometimes fail and how next-generation approaches aim to fix that. It covers how bispecific antibodies (including BiTEs) force the formation of a synapse between T cells and myeloma cells, and how CAR-T cells build a modified version of that interface with distinct structural properties — comparing where these mechanisms overlap and where they diverge.

The review then looks ahead to approaches designed to build more durable and context-aware synaptic connections: trispecific antibodies, CAR-T constructs engineered with additional functional features, agents that modify the bone marrow niche itself, and emerging nanotechnology-based tools. Throughout, the authors separate findings from preclinical models from those with clinical evidence — an explicit methodological choice to avoid presenting hypothesis-generating data as equivalent to patient outcome data.

"Targeting the proteasome in cancer therapy: development and future opportunities in natural products"

Source

Zhao X, Liu S, Zeng X, Liao Y, Zhang M, Wang Q, Zhang D, Chen Q, Xian M and Qin Y (2026) Targeting the proteasome in cancer therapy: development and future opportunities in natural products. Front. Pharmacol. 17:1806787. doi: 10.3389/fphar.2026.1806787 May 3, 2026.     

Overview

Proteasome inhibitors — bortezomib, carfilzomib, and ixazomib — are central to myeloma treatment, but each carries meaningful toxicity (peripheral neuropathy, cardiovascular effects, and gastrointestinal side effects, respectively), and resistance, both at the outset and acquired over time, limits their long-term utility. This review examines whether natural product-derived compounds could yield next-generation proteasome inhibitors or help restore sensitivity in resistant disease.

The authors survey compounds that either inhibit the proteasome directly or enhance the effectiveness of existing inhibitors through separate mechanisms. Most face significant barriers to clinical use: poor bioavailability, short half-lives, off-target effects, and structural complexity that makes large-scale production difficult. Marizomib, derived from a marine bacterium, is the only natural product-derived proteasome inhibitor to reach clinical trials, though results in myeloma and solid tumors have so far been limited. Notably, the natural compound epoxomicin served as the structural basis for carfilzomib, illustrating how natural products can function as starting points for clinically approved drugs even when they cannot be used directly.

Beyond natural products, the review identifies emerging directions: targeting the 19S regulatory particle of the proteasome rather than its catalytic core (which sidesteps common resistance mutations), allosteric modulation strategies, and combinations with HSP90 or HDAC inhibitors. The authors also note that AI-assisted molecular screening may accelerate structural optimization of natural compound candidates. For people with myeloma who have developed resistance to current proteasome inhibitors, these alternative approaches represent the most plausible near-term paths to restoring treatment sensitivity.

"Immunomodulatory Agent Adherence Trajectories and Survival Among Older Patients With Multiple Myeloma"

Source

Rong Wang et al. Immunomodulatory Agent Adherence Trajectories and Survival Among Older Patients With Multiple Myeloma. JCO Oncol Pract 0, OP-25-00615 DOI:10.1200/OP-25-00615 May 4, 2026.     

Overview

Proteasome inhibitors — bortezomib, carfilzomib, and ixazomib — are central to myeloma treatment, but each carries meaningful toxicity (peripheral neuropathy, cardiovascular effects, and gastrointestinal side effects, respectively), and resistance, both at the outset and acquired over time, limits their long-term utility. This review examines whether natural product-derived compounds could yield next-generation proteasome inhibitors or help restore sensitivity in resistant disease.

The authors survey compounds that either inhibit the proteasome directly or enhance the effectiveness of existing inhibitors through separate mechanisms. Most face significant barriers to clinical use: poor bioavailability, short half-lives, off-target effects, and structural complexity that makes large-scale production difficult. Marizomib, derived from a marine bacterium, is the only natural product-derived proteasome inhibitor to reach clinical trials, though results in myeloma and solid tumors have so far been limited. Notably, the natural compound epoxomicin served as the structural basis for carfilzomib, illustrating how natural products can function as starting points for clinically approved drugs even when they cannot be used directly.

Beyond natural products, the review identifies emerging directions: targeting the 19S regulatory particle of the proteasome rather than its catalytic core (which sidesteps common resistance mutations), allosteric modulation strategies, and combinations with HSP90 or HDAC inhibitors. The authors also note that AI-assisted molecular screening may accelerate structural optimization of natural compound candidates. For people with myeloma who have developed resistance to current proteasome inhibitors, these alternative approaches represent the most plausible near-term paths to restoring treatment sensitivity.

"IgG2a-formatted 4-1BB agonism combined with S100A9 inhibition enhances T cell activation and tumor control in a preclinical model of multiple myeloma"

Source

Satilmis, H., Denis, A., Verheye, E. et al. IgG2a-formatted 4-1BB agonism combined with S100A9 inhibition enhances T cell activation and tumor control in a preclinical model of multiple myeloma. J Exp Clin Cancer Res (2026). https://doi.org/10.1186/s13046-026-03716-4 May 4, 2026.      

Overview

One reason immunotherapy often fails to produce lasting responses in myeloma is the bone marrow environment itself — it actively suppresses immune activity by impairing T and NK cell function and accumulating myeloid cells that block anti-tumor responses. This study tested whether simultaneously addressing both problems, boosting T and NK cell activity through a receptor called 4-1BB while reducing suppressive myeloid cells with a drug called tasquinimod, could improve outcomes in myeloma models.

4-1BB expression on T and NK cells increased as myeloma progressed in mice, and in bone marrow samples from newly diagnosed patients, stimulating 4-1BB with an experimental antibody called urelumab enhanced T cell and NK cell effector activity. In mouse models, however, the antibody's effectiveness depended heavily on its structural subtype: the IgG2a clone (3H3) reduced tumor burden meaningfully, while the IgG1 clone (LOB12.3) depleted NK cells and showed little anti-tumor effect — a finding with direct implications for how 4-1BB agonists are selected and developed clinically.

Combining 3H3 with tasquinimod produced the strongest results, reducing bone marrow plasmacytosis from 62.5% in untreated controls to 14.1%. The combination increased Granzyme B expression in T cells, promoted effector T cell differentiation, and stimulated dendritic cell maturation — collectively shifting the bone marrow environment from immunosuppressive to immune-active.
The results suggest that antibody subtype selection matters significantly for 4-1BB-based therapy, and that pairing 4-1BB stimulation with myeloid suppression inhibition may be a more effective approach than either strategy alone.

"Late and Durable Minimal Residual Disease Response Predicts Favorable Outcomes in Newly Diagnosed Multiple Myeloma"

Source

J.Zhou, W.Yan, Y.Liu, et al., “Late and Durable Minimal Residual Disease Response Predicts Favorable Outcomes in Newly Diagnosed Multiple Myeloma,” International Journal of Cancer (2026): 1–12, https://doi.org/10.1002/ijc.70465. May 4, 2026.      

Overview

MRD testing measures whether detectable myeloma cells remain after treatment. Achieving MRD negativity is associated with better outcomes, but most studies treat it as a single snapshot — either negative or positive at a given timepoint. This study asked whether the timing and duration of MRD response carries independent prognostic information, using data from 1,048 newly diagnosed people with myeloma across 5,406 MRD assessments collected over a decade in China.

Two findings stand out. First, people who took longer than six months to reach their best MRD response had better progression-free and overall survival than those who responded earlier — even when they never achieved full MRD negativity. Early responders were more likely to have high tumor burden and high-risk cytogenetic abnormalities, suggesting faster initial responses may reflect more aggressive disease biology rather than deeper disease control.

Second, sustaining a low and stable MRD level for 36 months or more predicted favorable outcomes regardless of whether MRD negativity was ever achieved, and regardless of cytogenetic risk or whether the person underwent stem cell transplant.

Combining both dimensions identified a "Late + Durable" pattern as the strongest predictor of long-term outcomes across all subgroups analyzed. The results make a practical case for tracking MRD longitudinally rather than relying on a single assessment, and suggest that stable low-level disease held over time may offset biological risk factors that would otherwise point toward poor prognosis.

"Delving into tRNA-derived small RNAs in multiple myeloma: elevated 3′U-tRFSerTGA leads to poor disease prognosis"

Source

Soureas, K., Malandrakis, P., Papadimitriou, MA. et al. Delving into tRNA-derived small RNAs in multiple myeloma: elevated 3′U-tRFSerTGA leads to poor disease prognosis. Br J Cancer (2026). https://doi.org/10.1038/s41416-026-03447-5 May 4, 2026.  

Overview

Accurate risk stratification in myeloma still relies heavily on cytogenetics and protein-based markers, but these don't capture the full picture of who will respond to treatment. This study investigated a different class of molecules — small RNA fragments derived from transfer RNAs, specifically a type called 3′U-tRFs — as potential prognostic markers in myeloma.

One fragment, 3′U-tRFSerTGA, was expressed at 14-fold higher levels in myeloma cell lines than in normal cells. In a cohort of 136 people with myeloma, elevated levels of this fragment in CD138-positive myeloma cells — measured at diagnosis — were associated with faster disease progression and worse survival. When incorporated into multivariate models alongside established risk factors, 3′U-tRFSerTGA improved the accuracy of risk stratification beyond what existing markers achieved alone, and decision curve analysis confirmed it added clinical utility rather than just statistical association.

The fragment's targets and downstream effects were mapped using gene ontology analysis, providing a mechanistic basis for its role in disease biology, though the review here focuses on its prognostic rather than functional implications.

The findings are limited to a single cohort and require external validation before clinical adoption. However, the marker is measurable by standard RT-qPCR from routine myeloma diagnostic material — CD138-positive cells already isolated during workup — which means it would not require additional invasive procedures if it moves toward clinical use.

"RAD23A promotes multiple myeloma cell survival through DNA damage response, proteostasis and enhanced metabolic activity"

Source

Hongxiu Liu, Yihua Wang, Xunru Liu, Ni Yang, Senxin Wang, Jie Zhao, Yaqi Shi, Huichao Wang, Yanping Ma, RAD23A promotes multiple myeloma cell survival through DNA damage response, proteostasis and enhanced metabolic activity, Toxicology and Applied Pharmacology, 2026, 117852, ISSN 0041-008X, https://doi.org/10.1016/j.taap.2026.117852. May 4, 2026. 

Overview

RAD23A is a protein with two established roles in normal cell biology: helping route damaged or misfolded proteins to the proteasome for disposal, and participating in DNA damage repair. This study examined whether RAD23A plays a functional role in myeloma, where both of those processes are already under therapeutic pressure.

Across multiple myeloma patient datasets, RAD23A was expressed at higher levels in myeloma cells than normal plasma cells, and higher expression correlated with greater disease burden and more advanced stage. Bioinformatics analysis suggested that myeloma cells with high RAD23A activity also showed elevated metabolic activity and increased protein trafficking.

Experimentally, silencing RAD23A in two myeloma cell lines suppressed cell growth in laboratory and mouse models, triggered DNA damage and endoplasmic reticulum stress, arrested cells at the G2/M phase of the cell cycle, and induced apoptosis. Metabolically, RAD23A knockdown reduced mitochondrial respiration, glycolytic activity, and glucose uptake — suggesting the protein supports the heightened energy demands of myeloma cells.

The finding with the most immediate therapeutic relevance is that RAD23A silencing increased myeloma cell sensitivity to bortezomib. Given that proteasome inhibitor resistance is a central challenge in myeloma management, and that RAD23A sits at the intersection of proteasome function and DNA repair — two pathways bortezomib directly stresses — the results position RAD23A as a plausible target for combination strategies aimed at overcoming or preventing resistance.

"Targeting Relapsed Multiple Myeloma with Elranatamab: A Bispecific Antibody Approach"

Source

Kumar S, Patel AK, Kumar D, Kumar V, Kumar S. Targeting Relapsed Multiple Myeloma with Elranatamab: A Bispecific Antibody Approach. Cardiovasc Hematol Agents Med Chem. 2026 May 4. doi: 10.2174/0118715257410908251210084136. Epub ahead of print. 

Overview

Elranatamab is a bispecific antibody that binds simultaneously to BCMA on myeloma cells and CD3 on T cells, physically bridging the two and triggering T cell-mediated killing of myeloma cells. It is approved for relapsed or refractory myeloma and has shown particular activity in penta-refractory disease — cases that have stopped responding to five or more prior treatment classes, where options are limited.

In clinical trials, elranatamab produced meaningful response rates in heavily pretreated people with myeloma. The main immune-related side effect is cytokine release syndrome (CRS), which occurs as T cells activate rapidly after the first doses; in trial data this was generally manageable, though monitoring and step-up dosing protocols are used to reduce severity.

The broader context for elranatamab is a wave of BCMA-directed therapies — including other bispecific antibodies and CAR-T cell products — that have reshaped the later-line treatment landscape in myeloma over the past several years. Where elranatamab fits within sequencing decisions, particularly relative to BCMA-targeted CAR-T therapy, remains an active area of investigation, as prior BCMA exposure can affect response to subsequent BCMA-directed treatment.

This review does not present new clinical data but synthesizes existing trial results and situates elranatamab within current and emerging combination strategies being studied to extend its effectiveness and address resistance.

"Isatuximab: an anti-CD38 therapy that addresses unmet needs and mechanisms of resistance in multiple myeloma"

Source

Liu, Y., Mo, C., Midha, S., Hartley-Brown, M., Lee, H. C., Franz, J., … Richardson, P. G. (2026). Isatuximab: an anti-CD38 therapy that addresses unmet needs and mechanisms of resistance in multiple myeloma. Expert Opinion on Investigational Drugs, 1–12. https://doi.org/10.1080/13543784.2026.2660911 May 4, 2026.  

Overview

Anti-CD38 antibodies have become a standard component of myeloma treatment across multiple lines of therapy. Daratumumab was first in class, but isatuximab — approved for both newly diagnosed and relapsed/refractory myeloma — targets CD38 through a distinct binding site and works through a different mix of mechanisms.

Most anti-CD38 antibodies kill myeloma cells primarily through immune-mediated pathways that depend on complement proteins. Isatuximab is less reliant on complement-dependent cytotoxicity and instead exerts more direct cytotoxic effects on myeloma cells. According to this review, that mechanistic difference may matter clinically in two specific situations: myeloma with 1q21 chromosomal abnormalities, a high-risk feature associated with treatment resistance, and extramedullary disease — myeloma growing outside the bone marrow — where complement activity may be less available or effective.

Clinical data reviewed here support a favorable benefit-risk profile across broad patient populations, including those with poor prognostic features, though this review does not present new trial data and does not directly compare isatuximab against daratumumab in head-to-head trials.

The review also notes that isatuximab is now available via an on-body injector, a subcutaneous delivery device that could reduce administration time compared to intravenous infusion — a practical consideration for people receiving ongoing maintenance or combination therapy requiring frequent dosing.

"Guidelines and consensus for minimal residual disease-adapted therapy in multiple myeloma from the Pan-Pacific multiple myeloma working group"

Source

Chen W, Cai Z, Chim CS, et al. Guidelines and consensus for minimal residual disease-adapted therapy in multiple myeloma from the Pan-Pacific multiple myeloma working group. Clinical Hematology International. 2026;8(2):7-25. doi:10.46989/001c.160933 May 4, 2026. 

Overview

MRD testing has moved from a research tool to a clinical priority in myeloma, particularly as CD38-based regimens — combining antibodies like daratumumab or isatuximab with standard backbones — produce deeper responses than earlier treatment generations. This expert consensus addresses how to integrate MRD assessment systematically into treatment decisions, given that practice has outpaced formal guidance.

The consensus recommends MRD assessment for nearly all people with myeloma, using a combination of bone marrow testing, imaging, and peripheral blood-based methods rather than any single approach. Both next-generation flow cytometry and next-generation sequencing are considered equivalent for prognostic purposes, giving centers flexibility based on available infrastructure. Peripheral blood-based MRD detection is flagged as a promising future direction that could reduce reliance on bone marrow biopsies for ongoing monitoring.

For people receiving CD38-based therapy, achieving and sustaining MRD negativity is strongly associated with better long-term outcomes. The consensus supports using CD38-based regimens as part of active maintenance, particularly in high-risk disease, and recommends that testing frequency and timing be adapted to treatment phase rather than applied at fixed intervals.

The broader shift the consensus reflects is from treating MRD as a one-time endpoint to treating it as a dynamic monitoring tool — one that can inform decisions about continuing, escalating, or de-escalating therapy over time. How that plays out in practice, particularly around treatment discontinuation in MRD-negative patients, remains an open question the consensus acknowledges but does not fully resolve.

"Infections in Patients Receiving Daratumumab for Newly Diagnosed Multiple Myeloma: A Pooled Analysis of MAIA and ALCYONE"

Source

Nizar J. Bahlis, Thierry Facon, Jesús F. San-Miguel, Saad Z. Usmani, Meletios-Athanasios A. Dimopoulos, Philippe Moreau, Sonja Zweegman, Aurore Perrot, Salomon Manier, Ajai Chari, Noopur S. Raje, Robert Z. Orlowski, Hartmut Goldschmidt, Supratik Basu, Cyrille Hulin, Katja C Weisel, Mohamad Mohty, Xavier Leleu, Torben Plesner, Andrzej J Jakubowiak, Gordon Cook, Hang Quach, Christopher P. Venner, Michele Cavo, Mai Ngo, Kasey Bolyard, Robin Carson, Fredrik Borgsten, Maria-Victoria Mateos, Shaji K Kumar; Infections in Patients Receiving Daratumumab for Newly Diagnosed Multiple Myeloma: A Pooled Analysis of MAIA and ALCYONE. Blood Adv 2026; bloodadvances.2025019323. doi: https://doi.org/10.1182/bloodadvances.2025019323 May 5, 2026.  

Overview

Daratumumab combined with standard doublet or triplet therapy has become a common approach for newly diagnosed myeloma in people who are not candidates for stem cell transplant, based on survival benefits shown in the MAIA and ALCYONE trials. Because myeloma and its treatment both suppress the immune system, infection risk is an ongoing concern — and adding daratumumab, which itself affects immune cell populations, raises questions about whether it compounds that risk.

This pooled analysis of both trials examined infection rates, timing, and management across a combined population with a median age of 72. Grade 3/4 infections (severe but not fatal) occurred in 36.9% of people receiving daratumumab-based therapy versus 22.4% in the control arms. Grade 5 infections (fatal) occurred in 3.0% versus 1.5%. However, when adjusted for the fact that people on daratumumab regimens stayed on treatment longer — and therefore had more exposure time — the rates between groups were more comparable.

The highest concentration of severe infections occurred in the first six months of treatment across both groups, pointing to that window as the period requiring the most active monitoring and preventive measures. Treatment discontinuation due to infection remained low at around 2% across all groups.

The practical implication is that while daratumumab-based regimens carry a higher absolute infection burden, much of that difference reflects longer treatment duration rather than a fundamentally different infection risk profile — though early treatment vigilance, prophylactic strategies, and adherence to IMWG infection management guidelines remain important throughout.

"Detection of cytokine release syndrome using wearables and cytokine profiling following CAR-T therapy for myeloma"

Source

Rajeeve S, Wilkes M, Zahradka N, Tomalin L, Quidwai M, Pan D, Calafat NJ, Cusack M, Aleman A, Serebryakova K, Kappes K, Jackson H, Agte S, Thibaud S, Sanchez L, Richard S, Richter J, Rodriguez C, Cho HJ, Chari A, Jagannath S, Laganà A, Rossi AC, Parekh S. Detection of cytokine release syndrome using wearables and cytokine profiling following CAR-T therapy for myeloma. JCI Insight. 2026 May 5:e203988. doi: 10.1172/jci.insight.203988.  

Overview

CAR-T cell therapy produces deep responses in relapsed or refractory myeloma, but cytokine release syndrome (CRS) — an immune reaction that can develop within days of infusion — currently requires inpatient monitoring, which limits where and how CAR-T can be delivered and adds significant cost. This pilot study tested whether consumer-grade wearable sensors could detect CRS early enough to be clinically useful.

Thirty people receiving ide-cel or cilta-cel were enrolled; 25 had sufficient data for analysis. CRS occurred in 20 of the 25. The best-performing wearable model detected 18 of those 20 CRS episodes, with sensitivity of 0.72 and specificity of 0.80, and identified CRS a median of seven hours before nursing staff recognized it through standard monitoring. Adherence to wearing the devices during high-risk periods was 71%.

Cytokine measurements taken before and after infusion showed that IFN-γ rose consistently alongside temperature in CRS episodes, reinforcing its potential as an early biochemical signal. Models combining wearable data with cytokine levels performed better than either alone.

The results are preliminary — 25 evaluable patients at a single center is a small sample — but the seven-hour lead time is clinically meaningful, as earlier CRS recognition allows earlier intervention with tocilizumab or corticosteroids before symptoms escalate. If validated in larger outpatient studies, wearable-based monitoring could be a practical step toward shifting CAR-T delivery outside the inpatient setting, expanding access for people with myeloma who face geographic or logistical barriers to specialized care centers.

"Smoldering multiple myeloma in transition: redefining early myeloma in the modern era"

Source 

Landgren, O. Smoldering multiple myeloma in transition: redefining early myeloma in the modern era. Leukemia (2026). https://doi.org/10.1038/s41375-026-02979-2 May 5, 2026. 

Overview

For decades, smoldering multiple myeloma (SMM) was managed with observation alone — monitoring for the organ damage or symptoms that would signal progression t…For decades, smoldering multiple myeloma (SMM) was managed with observation alone — monitoring for the organ damage or symptoms that would signal progression to active myeloma and trigger treatment. That approach has now been formally disrupted: the FDA approval of daratumumab for high-risk SMM marks the first time early intervention in SMM has regulatory backing, based on evidence that treatment at this stage can delay or prevent progression.

This review traces how the field reached this point, driven by three converging developments: more precise molecular characterization of plasma cell disorders, improved imaging that detects early bone involvement below the threshold of traditional CRAB criteria, and immunotherapy with activity earlier in the disease course than previously tested.

The approval raises questions that will define the next phase of SMM research. Current risk stratification tools, including the Mayo 2/20/20 model, were built to predict progression under observation — their calibration for a treated population is uncertain. Diagnostic boundaries between SMM, high-risk MGUS, and early myeloma are increasingly artificial as biology-based definitions replace symptom-based ones. The review raises the pointed question of whether, as reclassification continues in both directions — some SMM redefined as early myeloma warranting treatment, others as benign gammopathies that need only routine monitoring — there will eventually be any SMM patients left as a distinct category.

The limitations the authors acknowledge are practical: not everyone with high-risk SMM will progress, treatment carries toxicity and cost, and long-term outcome data from the daratumumab approval trial are still maturing.

"Microenvironmentally derived fatty acid–binding proteins 4 and 5 are novel therapeutic vulnerabilities in multiple myeloma"

Source 

Haylee Duval, Katherine Knox, Heather Fairfield, Ryan C. Chai, Alexander P. Corr, Ya-Wei Qiang, Kaitlyn Belknap, Kehinde Abayomi, Allyson Schimelman, Brian Nestor, Michelle Karam, Edward Jachimowicz, Patrizia J. Stohn, Xiangnan Guan, Matthew D. Lynes, Habib Hamidi, Peter I. Croucher, Sergey Ryzhov, Michaela R. Reagan; Microenvironmentally derived fatty acid–binding proteins 4 and 5 are novel therapeutic vulnerabilities in multiple myeloma. Blood Neoplasia 2026; 3 (2): 100229. doi: https://doi.org/10.1016/j.bneo.2026.100229 May 5, 2026. 

Overview

Obesity is associated with worse outcomes in myeloma, but the mechanisms connecting metabolic state to tumor progression in the bone marrow are poorly understood. This study focused on fatty acid-binding proteins 4 and 5 (FABP4 and FABP5) — proteins involved in fat metabolism and inflammation — asking whether versions of these proteins derived from the bone marrow microenvironment, rather than from myeloma cells themselves, contribute to disease progression.

In mice engineered to lack both FABP4 and FABP5, myeloma cell engraftment and tumor growth were lower than in normal mice. When fed a high-fat diet, the knockout mice were also protected from metabolic and skeletal deterioration, and showed further reductions in tumor incidence alongside improved survival — suggesting FABP4/5 contribute to myeloma progression through pathways that intersect with obesity-related biology.

The mechanism appears to involve immune suppression. In patient data, low FABP5 expression in granulocyte-monocyte progenitor cells — a cell population that normally dampens immune responses — was associated with better survival. The authors interpret this as evidence that FABP4/5 activity in these cells promotes immunosuppression within the bone marrow, limiting the immune system's ability to control myeloma.

Earlier research had identified FABP4/5 as relevant within myeloma cells themselves. These findings add a second, microenvironment-derived mechanism, suggesting that inhibiting FABP4/5 could simultaneously disrupt tumor-supportive signaling from outside the cancer cell and reduce immune suppression within the bone marrow — a two-pronged effect from a single target.

"Medication-related osteonecrosis of the jaw: incidence and risk factors in multiple myeloma patients undergoing pre-autologous stem cell transplant dental extractions"

Source 

Son, JE.D., Kim, J.W.J., Son, SH. et al. Medication-related osteonecrosis of the jaw: incidence and risk factors in multiple myeloma patients undergoing pre-autologous stem cell transplant dental extractions. Support Care Cancer 34, 502 (2026). https://doi.org/10.1007/s00520-026-10710-1 May 5, 2026. 

Overview

Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication where jaw bone tissue dies and fails to heal, most commonly triggered by dental procedures in people who have received intravenous bisphosphonates — drugs used in myeloma to reduce bone damage and fracture risk. This retrospective study examined how often MRONJ occurred after dental extractions performed before autologous stem cell transplant, and which factors increased that risk.

Among 320 people with myeloma who had teeth extracted prior to transplant at Princess Margaret Cancer Centre, 13 (4.1%) developed MRONJ. Periodontal disease was the most common reason extractions were performed in those who went on to develop the complication. Notably, even a single bisphosphonate dose before extraction was sufficient to cause MRONJ in some cases, and onset sometimes occurred years after the extraction itself.

The type of bisphosphonate mattered considerably. People prescribed zoledronic acid alone were nearly five times more likely to develop MRONJ than those on pamidronate alone. The highest risk group was people who had been switched from pamidronate to zoledronic acid, suggesting cumulative exposure and drug potency both contribute.

The findings have direct practical implications for dental planning before transplant. The decision to extract teeth in anyone with prior intravenous bisphosphonate exposure requires weighing the dental disease severity against a meaningful MRONJ risk — approximately 4% in this cohort. People in this situation should be informed of that risk and monitored for long enough after extraction to detect late-onset complications.

"Early mortality in multiple myeloma patients with renal impairment: a nested case-control study"

Source 

Li, Y., Tang, W., Xiang, B. et al. Early mortality in multiple myeloma patients with renal impairment: a nested case-control study. BMC Nephrol (2026). https://doi.org/10.1186/s12882-026-05018-5 May 6, 2026. 

Overview

Renal impairment affects a significant proportion of people with newly diagnosed myeloma — often caused by light chain deposition or hypercalcemia — and is associated with worse outcomes. This study focused specifically on early mortality, defined as death within 12 months of diagnosis, in 199 newly diagnosed people with myeloma and renal impairment treated at a single Chinese center between 2016 and 2022.

Early mortality occurred in 9.5% of the cohort. Pneumonia was the leading cause of death, reflecting the compounded immune vulnerability of myeloma combined with renal impairment. Comparing the 19 people who died within a year against 76 matched controls who survived beyond 12 months, two factors independently predicted early mortality: elevated LDH at diagnosis, a marker of high tumor burden and rapid cell turnover, and pneumonia present at diagnosis.

Elevated NT-proBNP and heart failure at diagnosis — which might be expected to predict early death given their cardiovascular implications — did not reach statistical significance in this analysis, though the small case numbers limit what can be concluded from negative findings.

One-year overall survival stratified cleanly by risk factor count: 95.3% with neither factor present, 85.2% with one, and 68.8% with both (p < 0.001). The risk score is simple enough for routine clinical use at diagnosis, and the findings suggest that people presenting with both elevated LDH and active pneumonia warrant particularly close monitoring and aggressive supportive care in the first year of treatment.

"The 'Hand as Foot' teaching method for IgA-type multiple myeloma"

Source 

Xiaoqin Pian, Cheng Jiang, Rui Liu, Donghai Han, The “Hand as Foot” teaching method for IgA-type multiple myeloma, Asian Journal of Surgery,2026, ISSN 1015-9584, https://doi.org/10.1016/j.asjsur.2026.04.089. May 6, 2026.  

Overview

Renal impairment affects a significant proportion of people with newly diagnosed myeloma — often caused by light chain deposition or hypercalcemia — and is associated with worse outcomes. This study focused specifically on early mortality, defined as death within 12 months of diagnosis, in 199 newly diagnosed people with myeloma and renal impairment treated at a single Chinese center between 2016 and 2022.

Early mortality occurred in 9.5% of the cohort. Pneumonia was the leading cause of death, reflecting the compounded immune vulnerability of myeloma combined with renal impairment. Comparing the 19 people who died within a year against 76 matched controls who survived beyond 12 months, two factors independently predicted early mortality: elevated LDH at diagnosis, a marker of high tumor burden and rapid cell turnover, and pneumonia present at diagnosis.

Elevated NT-proBNP and heart failure at diagnosis — which might be expected to predict early death given their cardiovascular implications — did not reach statistical significance in this analysis, though the small case numbers limit what can be concluded from negative findings.

One-year overall survival stratified cleanly by risk factor count: 95.3% with neither factor present, 85.2% with one, and 68.8% with both (p < 0.001). The risk score is simple enough for routine clinical use at diagnosis, and the findings suggest that people presenting with both elevated LDH and active pneumonia warrant particularly close monitoring and aggressive supportive care in the first year of treatment.

"B cell-centric immunosuppressive signature in the peripheral blood of newly diagnosed multiple myeloma"

Source 

Mohini Vig, Anil Kumar Gupta, Sandeep Rai, Atul Sharma, Lalit Kumar, Shweta Dubey, Ritu Gupta, B cell-centric immunosuppressive signature in the peripheral blood of newly diagnosed multiple myeloma, Clinical Immunology Communications, 2026, ISSN 2772-6134, https://doi.org/10.1016/j.clicom.2026.05.001. May 6, 2026. 

Overview

Most immune research in myeloma focuses on T cells and the bone marrow environment, but this study examined what happens to circulating B cells and antigen-presenting cells in the bloodstream of newly diagnosed people with myeloma — before any treatment has begun.

Compared to healthy donors, newly diagnosed people with myeloma showed expansion of three specific B cell populations: CD27-high memory B cells, PD-L1-expressing B cells, and regulatory B cells (Bregs). PD-L1 is an immune checkpoint protein more commonly discussed in the context of T cell suppression, but its expression on B cells can similarly dampen immune responses. Regulatory B cells actively suppress immune activity through cytokine signaling. The simultaneous expansion of both suggests the immune system is being pushed toward tolerance of myeloma cells even in peripheral blood, not just within the bone marrow.

At the same time, plasmacytoid dendritic cells (pDCs) — which normally coordinate early antiviral and antitumor immune responses — were significantly reduced. NK cells, conventional dendritic cells, and myeloid-derived suppressor cells showed no significant differences between groups.

The pattern points to a B cell-driven immunosuppressive shift occurring systemically at diagnosis, operating through checkpoint activation and regulatory cell expansion rather than through the myeloid suppression pathways more commonly studied. Whether these peripheral changes reflect or drive disease progression, and whether they normalize with treatment, are questions the study does not address but which follow logically from these findings.

"Central nervous system involvement in multiple myeloma as a first manifestation of relapse and potential diagnostic pitfall"

Source 

Ranaivomanana, J., Ryffel, L., Newinger, M., Mejri, A., Ojeda-Uribe, M., De Marini, P., Drénou, B., Le Garff-Tavernier, M., Lefebvre, T., & Debliquis, A. (2026). Central nervous system involvement in multiple myeloma as a first manifestation of relapse and potential diagnostic pitfall. Cytometry Part B: Clinical Cytometry, 1–7. https://doi.org/10.1002/cyto.b.70035 May 7, 2026. 

Overview

Central nervous system involvement in myeloma (CNS-MM) is rare but carries a poor prognosis, and its detection presents specific technical challenges. This case series reviewed 459 people with myeloma treated at a single center between 2016 and 2025, identifying four cases where malignant plasma cells were found in the cerebrospinal fluid (CSF).

Three of the four were in complete remission by standard assessments when CNS involvement was detected — meaning CNS-MM emerged as the first sign of relapse despite no evidence of systemic disease. Two had no lesions visible on imaging, underscoring that negative scans do not rule out CNS involvement. One presented with spinal cord compression rather than intracranial disease.

Two cases showed interference in flow cytometry analysis attributable to daratumumab, which appears to penetrate the CSF and bind to CD38 on plasma cells — the same mechanism that makes it therapeutically useful but which can mask malignant cells during diagnostic testing. This has direct implications for how CSF samples are analyzed in people who have received anti-CD38 therapy, as standard flow cytometry panels may underdetect disease in this setting.

IL-6 was elevated in CSF in some cases while IL-10 was low or undetectable, though the numbers are too small to draw firm conclusions about their diagnostic utility. Three of the four people died; one remained alive at two years.

The cases collectively make the case that any unexplained neurological symptoms in a person with myeloma — regardless of remission status or imaging findings — should prompt CSF analysis, and that flow cytometry panels used for that analysis need to account for the presence of anti-CD38 antibodies.

"Dual-antigen–targeting T-cell immunotherapies in MM: circumventing tumor heterogeneity and preventing antigen escape"

Source 

Niels W. C. J. van de Donk, Pieter Sonneveld, Hermann Einsele; Dual-antigen–targeting T-cell immunotherapies in MM: circumventing tumor heterogeneity and preventing antigen escape. Blood 2026; 147 (19): 2176–2193. doi: https://doi.org/10.1182/blood.2025032536 May 7, 2026. 

Overview

Most CAR-T and bispecific antibody therapies in myeloma target a single antigen — typically BCMA or GPRC5D. A well-documented reason for relapse after these treatments is antigen escape: myeloma cells lose or reduce expression of the targeted protein through deletion, mutation, or epigenetic changes, making them invisible to the therapy. Tumor heterogeneity compounds the problem, as subpopulations with low or absent antigen expression can be present from the outset and expand under treatment pressure.

Targeting two antigens simultaneously is the proposed solution. This review surveys dual-targeting strategies currently in development, including combinations of two separate bispecific antibodies, trispecific antibodies engineered to engage two tumor targets and CD3 simultaneously, and CAR-T products directed at more than one antigen.

Among bispecific combinations, teclistamab (BCMA-directed) combined with talquetamab (GPRC5D-directed) has shown activity that appears higher than either agent alone in comparable patient populations. Two trispecific antibodies — ramantamig, targeting BCMA and GPRC5D, and ISB 2001, targeting BCMA and CD38 — have produced promising early results in heavily pretreated myeloma. Dual-antigen CAR-T products have demonstrated efficacy in advanced disease, though none has yet shown clear superiority over cilta-cel, currently the benchmark single-target BCMA CAR-T, in direct comparison.

The review concludes that dual-targeting approaches need evaluation in large phase 3 trials against sequential single-target therapy with antigen switching — the current standard practice when one target is lost — before their place in treatment sequencing can be established.

"Ruxolitinib for ciltacabtagene autoleucel–associated refractory diarrhea"

Source 

Viktoria Blumenberg, Filippo Birocchi, Angela Shih, Giulia Escobar, Adele Mucci, Alexander Armstrong, Diana Cirstea, Deshea L. Harris, David J. Bozym, Benjamin R. Puliafito, Richard Newcomb, Tejaswini M. Dhawale, Patrick C. Johnson, Areej El-Jawahri, Richard Jeffrey, Alexis L. Barselau, Alex Li, Estelle Emmanuel-Alejandro, Daniella Cook, Kevin Lindell, Samantha O. Luk, Ryan Chaffee, Andrew J. Yee, Andrew Branagan, Noopur Raje, Charlotte E. Graham, Sarah P. Hammond, Frederic D. Bushman, Aoife M. Roche, Shantan Reddy, Alexander G. McFarland, Yi-Bin Chen, Bryan D. Choi, Christopher W. Mount, Michael Dougan, Valentina Nardi, Aliyah R. Sohani, Kathleen M. E. Gallagher, Marcela V. Maus, Matthew J. Frigault, Mark B. Leick; Ruxolitinib for ciltacabtagene autoleucel–associated refractory diarrhea. Blood 2026; 147 (19): 2215–2225. doi: https://doi.org/10.1182/blood.2025032347 May 7, 2026. 

Overview

Severe, treatment-resistant diarrhea has been identified as a complication of BCMA-directed CAR-T therapy in myeloma, with reported mortality rates of 36% to 50% in described cases — making it a clinically urgent problem without an established treatment approach. This case series describes five people who developed severe diarrhea after BCMA CAR-T treatment and reports on the use of ruxolitinib, a JAK inhibitor, as a potential treatment.

The rationale for trying ruxolitinib came from its established effectiveness in graft-versus-host disease after allogeneic bone marrow transplant and other immune-mediated gastrointestinal conditions — settings that share mechanistic similarities with CAR-T-associated diarrhea. Three of the five people received ruxolitinib and all three improved rapidly. In two cases where tissue biopsies were taken before and after treatment, both showed histopathologic signs of response. One of those two had a specific finding — CAR T-cell–associated indolent T-cell lymphoproliferative disease of the gastrointestinal tract — a rare diagnosis that adds complexity to understanding the underlying mechanism.

Five patients is a very small number, and without a control group or larger prospective data, firm conclusions about efficacy cannot be drawn. However, given the high mortality associated with this complication and the absence of any standard treatment, these results provide a rationale for prospective evaluation of ruxolitinib in this setting. For people with myeloma who have received BCMA CAR-T therapy and develop severe or persistent diarrhea, this case series represents currently one of the few available clinical references.

"Bispecific Antibodies in Hematologic Malignancies in the Outpatient and Community Settings"

Source 

Gonugunta, Amrit S., Haider, Asad, Mohlere, Virginia, Aljurf, Mahmoud, Hashmi, Shahrukh, Abid, Muhammad Bilal, Bispecific Antibodies in Hematologic Malignancies in the Outpatient and Community Settings, Advances in Hematology, 2026, 4529571, 11 pages, 2026. https://doi.org/10.1155/ah/4529571 May 7, 2026. 

Overview

Bispecific antibodies have become an important treatment option in relapsed or refractory myeloma, but most are currently administered in academic or specialized centers — creating access barriers for people who live far from those facilities or face other logistical constraints. This review examines whether bispecific antibodies can be safely moved into community oncology settings, and what infrastructure would be required to do so.

The core argument rests on a safety distinction: bispecific antibodies carry meaningfully lower rates of severe immune toxicity, particularly cytokine release syndrome, than CAR-T cell therapy. This makes them more amenable to outpatient and community administration, where intensive monitoring capacity is more limited. The review covers the specific toxicity profiles of FDA-approved bispecific antibodies and proposes a disease-agnostic framework — applicable across cancer types — for managing those toxicities outside specialized centers.

Practical barriers to broader deployment include provider unfamiliarity with step-up dosing protocols, limited experience managing CRS and immune effector cell-associated toxicities outside academic settings, and the absence of standardized community-facing guidelines. The authors identify education, protocol sharing between academic and community centers, and development of administrative templates as the primary levers for closing that gap.

The access dimension is clinically relevant for myeloma specifically, where bispecific antibodies are increasingly used in later lines of therapy and where treatment delays due to geographic barriers can affect outcomes. Expanding the number of sites capable of administering these therapies safely would bring them within reach of people who currently cannot access them.

"MGUS prevalence among active-duty military personnel"

Source 

Kazandjian, D., DeStefano, C., Darmon, S. et al. MGUS prevalence among active-duty military personnel. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01511-0 May 7, 2026. 

Overview

MGUS — the precursor condition that can progress to myeloma — has been linked to environmental exposures, raising questions about whether burn pit exposure during military deployment in Iraq increases prevalence among service members. This retrospective cohort study compared MGUS rates across three groups of active-duty service members: those deployed to Iraq with self-reported burn pit exposure, those deployed to Germany without burn pit exposure, and non-deployed service members. Serum samples were analyzed 11 to 14 years after deployment.

MGUS prevalence did not differ meaningfully across the three groups — 5.6% in the Iraq-deployed group, 4.3% in the Germany-deployed group, and 5.2% in non-deployed service members — suggesting burn pit exposure specifically did not drive elevated rates. However, overall MGUS prevalence of 5% across the cohort is higher than rates typically reported in age-matched civilian populations, pointing toward cumulative military service exposures — not specific to burn pits — as a possible contributor to plasma cell dysregulation.

The racial disparity was pronounced: MGUS prevalence was 10.4% in Black service members versus 3.9% in White service members, consistent with patterns seen in civilian populations and reinforcing the need for targeted screening approaches in higher-risk groups.

A methodological finding with practical implications: when conventional free light chain reference intervals were used, deployed service members appeared to have higher rates of light-chain MGUS. That association disappeared when updated reference intervals were applied, underscoring that the choice of reference range meaningfully affects how many people receive an MGUS diagnosis — and that outdated intervals risk overdiagnosis.

"Podocarpusflavone A Inhibits Multiple Myeloma Cells by Targeting the PI3K/AKT Pathway to Mediate c-Myc Downregulation and Activate the Intrinsic Apoptosis Pathway"

Source 

Jian Gao, Guanghui Cheng, Haimei Jiang, Jiawen Chu, Mengyuan Zhang, Podocarpusflavone A Inhibits Multiple Myeloma Cells by Targeting the PI3K/AKT Pathway to Mediate c-Myc Downregulation and Activate the Intrinsic Apoptosis Pathway, Toxicon, 2026, 109143, ISSN 0041-0101, https://doi.org/10.1016/j.toxicon.2026.109143. May 7, 2026. 

Overview

Podocarpusflavone A is a natural compound derived from Podocarpus plants with documented antitumor activity in other cancers, but its effects on myeloma had not previously been studied. This investigation used cell line experiments and bioinformatic analysis to characterize how it affects myeloma cells and which molecular pathways it engages.

In two myeloma cell lines (U266 and RPMI-8226), Podocarpusflavone A reduced cell viability with IC50 values of 8.87 μM and 17.49 μM respectively — concentrations at which half the cells were killed. It induced apoptosis in a dose-dependent manner by shifting the balance between pro-survival and pro-death proteins: Bcl-2 decreased while BAX and cleaved caspase-3 increased, activating the intrinsic, mitochondria-dependent cell death pathway.

Bioinformatic analysis identified the PI3K/AKT signaling pathway as a primary target, confirmed by Western blot. Suppressing this pathway reduced activity of c-Myc, an oncogenic driver frequently overactive in myeloma. The compound also increased intracellular reactive oxygen species, caused DNA damage, and disrupted mitochondrial membrane potential — effects that collectively amplify apoptotic signaling.

The findings are limited to cell line experiments; there are no animal model data or evidence of activity in primary patient samples. IC50 values in the low micromolar range are promising for a natural compound but would need to be evaluated for achievable concentrations in vivo before the therapeutic relevance can be assessed. The study establishes a mechanistic foundation for further investigation, particularly given the PI3K/AKT and c-Myc connections to known resistance mechanisms in myeloma.

"A dexamethasone-free daratumumab–ixazomib regimen in frail elderly patients with relapsed or refractory multiple myeloma: Results of the IFM 2018-02 phase II study."

Source 

Bobin A, Macro M, Touzeau C, Mariette C, Manier S, Brechignac S, et al. A dexamethasone-free daratumumab–ixazomib regimen in frail elderly patients with relapsed or refractory multiple myeloma: Results of the IFM 2018-02 phase II study. Br J Haematol. 2026;00:1–9. https://doi.org/10.1111/bjh.70512 May 7, 2026.  

Overview

Managing relapsed or refractory myeloma in older, frail people presents distinct challenges: standard regimens are often poorly tolerated, adverse events accumulate, and treatment discontinuations are common. Dexamethasone, a cornerstone of most myeloma combinations, is a particular concern in this population given its effects on blood sugar, bone density, mood, and infection risk. The IFM 2018-02 trial tested whether daratumumab combined with ixazomib — omitting dexamethasone entirely and substituting low-dose methylprednisolone — could produce meaningful responses with acceptable tolerability in frail older people with myeloma.

The 55 participants had a median age of 82, with 90% over 75, and all met formal frailty criteria. This is an older and more frail population than typically enrolled in myeloma trials. At first or second relapse, 32% achieved a very good partial response or better. Median progression-free survival was 19.5 months, and overall survival at 33.6 months was 75%, with median OS not yet reached at the time of analysis.

Grade 3 or higher adverse events occurred in 67% of participants, with cytopenias (low blood counts) in 18 people and infections — predominantly pneumonia — in 8. These rates reflect the vulnerability of this population rather than an unusually toxic regimen; the all-oral ixazomib component and subcutaneous daratumumab administration avoid infusion-related burdens that can be particularly challenging for frail older people.

The results position the dexamethasone-free daratumumab plus ixazomib combination as a viable option for frail older people with relapsed myeloma who may not tolerate more intensive standard regimens.

"CCT2 regulates the proliferation, apoptosis, and cell cycle arrest of multiple myeloma cells through the P53 signalling pathway"

Source 

Wang, H., Chen, X., Liu, Y. et al. CCT2 regulates the proliferation, apoptosis, and cell cycle arrest of multiple myeloma cells through the P53 signalling pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-51083-z May 7, 2026.  

Overview

CCT2 is a subunit of a molecular chaperone complex that helps proteins fold correctly — a process myeloma cells depend on heavily given their high rate of immunoglobulin production. This study examined whether CCT2 plays a functional role in myeloma progression and whether it could serve as a therapeutic target.

Across patient cohorts, CCT2 expression was higher in myeloma cells than normal cells, correlated positively with plasma cell burden, and correlated negatively with survival — meaning higher CCT2 expression was associated with worse outcomes. These associations held in both bioinformatic analysis and clinical sample data.

Functionally, silencing CCT2 in myeloma cell lines activated the p53 tumor suppressor pathway, induced apoptosis, and caused cell cycle arrest, collectively reducing proliferation. The same effects were confirmed in a mouse xenograft model, where CCT2 knockdown suppressed tumor growth in vivo. The mechanism appears to operate primarily through p53 — a pathway that is intact in many myeloma cases, though notably disrupted in high-risk disease with TP53 mutations or del(17p).

The findings position CCT2 as a regulator of myeloma cell survival that operates, at least in part, by suppressing p53 activity. Whether CCT2 inhibition would retain activity in TP53-mutated or deleted myeloma — where p53 reactivation would be ineffective — is a relevant question the study does not address. The results are limited to cell lines and mouse models and require validation in primary patient samples before therapeutic implications can be assessed.

"Therapeutic Horizon in Multiple Myeloma: Analysis of the Emerging Landscape of Clinical Trials."

Source 

Rodrigues, M.A., de Pádua, C.A.M., de Miranda Drummond, P.L. et al. Therapeutic Horizon in Multiple Myeloma: Analysis of the Emerging Landscape of Clinical Trials. Ther Innov Regul Sci (2026). https://doi.org/10.1007/s43441-026-00971-7 May 7, 2026. 

Overview

This analysis mapped the clinical trial landscape for myeloma across a decade, screening over 3,000 trial records from ClinicalTrials.gov and a drug intelligence database, and analyzing 365 studies in detail.

Cell therapies dominated the investigational pipeline, accounting for 47% of eligible trials. CAR-T products targeting BCMA led with 107 trials, followed by CD19 (16 trials) and GPRC5D (12 trials) — reflecting the rapid expansion of immune-targeting approaches that has reshaped later-line myeloma treatment over this period. Biologic agents overall made up 69% of investigational therapies, with phase 1 trials the most common stage, indicating that much of the pipeline remains in early development.

Trial activity grew at 1.86% per year before a statistical inflection point, then accelerated to 3.69% per year afterward — roughly doubling the pace of new trial initiation. Over the full decade, the average annual growth rate was 2.63%, translating to a meaningful and sustained expansion in the number of studies active at any given time.

The data reflect a field that has moved substantially away from chemotherapy-based approaches toward targeted biologics and cell therapies, with immunotherapy now the dominant research direction. The acceleration in trial growth after the joinpoint coincides with the emergence of bispecific antibodies and next-generation CAR-T products as active areas of investigation. For people with myeloma, the expanding trial landscape represents a growing number of potential access points to investigational therapies, particularly in relapsed or refractory settings where standard options have been exhausted.

"Clinical and Immune Features Associated With Chromosome 13q Deletion and PRKCSH Downregulation in Newly Diagnosed Multiple Myeloma"

Source 

Jiayuan Li, Zuxi Feng, Wen Yang, Xiaoping Wang, Wen Zhou, Liansheng Zhang, Lijuan Li, Clinical and Immune Features Associated With Chromosome 13q Deletion and PRKCSH Downregulation in Newly Diagnosed Multiple Myeloma, Leukemia Research, 2026, 108249, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2026.108249. May 8, 2026.  

Overview

Deletion of chromosome 13q is one of the most common cytogenetic abnormalities in myeloma, but its immunological consequences have received little attention. This study examined whether del(13q) is associated with measurable differences in the immune profile of newly diagnosed people with myeloma, combining peripheral blood flow cytometry and cytokine measurements in 132 patients with transcriptomic analysis of publicly available datasets.

People with del(13q) showed higher circulating levels of IL-8 and IL-10 — cytokines associated with immune suppression and tumor-supportive inflammation — alongside a redistribution of lymphocyte populations: fewer T cells, including a reduction in CD4+CD8+ double-positive T cells, and higher NK cell proportions. Clinically, del(13q) correlated with more advanced ISS stage, higher rates of co-occurring high-risk cytogenetic lesions, hypercalcemia, elevated beta-2 microglobulin, and greater bone marrow plasmacytosis — suggesting it marks a more systemically advanced disease state.

Transcriptomic analysis identified PRKCSH as a consistently downregulated gene in del(13q) myeloma and linked it to immune-related pathways. Lower PRKCSH expression was associated with higher R-ISS stage and worse progression-free and overall survival. Immune cell deconvolution showed that PRKCSH levels correlated positively with CD8+ T cells, resting dendritic cells, and follicular helper T cells, and inversely with naive CD4+ T cells and gamma-delta T cells — a pattern consistent with a less functional anti-tumor immune environment.

The findings suggest del(13q) is not simply a marker of tumor biology but is associated with a distinct systemic immune state, and that PRKCSH downregulation may be a mechanistic link between this chromosomal loss and adverse immune and clinical outcomes.

"Blood urea nitrogen as a predictor of 28-day mortality in ICU patients with multiple myeloma: A retrospective cohort study (MIMIC-IV, 2008–2019"

Source 

Lan, Tianbi MMa; Wang, Xiaoli MMb; Tu, Guang MMc; Cai, Zhonglan MMc; Xu, Ling MMd; Luo, Yijun MMb,*. Blood urea nitrogen as a predictor of 28-day mortality in ICU patients with multiple myeloma: A retrospective cohort study (MIMIC-IV, 2008–2019). Medicine 105(19):p e48694, May 08, 2026. | DOI: 10.1097/MD.0000000000048694   

Overview

Kidney involvement is common in myeloma, and people who require intensive care admission represent a particularly high-risk group. This retrospective study examined whether blood urea nitrogen (BUN) — a standard, inexpensive measure of kidney function available on routine admission bloodwork — could predict 28-day mortality in critically ill people with myeloma.

Among 304 ICU admissions drawn from a large US critical care database (2008–2019), BUN measured within the first 24 hours was an independent predictor of mortality after adjustment for other clinical variables. Each 1 mg/dL increase in BUN was associated with a 1% higher mortality risk. Divided into tertiles, the difference was pronounced: compared to those with BUN below 23 mg/dL, those in the middle tertile (23–44 mg/dL) had 3.47 times the mortality risk, and those above 44 mg/dL had 6.96 times the risk. Survival curves separated early and remained distinct across the follow-up period.

A threshold effect was observed at approximately 52.57 mg/dL, above which additional BUN elevation did not further increase risk — suggesting a ceiling effect rather than a linear relationship at the highest values.

The practical case for BUN as a risk stratification tool in this setting is straightforward: it is universally available, requires no additional testing, and is already collected on ICU admission. The findings suggest that people with myeloma admitted to intensive care with BUN above 44 mg/dL — and particularly above 52 mg/dL — represent a group where early, intensified intervention may be warranted.

"Ikaros degradation by mezigdomide reduces T-cell dysfunction and improves the efficacy of antimyeloma T-cell therapies"

Source 

Lucia Y Chen, Adolfo Aleman, Marta Larrayoz, Hsiling Chiu, Junfei Zhao, Oliver Van Oekelen, Geoffrey Kelly, Seunghee Kim-Schulze, Alessandro Lagana, Sundar Jagannath, Tracy T. Chow, Teresa Lozano, Juan J Lasarte, Joseph C. Hamley, Warren Baker, Benjamin L Ebert, Udo Oppermann, Michael D Amatangelo, Anita Krithivas Gandhi, Patrick Ryan Hagner, Jose A Martínez-Climent, Sarah Gooding, Thomas A Milne, Samir Parekh; Ikaros degradation by mezigdomide reduces T-cell dysfunction and improves the efficacy of antimyeloma T-cell therapies. Blood 2026; blood.2025030891. doi: https://doi.org/10.1182/blood.2025030891 May 8, 2026.  

Overview

T cell exhaustion — where T cells progressively lose their ability to recognize and kill cancer cells — is a central reason why CAR-T and bispecific antibody therapies eventually fail in myeloma, and why myeloma itself continues to progress despite an intact immune system. This study investigated whether mezigdomide, a next-generation cereblon modulator (CELMoD), can reverse T cell exhaustion and improve the effectiveness of T cell-based therapies.

In bone marrow samples from people with myeloma, mezigdomide reduced populations of T cells expressing TIGIT, an exhaustion marker associated with impaired anti-tumor function. In laboratory models of T cell dysfunction, mezigdomide improved T cell activity and cytotoxicity, including in the context of bispecific T cell engager therapy — suggesting it could enhance the effectiveness of these agents when used in combination.

The mechanistic work is the study's most novel contribution. Using four concurrent genomic profiling techniques on primary T cells, the researchers identified the transcription factor Ikaros as a direct regulator of TIGIT expression. Mezigdomide, which degrades Ikaros through cereblon-mediated pathways, reduces TIGIT upregulation by removing this transcriptional driver — providing a molecular explanation for how CELMoDs reduce exhaustion that was not previously established.

In a mouse model, mezigdomide combined with anti-BCMA CAR-T therapy improved survival compared to CAR-T alone. Together, the findings make a mechanistic and functional case for combining mezigdomide with CAR-T or bispecific antibody therapy in myeloma, with Ikaros-TIGIT signaling as the pathway being targeted.

"Real-world outcomes of patients with multiple myeloma who reach third-line therapy: a Canadian report"

Source 

Martha L. Louzada, Donna Reece, Christopher P. Venner, Darrell White, Jiandong Su, Michael P. Chu, Victor H. Jimenez- Zepeda, Arleigh Mccurdy, Kevin Song, Hira Mian, Michael Sebag, Debra Bergstrom, Julie Stakiw, Anthony Reiman, Rami Kotb, Muhammad Aslam, Rayan Kaedbey, Engin Gul, Smriti Sharma, Richard LeBlanc; Real-world outcomes of patients with multiple myeloma who reach third-line therapy: a Canadian report. Blood Neoplasia 2026; 3 (2): 100215. doi: https://doi.org/10.1016/j.bneo.2026.100215 May 9, 2026.    

Overview

Treatment decisions at third relapse in myeloma are complex, shaped by what therapies a person has already received, their remaining organ function, and how quickly they progressed through earlier lines. This retrospective analysis used the Canadian Myeloma Research Group database — covering over 10,000 people with plasma cell disorders across major Canadian centers — to examine what third-line regimens were actually chosen in practice between 2015 and 2020, and how they performed.

Among 1,125 people included, immunomodulatory agents were the most commonly used drug class (62%), followed by proteasome inhibitors (44%) and anti-CD38 antibodies (25%). The combination of daratumumab plus lenalidomide, with or without a corticosteroid, produced the longest progression-free survival at a median of 25.6 months — substantially better than other regimens analyzed. Anti-CD38 antibody combined with pomalidomide, and most PI-based regimens, produced median progression-free survival of six to nine months. Median overall survival across the full cohort was 29.7 months.

Several factors predicted worse outcomes: high-risk cytogenetics by FISH, shorter time from diagnosis to third-line therapy, prior exposure to all three major drug classes, previous proteasome inhibitor exposure, and lenalidomide refractoriness. The last two are particularly relevant given how most people arrive at third-line therapy today — typically having received lenalidomide in earlier lines — which means the strong performance of daratumumab-lenalidomide may be less replicable in current practice where lenalidomide refractoriness is more prevalent at this treatment stage.

"Electrorotation as a tool for the dielectric characterization of tumor plasma cells in multiple myeloma"

Source 

Scandura, G., Moscato, S., Dulcamare, I. et al. Electrorotation as a tool for the dielectric characterization of tumor plasma cells in multiple myeloma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-49392-4 May 8, 2026.   

Overview

Myeloma is clinically heterogeneous — different people, and even different cell populations within the same person, respond differently to the same treatments. Most approaches to characterizing that heterogeneity rely on genetic or protein biomarkers, which require specific reagents and can miss functional differences not captured at the molecular level. This proof-of-concept study tested whether the electrical properties of myeloma cells could distinguish between cell populations with different biological characteristics.

Using a technique called electrorotation (ROT), which measures how cells rotate in a rotating electric field based on their dielectric properties, the researchers analyzed three myeloma cell lines with distinct metabolic profiles and different sensitivity to proteasome inhibitors. Membrane capacitance and electrical impedance — physical properties of the cell membrane — differed between cell lines in ways that correlated with their metabolic activity, stress response pathway activation, and bortezomib sensitivity.

The significance is methodological: electrorotation requires no antibodies, fluorescent labels, or genetic assays. It characterizes cells based purely on their biophysical properties, which reflect the integrated state of membrane composition, cell size, and internal organization. In myeloma, where treatment resistance involves metabolic reprogramming and stress response adaptation alongside genetic changes, a label-free functional readout could complement existing characterization approaches.

The study is explicitly a proof of concept with three cell lines, and substantial development would be required before this approach could be applied clinically. However, the ability to discriminate proteasome inhibitor sensitivity through a purely physical measurement — without prior knowledge of which biomarkers to test — points toward potential applications in functional drug sensitivity testing.

"Retreatment with talquetamab and pomalidomide in triple-class–BCMA–GPRC5D refractory myeloma"

Source 

Rahbari, K.J., Galarza Fortuna, G.M., Dholaria, B., Sborov, D.W. and Baljevic, M. (2026), Retreatment with talquetamab and pomalidomide in triple-class–BCMA–GPRC5D refractory myeloma. Br J Haematol. https://doi.org/10.1111/bjh.70540 May 10, 2026. 

Overview

People with myeloma who have progressed through multiple drug classes — including BCMA- and GPRC5D-directed therapies — have very limited options, with median survival around one year in real-world data. This letter describes three people in exactly that situation who achieved deep, rapid responses after pomalidomide was reintroduced alongside talquetamab, despite all three having previously been refractory to both drugs individually.

All three had triple-class refractory disease with multiple high-risk features; two had also progressed through XPO-1 inhibition. Two achieved stringent complete responses and one achieved a complete response, in most cases after only a few treatment cycles. All three remained on the combination at 8 to 11 months with manageable toxicity — cytopenias, mild skin and nail changes, and taste disturbance — without serious infections or cytokine release syndrome.

The authors propose that the combination may restore T cell fitness in ways that neither drug achieves alone. Pomalidomide and related immunomodulatory drugs are known to improve CD8/CD4 ratios, promote stem cell-like memory T cell differentiation, and reduce regulatory T cells — effects that could counteract the T cell exhaustion that drives talquetamab resistance. Whether antigen escape, T cell dysfunction, or microenvironmental factors were the primary resistance mechanism in these cases is unknown.

Existing combination trials of talquetamab and pomalidomide have largely excluded patients with prior pomalidomide refractoriness or prior GPRC5D exposure, meaning these three cases sit outside the populations studied so far. The observations do not establish mechanism, but they raise a clinically relevant question about whether IMiD-mediated T cell modulation can resensitize tumors to T cell-redirecting therapy after resistance has developed.

"Melflufen in Multiple Myeloma: Clinical Limitations, Biological Rationale, and Future Perspectives"

Source 

Garibotto, M., Soncini, D., Lemoli, R. M., Cagnetta, A., & Cea, M. (2026). Melflufen in Multiple Myeloma: Clinical Limitations, Biological Rationale, and Future Perspectives. Cancers, 18(10), 1551. https://doi.org/10.3390/cancers18101551 May 10, 2026. 

Overview

Melflufen was designed to exploit a feature of myeloma cells: their high aminopeptidase activity. As a peptide-drug conjugate, it is taken up by cells and cleaved internally to release a concentrated alkylating payload — a mechanism intended to improve intracellular drug delivery while limiting systemic exposure. Early clinical results were encouraging enough to support FDA accelerated approval in 2021 for heavily pretreated relapsed or refractory myeloma.

The phase 3 OCEAN trial, however, found worse overall survival in the melflufen arm compared to the comparator, pomalidomide plus dexamethasone. This led to market withdrawal in the US — a relatively rare regulatory outcome and one that reflects how seriously the survival signal was taken, given that accelerated approval had already been granted based on response rate data.

This review traces melflufen's development from biological rationale through clinical trials to its regulatory withdrawal, and asks what can be salvaged from the experience. The authors argue that the underlying concept — using enzyme activity differences between tumor and normal cells to concentrate drug intracellularly — remains biologically valid even though melflufen itself failed to demonstrate a survival benefit. The OCEAN results may reflect issues specific to melflufen's design, the patient population studied, or the comparator chosen, rather than a fundamental flaw in the peptide-drug conjugate approach.

For people with myeloma, melflufen is no longer available in the US. The review's practical relevance lies in its assessment of what the trial data reveal about patient selection and biomarker-driven strategies that could inform future development of next-generation compounds using similar delivery mechanisms.

"Plasma cell myeloma: multiple calvarial lytic lesions of an individual from the Middle Ages"

Source 

Lorkiewicz-Muszyńska, D., Rzepczyk, S., Andrzejewska, M. et al. Plasma cell myeloma: multiple calvarial lytic lesions of an individual from the Middle Ages, Poland. npj Herit. Sci. (2026). https://doi.org/10.1038/s40494-026-02613-5 May 10, 2026. 

Overview

This case report describes the identification of multiple myeloma in an archaeological skull discovered by a farmer in rural Poland. The cranium, partially preserved with multiple lytic lesions, was initially reported to law enforcement before being transferred for scientific analysis.

Macroscopic and microscopic examination, CT imaging, and radiocarbon dating were performed. The biological profile indicated the remains belonged to an adult female, and CT findings — the same imaging used in current clinical practice — were consistent with plasma cell myeloma based on the pattern, size, and distribution of the lytic lesions. Radiocarbon dating placed the individual in the 11th to 12th centuries AD.

Diagnosis was necessarily limited to imaging, as blood, urine, and bone marrow analysis are not possible on skeletal remains of this age. The lytic lesion pattern visible on CT, however, is sufficiently characteristic that a confident retrospective diagnosis could be made without laboratory confirmation.

The case adds to a small body of paleopathological evidence for myeloma in pre-modern populations, contributing one of relatively few documented cases from Poland. Beyond its regional significance, it serves as a reminder that myeloma is not a disease of modern life or modern medicine — it has affected humans for at least a millennium, long before the diagnostic tools or treatments that define how the disease is understood and managed today existed.

"Plasma cell myeloma: multiple calvarial lytic lesions of an individual from the Middle Ages"

Source 

Lorkiewicz-Muszyńska, D., Rzepczyk, S., Andrzejewska, M. et al. Plasma cell myeloma: multiple calvarial lytic lesions of an individual from the Middle Ages, Poland. npj Herit. Sci. (2026). https://doi.org/10.1038/s40494-026-02613-5 May 10, 2026. 

Overview

This case report describes the identification of multiple myeloma in an archaeological skull discovered by a farmer in rural Poland. The cranium, partially preserved with multiple lytic lesions, was initially reported to law enforcement before being transferred for scientific analysis.

Macroscopic and microscopic examination, CT imaging, and radiocarbon dating were performed. The biological profile indicated the remains belonged to an adult female, and CT findings — the same imaging used in current clinical practice — were consistent with plasma cell myeloma based on the pattern, size, and distribution of the lytic lesions. Radiocarbon dating placed the individual in the 11th to 12th centuries AD.

Diagnosis was necessarily limited to imaging, as blood, urine, and bone marrow analysis are not possible on skeletal remains of this age. The lytic lesion pattern visible on CT, however, is sufficiently characteristic that a confident retrospective diagnosis could be made without laboratory confirmation.

The case adds to a small body of paleopathological evidence for myeloma in pre-modern populations, contributing one of relatively few documented cases from Poland. Beyond its regional significance, it serves as a reminder that myeloma is not a disease of modern life or modern medicine — it has affected humans for at least a millennium, long before the diagnostic tools or treatments that define how the disease is understood and managed today existed.

"Preliminary investigation into the association of serum free kappa light chains with risk stratification, clonal evolution and precision therapy in multiple myeloma"

Source 

Yang C, Xiao J, Zhao N, Liu X, Li Y, Huang Y, et al. Preliminary investigation into the association of serum free kappa light chains with risk stratification, clonal evolution and precision therapy in multiple myeloma. Br J Haematol. 2026;00:1–13. https://doi.org/10.1111/bjh.70541 May 11, 2026. 

Overview

Show more9:44 AMClaude responded: Serum free light chains (sFLCs) are already used routinely in myeloma to measure disease burden and track treatment response, but whether specific patterns — e…Serum free light chains (sFLCs) are already used routinely in myeloma to measure disease burden and track treatment response, but whether specific patterns — elevated kappa chains, elevated lambda chains, or an abnormal kappa-to-lambda ratio — carry independent prognostic meaning has not been firmly established. This retrospective study of 113 newly diagnosed people with myeloma examined whether abnormal sFLC kappa levels at diagnosis predict clinical features, cytogenetic findings, treatment response, and survival.

Among people with normal kidney function — an important restriction, since renal impairment itself elevates free light chains and would confound the analysis — abnormal sFLC kappa was associated with higher tumor burden, an anti-apoptotic and pro-angiogenic bone marrow environment, deletion of D13S319 (a chromosome 13 abnormality), and lower rates of deep remission after VRd induction therapy. Survival analyses confirmed abnormal sFLC kappa as an independent adverse prognostic factor.
Building on these findings, the researchers developed a modified staging model (MR-ISS) that incorporates sFLC kappa alongside the standard R-ISS components. In external temporal validation, MR-ISS outperformed R-ISS alone in separating patients into distinct risk groups.

The study is limited by its retrospective single-center design and relatively small cohort, and the MR-ISS model requires prospective validation before adoption. However, sFLC kappa is already measured at diagnosis in standard clinical practice, meaning its integration into risk stratification would not require additional testing — a practical advantage if the prognostic signal is confirmed in larger datasets.

"Monoclonal Gammopathy of Clinical Significance: A Multisystem Disorder Requiring a Multidisciplinary Approach"

Source 

YMeletios Athanasios Dimopoulos, Foteini Theodorakakou, Efstathios Kastritis, Monoclonal Gammopathy of Clinical Significance: A Multisystem Disorder Requiring a Multidisciplinary Approach, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.04.024. May 11, 2026. 

Overview

Most people are familiar with MGUS as a precursor to myeloma — detectable monoclonal protein, but no organ damage and no treatment required. Monoclonal gammopathy of clinical significance (MGCS) occupies a different and less well-recognized category: conditions where the monoclonal protein or the clonal cells themselves cause serious organ damage, even though the underlying plasma cell or B-cell disorder does not meet criteria for myeloma or a related malignancy.

The mechanisms vary. In some MGCS conditions, immunoglobulins deposit directly in tissues — kidneys, nerves, or skin. In others, immune complex activation, complement dysregulation, or cytokine-mediated effects drive the damage. Organizing these conditions by the organ system primarily affected has proven the most practical clinical framework: renal (MGRS), neurologic (MGNS), dermatologic (MGSS), and multisystemic syndromes including POEMS and TEMPI.

Because the clinical presentation of MGCS often resembles autoimmune, inflammatory, or idiopathic disorders, diagnosis requires a high index of suspicion — particularly in anyone with known MGUS who develops unexplained organ dysfunction. Establishing the diagnosis typically requires input from multiple specialists, and treatment is adapted from myeloma, AL amyloidosis, or lymphoproliferative disease protocols depending on the clonal lineage involved.

For people living with MGUS or low-level M-proteins, MGCS is relevant because it represents a pathway to serious organ damage that is distinct from progression to active myeloma — and one that requires active monitoring for symptoms beyond the standard myeloma progression criteria. Agreed diagnostic definitions and international registries are identified as priorities for advancing understanding of these conditions.

"Blood Cancer Clinical Trials Long-term Follow-up Using Integrated Healthcare Systems Data (BLISS): protocol for a data-linkage study integrating randomised clinical trials with national healthcare systems data"

Source 

Smith L, Hoang J, Gillson S, et al. Blood Cancer Clinical Trials Long-term Follow-up Using Integrated Healthcare Systems Data (BLISS): protocol for a data-linkage study integrating randomised clinical trials with national healthcare systems data BMJ Open 2026;16:e120416. doi: 10.1136/bmjopen-2026-120416 May 11, 2026. 

Overview

Clinical trials typically follow participants through scheduled clinic visits and trial-specific data collection — a process that is resource-intensive and ends when the trial closes, often leaving long-term outcomes unmeasured. This study protocol describes a data-linkage platform that connects participants from multiple myeloma trials conducted at the University of Leeds between 2008 and 2021 with routinely collected NHS England healthcare data, including death registrations, cancer records, hospital episodes, systemic treatment records, and radiotherapy data.

The primary methodological question is whether outcomes derived from routine healthcare data match those collected through trial-specific processes — a necessary validation step before healthcare system data can be relied upon as a substitute or supplement for trial follow-up. Outcomes being compared include mortality, treatment history, second cancer incidence, and major adverse events.

Beyond validation, the platform enables several analyses that trial data alone cannot support. Long-term overall survival will be estimated using national mortality records that extend beyond trial follow-up windows. Time to next treatment will be derived from treatment records as a surrogate for progression-free survival. NHS-derived frailty measures will be examined for prognostic value, and hospital and radiotherapy records will be used to characterize bone complications and skeletal-related treatments — an outcome domain relevant to myeloma that trials often capture incompletely.

The platform also addresses a persistent limitation of clinical trials: how representative their enrolled populations are of people with myeloma in routine care. Linking to national registry data allows direct comparison between trial participants and the broader myeloma population, informing how generalizable trial findings are to real-world practice.

"Microenvironmental Drivers of Bone Disease in Multiple Myeloma: Oxidative Stress, Sterile Inflammation, Autophagy–Lysosomal Remodeling, and the Iron–Lipid Peroxidation Axis"

Source 

Nasso, M. E., Bottaro, A., Fazio, M., Stagno, F., Gangemi, S., & Allegra, A. (2026). Microenvironmental Drivers of Bone Disease in Multiple Myeloma: Oxidative Stress, Sterile Inflammation, Autophagy–Lysosomal Remodeling, and the Iron–Lipid Peroxidation Axis. Biomolecules, 16(5), 710. https://doi.org/10.3390/biom16050710 May 11, 2026. 

Overview

Bone disease affects the majority of people with myeloma, causing pain, fractures, and spinal complications through a process where bone breakdown outpaces bone formation. The standard explanation centers on the RANK/RANKL/OPG signaling axis and Wnt pathway suppression, but this review argues that three additional interconnected stress programs drive the osteolytic process and have been underappreciated as therapeutic targets.

The first is oxidative stress, generated by mitochondria and NADPH oxidase enzymes, which primes osteoclasts toward bone resorption while suppressing osteoblast activity. The second is sterile inflammation — an immune response triggered not by infection but by damage signals released from stressed or dying cells, sustained by pro-inflammatory cytokines that further tip the balance toward bone breakdown. The third involves autophagy and lysosomal remodeling, governed by a transcription factor called TFEB, which regulates how cells recycle damaged components and intersects with bone cell function in ways that are still being characterized.

These three programs converge on iron metabolism and lipid peroxidation, influencing sensitivity to ferroptosis — a form of cell death increasingly recognized as relevant to bone marrow biology. How osteoclasts and osteoblasts respond to ferroptotic signals may shape the overall balance of bone remodeling in myeloma.

The review translates this mechanistic framework into a proposed monitoring and treatment strategy: standardized bone turnover markers combined with oxidative stress measurements and modern imaging, layered onto existing bone-protective treatments such as bisphosphonates or denosumab, with additional agents targeting NADPH oxidase, inflammatory signaling, and iron handling. The approach remains translational rather than established practice, but maps a path from mechanism to potential clinical application for myeloma bone disease.

"Fluoroquinolone Prophylaxis Uncovers High Prevalence Rates of Fluoroquinolone-Resistant Enterobacterales Colonization in Multiple Myeloma Autologous Transplant Patients: A Prospective Cohort Study. Cancers"

Source 

Patel, C., Terlecky, A. J., Baker, M., Lozy, T., Yen, K. K., Kaur, N., Machere, L., Ali, A., Cho, C., Donato, M. L., Munshi, P. N., Kreiswirth, B. N., & Rowley, S. D. (2026). Fluoroquinolone Prophylaxis Uncovers High Prevalence Rates of Fluoroquinolone-Resistant Enterobacterales Colonization in Multiple Myeloma Autologous Transplant Patients: A Prospective Cohort Study. Cancers, 18(10), 1566. https://doi.org/10.3390/cancers18101566 May 11, 2026.  

Overview

Fluoroquinolone antibiotics are commonly given as prophylaxis during autologous stem cell transplant to reduce fever and infection risk during the period of severe immune suppression following high-dose melphalan. A recognized tradeoff is that fluoroquinolone use can select for resistant bacteria in the gut. This prospective study tracked fluoroquinolone-resistant Enterobacterales (FRE) colonization in 117 people with myeloma undergoing transplant, using stool swabs at three timepoints: before transplant, at hospital discharge, and 12 to 16 weeks later.

Before transplant, 19.7% already carried FRE. By discharge — after nearly all participants had received fluoroquinolone prophylaxis — that rate rose to 29.6%, and remained at 30.4% at the 12 to 16 week follow-up. Across all three timepoints combined, 41% of participants tested positive for FRE at least once. Of the FRE isolates identified, 64% expressed extended-spectrum beta-lactamase (ESBL), a resistance mechanism that limits treatment options for bloodstream infections.

Three participants with FRE colonization developed FRE bloodstream infections; in two, the bloodstream isolate matched the organism identified before transplant, suggesting pre-existing gut colonization as the source.

The practical implication is that a meaningful proportion of people with myeloma arrive at transplant already colonized with resistant bacteria, and fluoroquinolone prophylaxis appears to amplify that colonization. Pre-transplant screening for FRE could identify who is at elevated risk and allow prophylactic antibiotic regimens to be tailored accordingly — avoiding fluoroquinolones in those already colonized and selecting empiric treatment regimens that account for likely resistance patterns if infection develops.

"Dynamic HALP Score as a Time-Dependent Prognostic Biomarker in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation. Cancers"

Source 

Aydın, Ö., Şahin, O., Akca, E., Kürekci, D. D., Aktimur, S. H., Kelkitli, E., & Turgut, M. (2026). Dynamic HALP Score as a Time-Dependent Prognostic Biomarker in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation. Cancers, 18(10), 1570. https://doi.org/10.3390/cancers18101570  May 11, 2026.  

Overview

The HALP score combines four routine blood measurements — hemoglobin, albumin, lymphocyte count, and platelet count — into a single index intended to reflect nutritional status, immune function, and systemic inflammation simultaneously. This retrospective study examined whether HALP scores measured at diagnosis and at day +100 after autologous stem cell transplant predict outcomes in 95 people with myeloma over a median follow-up of 50 months.

Baseline HALP showed an association with both progression-free and overall survival in unadjusted analysis, but that association weakened substantially after accounting for maintenance therapy — suggesting that baseline HALP may partly reflect factors already captured by treatment intensity rather than providing independent prognostic information.

Post-transplant HALP at day +100 performed more consistently. Its association with progression-free survival strengthened after multivariate adjustment, with people in the lower HALP group at day +100 having 3.27 times the risk of progression or death compared to those with higher scores. This timepoint reflects the immune and nutritional recovery state after transplant rather than pre-treatment disease burden, and may capture something about engraftment quality and immune reconstitution that baseline measurements miss.

The authors are appropriately cautious about the findings. The cohort is small, only 22 deaths occurred during follow-up limiting survival analysis power, cut-offs were derived from the same dataset being analyzed rather than validated externally, and cytogenetic and MRD data were unavailable. HALP at day +100 is worth investigating further as an accessible, low-cost prognostic tool, but the current evidence is exploratory and requires prospective validation in larger cohorts before clinical application.

"Sustained MRD Negative for 4 Years Is a Significant Marker of Prognosis in Patients with High-Risk Multiple Myeloma"

Source 

Liu, H., Chen, M., Li, X., Kuang, L., Li, J., Li, Y., & Li, J. (2026). Sustained MRD Negative for 4 Years Is a Significant Marker of Prognosis in Patients with High-Risk Multiple Myeloma. Cancers, 18(10), 1569. https://doi.org/10.3390/cancers18101569 May 11, 2026.  

Overview

Achieving MRD negativity after treatment is associated with better outcomes in myeloma, but how long that negativity needs to be sustained to confer meaningful benefit — and whether duration thresholds differ by cytogenetic risk — has not been well characterized. This single-center retrospective study examined 223 transplant-eligible newly diagnosed people with myeloma who achieved at least two consecutive MRD-negative assessments, tracking how duration of sustained negativity related to progression-free and overall survival.

The most clinically striking finding involves high-risk cytogenetics. People with high-risk disease who maintained MRD negativity for two or more years had progression-free survival comparable to standard-risk patients (70.77 vs 67.38 months), suggesting that sustained MRD negativity can partially offset the prognostic disadvantage of adverse cytogenetics. This is an exploratory finding based on limited case numbers, but the direction is consistent with the broader hypothesis that depth and durability of response matter more than cytogenetic risk alone in the context of deep remission.

In standard-risk patients, extending MRD negativity beyond three years did not produce a statistically significant improvement over two to three years, though the point estimates favored longer duration. In high-risk patients, a threshold around four to five years appeared relevant, with no additional benefit seen beyond five years in the available data.

Sustained MRD negativity beyond two years was associated with improved overall survival across all patients. The retrospective single-center design, absence of standardized MRD testing methodology details, and limited case numbers in subgroup analyses mean these findings require prospective validation — but they contribute to the growing evidence base for using MRD duration, not just achievement, as a treatment endpoint.

"Patient-reported outcomes after idecabtagene vicleucel vs. ciltacabtagene autoleucel CAR-T for multiple myeloma"

Source 

Oswald, L.B., Li, X., Gudenkauf, L.M. et al. Patient-reported outcomes after idecabtagene vicleucel vs. ciltacabtagene autoleucel CAR-T for multiple myeloma. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02899-w May 11, 2026. 

Overview

How people with myeloma actually feel during and after CAR-T therapy — beyond response rates and toxicity grades — has been largely unmeasured in real-world settings. This study tracked patient-reported quality of life and symptoms across 99 people receiving ide-cel or cilta-cel as standard of care, with assessments from before lymphodepletion through 90 days post-infusion.

The overall pattern was consistent: most quality of life measures either worsened or held stable in the week following infusion, then improved meaningfully after day 7. This trajectory held for overall quality of life, physical and functional wellbeing, fatigue, physical function, and social function. Anxiety, sleep disturbance, and pain measures were stable rather than worsening in the early period, then also improved after day 7 — suggesting the acute post-infusion period is difficult but time-limited, with recovery evident within the first month.

Ide-cel and cilta-cel recipients followed similar trajectories across most measures, which is reassuring given that the two products differ in their manufacturing and dosing schedules. Two exceptions emerged: social wellbeing trajectories diverged between groups before day 7, and cognitive function trajectories differed after day 7, with cilta-cel recipients showing a pattern worth further investigation given that neurotoxicity profiles differ between the two products.

The ide-cel group was notably older (median 73 vs 64 years), a difference that could influence how findings generalize. The 90-day follow-up window captures the acute and early recovery phase but leaves open what happens to quality of life beyond three months — particularly relevant given that CAR-T responses in myeloma can be durable and long-term functional recovery is an important patient priority.

"Exploring the prognostic value of the FIRST simplified frailty scale in elderly, transplant-ineligible, newly diagnosed multiple myeloma patients in real-world settings"

Source 

Zhou, Y., Qin, J., Shi, X. et al. Exploring the prognostic value of the FIRST simplified frailty scale in elderly, transplant-ineligible, newly diagnosed multiple myeloma patients in real-world settings. Eur J Med Res (2026). https://doi.org/10.1186/s40001-026-04603-6 May 12, 2026. 

Overview

Frailty assessment has become increasingly relevant in myeloma as more older people receive treatment, but most frailty tools are time-consuming to administer in routine clinical practice. The FIRST simplified frailty scale was developed to address that gap. This retrospective study evaluated its prognostic value in 43 people over 65 with newly diagnosed myeloma who were ineligible for transplant, treated at a single center between 2016 and 2023.

Using the FIRST scale, 29 were classified as frail and 14 as not frail. Overall response rates were high in both groups (97% vs 100%) and did not differ significantly — suggesting frailty did not prevent initial response to treatment. However, depth of response did differ: 93% of non-frail patients achieved at least a very good partial response, compared to 59% of frail patients. Adverse event rates were similar between groups, which may reflect that treating clinicians already adjusted doses or regimen intensity based on clinical judgment.

Survival outcomes separated substantially. Median progression-free survival was 12 months in frail patients versus 25.5 months in non-frail patients, and median overall survival was 17 months versus 34.7 months — differences that are clinically meaningful even in a small cohort.

The study is limited by its retrospective design, single-center setting, and small sample size of 43 patients, which constrains the conclusions that can be drawn. However, the FIRST scale's practical advantage is that it can be applied quickly in a clinic visit without specialist input, and these results support its use as a risk stratification tool to inform treatment planning and expectations in older people with myeloma who are not transplant candidates.

"Mezigdomide reverses T-cell exhaustion through degradation of IKZF1/IKZF3 and reinvigoration of cytokine production pathways"

Source 

Hsiling Chiu, Junfei Zhao, Tara Basavanhally, Chih-Chao Hsu, Michael D Amatangelo, Gaurav Jain, Chad C Bjorklund, Ting-Hsiang Huang, Lucia Y Chen, Thomas A Milne, Sarah Gooding, Samir Parekh, Anita Krithivas Gandhi, Maria Ortiz Estevez, Patrick Ryan Hagner; Mezigdomide reverses T-cell exhaustion through degradation of IKZF1/IKZF3 and reinvigoration of cytokine production pathways. Blood 2026; blood.2025030873. doi: https://doi.org/10.1182/blood.2025030873 May 12, 2026. 

Overview

T cell exhaustion limits how well bispecific antibodies and other T cell-engaging therapies work in myeloma — exhausted T cells lose their ability to kill cancer cells even when brought into direct contact with them. This study investigated whether IKZF1 and IKZF3, two transcription factors degraded by mezigdomide, are direct drivers of that exhaustion rather than incidental targets.

Using transcriptomic and epigenetic profiling of exhausted T cells generated in the laboratory, the researchers mapped where IKZF1 and IKZF3 bind across the genome and what happens to gene expression as a result. The findings show that as T cells undergo repeated stimulation — mimicking chronic antigen exposure in myeloma — IKZF1 binding increases at exhaustion-associated gene promoters and enhancers, driving their expression upward, while simultaneously binding to cytokine gene regions and suppressing inflammatory signaling. This dual action — amplifying exhaustion genes while silencing effector function genes — positions IKZF1 as a direct transcriptional enforcer of the exhausted state.

Treating exhausted T cells with mezigdomide reversed these effects: exhaustion marker expression fell, pro-inflammatory cytokine production increased, and T cell killing of myeloma cells was enhanced when combined with alnuctamab, a BCMA-targeting bispecific antibody.

This study complements earlier work identifying Ikaros (IKZF1) as a regulator of the exhaustion gene TIGIT, extending the mechanistic picture to show that both IKZF1 and IKZF3 operate broadly across the exhaustion gene program through direct chromatin-level control. Together, the findings provide a detailed molecular rationale for combining mezigdomide with bispecific antibody therapy to restore T cell function in myeloma.

"How we prevent infections in adults receiving bispecific antibody therapies for advanced B-cell malignancies"

Source 

Kai Rejeski, Rahul Banerjee, Joshua A. Hill; How we prevent infections in adults receiving bispecific antibody therapies for advanced B-cell malignancies. Blood 2026; blood.2025032298. doi: https://doi.org/10.1182/blood.2025032298 May 12, 2026. 

Overview

Bispecific antibodies have become a standard option in relapsed myeloma and are being studied in earlier treatment settings, but their infection-related risks have received less systematic attention than their efficacy. This "How I Treat" article addresses that gap, providing a practical framework for infection prevention and management across the full course of bispecific antibody therapy.

The infection risks associated with bispecific antibodies are distinct from those of CAR-T therapy and arise through multiple overlapping mechanisms. B cell and plasma cell depletion leads to hypogammaglobulinemia — low antibody levels that impair the ability to fight bacterial and viral infections. Early cytopenias reduce neutrophil and other immune cell counts. T cell exhaustion from repeated dosing, cytokine-mediated immune dysregulation, and the underlying immune suppression from myeloma itself all compound over time, creating a cumulative and evolving vulnerability that worsens the longer therapy continues. Infections are the leading cause of non-relapse mortality with these agents.

The framework is organized by treatment phase: pre-treatment evaluation (screening for latent infections, baseline immunoglobulin levels, vaccination status), the active treatment period (antimicrobial prophylaxis, immunoglobulin supplementation, monitoring), and long-term follow-up (ongoing assessment of immune recovery and infection risk after therapy ends). Representative cases are used throughout to illustrate decision points.

For people with myeloma receiving bispecific antibody therapy, the practical implication is that infection risk requires active, ongoing management rather than reactive treatment when problems arise — and that risk evolves over the course of therapy rather than remaining static.

"Collection of autologous CD34+ hematopoietic progenitor cells (HPC) in multiple myeloma: CD34 + cell collection yield in relation to molecular subtype, karyotype, and FISH results"

Source 

Rjoop A, Perez I, Al Aruri DO, AlBarakat MM, van Rhee F, Drobena G. Collection of autologous CD34+ hematopoietic progenitor cells (HPC) in multiple myeloma: CD34 + cell collection yield in relation to molecular subtype, karyotype, and FISH results. PLoS One. 2026 May 12;21(5):e0349212. doi: 10.1371/journal.pone.0349212. 

Overview

Bispecific antibodies have become a standard option in relapsed myeloma and are being studied in earlier treatment settings, but their infection-related risks have received less systematic attention than their efficacy. This "How I Treat" article addresses that gap, providing a practical framework for infection prevention and management across the full course of bispecific antibody therapy.

The infection risks associated with bispecific antibodies are distinct from those of CAR-T therapy and arise through multiple overlapping mechanisms. B cell and plasma cell depletion leads to hypogammaglobulinemia — low antibody levels that impair the ability to fight bacterial and viral infections. Early cytopenias reduce neutrophil and other immune cell counts. T cell exhaustion from repeated dosing, cytokine-mediated immune dysregulation, and the underlying immune suppression from myeloma itself all compound over time, creating a cumulative and evolving vulnerability that worsens the longer therapy continues. Infections are the leading cause of non-relapse mortality with these agents.

The framework is organized by treatment phase: pre-treatment evaluation (screening for latent infections, baseline immunoglobulin levels, vaccination status), the active treatment period (antimicrobial prophylaxis, immunoglobulin supplementation, monitoring), and long-term follow-up (ongoing assessment of immune recovery and infection risk after therapy ends). Representative cases are used throughout to illustrate decision points.

For people with myeloma receiving bispecific antibody therapy, the practical implication is that infection risk requires active, ongoing management rather than reactive treatment when problems arise — and that risk evolves over the course of therapy rather than remaining static.

"SSTNIV, a syndecan-1-targeting peptide chimera, reverses immune suppression and inhibits myeloma progression"

Source 

Jung, O., Beauvais, D.M., Ibaan, G.L. et al. SSTNIV, a syndecan-1-targeting peptide chimera, reverses immune suppression and inhibits myeloma progression. Sig Transduct Target Ther 11, 175 (2026). https://doi.org/10.1038/s41392-026-02709-1 May 12, 2026. 

Overview

CD138 (Syndecan-1) is the protein used to identify myeloma cells in bone marrow biopsies and flow cytometry, but its role extends beyond a surface marker — it actively promotes myeloma cell survival, supports new blood vessel formation, and helps myeloma evade immune attack. This study investigated whether disrupting CD138-mediated signaling with a novel peptide called SSTNIV could inhibit myeloma progression.

In laboratory models, SSTNIV reduced myeloma cell invasion, induced apoptosis, and reversed immune suppression. In mouse models of advanced myeloma, it extended survival, reduced tumor burden in the bone marrow, and improved overall marrow cellularity — a measure of how well normal blood cell production is maintained alongside tumor control.

The combination of SSTNIV with bortezomib produced the strongest results, substantially reducing myeloma cells in the bone marrow, reducing extramedullary disease, and restoring normal hematopoiesis. This additive or synergistic effect with an established proteasome inhibitor is relevant because it suggests SSTNIV targets mechanisms distinct from proteasome inhibition, making combination use rational rather than redundant.

Mechanistic analysis using human bone marrow tissue confirmed that CD138 forms complexes with receptor tyrosine kinases and integrins specifically in myeloma tumors but not in normal bone marrow — a selectivity that supports the therapeutic window for this approach and reduces concern about on-target toxicity in healthy tissue.

The findings are limited to preclinical models and require clinical validation. However, CD138's dual role in myeloma cells and the bone marrow microenvironment makes it an attractive target, and SSTNIV's activity in both compartments addresses a limitation of therapies that target only the tumor cell itself.

"Talquetamab: Mechanism of Action, Clinical, and Translational Science"

Source 

Y.Wang, J.Gong, N.Au, et al., “Talquetamab: Mechanism of Action, Clinical, and Translational Science,” Clinical and Translational Science19, no. 5 (2026): e70574, https://doi.org/10.1111/cts.70574. May 13, 2026. 

Overview

Talquetamab targets GPRC5D, a protein expressed at high levels on myeloma cells but with limited presence in most normal tissues — a profile that makes it attractive as a therapeutic target, particularly for people who have already received BCMA-directed therapy. Like other bispecific antibodies in myeloma, it works by simultaneously binding its tumor target and CD3 on T cells, bringing T cells into contact with myeloma cells and triggering their destruction.

Two subcutaneous dosing regimens are approved: 0.4 mg/kg weekly and 0.8 mg/kg every two weeks, both preceded by step-up doses to reduce cytokine release syndrome risk. The step-up schedule — starting at 0.01 mg/kg and escalating over one to two weeks — is a standard approach with bispecific antibodies to allow gradual immune activation rather than abrupt full-dose exposure.

In clinical studies of heavily pretreated relapsed or refractory myeloma, talquetamab produced durable responses with a benefit-risk profile that supported regulatory approval in both the US and EU. The most clinically distinctive adverse effects — beyond the cytokine release syndrome and hematologic toxicities shared with other bispecific antibodies — are oral side effects including taste disturbance (dysgeusia) and skin and nail changes, reflecting low-level GPRC5D expression in those tissues.

Around 36% of participants developed anti-drug antibodies during treatment, including 18% with neutralizing antibodies, but these did not appear to affect drug levels, efficacy, or safety in a clinically meaningful way. Talquetamab is under ongoing investigation in combination regimens and earlier treatment lines.

"Burden and management of infectious diseases in patients treated by chimeric antigen-receptor T (CAR-T)-cell therapy for refractory or relapsing diffuse large B-cell lymphoma or multiple myeloma"

Source 

Pisaturo M, Grimaldi P, Di Palma M, Onorato L, D'Ambrosio A, Frigeri F, Coppola N. Burden and management of infectious diseases in patients treated by chimeric antigen-receptor T (CAR-T)-cell therapy for refractory or relapsing diffuse large B-cell lymphoma or multiple myeloma. Eur J Cancer. 2026 May 13;242:116790. doi: 10.1016/j.ejca.2026.116790.   

Overview

CAR-T therapy produces deep responses in relapsed or refractory myeloma and lymphoma, but the immune suppression it causes is profound and prolonged — creating a sustained window of infection vulnerability that differs meaningfully from other treatment modalities. This review maps infection risks across four distinct phases: pre-CAR-T (during lymphodepletion and conditioning), early post-infusion, the prolonged immunosuppression phase, and late recovery, with management strategies tailored to each.

Bacterial, viral, and fungal infections all occur, with frequencies drawn from both clinical trial data and real-world experience. The review covers pre-infusion screening, antimicrobial prophylaxis, vaccination, and immunoglobulin supplementation as the primary prevention tools, noting that current practice largely extrapolates from stem cell transplant protocols — an imperfect fit given that CAR-T induces a different pattern of immune reconstitution.

A practical tool highlighted is the CAR-HEMATOTOX score, calculated before lymphodepletion using bone marrow reserve indicators (platelets, hemoglobin, neutrophils) and inflammatory markers (CRP and ferritin). High scorers face substantially higher rates of severe infection post-infusion (40% vs 8%), making the score useful for calibrating prophylaxis intensity and monitoring frequency to individual risk before treatment begins.

The review's central limitation acknowledgment is important: CAR-T-specific infection management data remain sparse, cohorts are small, and variability between products and patient populations makes generalization difficult. The authors call for dedicated research to develop evidence-based CAR-T infection guidelines, and emphasize that close collaboration between hematologists and infectious disease specialists is not optional but necessary given the complexity of managing immunosuppression in this setting.

"Experiences and expert panel consensus on bridging therapy before anti-BCMA CAR-T cell therapy in multiple myeloma"

Source 

Rasche, L., Krauth, M.T., Agis, H. et al. Experiences and expert panel consensus on bridging therapy before anti-BCMA CAR-T cell therapy in multiple myeloma. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02905-1 May 13, 2026. .   

Overview

Before receiving CAR-T cell therapy, people with myeloma often require bridging therapy — treatment given during the weeks between CAR-T manufacturing and infusion, with the goals of controlling disease, reducing tumor burden, and maintaining enough physical fitness to tolerate the infusion itself. The choice of bridging therapy has become more complex as the available options have expanded, and there is no established standard.

This consensus document draws on qualitative interviews and a workshop with ten European experts to address bridging therapy selection before anti-BCMA CAR-T therapy, with particular focus on heavily pretreated people and newer options including bispecific antibodies. Experts agreed that effective bridging therapy should reduce tumor burden and preserve or improve performance status, while avoiding toxicities — particularly prolonged cytopenias or infections — that could delay or prevent CAR-T infusion. The balance between treatment duration and depth of response matters: bridging therapy that works slowly or requires many cycles may consume the manufacturing window without delivering adequate disease control.

The consensus gives particular attention to talquetamab, a GPRC5D-directed bispecific antibody, as a bridging option before BCMA-targeted CAR-T. Because talquetamab targets a different antigen than the subsequent CAR-T product, using it as bridging therapy does not deplete the BCMA target that the CAR-T will need to engage. Its rapid response rates in clinical trials and growing real-world experience support its consideration in this role, according to the experts consulted.

Patient-specific factors — disease biology, prior treatment history, performance status, and comorbidities — are identified as the primary drivers of bridging therapy selection, reflecting that no single approach fits all people proceeding to CAR-T.

"Bone marrow stromal cells enhance multiple myeloma cells proliferation through regulating LncRNA OVAAL/ENPP1 axis"

Source 

Cai, Z., Chen, X., Zheng, H., Zheng, R., Zheng, R. & Lin, W. (2026). Bone marrow stromal cells enhance multiple myeloma cells proliferation through regulating LncRNA OVAAL/ENPP1 axis. Open Life Sciences, 21(1), 20251322. https://doi.org/10.1515/biol-2025-1322.   

Overview

Bone marrow stromal cells support myeloma cell survival and proliferation through direct contact and secreted signals, but the specific molecular pathways involved are incompletely characterized. This study used a co-culture system — growing myeloma cells alongside bone marrow stromal cells — combined with RNA sequencing to identify which genes the stromal cells activate in myeloma cells, and which of those drive proliferation.

Stromal cell co-culture altered the expression of nearly 700 RNAs in myeloma cells. Pathway analysis of the affected genes converged on the pantothenate and coenzyme A biosynthesis pathway, identifying a protein called ENPP1 as a key node. Further analysis traced the upstream regulation to a long non-coding RNA called OVAAL, which stromal cells upregulate in myeloma cells and which in turn drives ENPP1 expression.

Functionally, knocking down OVAAL reduced markers of metabolic activity in myeloma cells — lower lactate dehydrogenase, glucose, and ATP levels, alongside increased reactive oxygen species — a profile consistent with impaired energy metabolism and increased oxidative stress. Knocking down ENPP1 directly suppressed myeloma cell proliferation. Critically, both of these suppressive effects were rescued when the cells were returned to co-culture with stromal cells, confirming that the stromal environment actively maintains this pathway rather than simply initiating it.

The findings identify a stromal-to-myeloma signaling axis — OVAAL upregulation driving ENPP1-mediated metabolic reprogramming — as a mechanism through which the bone marrow microenvironment supports myeloma progression. Both OVAAL and ENPP1 represent potential targets for disrupting stromal support of myeloma, though the work is currently limited to cell line models.

"Triplet or Quadruplet Regimen Utilization and Overall Survival in Patients Diagnosed With Multiple Myeloma Between 2017 and 2023"

Source 

E. R.Wesley, F.Anwer, M. B.Rothberg, et al. “Triplet or Quadruplet Regimen Utilization and Overall Survival in Patients Diagnosed With Multiple Myeloma Between 2017 and 2023.” eJHaem7, no. 3 (2026): e70309. https://doi.org/10.1002/jha2.70309 May 14, 2026. 

Overview

Researchers at the Cleveland Clinic examined how often patients with newly diagnosed multiple myeloma received guideline-recommended triplet or quadruplet therapy in routine clinical practice between 2017 and 2023. The study included 1,230 patients treated in Ohio and Florida.

Within one year of diagnosis, 57.5% of patients received a triplet or quadruplet regimen. Use of these combination approaches increased over time, rising from 57.1% in 2017 to 65.9% in 2023.

Several factors affected treatment selection. Older patients and those living in more disadvantaged neighborhoods were less likely to receive triplet or quadruplet therapy. Patients treated at a Florida regional hospital were also less likely to receive these regimens compared with those treated at the Taussig Cancer Center. In contrast, patients diagnosed in 2023, those treated at an Ohio regional hospital, patients with reduced kidney function (eGFR below 60), and those with higher comorbidity scores were more likely to receive triplet or quadruplet therapy.

The estimated 5-year overall survival rate for the full group was 62.1%. The authors reported that survival outcomes in this real-world population were better than historical results reported in earlier periods of myeloma treatment.
 

"Timing and Pattern of Extraosseous Dissemination Are Key Determinants of Survival in Multiple Myeloma"

Source 

M.Tordjman, A.Meribout, A.Geahchan, et al., “Timing and Pattern of Extraosseous Dissemination Are Key Determinants of Survival in Multiple Myeloma,” American Journal of Hematology (2026): 1–12, https://doi.org/10.1002/ajh.70370. May 14, 2026. 

Overview

Researchers analyzed extraosseous (EO) disease in 543 patients with multiple myeloma followed between 2010 and 2025 using whole-body MRI and, in some cases, FDG-PET/CT imaging. EO disease occurs when myeloma cells spread outside the bone marrow and is often associated with more aggressive disease biology.

EO involvement was identified in about one-quarter of patients. The study found that survival outcomes depended strongly on when and how the disease spread beyond the bone marrow. Patients with paraskeletal (PS) lesions present at diagnosis had worse outcomes than patients whose disease remained confined to the marrow. Outcomes were poorer when PS lesions developed later during the disease course, and were worst in patients who developed secondary extramedullary disease (EMD).

Patients with PS lesions at diagnosis also had a 2.6-fold higher risk of later developing secondary EMD. In contrast, the size and location of EO lesions did not appear to affect survival. Other factors linked to shorter survival after EO diagnosis included R2-ISS stage IV disease, TP53 mutation, and receiving multiple prior lines of therapy.

The investigators concluded that the timing and pattern of EO spread provide more prognostic information than tumor burden alone. They also reported that whole-body imaging can help identify patients transitioning into higher-risk disease states.
 

"The PETHEMA/GEM cooperative group, Genetic Evidence against Clonotypic B Lymphocytes as a Reservoir for Plasma Cell Cancers"

Source 

Carmen Gonzalez, Juan-Jose Garces, Hector Gracia, Camila Guerrero, Mattia D’Agostino, Alejandro Medina-Herrera, Mario Nuvolone, Noemi Puig, Maria-Teresa Cedena, Marta Lasa, Diego Alignani, Aitziber Lopez, Sarai Sarvide, Paula Aguirre-Ruiz, José Maria Lamo-Espinosa, Felipe Prosper, Paula Rodriguez-Otero, Jose A. Martinez-Climent, Francesca Lattarulo, Alice Nevone, Margherita Massa, Giovannni Palladini, Giuseppe Bertuglia, Francesca Gay, Laura Rosiñol, Ramón García-Sanz, Joaquin Martinez-Lopez, Maria-Victoria Mateos, Juan-Jose Lahuerta, Joan Bladé, Jesus F. San-Miguel, Bruno Paiva; the PETHEMA/GEM cooperative group, Genetic Evidence against Clonotypic B Lymphocytes as a Reservoir for Plasma Cell Cancers. Blood Cancer Discov 2026; https://doi.org/10.1158/2643-3230.BCD-25-0102 May 14, 2026. . 

Overview

Researchers used single-cell and exome sequencing to investigate where multiple myeloma and light-chain amyloidosis begin during B-cell development. The study examined highly purified patient samples to determine whether the genetic changes that drive these diseases are found mainly in plasma cells or in earlier B-cell stages.

Clonotypic B-cell receptors were identified in a very small percentage of immature and mature B cells — 0.4% or less. Single-cell analysis confirmed that these cells had an immature B-cell phenotype. However, the genetic driver alterations linked to myeloma and AL amyloidosis were found primarily in malignant plasma cells and were only rarely detected in immature B cells during treatment.

The findings suggest that clonotypic B cells may act as early precursors to malignant plasma cells but are unlikely to play a major role in ongoing disease progression. The researchers also noted that these rare clonotypic B cells could occasionally cause false-positive minimal residual disease (MRD) results when next-generation sequencing methods based on B-cell receptor analysis are used.

The study provides new information about the cellular origin of myeloma and AL amyloidosis and may help refine future approaches to MRD monitoring.
 

"European Recommendations for Transitioning the Care of Patients With Multiple Myeloma Treated With B-Cell Maturation Antigen Bispecific Antibodies From Academic Hospitals to Community-Based Centers and for Outpatient Step-Up Dosing"

Source 

M.Mateos, E.Zamagni, M.Gentile, et al. “European Recommendations for Transitioning the Care of Patients With Multiple Myeloma Treated With B-Cell Maturation Antigen Bispecific Antibodies From Academic Hospitals to Community-Based Centers and for Outpatient Step-Up Dosing.” eJHaem7, no. 3 (2026): e70290. https://doi.org/10.1002/jha2.70290 May 14, 2026. 

Overview

European multiple myeloma specialists developed recommendations for the safe outpatient use of BCMA-targeting bispecific antibodies during step-up dosing, the phase of treatment when the risk of cytokine release syndrome (CRS) and neurologic side effects is highest.

The guidance was created through a modified Delphi process involving 53 clinicians from France, Germany, Italy, Portugal, Spain, and the United Kingdom, including hematologists, nurses, and pharmacists. The panel reached consensus on 84 recommendations related to outpatient treatment and the transition of care from academic centers to community clinics.

The group recommended that patients should be clinically stable before receiving treatment in a community setting. Suggested criteria included being fever-free for at least 24 hours, having no active CRS or immune effector cell-associated neurotoxicity syndrome (ICANS), and maintaining stable organ function.

The panel also outlined requirements for community treatment centers. Staff should be trained to recognize and manage BCMA bispecific antibody toxicities, rapid laboratory testing should be available, and medications such as tocilizumab and corticosteroids should be immediately accessible. Centers should also maintain 24-hour escalation pathways for urgent care.

The recommendations included infection prevention measures such as cytomegalovirus testing, immunoglobulin monitoring, antiviral prophylaxis, Pneumocystis jirovecii pneumonia prophylaxis, and immunoglobulin replacement for patients with IgG levels below 400 mg/dL.
 

"Early-Life Exposures and Risk of Multiple Myeloma: A Population-Based Case–Control Study in Australia"

Source 

Z.Sun, J. K.Bassett, S.Cheah, et al., “Early-Life Exposures and Risk of Multiple Myeloma: A Population-Based Case–Control Study in Australia,” International Journal of Cancer (2026): 1–10, https://doi.org/10.1002/ijc.70539. May 14, 2026. 

Overview

Researchers examined whether exposures during pregnancy and early childhood may influence the risk of developing multiple myeloma later in life. The study included 782 patients with multiple myeloma and 1,121 control participants.

Several childhood exposures linked to greater microbial exposure were associated with a lower risk of myeloma. People who grew up in households with five or more children had a 43% lower risk of developing myeloma. Sharing a bedroom before age 11 and having pets during early childhood were also associated with reduced risk.

The findings support the “hygiene hypothesis,” which proposes that early exposure to microbes and common infections may help train the immune system and reduce the risk of some immune-related diseases later in life. The researchers suggested that early immune stimulation could influence the biological pathways involved in myeloma development or progression from precursor conditions such as MGUS.

The study did not identify clear links between myeloma risk and maternal smoking during pregnancy, breastfeeding, or childhood height patterns.

The authors noted several limitations, including reliance on self-reported childhood exposures and the possibility of recall bias. They also emphasized that the study does not prove causation. Additional research is needed to better understand how early-life immune and microbial exposures may affect myeloma risk decades later.
 

"Advances in monitoring and therapy from minimal residual disease to CAR-T cells in multiple myeloma and precursor disorders"

Source 

Amr Ali Mohamed Abdelgawwad El-Sehrawy, Ghaleb Oriquat, Sokhib Saidov, Uktam Ruzikulov, Gulnora Shakhmurova, Bnyn Jasb Jbl, Divya Singhal,  Shefali, Advances in monitoring and therapy from minimal residual disease to CAR-T cells in multiple myeloma and precursor disorders, Clinica Chimica Acta, 2026, 121066, ISSN 0009-8981, https://doi.org/10.1016/j.cca.2026.121066. May 14, 2026.

Overview

Researchers reviewed recent advances in the diagnosis and treatment of monoclonal gammopathies, including MGUS, smoldering multiple myeloma (SMM), and active multiple myeloma. The report focused on how newer diagnostic tools and immunotherapies are changing disease monitoring and treatment decisions.

Highly sensitive techniques such as mass spectrometry, next-generation flow cytometry, next-generation sequencing, PET-CT imaging, and circulating tumor cell testing can detect lower levels of disease than older methods. These technologies are improving the ability to identify residual myeloma cells after treatment and detect disease progression earlier.

Minimal residual disease (MRD) negativity continues to emerge as an important marker in myeloma care. Patients who achieve MRD-negative status generally experience longer progression-free survival and overall survival compared with patients who remain MRD-positive.

The review also examined how clonal evolution, genetic changes, and the bone marrow microenvironment contribute to treatment resistance and relapse.

On the treatment side, BCMA-directed CAR T-cell therapy and bispecific antibodies have produced deep and durable responses in many patients with relapsed or refractory myeloma. Researchers are also developing dual-targeted therapies and “off-the-shelf” cellular therapies designed to improve access and reduce manufacturing delays.

The authors noted several ongoing challenges, including standardizing MRD testing methods, managing CAR T-cell toxicities, and improving access to advanced therapies across different regions and healthcare systems.

 

"Targeting CD74 may mitigate immune-escape features and enhance BCMA CAR-T activity in preclinical models of relapsed/refractory multiple myeloma"

Source 

Chen X, Zhang J, Chen H, Huang R, Zhou X, Wang H, et al. Targeting CD74 may mitigate immune-escape features and enhance BCMA CAR-T activity in preclinical models of relapsed/refractory multiple myeloma. Journal for ImmunoTherapy of Cancer. 2026;14:e013255. https://doi.org/10.1136/jitc-2025-013255 May 14, 2026. 

Overview

Understanding why myeloma cells persist after CAR-T therapy — and what makes them resistant — is central to improving long-term outcomes. This study used single-cell RNA sequencing on bone marrow samples collected before and after BCMA CAR-T treatment to characterize the myeloma cells that survive therapy.

Residual myeloma cells after CAR-T treatment showed elevated expression of CD74 and its binding partner MIF (migration inhibitory factor) compared to pre-treatment samples. Exposure to CAR-T cells in laboratory models actively induced CD74 expression and MIF secretion in myeloma cells — suggesting that immune pressure from CAR-T therapy itself drives upregulation of this survival pathway, rather than CD74-high cells simply being pre-selected from the outset.

Functionally, high CD74 expression enhanced myeloma cell proliferation and resistance to apoptosis, while knocking it down impaired cell viability. In a mouse xenograft model, blocking CD74 with milatuzumab — an existing anti-CD74 monoclonal antibody — combined with BCMA CAR-T therapy reduced tumor burden and extended survival more than either approach alone, while also suppressing CD74 expression in residual cells.

The MIF-CD74/CD44 signaling axis appears to be the mechanism sustaining residual disease under immune pressure — a pathway activated by the therapy itself rather than present independently of it.

The findings identify CD74 as a resistance mechanism that emerges in response to CAR-T treatment, and milatuzumab as a clinically available agent that could potentially be combined with BCMA CAR-T therapy to address it. Prospective clinical evaluation of this combination would be the logical next step.

 

"BCMA-Engineered Dendritic Cell-Derived Exosomes as Bi-Functional Therapeutics Orchestrating Cytokine Sequestration and Immune Activation for Multiple Myeloma

Source 

Y.Zeng, C.He, Z.He, H.Chen, F.Cheng, and Y.Zheng, “BCMA-Engineered Dendritic Cell-Derived Exosomes as Bi-Functional Therapeutics Orchestrating Cytokine Sequestration and Immune Activation for Multiple Myeloma.” Advanced Science (2026): e75686. https://doi.org/10.1002/advs.75686 May 15, 2026. 

Overview

The immunosuppressive bone marrow microenvironment (BMM) and cytokine dysregulation limit the durability of multiple myeloma (MM) treatments. B-cell maturation antigen (BCMA)-targeted therapies also face limitations from antigen escape and low immune activation. To address this, DB Exo was developed as a cell-free platform using allogeneic dendritic cell-derived exosomes engineered to display BCMA on their surface.

Mechanistically, DB Exo sequesters soluble APRIL and attenuates BAFF, which disrupts NF-κB pro-survival signaling in MM cells. Simultaneously, the platform uses inherited costimulatory molecules (CD80, CD86, and MHC-II) to stimulate host immune responses, which expands CD8+ T cells and increases cytotoxic effector molecule secretion.

In an orthotopic murine model, DB Exo reduced tumor burden by 72% and altered the BMM by increasing cytotoxic T-lymphocyte infiltration and elevating serum IFN-γ and Granzyme B levels. In a subcutaneous model, DB Exo reduced tumor weight by 75%. These data demonstrate that the bi-functional exosome platform combines targeted cytokine blockade with in situ immune activation for MM treatment.

 

"Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen–Directed CAR T-Cell Therapy"

Source 

Kuipers, M.T., Migchelbrink, J., Kramer, A.M. et al. Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen–Directed CAR T-Cell Therapy. BioDrugs (2026). https://doi.org/10.1007/s40259-026-00784-y May 15, 2026. 

Overview

B-cell maturation antigen (BCMA) directed CAR T-cell therapy is a treatment for relapsed or refractory multiple myeloma. While clinical outcomes show response rates and remissions, the therapy causes a range of common and rare toxicities that contribute to non-relapse mortality if unmanaged. Frequent adverse events include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity, and infections. Less frequent toxicities include non-ICANS neurotoxicity, such as parkinsonian-like movement disorders, immune-mediated enterocolitis, hemophagocytic lymphohistiocytosis, and secondary malignancies. Toxicity timing and severity correlate with CAR T-cell expansion, persistence, and baseline patient factors. This review summarizes clinical safety data for approved BCMA-targeted CAR T-cell therapies, outlining toxicities, proposed biological mechanisms, and management protocols.

 

"Population Pharmacokinetics and Model-Informed Precision Dosing of Lenalidomide Incorporating Total and Unbound Plasma Concentrations in Renally Impaired Patients with Multiple Myeloma"

Source 

Kim, H., Park, S. S., Choi, S., Han, S., Han, S., Lee, Y., … Chung, E. K. (2026). Population Pharmacokinetics and Model-Informed Precision Dosing of Lenalidomide Incorporating Total and Unbound Plasma Concentrations in Renally Impaired Patients with Multiple Myeloma. Drug Design, Development and Therapy, 20. https://doi.org/10.2147/DDDT.S605741 May 16, 2026.  

Overview

To develop a population pharmacokinetic (PK) model of lenalidomide and evaluate dosing regimens based on total and unbound concentrations, 30 multiple myeloma patients receiving oral lenalidomide were enrolled and stratified by renal function. The cohort included 11 patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 $m^2$, 11 with eGFR $\ge$ 30 to < 60 mL/min/1.73 $m^2$, and 8 with eGFR $\ge$ 60 mL/min/1.73 $m^2$. Serial plasma samples were collected at steady state, and total and unbound concentrations were analyzed via population PK modeling using NONMEM. Monte Carlo simulations evaluated dosing regimens against the reference systemic exposure (area under the plasma concentration-time curve, AUC) of patients with normal renal function receiving 25 mg/day. A two-compartment model with linear protein binding described the plasma lenalidomide concentration-time data. Apparent unbound clearance ($CL/F$) increased with higher eGFR and body surface area (BSA), while apparent central volume of distribution ($V_1/F$) increased with higher BSA ($P < 0.05$). Other PK parameters showed no significant association with patient characteristics, including ABCB1 genotypes. Simulations indicated that standard labeled dosing matched reference exposures in the majority of subjects, but BSA-stratified adjustments altered exposure precision. Simulated patients with BSA < 1.6 $m^2$ required dose reductions to maintain target exposure without exceeding reference limits, while patients with BSA $\ge$ 2.0 $m^2$ required dose escalation to reach target exposure. The model quantifies the effects of eGFR and BSA on lenalidomide clearance and volume of distribution in patients with renal impairment.

 

"Characteristics of immunoglobulin gene rearrangements in Vietnamese newly diagnosed multiple myeloma patients"

Source 

Cao Sy Luan, Nguyen Vu Hai Son, Phan Ngo Quang Thach, Cao Van Dong, Nguyen Quoc Dung, Trinh Thuy Duong, Phu Chi Dung, Hoang Anh Vu, Phan Thi Xinh, CHARACTERISTICS OF IMMUNOGLOBULIN GENE REARRANGEMENTS IN VIETNAMESE NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS, Leukemia Research Reports, 2026, 100594, ISSN 2213-0489, https://doi.org/10.1016/j.lrr.2026.100594. May 16, 2026. .  

Overview

An observational study from June 2019 to June 2023 evaluated bone marrow samples from 111 newly diagnosed multiple myeloma (MM) patients at Blood Transfusion Hematology Hospital to characterize immunoglobulin (IG) gene rearrangements. Among the cohort, bone lesions were present in 100% of patients, anemia in 77.5%, and 91.9% were classified as revised International Staging System (rISS) stage III. Cytogenetic analysis identified high-risk abnormalities in 28.8% of patients. Malignant plasma cells predominantly displayed a CD38+CD138+CD19–CD56+ immunophenotype. Clonal IG gene rearrangements occurred in 104 patients (93.7%), with double and triple rearrangements detected in 69.4% and 18.9% of patients, respectively. Within the IGH repertoire, VH3, VH4, DH3, and JH4 were the most frequent segments. In IGK rearrangements, VK1 and JK4 were the most frequent segments, and kappa deleting element (KDE) rearrangements occurred in 42.5% of patients. In IGL rearrangements, VL1 and JL3 predominated. The rate of clonal IGH gene rearrangements differed between heavy-chain and light-chain-only MM variants. This study establishes the baseline frequency and repertoire of IG gene rearrangements in Vietnamese MM patients.

 

"Impact of Renal Impairment and Lymphodepletion Regimen on Outcomes after CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma"

Source 

Nora Grieb, Thomas Wiemers, Patrick Born, David Fandrei, Luise Fischer, Maximilian Ferle, Stefan Franke, Johannes Keller, Song Yau Wang, Madlen Jentzsch, Carmen Herling, Klaus H. Metzeler, Marco Herling, Simone Heyn, Thomas Neumuth, Uwe Platzbecker, Vladan Vučinić, Georg-Nikolaus Franke, Maximilian Merz, Impact of Renal Impairment and Lymphodepletion Regimen on Outcomes after CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma, Transplantation and Cellular Therapy, 2026, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2026.05.022. May 16, 2026.  

Overview

To analyze clinical outcomes and cellular dynamics based on renal function and lymphodepletion (LDP) regimen in relapsed/refractory multiple myeloma, data were retrospectively evaluated from 87 patients treated with idecabtagene vicleucel (Ide-cel) or ciltacabtagene autoleucel (Cilta-cel). The cohort included 53 patients with none/mild chronic kidney disease (CKD) and 34 with moderate/severe CKD. LDP consisted of standard-dose fludarabine and cyclophosphamide (Flu/Cy) ($n=67$), reduced-dose Flu/Cy ($n=11$), or bendamustine ($n=9$). Patients with moderate/severe CKD received standard Flu/Cy less frequently than those with none/mild CKD (55.9% versus 96.2%, $p<0.001$) and bendamustine more frequently (26.5% versus 0%, $p<0.001$). CKD status alone did not alter overall survival ($p=0.93$) or progression-free survival (PFS, $p=0.82$). LDP regimen also did not independently alter PFS ($p=0.21$). However, among Cilta-cel recipients, none/mild CKD correlated with prolonged PFS compared to moderate/severe CKD ($p=0.026$). A Cox model identified an interaction between CKD status and CAR T product (HR 19.32, 95% CI 1.25–2176, $p=0.03$). Cilta-cel extended PFS relative to Ide-cel in patients with none/mild CKD ($p<0.001$), but this difference was absent in the moderate/severe CKD subgroup. Absolute lymphocyte count (ALC) nadir occurred at day -1 for Flu/Cy and day +1 for bendamustine. At infusion, median ALC was higher in the bendamustine group than the standard Flu/Cy group ($p=0.03$). CAR T-cell expansion kinetics did not vary by CKD or LDP status. Bendamustine-based LDP correlated with reduced early neutropenia/immune effector cell-associated hematotoxicity ($p=0.002$) and a higher absolute neutrophil count nadir ($p<0.001$), with similar cytokine release syndrome and neurotoxicity rates across groups..

 

"Impact of Renal Impairment and Lymphodepletion Regimen on Outcomes after CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma"

Source 

Nora Grieb, Thomas Wiemers, Patrick Born, David Fandrei, Luise Fischer, Maximilian Ferle, Stefan Franke, Johannes Keller, Song Yau Wang, Madlen Jentzsch, Carmen Herling, Klaus H. Metzeler, Marco Herling, Simone Heyn, Thomas Neumuth, Uwe Platzbecker, Vladan Vučinić, Georg-Nikolaus Franke, Maximilian Merz, Impact of Renal Impairment and Lymphodepletion Regimen on Outcomes after CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma, Transplantation and Cellular Therapy, 2026, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2026.05.022. May 16, 2026.  

Overview

To analyze clinical outcomes and cellular dynamics based on renal function and lymphodepletion (LDP) regimen in relapsed/refractory multiple myeloma, data were retrospectively evaluated from 87 patients treated with idecabtagene vicleucel (Ide-cel) or ciltacabtagene autoleucel (Cilta-cel). The cohort included 53 patients with none/mild chronic kidney disease (CKD) and 34 with moderate/severe CKD. LDP consisted of standard-dose fludarabine and cyclophosphamide (Flu/Cy) ($n=67$), reduced-dose Flu/Cy ($n=11$), or bendamustine ($n=9$). Patients with moderate/severe CKD received standard Flu/Cy less frequently than those with none/mild CKD (55.9% versus 96.2%, $p<0.001$) and bendamustine more frequently (26.5% versus 0%, $p<0.001$). CKD status alone did not alter overall survival ($p=0.93$) or progression-free survival (PFS, $p=0.82$). LDP regimen also did not independently alter PFS ($p=0.21$). However, among Cilta-cel recipients, none/mild CKD correlated with prolonged PFS compared to moderate/severe CKD ($p=0.026$). A Cox model identified an interaction between CKD status and CAR T product (HR 19.32, 95% CI 1.25–2176, $p=0.03$). Cilta-cel extended PFS relative to Ide-cel in patients with none/mild CKD ($p<0.001$), but this difference was absent in the moderate/severe CKD subgroup. Absolute lymphocyte count (ALC) nadir occurred at day -1 for Flu/Cy and day +1 for bendamustine. At infusion, median ALC was higher in the bendamustine group than the standard Flu/Cy group ($p=0.03$). CAR T-cell expansion kinetics did not vary by CKD or LDP status. Bendamustine-based LDP correlated with reduced early neutropenia/immune effector cell-associated hematotoxicity ($p=0.002$) and a higher absolute neutrophil count nadir ($p<0.001$), with similar cytokine release syndrome and neurotoxicity rates across groups.

 

"Condensed vs. Standard Step-Up Dosing Schedule of Talquetamab in Relapsed/Refractory Multiple Myeloma"

Source 

G.Elsey, J. A.Davis, K.Julian, et al., “Condensed vs. Standard Step-Up Dosing Schedule of Talquetamab in Relapsed/Refractory Multiple Myeloma,” European Journal of Haematology (2026): 1–6, https://doi.org/10.1111/ejh.70221. May 18, 2026.   

Overview

To evaluate step-up dosing (SUD) schedules for talquetamab in patients with relapsed/refractory multiple myeloma, a multicenter retrospective study across seven academic medical centers in the United States compared a standard schedule (days 1, 4, 7, and 10) with a condensed schedule (days 1, 3, 5, and 7). The analysis included 144 patients: 33 received the standard SUD schedule and 111 received the condensed SUD schedule. The incidence of cytokine release syndrome (CRS) was 76% in the standard cohort and 56% in the condensed cohort ($p = 0.101$). The incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 9% in the standard cohort and 16% in the condensed cohort ($p = 0.41$). No statistically significant differences were observed in the severity grades of CRS or ICANS between the two cohorts. These data indicate that the condensed talquetamab step-up dosing schedule does not alter the incidence or severity of CRS and ICANS compared to the standard schedule.

 

"Elevated desmoglein-2 expression in multiple myeloma is a prognostic marker across genomic subtypes with impact on high-risk cytogenetics and a distinct gene expression profile"

Source 

McClure, B.J., Toubia, J., Toomes, C.E.J., Best, O.G., Yong, A., Lee, C.H., Bonder, C.S. and Kok, C.H. (2026), Elevated desmoglein-2 expression in multiple myeloma is a prognostic marker across genomic subtypes with impact on high-risk cytogenetics and a distinct gene expression profile. Br J Haematol. https://doi.org/10.1111/bjh.70554 May 18, 2026.   

Overview

Current risk stratification in myeloma relies heavily on established cytogenetic markers — translocations, deletions, and copy number changes — but some people with apparently standard-risk cytogenetics still fare poorly, pointing to additional biological factors that existing tools do not capture. This study examined desmoglein-2 (DSG2), a cell surface protein previously linked to a fourfold increased risk of death in myeloma, to determine whether its prognostic impact holds within specific cytogenetic subgroups.

Using transcriptomic data from 678 newly diagnosed people with myeloma in the MMRF CoMMpass dataset, high DSG2 expression (top quartile) was associated with shorter progression-free survival (median 27.8 vs 37.2 months) and overall survival (54.9 months vs not reached) compared to low expressers, independent of age, sex, ISS stage, transplant, and treatment.

The cytogenetic subgroup findings are particularly useful. In people with t(11;14) — conventionally considered standard risk — high DSG2 expression identified a subset with significantly worse survival, suggesting DSG2 could flag high-risk disease within a group not currently prioritized for intensified treatment. In people with 1q+ abnormalities, high DSG2 expression was similarly associated with worse outcomes, and this held even after excluding cases with co-existing t(4;14). In contrast, DSG2 did not add prognostic information in people with established high-risk translocations t(4;14) and t(14;16), where prognosis is already poor regardless.

Gene expression analysis in DSG2-high myeloma cells showed downregulation of ribosomal and translation pathways — a pattern previously linked to suboptimal bortezomib response — alongside upregulation of genes involved in proliferation and dissemination. DSG2 is measurable from routine CD138-positive plasma cell samples at diagnosis, positioning it as a potentially accessible addition to current risk stratification without requiring new biopsy procedures.

 

"Real-world outcomes of melflufen plus dexamethasone in heavily pretreated relapsed/refractory multiple myeloma after exposure to immunotherapies"

Source 

David Martínez-Campuzano, Clara Sopeña, María José Moreno, María Sánchez, Adriana Gascón, Pablo Lorente, Mario Montagud, Jaime Pascual Martí, Silvina Ríos, Mario Arnao, Javier de la Rubia, Real-world outcomes of melflufen plus dexamethasone in heavily pretreated relapsed/refractory multiple myeloma after exposure to immunotherapies, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.05.002. May 18, 2026. 

Overview

Melflufen combined with dexamethasone received approval for heavily pretreated relapsed or refractory myeloma, but real-world data — particularly in people who have already received the newer immunotherapies that have reshaped later-line treatment — remain sparse. This retrospective analysis from eight Spanish centers captures 19 people treated between June 2024 and May 2025, representing one of the first datasets in a post-immunotherapy exposed population.

The cohort was heavily pretreated: median five prior lines, 95% triple-class refractory, 74% penta-class refractory, and 74% with prior anti-BCMA or GPRC5D therapy exposure including five with dual immunotherapy exposure. Seven had high-risk cytogenetics, four with two or more high-risk abnormalities simultaneously.

Overall response rate was 28% across the full cohort and 33% in the immunotherapy-exposed subgroup — modestly encouraging given the extent of prior treatment, though stable disease in an additional 42 to 44% suggests some disease control beyond formal response. Median progression-free survival was 4.8 months. Median overall survival had not been reached at a median follow-up of 5.75 months, and three people remained alive and responding beyond nine months.

Hematologic toxicity was substantial: thrombocytopenia and neutropenia each occurred in 68%, anemia in 47% at grade 3 or higher. Infections affected ten people, mostly low grade. One person discontinued due to severe thrombocytopenia with bleeding and one died of sepsis — findings consistent with melflufen's known toxicity profile and the fragility of this population.

The data provide preliminary evidence that melflufen retains activity after immunotherapy exposure, but the small cohort, short follow-up, and absence of a comparison group limit what can be concluded about its place in current sequencing decisions.

 

"Uncovering the Clinical Factors Determining the Survival of Multiple Myeloma Patients with Extramedullary Disease: Insights from a Single-Centre Study"

Source 

Bayar, A., Yılmaz, A.F., Toptaş, T. et al. Uncovering the Clinical Factors Determining the Survival of Multiple Myeloma Patients with Extramedullary Disease: Insights from a Single-Centre Study. Indian J Hematol Blood Transfus (2026). https://doi.org/10.1007/s12288-026-02419-2 May 18, 2026.  

Overview

Extramedullary disease (EMD) — myeloma growing outside the bone marrow — is associated with more aggressive disease biology and worse outcomes than bone marrow-confined myeloma. This retrospective single-center study analyzed 99 people with EMD treated between 2010 and 2022, examining which clinical features predicted survival.

The majority (92 of 99) had EMD present at diagnosis rather than at relapse. Most involvement was bone-related (72 patients) rather than extraosseous soft tissue disease (27 patients), and 56 had involvement at a single site. PET/CT was the primary diagnostic tool in 75 cases.

Several factors independently predicted worse survival: advanced ISS stage, secondary EMD (appearing at relapse rather than diagnosis), light chain disease (median overall survival 24 vs 78 months), elevated creatinine, and elevated beta-2 microglobulin. Secondary EMD carried nearly three times the progression risk of primary EMD, consistent with its association with clonal evolution and acquired resistance. High-risk cytogenetics and multiple involvement sites trended toward worse outcomes but did not reach statistical significance, likely reflecting the modest sample size.

Notably, the type of extramedullary involvement — bone-related versus extraosseous — did not significantly affect progression-free survival (49 vs 63 months, p=0.209), suggesting that the distinction between EM-B and EM-E may matter less than other disease characteristics in determining outcomes.

Autologous stem cell transplant was associated with substantially better overall survival (hazard ratio 0.28), reinforcing its value in transplant-eligible people with EMD. Induction regimen choice did not significantly affect survival across the groups compared, though treatment options were more limited during the study period than in current practice.

 

"Disparity in Access to Multiple Myeloma CAR-T: A Geospatial Analysis of Distance to CAR-T Centers"

Source 

Michael Daunov, R. Benjamin Gorham, Olga Lytvynova, Ok-kyong Chaekal, Timothy O’Brien, Koen van Besien, Weichuan Dong, Siran Koroukian, James J Ignatz-Hoover; Disparity in Access to Multiple Myeloma CAR-T: A Geospatial Analysis of Distance to CAR-T Centers. Blood Immunology & Cellular Therapy 2026; 100064. doi: https://doi.org/10.1016/j.bict.2026.100064  May 18, 2026. 

Overview

 CAR-T therapy has produced the deepest and most durable responses seen in heavily pretreated myeloma, but its delivery is concentrated in specialized academic centers — raising questions about who can realistically access it. This geospatial analysis mapped the distance between the US population and CAR-T treatment centers, finding that large portions of the country are hours away from the nearest facility.

The gap is not evenly distributed. Regions including Appalachia and the Deep South — areas with historically limited healthcare infrastructure — have the greatest geographic distance from CAR-T centers. People in these regions also scored higher on the CDC Social Vulnerability Index, a composite measure of socioeconomic disadvantage that captures factors including poverty, lack of vehicle access, and housing instability. Geographic distance compounds these existing disadvantages: traveling hours for a multi-week treatment process requiring close monitoring is a substantially greater burden for someone without reliable transportation, flexible employment, or financial reserves.

The analysis points to a widening gap between myeloma care at large academic centers, where CAR-T and other novel therapies are available, and community oncology practices, where most people with myeloma actually receive treatment. This divide affects not just CAR-T access but the broader trajectory of treatment in later lines of therapy.

The authors identify three practical directions for narrowing the gap: insurance coverage that explicitly includes travel and lodging costs associated with CAR-T treatment; development of manufacturing platforms that could support CAR-T delivery at community centers; and continued investment in therapies — bispecific antibodies, small molecules — that can be administered in community settings without specialized infrastructure.

"Sociodemographic, Clinical, and Therapeutic Characterization of Multiple Myeloma Patients (CharisMMa Study) with Symptomatic Relapse and/or Refractory Disease: An Observational, Multicenter Study in Portugal"

Source 

Bergantim, R., Freitas, J. G., Gonçalves, C., Martins, H., Marques, H., Coelho, H., Seabra, P., Roque, A., Tavares, M., Pinto, P., Francisco, A. R., Tato, J., & Geraldes, C. (2026). Sociodemographic, Clinical, and Therapeutic Characterization of Multiple Myeloma Patients (CharisMMa Study) with Symptomatic Relapse and/or Refractory Disease: An Observational, Multicenter Study in Portugal. Hematology Reports, 18(3), 34. https://doi.org/10.3390/hematolrep18030034 May 19, 2026. 

Overview

Real-world data on how relapsed or refractory myeloma is managed outside clinical trials — and outside large academic centers in Northern Europe or North America — remains limited. This cross-sectional observational study from seven Portuguese hospitals enrolled 62 people with relapsed or refractory myeloma between 2020 and 2022, describing who they were and how they were being treated.

The cohort was predominantly male (55%), with a mean age of 66, and most were living with family. Around 70% had R-ISS stage II disease at diagnosis, and bone lesions were the most common disease-defining feature at presentation (59%). Nearly two-thirds had at least one comorbidity, reflecting the real-world complexity of this population compared to trial enrollees.

At the time of data collection, 70% were receiving second-line therapy. Proteasome inhibitors combined with immunomodulatory drugs were the most commonly used agents, with monoclonal antibodies also prominent. Triplet regimens were the standard across treatment lines. Oral and oral-plus-subcutaneous administration routes predominated — a pattern consistent with efforts to reduce hospital visits and improve convenience, though it also reflects the treatment options available during the study period, before bispecific antibodies became widely accessible in Portugal.

The dataset predates the broader availability of newer immunotherapies in routine Portuguese practice, which limits its direct applicability to current decision-making but provides a useful baseline for tracking how treatment patterns evolve as newer agents reach reimbursement. The authors note the findings should inform efforts to standardize myeloma care across centers in Portugal, where variability between institutions remains a practical concern.

"Molecular insight into the interplay among heterogeneous plasmacytes and microenvironment cells and their clinical relevance in myeloma"

Source 

L. Jiang,C. Liu,Y. Zhang,N. Qiao,J. Li,S. Yang,X. Shen,M. Chen,S. Wang,T. Wu,B. Chen,S. Yu,F. Jiang,S. Wang,Y. Liu,Y. Wang,Y. Tao,Z. Chen,J. Mi,[...] & S. Chen,  Molecular insight into the interplay among heterogeneous plasmacytes and microenvironment cells and their clinical relevance in myeloma, Proc. Natl. Acad. Sci. U.S.A. 123 (21) e2537965123, https://doi.org/10.1073/pnas.2537965123 (2026). May 19, 2026.  

Overview

Most large-scale genomic studies of myeloma have been conducted in Western populations, leaving gaps in understanding whether disease biology differs in Chinese patients. This study — the Shanghai MM Omics (SMMO) project — analyzed 277 newly diagnosed people with myeloma using whole-genome or whole-exome sequencing, RNA sequencing, and single-cell RNA sequencing, with 30 healthy controls for comparison.

Genomic analysis identified three genetic groups broadly consistent with those described in Western cohorts: MY (MYC-driven), HRD (hyperdiploidy), and MS/CD (translocation-defined subtypes). Single-cell RNA sequencing of myeloma plasma cells identified eight distinct subpopulations (mSP1–mSP8), each with a unique gene expression signature, arranged along a differentiation trajectory. One subpopulation, mSP2, stood out for high proliferative activity and became the basis for a prognostic scoring tool.

The immune microenvironment analysis found broad T cell dysfunction across helper, regulatory, and cytotoxic T cell subsets, alongside increased myeloid-derived suppressor cells — predominantly macrophages polarized toward the M2 (immune-suppressive) state. This combination creates conditions that favor myeloma cell growth and immune evasion, consistent with findings in Western patient datasets.

The study mapped communication between myeloma cells and microenvironment cells through ligand-receptor pair analysis, identifying specific signaling interactions that sustain this immunosuppressive niche. The mSP2 proliferative signature was then applied to bulk RNA sequencing data from 235 patients to generate a continuous score (Score100) with independent prognostic value. Combined with ISS staging and genomic staging, Score100 forms the basis of a proposed stratification model aimed at identifying aggressive myeloma at diagnosis — an approach requiring external validation but grounded in multi-layered molecular characterization.

"Long-term prognostic impact of chromosome 1 abnormalities in newly diagnosed multiple myeloma patients: a monocentric study"

Source 

Iannozzi, N.T., Sammarelli, G., Poletti, A. et al. Long-term prognostic impact of chromosome 1 abnormalities in newly diagnosed multiple myeloma patients: a monocentric study. Ann Hematol (2026). https://doi.org/10.1007/s00277-026-07072-3 May 19, 2026. 

Overview

Researchers evaluated whether abnormalities involving chromosome 1 affect outcomes in patients with newly diagnosed multiple myeloma. The study included 95 patients who were followed for a median of more than five years.

The investigators found that gain or amplification of chromosome 1q, a genetic abnormality commonly seen in myeloma, was not associated with shorter overall survival, progression-free survival, or time to next treatment in this patient group.

Deletion of chromosome 1p [del(1p)] was associated with poorer outcomes in the initial analysis. However, the strongest effect was observed when del(1p) occurred together with deletion of chromosome 17p [del(17p)], another high-risk genetic abnormality linked to loss of the TP53 tumor suppressor gene.

Patients whose myeloma carried both del(1p) and del(17p) experienced substantially worse outcomes than patients without this combination. The presence of both abnormalities was associated with shorter overall survival, shorter progression-free survival, and a shorter time before additional treatment was needed.

The findings suggest that del(1p) may have the greatest prognostic significance when it occurs alongside del(17p), identifying a subgroup of patients with particularly high-risk disease.

 

"Real-World Evaluation of Talquetamab for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): An International Myeloma Working Group Immunotherapy Registry Real-World Analysis"

Source 

M. Janakiram, C. R. Tan, H. Mian, et al., “Real-World Evaluation of Talquetamab for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): An International Myeloma Working Group Immunotherapy Registry Real-World Analysis,” American Journal of Hematology (2026): 1–10, https://doi.org/10.1002/ajh.70376. May 19, 2026. 

Overview

This international real-world study evaluated talquetamab in 151 patients with relapsed or refractory multiple myeloma across five countries. More than half of the patients would not have met the eligibility criteria for the MonumenTAL-1 clinical trial, reflecting a broader and more medically complex population than those typically enrolled in clinical studies.

Patients had received a median of six prior lines of therapy, 53% had penta-refractory disease, and 75% had previously received a BCMA-targeted treatment. High-risk cytogenetic abnormalities were present in 42% of patients.

Talquetamab produced an overall response rate of 67.6%. With a median follow-up of 12.7 months, median progression-free survival was 7 months and the 12-month overall survival rate was 65%.

Side effects affecting the skin, nails, mouth, and sense of taste were common. Nail changes occurred in 75.5% of patients, oral toxicities in 62.9%, taste changes in 60.4%, and skin toxicities in 39.7%. Severe events were uncommon, occurring in 4% or fewer patients, and treatment interruptions due to these side effects were relatively infrequent.

In an analysis of factors associated with outcomes, a platelet count below 50 was linked to shorter progression-free survival. Prior BCMA-targeted therapy, penta-refractory disease, and low lymphocyte counts were not significantly associated with worse outcomes.

The findings suggest that talquetamab can remain effective in heavily pretreated patients, including many who have previously received BCMA-directed therapies

"Recognising disease progression in MGUS and smouldering myeloma: Biomarkers, symptom monitoring and imaging"

Source 

Haslam A, Iqbal G, Drayson M, Pratt G, Yong K, Dunn J, Atkin C, Bunce C, Howe D, Bowcock S. Recognising disease progression in MGUS and smouldering myeloma: Biomarkers, symptom monitoring and imaging. Br J Haematol. 2026 May 20. doi: 10.1111/bjh.70492. 

Overview

Researchers analyzed data from 133 patients with previously diagnosed MGUS or smoldering multiple myeloma (SMM) who later developed active multiple myeloma. The patients participated in the TEAMM trial, which enrolled 977 newly diagnosed myeloma patients from 93 hospitals across the United Kingdom.

Patients with a known precursor condition experienced symptoms for much longer before being diagnosed with active myeloma than patients without a recognized precursor stage. Despite ongoing monitoring, only 29% reported new myeloma-related symptoms after their first hematology appointment. In contrast, 70% showed a substantial increase in paraprotein levels before progression, and risk scores for MGUS and SMM also increased over time.

One of the most concerning findings involved bone health. Twenty-five percent of patients experienced fractures before their myeloma diagnosis, even while under surveillance. These fractures were difficult to predict. Blood-based biomarkers were not specific enough to reliably identify which patients were at greatest risk, and only 40% of patients with vertebral fractures reported back pain.

The findings suggest that monitoring paraprotein levels and risk scores can help identify disease progression, but current approaches remain imperfect. The study also highlights the difficulty of detecting bone damage early, even in patients receiving regular follow-up for MGUS or smoldering myeloma.
 

"Application of the New IMWG/IMS High-Risk Classification for Multiple Myeloma: Analysis of a Large Real-World Romanian Cohort"

Source 

Badelita, S. N., Barbu, S., Calugaru, O.-T., Jardan, C., Popa, C. D., Zidaru, L., Himcinschi, M. E., Smadu, B. N., Ursuleac, I., & Coriu, D. (2026). Application of the New IMWG/IMS High-Risk Classification for Multiple Myeloma: Analysis of a Large Real-World Romanian Cohort. International Journal of Molecular Sciences, 27(10), 4620. https://doi.org/10.3390/ijms27104620 May 20, 2026. 

Overview

Researchers evaluated recently updated International Myeloma Working Group (IMWG) and International Myeloma Society (IMS) criteria for high-risk multiple myeloma in a real-world study of 738 patients. Of these, 408 had cytogenetic testing results available at diagnosis.

Using the updated criteria, 25% of patients were classified as having high-risk disease. The most common high-risk abnormality was deletion 17p [del(17p)], which was identified in 14.7% of patients. Patients classified as high risk had shorter survival outcomes than those with standard-risk disease. Median overall survival was 52.4 months in the high-risk group compared with 68.4 months in the standard-risk group, while median progression-free survival was 16 months versus 28 months.

Response rates to treatment remained high in both groups, but relapse occurred more frequently among high-risk patients. The study found that prognosis was influenced not only by individual genetic abnormalities but also by the combination of abnormalities present. Patients with isolated del(17p) generally had better outcomes than those with del(17p) plus additional high-risk lesions. Patients with double-hit or triple-hit disease had the poorest outcomes. Chromosome 1 abnormalities combined with IGH translocations were also associated with worse survival.

Among high-risk patients who underwent autologous stem cell transplantation, outcomes were similar for those who received tandem transplants and those who received a single transplant. The findings suggest that the overall complexity of a patient's cytogenetic profile is an important factor in determining prognosis and treatment outcomes.

 

"Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: a US subgroup analysis from MagnetisMM-3"

Source 

Nooka AK, Strouse C, Larson SM, et al. Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: a US subgroup analysis from MagnetisMM-3. Cancer. 2026;e70442. doi:10.1002/cncr.70442 May 20, 2026

Overview

This analysis examined long-term outcomes in U.S. patients with relapsed or refractory multiple myeloma who received elranatamab in the MagnetisMM-3 clinical trial. All patients were BCMA-naive, meaning they had not previously received a BCMA-targeted therapy.

Among 47 U.S. patients, the overall response rate was 66.0%, and 42.6% achieved a complete response or better. After a median follow-up of nearly 40 months, the median duration of response was 40.8 months. Median progression-free survival was 27.3 months, and median overall survival was 43.6 months.

Patients initially received weekly elranatamab after step-up dosing. Those with sustained responses could transition to dosing every two weeks and, later, every four weeks. Most patients maintained or improved their responses after moving to less frequent dosing. Among responders who switched from weekly to every-two-week dosing, 77.8% maintained or deepened their response for at least six months. Among those who later switched to every-four-week dosing, 87.5% maintained or improved their response.

The most common side effects were infections (70.2%), fatigue (61.7%), and cytokine release syndrome (61.7%). Severe cytokine release syndrome was not reported, although severe infections occurred in 42.6% of patients.

The findings suggest that elranatamab can produce durable responses in heavily pretreated patients, with many responders able to transition successfully to less frequent dosing schedules.
 

"Peptidomic Profiling Reveals Extracellular Matrix Remodeling Signatures Discriminative of Multiple Myeloma"

Source 

M.Frantzi, M.Ahangar, A.Vlahou, et al. “Peptidomic Profiling Reveals Extracellular Matrix Remodeling Signatures Discriminative of Multiple Myeloma.” PROTEOMICS (2026): e70143. https://doi.org/10.1002/pmic.70143 May 19, 2026. 

Overview

Researchers investigated whether proteins and protein fragments found in urine could help distinguish active multiple myeloma from its precursor conditions, MGUS and smoldering multiple myeloma (SMM). Current risk models estimate the likelihood of progression but do not fully capture the biological changes occurring as the disease evolves.

The study analyzed urine samples from 314 individuals using a technique called capillary electrophoresis–mass spectrometry (CE-MS). Researchers identified 121 urinary peptides that differed significantly between patients with MGUS and those with active myeloma. Many of these peptides were derived from collagen, beta-2 microglobulin, alpha-1 antitrypsin, and antithrombin III. The levels of these peptides changed progressively across the disease spectrum from MGUS to SMM to active myeloma.

Using these peptide patterns, the investigators developed a predictive model that distinguished active myeloma from precursor conditions with high accuracy. In an independent validation group, the model achieved 100% sensitivity, correctly identifying all patients with myeloma, and 82% specificity, meaning most patients without active myeloma were correctly classified.

The findings suggest that urine-based peptide testing may provide a noninvasive way to detect biological changes associated with myeloma progression. Larger prospective studies will be needed to determine whether this approach can help predict which patients with MGUS or SMM are most likely to develop active myeloma.
 

"Comparative economic analysis of B-cell maturation antigen-targeted bispecific antibodies in triple-class exposed relapsed/refractory multiple myeloma: linvoseltamab versus teclistamab and elranatamab"

Source 

Portuguese, A. J., Inocencio, T. J., Quon, P., Harnett, J., Zhou, Z. Y., Hazra, N. C., … Ma, Q. (2026). Comparative economic analysis of B-cell maturation antigen-targeted bispecific antibodies in triple-class exposed relapsed/refractory multiple myeloma: linvoseltamab versus teclistamab and elranatamab. Current Medical Research and Opinion, 1–13. https://doi.org/10.1080/03007995.2026.2665022 May 20, 2026. 

Overview

Researchers compared the projected healthcare costs associated with linvoseltamab, teclistamab, and elranatamab in patients with relapsed or refractory multiple myeloma whose disease had already been exposed to the three major treatment classes: immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies.

Using a matching-adjusted indirect comparison model, the investigators estimated treatment costs from the perspective of a U.S. commercial insurer. The analysis included drug costs, administration, monitoring, management of side effects, disease progression, and end-of-life care.

Compared with teclistamab, linvoseltamab was associated with lower total costs over both one- and two-year periods. Estimated two-year costs were approximately $488,000 for linvoseltamab versus $639,000 for teclistamab. Linvoseltamab also had lower costs per progression-free month and lower costs per treatment response.

When compared with elranatamab, total costs were similar despite a longer median treatment duration with linvoseltamab (11.3 months versus 5.6 months). Linvoseltamab also showed lower costs per progression-free month and lower costs per response in the model.

Because this was an indirect comparison based on clinical trial data and modeling assumptions rather than a head-to-head clinical trial, the results should be interpreted cautiously. The analysis suggests that linvoseltamab may provide a lower overall economic burden than teclistamab and comparable or more favorable cost-effectiveness than elranatamab in heavily pretreated patients with relapsed or refractory myeloma.
 

"RNF5-DNAJA1 axis dictates selinexor sensitivity of multiple myeloma by regulating mitochondrial unfolded protein response"

Source 

Mengqi Wang, Hao Cheng, Danchen Su, Huang Tan, Zhenye Zhu, Ying Xie, Jing Guo, Ziyi Peng, Jingjing Wang, Yixuan Wang, Tiantian Li, Linchuang Jia, Mu Qiao, Xinyang Li, Wenjing Li, Mingru Jiang, Yafei Wang, Zhiqiang Liu, RNF5-DNAJA1 axis dictates selinexor sensitivity of multiple myeloma by regulating mitochondrial unfolded protein response, Journal of the National Cancer Center, 2026, ISSN 2667-0054, https://doi.org/10.1016/j.jncc.2026.04.005. May 20, 2026.  

Overview

Researchers investigated why some patients with relapsed or refractory multiple myeloma respond better to selinexor than others. Selinexor blocks XPO1, a protein that transports other proteins from the nucleus to the cytoplasm, but the biological factors that influence treatment sensitivity are not fully understood.

The study identified a protein called RNF5 as an important XPO1 cargo. Higher levels of RNF5 transport were associated with poorer responses to selinexor. The researchers found that RNF5 modifies another protein, DNAJA1, through a process called ubiquitination. This strengthens the interaction between DNAJA1 and HSP70, activating a cellular stress-response pathway known as the mitochondrial unfolded protein response (UPRmt).

Activation of the UPRmt pathway appeared to help myeloma cells maintain mitochondrial function and survive despite treatment with selinexor. When researchers blocked RNF5 or DNAJA1 using experimental inhibitors, the protective pathway was disrupted, making myeloma cells more sensitive to selinexor in laboratory and animal models.

The findings identify the XPO1-RNF5-DNAJA1 pathway as a potential mechanism of selinexor resistance. The results also suggest that combining selinexor with therapies targeting RNF5 or DNAJA1 could be a future strategy for improving responses in patients with relapsed or refractory multiple myeloma.

 

"Standard-of-care ciltacabtagene autoleucel in earlier versus later lines of therapy for relapsed or refractory multiple myeloma: a nationwide registry analysis"

Source 

Gagelmann, N., Einsele, H., Flossdorf, S. et al. Standard-of-care ciltacabtagene autoleucel in earlier versus later lines of therapy for relapsed or refractory multiple myeloma: a nationwide registry analysis. J Hematol Oncol (2026). https://doi.org/10.1186/s13045-026-01806-6 May 20, 2026.   

Overview

This real-world study examined outcomes in 606 patients with relapsed or refractory multiple myeloma who received ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in Germany between 2022 and 2025. Researchers compared patients treated earlier in their disease course (after one to three prior lines of therapy) with those treated after more than three prior lines.

Patients treated earlier achieved strong outcomes. The overall response rate was 91%, and 63% achieved a complete response. At 12 months, progression-free survival was 79% in the earlier-line group compared with 70% in patients treated later.

The depth of response was the strongest predictor of outcome. Patients who achieved and maintained a complete response had 100% progression-free survival at 12 months, regardless of when they received CAR T-cell therapy. Extramedullary disease was associated with poorer outcomes in both groups. High-risk cytogenetic abnormalities did not appear to reduce progression-free survival among patients treated earlier in their disease course.

Side effects were generally consistent with the known safety profile of cilta-cel. Non-ICANS neurologic toxicities occurred less frequently in the earlier-line group (3% versus 8%), while non-relapse mortality was similar between the two groups.

The findings provide real-world support for using cilta-cel as early as first relapse, with outcomes similar to those reported in the CARTITUDE-4 clinical trial.

"Treatment of Multiple Myeloma: ASCO Living Guideline"

Source 

Rahul Banerjee et al. Treatment of Multiple Myeloma: ASCO Living Guideline, Version 2026.1.1. J Clin Oncol 0, 10.1200/JCO-26-01139 DOI:10.1200/JCO-26-01139  

Overview

"Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix I and Appendix II). Updates are published regularly and can be found on the ASCO Publications website."

"APN Inhibitor Bestatin Induces MM Cell Differentiation Through the CD79B/BTK/STAT3 Pathway Cells"

Source 

Wang, X., Fang, C., Li, S., Zeng, H., Liu, J., Duan, X., Zhang, X., Jiang, W., & Wang, X. (2026). APN Inhibitor Bestatin Induces MM Cell Differentiation Through the CD79B/BTK/STAT3 Pathway. Cells, 15(10), 949. https://doi.org/10.3390/cells15100949 May 20, 2026. 

Overview

Most myeloma treatments work by killing cancer cells directly. Differentiation therapy takes a different approach — pushing malignant cells to mature into a more normal, less proliferative state. This study investigated how bestatin, an inhibitor of the enzyme aminopeptidase N (APN), induces differentiation in myeloma cells and which molecular pathway drives that effect.

APN was expressed at elevated levels across three myeloma cell lines. Bestatin treatment induced differentiation in a dose-dependent manner, evidenced by upregulation of the differentiation marker CD49e, increased immunoglobulin light chain secretion, and elevated cellular senescence — alongside reduced proliferation and suppressed APN enzymatic activity.

The mechanism operates through the CD79B/BTK signaling pathway. Bestatin downregulates this pathway, which in turn activates the transcription factor STAT3. Two experiments confirmed this axis: inhibiting CD79B/BTK directly was sufficient to induce differentiation on its own, while blocking STAT3 completely prevented bestatin's differentiation-promoting effect. An antibody that neutralizes APN (WM15) produced the same results as bestatin, validating that APN inhibition is the upstream trigger.

The combination findings are clinically relevant. Bestatin synergized with ixazomib, a proteasome inhibitor already approved for myeloma, and enhanced the anti-proliferative effect of IL-6. Ibrutinib (a BTK inhibitor) and a STAT3 activating compound also potentiated ixazomib cytotoxicity, suggesting multiple entry points into this pathway could be exploited in combination strategies.

The work is limited to cell line experiments and requires validation in primary patient samples and animal models. However, the identification of a specific, druggable signaling axis connecting APN inhibition to myeloma cell differentiation provides a mechanistic foundation for combination approaches with existing approved agents.

"Inhibition of the oncogenic GTPase dynamin-related protein 1 (DRP1) by the FDA-approved drug fosaprepitant: In silico, biophysical, and in vitro characterization of its anti-myeloma activity"

Source 

Emanuela Marchese, Pierpaolo Murfone, Ilenia Valentino, Maria Eugenia Gallo Cantafio, Francesca Alessandra Ambrosio, Irene Gado, Noemi Puccio, Massimo Gentile, Antonino Neri, Giuseppe Viglietto, Stefano Alcaro, Francesca Vasile, Giosuè Costa, Nicola Amodio, Inhibition of the oncogenic GTPase dynamin-related protein 1 (DRP1) by the FDA-approved drug fosaprepitant: In silico, biophysical, and in vitro characterization of its anti-myeloma activity, International Journal of Biological Macromolecules, 2026, 152633, ISSN 0141-8130, https://doi.org/10.1016/j.ijbiomac.2026.152633. May 20, 2026. 

Overview

Myeloma cells depend heavily on mitochondrial function to meet their energy demands, making mitochondrial biology an emerging area of therapeutic interest. This study focused on DRP1, a protein that controls mitochondrial fission — the process by which mitochondria divide. When fission is inhibited, mitochondria fuse into elongated networks (hyperfusion), which disrupts normal energy production and can trigger cell death.

Starting from a virtual screen of FDA-approved drugs against the GTPase domain of DRP1, researchers identified fosaprepitant — currently used clinically as an antiemetic to prevent chemotherapy-induced nausea — as a candidate DRP1 inhibitor. Computational docking predicted binding interactions, GTPase activity assays confirmed inhibitory activity, and NMR spectroscopy demonstrated direct physical binding between fosaprepitant and DRP1, mapping the specific contact sites on the protein.

In myeloma cell lines, fosaprepitant treatment produced the expected consequences of DRP1 inhibition: mitochondrial hyperfusion, reduced cell viability, impaired colony formation, and disruption of oxidative phosphorylation. These effects were DRP1-dependent — confirming the mechanism rather than attributing activity to off-target effects — and culminated in apoptotic cell death.

The drug repurposing angle is the study's most immediately translatable aspect. Fosaprepitant is already approved, with a known safety profile in cancer patients, which shortens the path to clinical testing compared to a novel compound. The findings are limited to cell line experiments and require validation in animal models and primary myeloma samples before the therapeutic potential can be fully assessed, but the identification of a specific binding interaction with DRP1 provides a solid mechanistic foundation for further investigation.

"mHealth-Supported Exercise Rehabilitation to Reverse Frailty After Autologous Transplantation in Multiple Myeloma: Randomized Controlled Trial"

Source 

Lee K, Shamunee J, Lee H, Du X, Lindenfeld L, Krishnan A, Nathwani N, Wong FL, Armenian S. mHealth-Supported Exercise Rehabilitation to Reverse Frailty After Autologous Transplantation in Multiple Myeloma: Randomized Controlled Trial. JMIR Mhealth Uhealth. 2026 May 21;14:e87628. doi: 10.2196/87628. 

Overview

Frailty is common after autologous stem cell transplant in myeloma, and the early post-transplant period — when physical recovery is most needed — is also when access to center-based rehabilitation is most difficult. This randomized controlled trial tested whether a 16-week exercise program delivered via a mobile health platform could reduce frailty and improve physical function in people within 180 days of transplant.

Thirty-two participants with a mean age of 64.6 years were randomized to the exercise intervention or usual care; 94% were classified as frail at baseline. The program consisted of eight weeks of supervised tele-exercise (three sessions per week, 50 minutes each) followed by eight weeks of independent home-based exercise using the same platform, with intensity guided by perceived exertion and symptom response. Adherence was 85% during the supervised phase and 78% during the unsupervised phase — both strong for a remote rehabilitation program in a post-transplant population.

The exercise group showed significantly greater reductions in frailty score at both the midpoint and end of the 16-week program. Chair stand time — a measure of lower limb strength and functional mobility — improved significantly and was sustained through week 17. Other physical performance measures and handgrip strength favored the exercise group but did not reach statistical significance, likely reflecting the small sample size. No serious adverse events occurred.

The trial is limited by its single-center design, small cohort, and absence of an attention-matched control, meaning some benefit could reflect engagement with the program rather than exercise specifically. Nonetheless, the results establish feasibility and safety, and the adherence rates suggest that remote delivery is acceptable to people navigating early transplant recovery — a population for whom travel to rehabilitation facilities is often impractical.

"Single-cell sequencing identifies characteristics of disease and bone marrow in concurrent multiple myeloma and myelodysplastic syndrome"

Source 

Wang, Jingjing1; Zhong, Yuping2; Sun, Xiuli3; Fu, Yesong4; Xie, Ying1; Guo, Jing1; Liu, Huanhuan1; Huang, Wenrong5; Liu, Zhiqiang1. Single-cell sequencing identifies characteristics of disease and bone marrow in concurrent multiple myeloma and myelodysplastic syndrome. Chinese Medical Journal ():10.1097/CM9.0000000000004128, May 21, 2026. | DOI: 10.1097/CM9.0000000000004128  

Overview

Myeloma and myelodysplastic syndrome (MDS) are distinct bone marrow malignancies that occasionally occur together, but the molecular characteristics of this co-occurrence have not previously been examined at single-cell resolution. This study applied single-cell RNA sequencing to bone marrow samples from four people with concurrent MM and MDS (MM-MDS), using myeloma-only and healthy donor samples for comparison.

Several features distinguished MM-MDS from classical myeloma. Plasma cells in MM-MDS showed greater dependence on endoplasmic reticulum protein processing and oxidative phosphorylation pathways than those in myeloma alone — potentially relevant to proteasome inhibitor sensitivity. Communication between plasma cells and bone marrow cells was less active in MM-MDS than in myeloma, where plasma cells showed the highest level of signaling with hematopoietic stem cells and monocytes, particularly through the TNFRSF13B pathway. Elevated TNFRSF13B expression in myeloma was also associated with worse outcomes in the MMRF CoMMpass dataset, adding external validation to this finding.

Within the MM-MDS group, high- and low-risk subgroups emerged based on plasma cell burden and copy number variation. High-risk cases showed stronger activation of cancer growth pathways and MAPK/NF-κB signaling. Low-risk MM-MDS shared features with low-risk MDS, including a distinctive neutrophil-like monocyte (Neu-like Mo) population driven by CEBPE activation — a cell type absent in high-risk cases and proposed as a potential risk stratification biomarker.

The MM-MDS bone marrow environment was characterized by elevated B cells, neutrophils, and activated T cells in an inflammatory state distinct from either condition alone. CD8+ T cells in high-risk MDS showed increased exhaustion. The study is limited to four patients and requires validation in larger cohorts, but provides the first single-cell molecular characterization of this rare co-occurrence.

"New Insights into the Role of Clonotypic B Cells in Plasma-cell Neoplasia"

Source 

Sungjae Kim, Irene M. Ghobrial; New Insights into the Role of Clonotypic B Cells in Plasma-cell Neoplasia. Blood Cancer Discov 2026; https://doi.org/10.1158/2643-3230.BCD-26-0109 May 21, 2026  

Overview

This study examines whether clonotypic B cells — B cells carrying the same immunoglobulin gene rearrangement as the malignant plasma cell clone — represent a true disease reservoir in myeloma and light-chain amyloidosis, or whether they are biologically distinct from the cells actually driving disease.

Gonzalez and colleagues found that the key genetic abnormalities defining the malignant clone are largely confined to plasma cells rather than shared with clonotypic B cells. This suggests that clonotypic B cells do not carry the same malignant potential as the plasma cell population, and are unlikely to serve as a reservoir from which disease regenerates after treatment.

The finding has a direct practical implication for MRD testing. Assays that detect residual disease by identifying cells with the disease-defining immunoglobulin sequence could flag clonotypic B cells as evidence of persistent myeloma when those cells may not themselves be malignant. This raises the possibility of false-positive MRD results — a consequential error given that MRD status increasingly informs decisions about continuing, escalating, or stopping treatment. Assay design and result interpretation may need to account for the presence of clonotypic B cells as a potential confounding signal distinct from true residual plasma cell disease.

"New Insights into the Role of Clonotypic B Cells in Plasma-cell Neoplasia"

Source 

Dian Zhou, Yuekun Qi, Sha Ma, Qian Sun, Weiying Gu, Jieyun Xia, Xiaotian Zhang, Wei Chen, Hai Cheng, Kunming Qi, Feng Zhu, Fan Xia, Lili Zhu, Hujun Li, Huanxin Zhang, Dongmei Yan, Tingting Qiu, Yanlei Zhang, Shuixiu Peng, Wei Sang, Depeng Li, Alex H Chang, Bin Pan, Zhiling Yan; Anti-BCMA/GPRC5D CAR T in relapsed or refractory multiple myeloma patients with extraosseous extramedullary disease. Blood 2026; blood.2026033506. doi: https://doi.org/10.1182/blood.2026033506 May 21, 2026. 

Overview

Extraosseous extramedullary disease — myeloma growing in soft tissues outside the bone and bone marrow — is one of the most treatment-resistant presentations of relapsed or refractory myeloma, with consistently worse outcomes than bone marrow-confined disease. Standard therapies and even single-target CAR-T products have shown limited activity in this setting, partly because antigen escape and tumor heterogeneity are more pronounced in extramedullary lesions.

This phase 2 trial enrolled 37 people with relapsed or refractory myeloma and extraosseous extramedullary disease, treating them with a bispecific CAR-T product engineered to target both BCMA and GPRC5D simultaneously — an approach designed to reduce the risk of antigen escape by requiring loss of both targets for resistance to develop.

Results were striking for this difficult population: 36 of 37 participants (97%) achieved an overall response and MRD negativity, with 43% reaching stringent complete response. Median progression-free survival was 5.8 months — modest in absolute terms but notable given the historically poor outcomes in extraosseous EMD. Median overall survival had not been reached at a median follow-up of 10.1 months.

All 37 participants experienced grade 3 or worse hematologic toxicity, reflecting the expected bone marrow suppression following lymphodepletion and CAR-T infusion. CRS occurred in 73% but was grade 1 or 2 in all cases. ICANS was rare, occurring in two participants.

The near-universal response rate in a population where most therapies produce limited benefit supports dual-antigen targeting as a strategy specifically suited to extramedullary disease, where antigen heterogeneity is a primary resistance driver. Longer follow-up is needed to determine whether the depth of response translates into durable disease control.

"Prospective Study of Cytomegalovirus Reactivation in Patients with Multiple Myeloma Receiving anti-CD38 and BCMA Therapies"

Source 

Emily Baneman, Samantha E. Jacobs, Meenakshi Rana, Larysa Sanchez, Hulya Kocyigit, Erin Moshier, Prospective Study of Cytomegalovirus Reactivation in Patients with Multiple Myeloma Receiving anti-CD38 and BCMA Therapies, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.05.008. May 21, 2026. 

Overview

CMV reactivation is a well-recognized complication in severely immunocompromised people, particularly after stem cell transplant, but its frequency and clinical significance in people with myeloma receiving modern immunotherapy — anti-CD38 and BCMA-directed agents — has not been well characterized. This prospective observational study monitored 40 CMV-seropositive people with myeloma (15 newly diagnosed, 25 relapsed) with biweekly CMV PCR testing over 12 weeks.

Low-level CMV detection was common: 24 of 40 participants had detectable CMV at some point during follow-up. However, clinically significant viremia — defined as CMV PCR of 500 IU/mL or above — occurred in only three participants (7.5%), and only one required preemptive antiviral treatment. No participant developed symptomatic CMV infection or end-organ disease during the study period.

Factors associated with higher risk of CMV detection included lymphopenia at the preceding visit, prior CMV infection history, relapsed rather than newly diagnosed disease, and younger age. The lymphopenia association is mechanistically plausible — CD38 and BCMA-directed therapies deplete immune effector cells, and the degree of lymphopenia likely reflects the cumulative immunosuppressive burden.

The findings suggest that routine CMV prophylaxis or universal preemptive monitoring may not be warranted in this population, given that most detectable viremia was self-limiting and did not progress to symptomatic disease. However, the 12-week follow-up window and 40-patient cohort limit what can be concluded about rarer but serious CMV complications. People with significant lymphopenia or a history of prior CMV infection may represent a subgroup warranting closer monitoring.

"Circadian Deregulation in Multiple Myeloma: BMAL1/CLOCK Expression Patterns and Diagnostic Performance"

Source 

H.Albayrak, M. E.Ay, A.Tombak, et al., “Circadian Deregulation in Multiple Myeloma: BMAL1/CLOCK Expression Patterns and Diagnostic Performance,” International Journal of Laboratory Hematology (2026): 1–10, https://doi.org/10.1111/ijlh.70154. May 21, 2026. 

Overview

The circadian clock — the molecular machinery that regulates 24-hour biological rhythms — is increasingly recognized as relevant to cancer biology, with disruption of clock gene expression linked to tumor progression in several cancer types. This study examined two core circadian clock proteins, BMAL1 and CLOCK, in bone marrow samples from 46 newly diagnosed people with myeloma and 13 healthy controls.

BMAL1 expression was significantly higher in myeloma than in controls, with a moderate effect size (Cohen's d = 0.83). CLOCK alone did not differ significantly between groups, but the two genes were strongly correlated in myeloma samples (ρ ≈ 0.80), a relationship that persisted after adjusting for age, ISS stage, and beta-2 microglobulin. This suggests the circadian imbalance in myeloma involves a preserved but skewed BMAL1/CLOCK relationship rather than wholesale disruption of both genes.

Diagnostically, BMAL1 alone achieved an AUC of 0.729, and combining both genes modestly improved this to 0.756. A random forest classifier using both genes reached an AUC of 0.832, though specificity was limited across all models. The authors appropriately frame these as exploratory findings requiring external validation in larger cohorts before any diagnostic application could be considered.

The multivariate logistic regression produced an unusually large odds ratio for BMAL1 (OR 3343), which likely reflects overfitting in a dataset of 59 participants rather than a true effect of that magnitude — a limitation the study acknowledges by emphasizing the need for validation. The consistent directional signal across multiple statistical approaches is the more reliable takeaway, pointing to BMAL1 upregulation as a reproducible feature of myeloma biology worth investigating further.

"Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma"

Source 

Fuentes-Lacouture MC, Nandana D, Ramasamy K, Thakurta A. Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma. FEBS J. 2026 May 21. doi: 10.1111/febs.70599. Epub ahead of print. 

Overview

Immunomodulatory drugs — lenalidomide and pomalidomide — have been central to myeloma treatment for over a decade, used across newly diagnosed and relapsed settings in combination with proteasome inhibitors, dexamethasone, and anti-CD38 antibodies. Despite their established role, resistance to IMiD-based therapy develops in virtually all people with myeloma and represents one of the most common clinical challenges encountered in practice.

This review synthesizes current understanding of how and why that resistance develops. Three overlapping mechanisms are examined: genetic and epigenetic alterations — including mutations in CRBN, the gene encoding cereblon, the primary molecular target of IMiDs — changes in downstream signaling pathways that bypass cereblon-mediated degradation of target proteins, and dysregulation of the bone marrow immune microenvironment that reduces the immune-activating effects IMiDs depend on.

The review also addresses how to approach treatment when IMiD resistance has developed. CELMoDs — next-generation cereblon modulators including mezigdomide and iberdomide — are designed to overcome some forms of IMiD resistance by engaging cereblon more potently or with a different binding profile, and their combinations with existing and novel agents are discussed. Immunotherapy combinations, particularly pairing CELMoDs with CAR-T therapy or bispecific antibodies to enhance T cell function, represent a key area of active investigation given CELMoDs' demonstrated ability to reverse T cell exhaustion.

For people with myeloma who have progressed on lenalidomide or pomalidomide — an increasingly common clinical scenario as these drugs are used earlier and longer — understanding the specific resistance mechanism may eventually guide selection of the next treatment. However, routine molecular profiling of resistance is not yet standard practice.

"Multiple Myeloma in Children and Young Adults: A Systematic Literature Review"

Source 

Poultsaki, G., Vassilakopoulos, T.P., Terpos, E. et al. Multiple Myeloma in Children and Young Adults: A Systematic Literature Review. Clin Exp Med (2026). https://doi.org/10.1007/s10238-026-02148-w May 21, 2026.  

Overview

Myeloma is overwhelmingly a disease of older adults, with a median diagnosis age in the mid-60s. Cases in people aged 25 or younger are rare enough that no systematic characterization has previously been possible from prospective data — knowledge comes entirely from case reports and small series. This systematic review consolidates 42 such cases from 33 publications, with a median patient age of 17 (range 8–25).

The clinical picture in this age group differs from typical adult myeloma in several respects. Plasmacytomas were present in 62% of cases — substantially higher than in adult myeloma — including both extramedullary soft tissue involvement (31%) and paramedullary disease adjacent to bone (58%). Bone pain was the most common presenting symptom (43%), followed by neurological symptoms (21%), the latter likely reflecting the high rate of plasmacytomas in locations that compress nerves or the spinal cord. IgG subtype predominated, consistent with adult disease, and cytogenetic abnormalities were detected in 75% of evaluable cases.

Treatment approaches varied by era, reflecting the evolution of available agents. Among the 16 patients with evaluable responses, 75% responded to first-line therapy. Stem cell transplant was performed in 10 patients and was associated with deeper responses. No treatment-related deaths were reported with contemporary regimens.

The rarity of the condition means this 42-patient dataset, assembled across decades and multiple countries, represents the entirety of published experience. Meaningful conclusions about optimal treatment sequencing, the prognostic significance of specific cytogenetic abnormalities, or long-term survival are not possible from this data alone. The review's primary contribution is establishing that modern myeloma regimens appear feasible and tolerable in very young people, and that the high plasmacytoma rate may reflect a biologically distinct disease presentation in this age group.

"Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial"

Source 

Jia xiang Jin et al. Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial. J Clin Oncol 0, JCO-25-02957 DOI:10.1200/JCO-25-02957  May 21, 2026. 

Overview

Standard methods for detecting residual myeloma protein — serum protein electrophoresis and immunofixation — lack sensitivity at low concentrations, potentially missing small amounts of disease that predict relapse. Mass spectrometry offers greater analytical precision and the ability to distinguish therapeutic antibodies (like daratumumab) from the patient's own monoclonal protein, a distinction that standard electrophoresis cannot reliably make. This study evaluated MS-based monitoring in 3,301 serum samples from 617 people enrolled in the phase 3 GMMG-HD7 trial.

MS reliably tracked the diagnostic M protein over time, distinguished it from therapeutic antibodies, and outperformed serum protein electrophoresis at low disease concentrations. MS negativity was associated with better progression-free survival at all assessed timepoints, with the strongest prognostic separation at 12 months of maintenance therapy (hazard ratio 0.25 for MS-negative vs MS-positive).

The combination of serum MS with bone marrow MRD testing produced the most refined risk stratification. People who were positive by both methods had the worst progression-free survival, while the three remaining groups — MS negative/MRD negative, MS negative/MRD positive, and MS positive/MRD negative — showed comparably favorable outcomes. This suggests that MS and bone marrow MRD provide partially overlapping but complementary information, and that dual positivity identifies a particularly high-risk group.

MS and MRD results converged more closely over time. Early discordance was most common in IgG myeloma, attributable to IgG recycling mechanisms that slow M protein clearance from serum relative to bone marrow tumor clearance. The practical appeal of serum MS lies in its minimal invasiveness — a blood draw rather than a bone marrow biopsy — positioning it as a candidate for frequent longitudinal monitoring between scheduled bone marrow assessments.

"Machine Learning Model Predicts Monoclonal Gammopathy Using Routine Laboratory Values"

Source 

Mercedeh Movassagh et al. Machine Learning Model Predicts Monoclonal Gammopathy Using Routine Laboratory Values. JCO Clin Cancer Inform 10, e2600013(2026). DOI:10.1200/CCI-26-00013 May 21, 2026. 

Overview

Early identification of MGUS — before progression to myeloma — is associated with better survival outcomes, but MGUS remains substantially underdiagnosed because it requires a specific protein electrophoresis test that is not part of routine blood work. This study asked whether a machine learning model trained on commonly available laboratory values could predict which people are likely to have a monoclonal protein, without requiring electrophoresis as an input.

Using longitudinal laboratory data from 232,813 people in a large US outpatient network, researchers identified 1,610 who met inclusion criteria — aged 50 to 85, with multiple routine blood tests and at least one protein electrophoresis result on record. An XGBoost classifier was trained to predict M-protein presence using only seven variables available from standard complete blood count and metabolic panels: absolute lymphocyte trajectory over time, age, red blood cell count, total protein, red blood cell distribution width, blood urea nitrogen, and relative eosinophil percentage.

The model achieved an AUC of 0.84 for predicting M-protein within five years — a strong performance for a tool built entirely from routine data. The inclusion of lymphocyte trajectory (change over time rather than a single value) as the top predictor is notable, as it captures a dynamic immune shift that single-timepoint measurements would miss.

The practical application would be embedding this model in outpatient laboratory systems to flag people whose routine bloodwork patterns suggest elevated M-protein risk, prompting targeted electrophoresis testing in those identified. The study is retrospective and requires prospective validation before clinical deployment, but the seven-variable model's simplicity and reliance on universally available data make it a feasible candidate for population-level MGUS screening.

"Overcoming resistance in CD44-overexpressing myeloma through combination therapy with ATRA, bortezomib, and NK cells"

Source 

Nguyen, VT., Thi, T.N., Tran, VDH. et al. Overcoming resistance in CD44-overexpressing myeloma through combination therapy with ATRA, bortezomib, and NK cells. Cancer Immunol Immunother (2026). https://doi.org/10.1007/s00262-026-04418-8 May 21, 2026. 

Overview

CD44 is a cell surface protein involved in cell adhesion, migration, and survival signaling, and its overexpression has been linked to aggressive disease in multiple cancer types. This study examined whether CD44 expression level predicts outcomes in myeloma, and whether pharmacologically reducing CD44 on myeloma cells could enhance NK cell-mediated killing.

In the CoMMpass dataset, high CD44 expression was associated with worse overall survival across all three R-ISS stages — indicating that the adverse prognostic effect is not simply a proxy for advanced disease stage but operates independently within each risk category.

In laboratory models, combining ATRA (a vitamin A derivative with differentiation-promoting properties) with bortezomib reduced CD44 expression and beta-catenin signaling in CD44-high myeloma cell lines, and inhibited proliferation, migration, and invasion. Critically, this drug combination also upregulated surface markers on myeloma cells — including MICA/B, Fas, and TRAIL-R2 — that make them more visible and susceptible to NK cell attack. When NK cells expanded from healthy donors were added, cytotoxicity increased substantially compared to either approach alone.

In a mouse xenograft model, the triple combination of NK cells, ATRA, and bortezomib suppressed CD44 expression, reduced extramedullary spread, and extended survival without notable toxicity.

The strategy being tested is tumor priming — using drugs to remodel the surface of myeloma cells in ways that enhance immune recognition — rather than relying solely on direct cytotoxicity. The findings are limited to cell lines and a single xenograft model, and the authors note that validation in patient-derived samples with greater biological heterogeneity is needed before clinical implications can be drawn.

"The miR4261/PAMM axis in multiple myeloma promotes bone resorption"

Source 

Cui, J., Bian, S., Hao, Z. et al. The miR4261/PAMM axis in multiple myeloma promotes bone resorption. Sci Rep (2026). https://doi.org/10.1038/s41598-026-51665-x May 22, 2026. 

Overview

Bone destruction in myeloma results from osteoclasts — bone-resorbing cells — becoming overactive while bone-forming osteoblasts are simultaneously suppressed. This study investigated whether myeloma cell-derived exosomes contribute to that imbalance by delivering microRNAs to monocytes that then differentiate into osteoclasts.

The researchers identified miR4261 as a microRNA transferred from myeloma cells to THP-1 monocytes in co-culture experiments. Dual-luciferase assays confirmed that miR4261 directly binds to the 3'-UTR of PAMM — a gene expressed in monocytes stimulated by M-CSF — suppressing its expression. When THP-1 cells were transfected with miR4261 mimics or had PAMM silenced directly, osteoclast differentiation increased, confirmed by TRAP staining and micro-CT measurements of bone mineral content.

In bone marrow samples from people with myeloma bone disease, miR4261 levels were elevated and correlated inversely with PAMM expression — consistent with the laboratory findings and suggesting the axis operates in human disease rather than only in cell line models. Gene set enrichment analysis in PAMM-silenced cells showed downregulation of genes that normally restrain osteoclast differentiation, mapping the downstream consequences of PAMM loss.

The mechanistic picture that emerges is that myeloma cells package miR4261 into exosomes, deliver it to local monocytes, suppress PAMM, and thereby promote excessive osteoclast activity and bone destruction. Both miR4261 and PAMM are proposed as therapeutic targets, though the work is entirely preclinical. Whether inhibiting miR4261 or restoring PAMM expression in vivo can reduce bone destruction without disrupting normal bone remodeling remains to be tested.

"The safety profile of lenalidomide, dexamethasone, daratumumab, and bortezomib combinations in multiple myeloma: a retrospective analysis of the FAERS database"

Source 

Li, D., Xiao, Q., Yu, Z. et al. The safety profile of lenalidomide, dexamethasone, daratumumab, and bortezomib combinations in multiple myeloma: a retrospective analysis of the FAERS database. Naunyn-Schmiedeberg's Arch Pharmacol (2026). https://doi.org/10.1007/s00210-026-05472-w May 22, 2026. 

Overview

Randomized trials establish efficacy and capture common adverse events, but post-marketing surveillance databases can detect safety signals across larger and more diverse populations than trials enroll. This analysis examined 54,243 cases from the FDA Adverse Event Reporting System (FAERS) between 2004 and 2025 to compare real-world safety profiles of three standard first-line myeloma regimens: Rd (lenalidomide-dexamethasone), VRd (bortezomib-lenalidomide-dexamethasone), and DRd (daratumumab-lenalidomide-dexamethasone).

Trend analysis showed DRd reporting rising steadily since its 2016 introduction, while Rd reports declined after 2021 and VRd reports decreased modestly after 2020 — patterns consistent with DRd displacing older doublet and triplet regimens in newly diagnosed transplant-ineligible myeloma.

The disproportionality analysis — which identifies whether specific adverse events are reported more frequently than expected given overall reporting patterns — found elevated infection signals with DRd and neurological disorder signals with VRd. Infections with DRd also appeared earlier in the treatment course than with the other regimens, based on time-to-onset modeling. Co-medication patterns suggested potential drug interaction contributions to both signals.

The practical implications align with what is already recommended in clinical practice: infection prophylaxis and monitoring are particularly important for people on DRd, while subcutaneous bortezomib administration (which reduces peripheral neuropathy risk compared to intravenous) and neurological surveillance are relevant for VRd recipients.

FAERS data carry well-known limitations — reporting is voluntary, incomplete, and subject to confounding by indication and co-medication — so the signals identified here should be interpreted as hypothesis-generating and complementary to trial data rather than definitive safety assessments.

"Smoldering Multiple Myeloma: From Clinical to Immunogenomic Risk Stratification and Therapeutic Implications of Early Intervention"

Source 

Nizar J. Bahlis et al. Smoldering Multiple Myeloma: From Clinical to Immunogenomic Risk Stratification and Therapeutic Implications of Early Intervention. Am Soc Clin Oncol Educ Book 46, e517488(2026). DOI:10.1200/EDBK-26-517488  May 23, 2026. 

Overview

Smoldering myeloma occupies a clinical gray zone — detectable disease without the organ damage that has traditionally defined when to start treatment. That boundary is shifting. Three randomized phase 3 trials have now demonstrated benefit from early intervention in high-risk SMM, with one (QuiRedex) showing an overall survival advantage and another (AQUILA) showing a trend in that direction. Identifying who qualifies as high-risk has therefore become a treatment-consequential question rather than an academic one.

Current standard risk stratification uses the IMWG 20/2/20 model — serum M-protein above 2 g/dL, bone marrow plasma cells above 20%, and an involved-to-uninvolved free light chain ratio above 20. Having two or more of these factors places the two-year progression risk at 40–50%, rising further with adverse cytogenetics including del13, t(4;14), t(14;16), and 1q gain.

The model's limitation is that it captures tumor burden and cytogenetics but not the genomic features that predict how a clone will evolve. This review identifies four categories of genomic alterations that independently predict progression: MAPK pathway mutations (KRAS and NRAS), DNA repair pathway alterations (TP53, ATM mutations, and del17p), MYC alterations, and APOBEC-associated mutational signatures. Each reflects a different aspect of genomic instability or proliferative pressure that tumor burden measurements do not capture.

The conceptual shift underlying this discussion is the reframing of MGUS, SMM, and active myeloma as points on a continuous genomic gradient rather than discrete clinical categories — a view supported by molecular sequencing studies showing that driver mutations accumulate progressively across this spectrum. Integrating genomic predictors of clonal evolution with existing clinical models is described as the central unsolved problem in SMM risk stratification.

"The Role of RNA Modifications in the Pathological Mechanisms and Therapeutic Targeting of Multiple Myeloma"

Source 

Hao Chen, Hefei Ren, Xin Wang, Chang Liu, Liansheng Jiang, Shuyue Zang, Tingyu Liu, Sijie Wang, Weiwen Huang, Lin Zhou, The Role of RNA Modifications in the Pathological Mechanisms and Therapeutic Targeting of Multiple Myeloma, Molecular and Cellular Probes, 2026, 102073, ISSN 0890-8508, https://doi.org/10.1016/j.mcp.2026.102073. May 23, 2026. 

Overview

Gene mutations and chromosomal abnormalities are well-established drivers of myeloma, but an additional regulatory layer — chemical modifications to RNA molecules themselves — has received less attention. This review examines the emerging field of epitranscriptomics in myeloma: how reversible modifications to RNA affect which genes are ultimately expressed, and how dysregulation of this system contributes to disease progression, bone destruction, drug resistance, and immune evasion.

The most studied RNA modification in cancer is m6A methylation, controlled by writer enzymes (METTL3), eraser enzymes (FTO, ALKBH5), and reader proteins (YTHDF1) that add, remove, and interpret these chemical marks. In myeloma, evidence supports roles for several of these regulators in controlling the stability and translation of disease-relevant transcripts — affecting how much of certain proteins gets made from a given gene, independent of the gene's sequence. The review distinguishes between findings validated specifically in myeloma and those extrapolated from other cancers, an important methodological distinction given how tissue-specific epitranscriptomic effects can be.

RNA modifications also influence non-coding RNAs and the contents of extracellular vesicles — packages that myeloma cells release into the bone marrow environment. Through these mechanisms, the epitranscriptome connects to osteoclast and osteoblast regulation, linking RNA-level dysregulation to the bone destruction that causes much of myeloma's clinical morbidity.

On the therapeutic side, small molecule inhibitors targeting writer, eraser, and reader enzymes are in early development, alongside RNA-based approaches targeting specific non-coding RNAs implicated in resistance. The field is early-stage for myeloma specifically, and the review is careful to frame cross-cancer findings as hypothesis-generating rather than established — a useful caution given how frequently findings in one cancer type fail to replicate in another.

"Diagnostic and potential prognostic associations of long noncoding RNAs LIFR-AS1 and SLCO4A1-AS1 in multiple myeloma"

Source 

Khosravi, M., Khandani, B.K., Farsinejad, A. et al. Diagnostic and potential prognostic associations of long noncoding RNAs LIFR-AS1 and SLCO4A1-AS1 in multiple myeloma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-52109-2 May 24, 2026. 

Overview

Long non-coding RNAs (lncRNAs) regulate gene expression without encoding proteins, and their dysregulation has been implicated in multiple cancers including myeloma. This study examined two lncRNAs — LIFR-AS1 and SLCO4A1-AS1 — in 30 newly diagnosed people with myeloma and 30 healthy controls, measuring their expression levels and correlating them with clinical and laboratory parameters.

Both lncRNAs were significantly downregulated in myeloma compared to healthy controls. Lower expression correlated with higher beta-2 microglobulin, LDH, and ESR — markers associated with greater disease burden and inflammation — and with lower albumin and hemoglobin, consistent with more advanced disease. Both lncRNAs also showed inverse correlations with IL-17A, RORC, and serum IL-17 levels, linking their reduced expression to activation of the IL-17/NF-κB inflammatory signaling pathway, which has established roles in myeloma pathogenesis.

ROC analysis showed moderate diagnostic performance: AUC of 0.691 for LIFR-AS1 and 0.711 for SLCO4A1-AS1. The specificity at the chosen cutoffs was 100% for both, meaning few false positives, but sensitivity was low for LIFR-AS1 (30%) and moderate for SLCO4A1-AS1 (80%) — profiles that limit standalone diagnostic utility but might contribute within a multi-marker panel.

The study is substantially limited by its small cohort of 60 participants and single-center design. Whether reduced expression of these lncRNAs drives myeloma biology or simply reflects disease state is unknown, as no functional experiments were performed. The correlations with disease burden markers and inflammatory signaling are hypothesis-generating and warrant investigation in larger cohorts with functional validation before any clinical application can be considered.

"Long-term follow-up results of anti-BCMA CAR-T cell therapy combined with autologous hematopoietic stem cell transplantation in relapsed/refractory multiple myeloma with extramedullary disease"

Source 

Li, X., Liu, C., Niu, S. et al. Long-term follow-up results of anti-BCMA CAR-T cell therapy combined with autologous hematopoietic stem cell transplantation in relapsed/refractory multiple myeloma with extramedullary disease. J Transl Med (2026). https://doi.org/10.1186/s12967-026-08302-y May 25, 2026.  

Overview

Extramedullary myeloma — disease growing outside the bone marrow — responds poorly to most therapies and carries a worse prognosis than bone marrow-confined disease. CAR-T therapy has shown activity in this setting but frequently produces early progression despite initial responses. This retrospective study examined whether combining anti-BCMA CAR-T therapy with autologous stem cell transplant could improve outcomes in 18 people with relapsed or refractory myeloma and extramedullary disease.

Eight received the combination (CAR-T plus auto-HSCT) and ten received CAR-T alone. All eight in the combination group achieved an overall response by both hematologic and imaging criteria — the latter being the more stringent requirement for extramedullary disease. In the CAR-T alone group, eight of ten met hematologic response criteria but only six showed radiographic response in extramedullary lesions. Progression-free and overall survival were meaningfully better in the combination group over three years of follow-up.

The combination group also showed higher peak CAR-T cell expansion and higher IL-6 levels, alongside a greater proportion of CD4+ T cells at day 28 — a finding the authors suggest may underlie the more durable responses, given CD4+ T cell support for sustained CAR-T activity.

The toxicity tradeoff is relevant: CRS tended to be more severe in the combination group, and hematologic recovery was delayed, with three of eight developing poor graft function. No treatment-related deaths occurred in either group.

The small cohort and retrospective design limit firm conclusions, and the combination approach adds substantial treatment complexity and toxicity burden. The results are hypothesis-generating but suggest that auto-HSCT may enhance CAR-T durability in extramedullary disease in ways worth investigating prospectively.

"Prevalence of monoclonal gammopathy of undetermined significance (MGUS) using a sensitive mass spectrometry assay in young individuals 10–49 years of age: a population-based study from the National Health and Nutritional Examination Survey"

Source 

Kumar, S., Murray, D., Larson, D.R. et al. Prevalence of monoclonal gammopathy of undetermined significance (MGUS) using a sensitive mass spectrometry assay in young individuals 10–49 years of age: a population-based study from the National Health and Nutritional Examination Survey. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01518-7 May 25, 2026.   

Overview

Most MGUS prevalence data come from studies of older adults, leaving the natural history of the condition in younger people — and questions about when racial disparities in prevalence emerge — largely uncharacterized. This population-based study used mass spectrometry, which is more sensitive than standard protein electrophoresis, to screen 12,378 people aged 10 to 49 drawn from the NHANES III national survey, including substantial numbers of White, Black, and Mexican American participants.

MGUS was identified in 1.28% of the overall cohort. Detection began in the second decade of life — 0.2% of those aged 10 to 19 had MGUS — and prevalence rose progressively with age: 0.88% at ages 20–29, 1.46% at 30–39, and 2.82% at 40–49. The finding of MGUS in adolescents, while rare, establishes that monoclonal gammopathy can begin decades earlier than previously appreciated from studies relying on less sensitive detection methods.

The racial disparity data are particularly striking. Age-adjusted MGUS prevalence was significantly higher in Black participants (1.49%) than White participants (0.82%). The gap emerged clearly by ages 30–39 (2.94% vs 1.42%) and widened further at ages 40–49 (5.2% vs 2.8%). This earlier onset and steeper age-related increase in Black individuals is consistent with the well-documented higher incidence of myeloma in Black Americans, and suggests the excess risk accumulates over decades rather than emerging late in life. No significant difference was found between White and Mexican American participants across any age group.

The use of mass spectrometry is central to these findings — less sensitive standard methods would have missed a substantial proportion of cases, particularly at younger ages and lower M-protein concentrations.

"Pegfilgrastim versus Filgrastim for Chemo-Mobilized Stem Cell Collection in Multiple Myeloma: A Retrospective Real-World Study,"

Source 

Yan-Lin Zhang, Xin-Yi Qin, Chun Cao, Zhi-Ming Luo, Ying Zhang, Han-Qing Zeng, Jian-Chuan Deng, Yun Luo, Pegfilgrastim versus Filgrastim for Chemo-Mobilized Stem Cell Collection in Multiple Myeloma: A Retrospective Real-World Study, Cancer Treatment and Research Communications, 2026, 101263, ISSN 2468-2942, https://doi.org/10.1016/j.ctarc.2026.101263. May 26, 2026. .   

Overview

Stem cell mobilization before autologous transplant requires growth factor support to drive hematopoietic progenitor cells from the bone marrow into the bloodstream for collection. Filgrastim (daily injections) and pegfilgrastim (a longer-acting formulation requiring fewer doses) are both used for this purpose, but direct comparisons in myeloma with consistent chemotherapy mobilization regimens have been limited. This retrospective single-center study compared outcomes in 102 people with myeloma — 49 receiving pegfilgrastim and 53 receiving filgrastim — using propensity score matching and overlap weighting to account for baseline differences.

CD34+ cell yields were equivalent between groups (median 3.90 vs 4.99 × 10⁶/kg, p=0.096), as were mobilization success rates, engraftment kinetics, safety profiles, and total hospitalization costs. Filgrastim produced a higher total mononuclear cell count, though this did not translate into differences in the clinically relevant CD34+ yield or transplant outcomes.

The meaningful difference between regimens was logistical. In the chemo-mobilization subgroup, pegfilgrastim reduced mobilization duration from 15 to 10 days and required fewer collection sessions — findings confirmed by overlap weighting analysis. This efficiency advantage did not come at additional cost.

For people with myeloma undergoing transplant, the practical implication is that pegfilgrastim achieves equivalent stem cell collection with fewer clinic visits and a shorter overall mobilization period — a meaningful quality-of-life consideration during an already demanding treatment phase. The single-center retrospective design limits generalizability, and larger prospective comparisons would strengthen the evidence base, but current data support pegfilgrastim as a viable and more convenient alternative to daily filgrastim..

"Design, radiolabeling, and biological evaluation of a novel 177Lu-AAZTA5-Carfilzomib conjugate as a proteasome-targeted theranostic agent for multiple myeloma"

Source 

Mohamed A. Gizawy, Fawzy A. Marzook, Hanan M. El-Shershaby, Amal Elrefaei, M.A. Motaleb, Kamel A. Moustafa, Hesham A. Shamsel-Din, Design, radiolabeling, and biological evaluation of a novel 177Lu-AAZTA5-Carfilzomib conjugate as a proteasome-targeted theranostic agent for multiple myeloma, Journal of Pharmaceutical Sciences, 2026, 104347, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2026.104347. May 26, 2026.    

Overview

Radioimmunotherapy and targeted radionuclide therapy have transformed treatment in several cancers by delivering radiation directly to tumor cells while sparing surrounding tissue. This study applied that principle to myeloma by conjugating carfilzomib — a proteasome inhibitor that binds irreversibly to its target — to a radioactive isotope, lutetium-177, creating a compound designed to deliver localized radiation specifically to proteasome-expressing myeloma cells.

The conjugate was synthesized by linking carfilzomib to a chelator molecule (AAZTA5) that captures lutetium-177, and radiolabeling was achieved efficiently under mild conditions with high radiochemical yield. The compound remained stable in both laboratory buffer and serum, an important prerequisite for in vivo use.

In myeloma cell lines, the radiolabeled conjugate produced greater cytotoxicity than either free carfilzomib or lutetium-177 alone — suggesting the combination of proteasome inhibition and localized radiation produces additive or synergistic cell killing beyond what either component achieves independently. Molecular docking confirmed strong binding within the proteasome's catalytic pocket, with a binding affinity of −8.1 kcal/mol, consistent with carfilzomib's known mechanism of action being preserved in the conjugate.

In tumor-bearing mice, the compound showed meaningful tumor uptake (6.8% of injected dose per gram at two hours) with rapid clearance from blood and normal tissues — a favorable biodistribution profile suggesting selective tumor targeting rather than broad tissue accumulation.

The work is entirely preclinical, and the mouse model used (Ehrlich tumor) is not a myeloma-specific model, which limits direct translation of the biodistribution findings. Validation in myeloma-specific animal models and assessment of dosimetry and toxicity would be necessary steps before any clinical development could be considered.

"Mitigating Teclistamab Toxicity: Prophylactic Tocilizumab and Timing of Immunoglobulin Replacement Therapy in a Nationwide Cohort"

Source 

A. H.Torpe, J.Thorsen, G.Mathiasen, et al., “Mitigating Teclistamab Toxicity: Prophylactic Tocilizumab and Timing of Immunoglobulin Replacement Therapy in a Nationwide Cohort,” American Journal of Hematology (2026): 1–5, https://doi.org/10.1002/ajh.70383. May 26, 2026.  

Overview

Teclistamab produces meaningful responses in relapsed or refractory myeloma but carries two clinically significant toxicities: cytokine release syndrome (CRS) during step-up dosing, and infections driven by progressive hypogammaglobulinemia. This real-world study from Denmark's nationwide ABCD registry examined whether prophylactic tocilizumab before the first step-up dose and early immunoglobulin replacement therapy (IgRT) could reduce these risks without compromising efficacy.

The natural variation in practice across Danish centers — Copenhagen implemented prophylactic tocilizumab from May 2024 while other centers did not — created a comparison group within an otherwise unselected consecutive cohort. CRS of any grade occurred in 69% of the 52 people who did not receive prophylactic tocilizumab versus 8% of the 53 who did. Grade 2 CRS specifically fell from 29% to 2%. No grade 3 or higher CRS occurred in either group, and recurrent CRS was absent in the prophylaxis group. Efficacy outcomes were similar between groups, and infection rates were unaffected by tocilizumab prophylaxis.

On infections, 65% of the overall cohort experienced infections of any grade and 31% had grade 3 or higher events, including two deaths — rates somewhat higher than previously published real-world data. The timing of IgRT initiation proved important: people who started IgRT before or promptly after beginning teclistamab had substantially longer grade 3 or higher infection-free survival than those who started IgRT only after a severe infection had already occurred (median 14.7 and 10.5 months respectively, versus 0.5 months for secondary prophylaxis). The finding that prior IgRT users fared worse than those starting primary prophylaxis likely reflects that prior IgRT identified people with pre-existing severe immune deficiency rather than a failure of the intervention itself.

Together the results support prophylactic tocilizumab before the first step-up dose and early IgRT initiation as practical strategies that reduce two of teclistamab's most clinically significant toxicities without affecting its effectiveness.

"Real-World Incidence and Management of Non-Immune Effector Cell-Associated Neurotoxicity Syndrome Neurologic Events Following Ciltacabtagene Autoleucel in Multiple Myeloma"

Source 

Hansen, D. K., Castaneda Puglianini, O. A., Grajales-Cruz, A., Nagar, S. P., Ghosh, S., Alegria, V., … Janakiram, M. (2026). Real-World Incidence and Management of Non-Immune Effector Cell-Associated Neurotoxicity Syndrome Neurologic Events Following Ciltacabtagene Autoleucel in Multiple Myeloma. Clinical Epidemiology, 18. https://doi.org/10.2147/CLEP.S615866 May 26, 2026. 

Overview

Cilta-cel is associated with a distinctive neurological toxicity profile that extends beyond ICANS — the immune effector cell-associated neurotoxicity more commonly discussed with CAR-T therapy. Rare but serious non-ICANS neurological events including cranial nerve palsy, parkinsonism, and Guillain-Barré syndrome have been reported, and this real-world study characterized their incidence and outcomes in 171 people treated with cilta-cel between 2022 and 2025.

Among 73 people with one to three prior lines of therapy (median follow-up 6.1 months), cranial nerve palsy occurred in four patients and symptoms improved in three. No parkinsonism or Guillain-Barré syndrome occurred in this group. Among 98 people with four or more prior lines (median follow-up 17.4 months), cranial nerve palsy occurred in three, parkinsonism in one, and Guillain-Barré syndrome in one. All cranial nerve palsy cases showed improvement and the Guillain-Barré syndrome case resolved.

A consistent finding across both groups was that people who developed non-ICANS neurological events had substantially higher peak absolute lymphocyte counts after infusion than those who did not — a pattern consistent with prior reports and suggesting that the degree of lymphocyte expansion following CAR-T infusion may be a risk marker for these complications. Whether this could guide monitoring intensity or early intervention warrants prospective investigation.

Notably, all people who developed neurological events had at least a partial response to cilta-cel and remained alive at the end of follow-up, suggesting these complications did not preclude treatment benefit. The overall incidence was low, and the outcomes were generally favorable, but the longer follow-up in the heavily pretreated group likely contributes to the higher event count there — a reminder that longer observation may reveal events not captured in shorter follow-up windows.

"Outcomes Among MM Patients Receiving Early Intervention for MRD Progression Following Autologous Stem Cell Transplantatio"

Source 

Li X, Chen M, Kuang L, Liu J, Huang B, Li J. Outcomes Among MM Patients Receiving Early Intervention for MRD Progression Following Autologous Stem Cell Transplantation. Cancer Med. 2026 May;15(5):e71911. doi: 10.1002/cam4.71911. 

Overview

MRD testing can detect disease re-emergence before it becomes visible through standard clinical or biochemical markers — a window during which treatment modification might theoretically prevent or delay frank relapse. This retrospective study examined whether acting on MRD progression before meeting standard progression criteria improves outcomes in people with myeloma following autologous stem cell transplant.

Among 42 newly diagnosed people who developed MRD progression after transplant, nine had treatment modified at the point of MRD progression (early intervention group) while 33 had treatment delayed until standard progression criteria were met. At a median follow-up of 25 months, the early intervention group had longer time to progression (median 34.8 vs 6.6 months), better overall survival (median not reached vs 41.0 months), and substantially faster MRD re-negativity (median 12.6 vs 75.9 months). Multivariate analysis identified early intervention as independently associated with achieving MRD re-negativity.

The findings are directionally compelling but the study's limitations are substantial and the authors acknowledge them explicitly: nine patients in the early intervention group is too small for reliable conclusions, the nonrandomized design means the two groups likely differed in unmeasured ways that influenced outcomes, and selection bias — clinicians may have chosen early intervention for people with more favorable biology — cannot be excluded. The unusually large difference in time to MRD re-negativity (12.6 vs 75.9 months) in particular warrants cautious interpretation given the small numbers.

The value of this study lies in its contribution to the design rationale for prospective randomized trials addressing MRD-guided treatment decisions — a question of growing clinical relevance as MRD monitoring becomes more routine in post-transplant follow-up.

"Evaluation of TIE-2 levels in newly diagnosed and untreated multiple myeloma patients"

Source 

Aygün, B., Karabulut, Z., Suyanı, E. et al. Evaluation of TIE-2 levels in newly diagnosed and untreated multiple myeloma patients. BMC Cancer (2026). https://doi.org/10.1186/s12885-026-16244-3 May 26, 2026. 

Overview

New blood vessel formation — angiogenesis — supports myeloma progression by supplying the tumor with nutrients and oxygen, and markers of angiogenic activity have been explored as potential diagnostic and prognostic tools. This prospective case-control study measured serum levels of TIE-2, a receptor involved in blood vessel remodeling and stabilization, in 38 newly diagnosed untreated people with myeloma and 37 healthy controls matched for age and sex.

TIE-2 levels were significantly higher in myeloma patients than controls (1.4 vs 0.9 ng/mL, p<0.001). ROC analysis yielded an AUC of 0.756, indicating moderate discriminative ability. At the optimal cutoff of 0.99 ng/mL, sensitivity was 89.5% — meaning the test identified most myeloma cases — but specificity was only 59.5%, meaning a substantial proportion of healthy controls also exceeded this threshold and would be flagged as positive.

The high sensitivity but limited specificity profile means TIE-2 would generate too many false positives to function as a standalone diagnostic marker. Its potential utility lies in combination with other markers, where its sensitivity could help ensure few cases are missed while additional markers filter out false positives.

The study is limited by its small cohort of 75 participants, single-center design, and case-control structure — which cannot address whether TIE-2 levels predict disease progression, treatment response, or outcomes over time. The findings establish that TIE-2 is elevated in myeloma and correlates with disease presence, but characterizing its clinical value beyond this exploratory observation requires larger prospective studies with longitudinal follow-up.

"Outcomes Among MM Patients Receiving Early Intervention for MRD Progression Following Autologous Stem Cell Transplantatio"

Source 

Li X, Chen M, Kuang L, Liu J, Huang B, Li J. Outcomes Among MM Patients Receiving Early Intervention for MRD Progression Following Autologous Stem Cell Transplantation. Cancer Med. 2026 May;15(5):e71911. doi: 10.1002/cam4.71911. 

Overview

MRD testing can detect disease re-emergence before it becomes visible through standard clinical or biochemical markers — a window during which treatment modification might theoretically prevent or delay frank relapse. This retrospective study examined whether acting on MRD progression before meeting standard progression criteria improves outcomes in people with myeloma following autologous stem cell transplant.

Among 42 newly diagnosed people who developed MRD progression after transplant, nine had treatment modified at the point of MRD progression (early intervention group) while 33 had treatment delayed until standard progression criteria were met. At a median follow-up of 25 months, the early intervention group had longer time to progression (median 34.8 vs 6.6 months), better overall survival (median not reached vs 41.0 months), and substantially faster MRD re-negativity (median 12.6 vs 75.9 months). Multivariate analysis identified early intervention as independently associated with achieving MRD re-negativity.

The findings are directionally compelling but the study's limitations are substantial and the authors acknowledge them explicitly: nine patients in the early intervention group is too small for reliable conclusions, the nonrandomized design means the two groups likely differed in unmeasured ways that influenced outcomes, and selection bias — clinicians may have chosen early intervention for people with more favorable biology — cannot be excluded. The unusually large difference in time to MRD re-negativity (12.6 vs 75.9 months) in particular warrants cautious interpretation given the small numbers.

The value of this study lies in its contribution to the design rationale for prospective randomized trials addressing MRD-guided treatment decisions — a question of growing clinical relevance as MRD monitoring becomes more routine in post-transplant follow-up.

"From episodic assessment to comprehensive assessment: integrating real-world monitoring in relapsed/refractory multiple myeloma"

Source 

Awadallah, C., Atrash, S., Paul, B., Khan, A. M., Shaikh, H., Strouse, C., … Abdallah, A. O. (2026). From episodic assessment to comprehensive assessment: integrating real-world monitoring in relapsed/refractory multiple myeloma. Expert Review of Hematology. https://doi.org/10.1080/17474086.2026.2681764 May 27, 2026. 

Overview

People with relapsed or refractory myeloma now receive treatment across many years and multiple lines of therapy, accumulating toxicities and functional decline between clinic visits that standard monitoring — scheduled appointments, laboratory values, imaging — is not designed to capture. This review examines the evidence and infrastructure for continuous, between-visit monitoring in this population, covering patient-reported outcome instruments, real-world data sources, and digital health technologies.

The case for integrating patient-reported outcomes rests on evidence from oncology more broadly: structured PRO collection detects symptom deterioration earlier than clinician assessment and has been shown in randomized trials to reduce avoidable acute care use and improve survival. Across the multi-year treatment course typical of relapsed myeloma, the cumulative benefit of earlier symptom detection is substantial — and the largest volume of patient-time occurs on conventional regimens (proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies) rather than on the newer immunotherapies that attract most research attention.

CAR-T and bispecific antibody therapies introduce specific monitoring requirements: CRS detection in the early post-infusion period (where wearable sensors offer a qualitatively new capability), and surveillance for late neurocognitive effects and prolonged cytopenias that emerge after patients transition from specialty centers back to community oncology. The review notes that the supervised post-infusion window is short relative to the period when late toxicities develop.

An equity dimension runs throughout: disparities in access to advanced therapies are well documented in myeloma, and monitoring infrastructure that relies on smartphones, broadband access, or English-language tools would deepen rather than address those gaps. The review proposes a four-layer implementation framework integrating patient context, continuous data streams, analytic tools, and defined clinical action triggers — with explicit attention to low-tech alternatives and community-inclusive platforms as prerequisites for equitable deployment.

"Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma"

Source 

Adam S. Sperling et al. Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma.Sci. Transl. Med.18,eadx1799(2026). DOI:10.1126/scitranslmed.adx1799  May 27, 2026 

Overview

Standard CAR-T manufacturing takes four to eight weeks, during which patients may progress, become too ill to receive treatment, or have their T cells collected at a point when those cells are already functionally compromised. Durcabtagene autoleucel was developed with a rapid manufacturing platform designed to shorten that window and preserve T cell stemness — the capacity for self-renewal and long-term persistence that correlates with durable responses.

In this phase 1 study, durcabtagene autoleucel was successfully manufactured for all 55 enrolled patients with a median vein-to-vein time of 24 days. Immunophenotyping and transcriptomic analysis confirmed that the final product retained a stem-like T cell phenotype, validating the manufacturing approach's core premise.

Efficacy results were strong: overall response rate was 98% and stringent complete response rate was 55%. MRD negativity was achieved in 80% of evaluable patients. These figures compare favorably with approved BCMA-directed CAR-T products, though cross-trial comparisons are confounded by differences in patient populations and prior treatment exposure.

No unexpected safety signals emerged and no delayed neurotoxicity was reported — a relevant finding given that delayed neurological events have been observed with some BCMA-directed CAR-T products, particularly cilta-cel. CRS and hematologic toxicity profiles were not detailed in this abstract but are described as within expected parameters.

The combination of a 24-day manufacturing turnaround, preserved stem-like phenotype, high response rates, and a clean safety signal in phase 1 supported initiation of a phase 2 trial in heavily pretreated aggressive relapsed or refractory myeloma. Whether the stem-like phenotype preservation translates into more durable responses than existing products will be a key question for longer-term follow-up data.

"Association Between Socioeconomic Inequalities and Health-Related Quality of Life in Patients With Relapsed/Refractory Multiple Myeloma"

Source 

Francesco Sparano et al. Association Between Socioeconomic Inequalities and Health-Related Quality of Life in Patients With Relapsed/Refractory Multiple Myeloma. JCO Oncol Pract 0, OP-25-0097 DOI:10.1200/OP-25-00975 May 27, 2026. 

Overview

Treatment for relapsed or refractory myeloma extends over many years and multiple lines of therapy, generating substantial financial burden alongside physical and emotional demands. This cross-sectional study examined whether socioeconomic status predicts quality of life in 505 people with relapsed or refractory myeloma in Italy and the United Kingdom, and whether financial toxicity explains part of that relationship.

Using a composite socioeconomic index based on education, employment, and living situation, 15.6% of participants were classified as low SES, 49.3% middle, and 35.1% high. People with low SES reported clinically meaningful worse scores across 11 of the EORTC quality of life scales compared to those with high SES. The differences were largest for pain (odds ratio 3.55 for clinically important pain), financial difficulties (OR 2.97), and physical functioning (OR 2.96) — three domains that compound each other, as pain limits function and financial strain limits access to supportive care.

Mediation analysis found that financial toxicity accounted for 46.3% of the total effect of SES on quality of life — meaning nearly half of the quality of life disadvantage experienced by lower-SES people with myeloma operates through the financial burden of treatment rather than through other aspects of socioeconomic disadvantage. The remaining 54% reflects other pathways, including reduced access to supportive care, worse baseline health, and psychosocial factors.

The finding that financial toxicity is a major mediator rather than simply a correlate of poor outcomes is clinically actionable: it suggests that interventions specifically targeting financial burden — such as copayment assistance, transportation support, and social work integration — could meaningfully narrow quality of life disparities in this population without requiring changes to the underlying disease biology or treatment landscape.

"Photon-counting detector computed tomography (PCD-CT) in multiple myeloma: a systematic review and trial sequential meta-analysis on image quality and radiation dose"

Source 

Ohannesian, V.A., Taneja, B.C., do Amaral e Castro, A. et al. Photon-counting detector computed tomography (PCD-CT) in multiple myeloma: a systematic review and trial sequential meta-analysis on image quality and radiation dose. Skeletal Radiol (2026). https://doi.org/10.1007/s00256-026-05242-y May 27, 2026. 

Overview

CT imaging is central to myeloma diagnosis and monitoring, used to detect lytic bone lesions and assess disease extent. Photon-counting detector CT (PCD-CT) is a newer technology that captures X-ray photons differently than conventional energy-integrating detector CT (EID-CT), with theoretical advantages in image resolution and the potential to reduce radiation exposure. This meta-analysis compared the two technologies specifically in myeloma patients with bone lesions, pooling data from five studies covering 170 patients.

PCD-CT produced significantly sharper images than EID-CT, with a pooled mean difference of 0.99 points on image sharpness scales (95% CI 0.62–1.37). Trial sequential analysis confirmed this finding is stable and unlikely to be overturned by additional studies — the evidence for image quality improvement is considered conclusive within the available data.

For radiation dose, PCD-CT showed a reduction of approximately 4.95 milligrays compared to EID-CT. This difference was statistically significant in conventional meta-analysis, but trial sequential analysis indicated the cumulative evidence remains insufficient to draw firm conclusions about the true magnitude of the reduction. More data are needed before the radiation dose benefit can be quantified with confidence.

The evidence base is limited by the small number of eligible studies (five) and the total patient count of 170, reflecting how recently PCD-CT has become available in clinical settings. For people with myeloma who undergo repeated CT imaging over years of disease monitoring, even modest reductions in per-scan radiation dose accumulate meaningfully over time — making confirmation of the dose reduction benefit a clinically worthwhile question for larger prospective studies.

"Junctional Adhesion Molecule-A (JAM-A) Associates With High-Risk Disease in Multiple Myeloma Patients and a Structure-Based Rationally-Designed Peptide Inhibitor Attenuates Tumorigenic Features In Vitro and In Vivo"

Source 

N.McAuley, R.McAvera, D.Bong, et al., “Junctional Adhesion Molecule-A (JAM-A) Associates With High-Risk Disease in Multiple Myeloma Patients and a Structure-Based Rationally-Designed Peptide Inhibitor Attenuates Tumorigenic Features In Vitro and In Vivo,” European Journal of Haematology (2026): 1–12, https://doi.org/10.1111/ejh.70225. May 27, 2026. 

Overview

Chromosome 1q gain or amplification is one of the most common high-risk cytogenetic abnormalities in myeloma, present in roughly 40% of newly diagnosed cases and associated with worse outcomes and treatment resistance. The 1q region contains many genes, and identifying which ones drive the adverse biology of 1q+ myeloma remains an active area of investigation. This study focused on F11R, which encodes Junctional Adhesion Molecule-A (JAM-A), a cell surface protein involved in cell adhesion and signaling.

In the CoMMpass dataset, F11R expression was significantly higher in myeloma patients with 1q gain or amplification than in those without, and higher expression correlated with worse overall survival. Elevated F11R was also associated with increased circulating CD138+ plasma cells — a finding the authors suggest may reflect early extramedullary disease, consistent with JAM-A's known role in promoting cell migration and adhesion.

JAM-A promotes tumor-supportive signaling through a mechanism called cis-dimerization — binding to itself on the same cell surface to activate downstream pathways. The study used structural modeling to design peptides that selectively disrupt this dimerization without broadly blocking JAM-A's other functions. In myeloma cell lines and primary CD138+ cells from patients, these peptides reduced proliferation and induced cellular senescence. In a chick chorioallantoic membrane xenograft model, candidate peptide P4 significantly inhibited plasmacytoma-like tumor growth in vivo.

The findings position JAM-A as a candidate therapeutic target specifically relevant to 1q+ myeloma — a subgroup where current treatments are least effective — and establish proof of concept for a peptide-based inhibition strategy. Validation in mammalian animal models and assessment of pharmacokinetics and toxicity would be necessary next steps before clinical translation.

"Ixazomib, Cyclophosphamide, and Dexamethasone (ICd), with or without Daratumumab in Relapsed Multiple Myeloma"

Source 

Shaji K. Kumar, Betsy Knopf, Erik Asmus, Morie Gertz, Prashant Kapoor, Suzanne Hayman, Vivek Roy, Amie Fonder, Lisa Christenson, Miriam Hobbs, Leif Bergsagel, Rafael Fonseca, David Dingli, Angela Dispenzieri, Wilson Gonsalves, Taxiarchis Kourelis, Taimur Sher, Mustaqeem Siddiqi, Rahma Warsame, Sikander Ailawadhi, S. Vincent Rajkumar, Francis Buadi, Ixazomib, Cyclophosphamide, and Dexamethasone (ICd), with or without Daratumumab in Relapsed Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.05.004. May 27, 2026 . 

Overview

Access to newer myeloma therapies remains uneven globally, and fully oral regimens offer practical advantages for people who face barriers to frequent infusion center visits. This phase 2 study evaluated two all-oral or predominantly oral combinations for relapsed myeloma: ixazomib, cyclophosphamide, and dexamethasone (ICd) with and without daratumumab.

Among 33 people treated with ICd, the overall response rate was 73% and 45% achieved at least a very good partial response. Median progression-free survival was 27.1 months at a median follow-up of 27 months, with median overall survival not reached. Among 24 people treated with daratumumab added to ICd, response rates were similar (75% ORR, 54% ≥VGPR) but progression-free survival was longer at 37.7 months after a median follow-up of 41 months, with overall survival also not reached.

The indirect comparison — not a randomized head-to-head — suggests adding daratumumab deepens responses and extends progression-free survival, consistent with daratumumab's established benefit when added to other backbone regimens. Grade 3 or higher hematologic toxicity occurred in approximately 75% of patients in both arms, reflecting the myelosuppressive contribution of cyclophosphamide in a pretreated population.

The results are relevant for settings where intravenous or subcutaneous bispecific antibodies and CAR-T therapy are unavailable or inaccessible, and where an oral proteasome inhibitor-based regimen represents a practical treatment option. The progression-free survival figures compare reasonably with other regimens used at this stage of disease, supporting ICd and daratumumab-ICd as viable options in resource-limited or community settings where treatment delivery flexibility matters.

"Incorporating the Next Generation of Immunotherapies Into the Treatment of Multiple Myeloma"

Source 

Miller, K. C., Firestone, R. S., & Hultcrantz, M. (2026). Incorporating the Next Generation of Immunotherapies Into the Treatment of Multiple Myeloma. Journal of the National Comprehensive Cancer Network (published online ahead of print 2026). Retrieved May 27, 2026, from https://doi.org/10.6004/jnccn.2026.7004 . 

Overview

Immunotherapy has reshaped myeloma treatment more rapidly than almost any other development in the field's history. This review traces that transformation — from the biological rationale for targeting plasma cell surface antigens through the current approved landscape to emerging frontline and early-intervention strategies.

CAR-T therapy targeting BCMA has produced responses in heavily pretreated myeloma that were previously unattainable, with cilta-cel demonstrating 33% of patients remaining in complete response with undetectable MRD at five years in a phase I/II trial — without maintenance therapy. Both approved BCMA-directed CAR-T products (ide-cel and cilta-cel) have now demonstrated benefit in earlier treatment lines through randomized phase III trials. Bispecific antibodies targeting BCMA (teclistamab, elranatamab, linvoseltamab) and GPRC5D (talquetamab) are approved for later-line disease, with teclistamab plus daratumumab recently approved after one prior line based on MajesTEC-3 data showing a three-year progression-free survival of 83.4% versus 29.7% for standard therapy. Belantamab mafodotin, a BCMA-directed antibody-drug conjugate, occupies a different niche — no step-up dosing required, lower infection risk, but intensive ophthalmologic monitoring needed for ocular toxicity.

On sequencing, no prospective trial data exist to guide decisions, but most experts favor CAR-T over bispecific antibodies as the first immunotherapy choice in fit patients, given higher response rates and the observation that BCMA loss after bispecific antibody therapy may be more common than after CAR-T. Talquetamab is increasingly used as bridging therapy during CAR-T manufacturing.

Looking ahead, trispecific antibodies targeting two tumor antigens simultaneously — including ramantamig (BCMA×GPRC5D) with an 84% overall response rate in phase I — aim to address antigen escape. Multiple phase III trials are now testing CAR-T and bispecific antibodies in frontline treatment and even in smoldering myeloma, though the review notes that elevated infection risk and rare but serious late toxicities warrant careful evaluation before these approaches move into earlier, asymptomatic disease stages outside of trials.

"Ixazomib, Cyclophosphamide, and Dexamethasone (ICd), with or without Daratumumab in Relapsed Multiple Myeloma"

Source 

Shaji K. Kumar, Betsy Knopf, Erik Asmus, Morie Gertz, Prashant Kapoor, Suzanne Hayman, Vivek Roy, Amie Fonder, Lisa Christenson, Miriam Hobbs, Leif Bergsagel, Rafael Fonseca, David Dingli, Angela Dispenzieri, Wilson Gonsalves, Taxiarchis Kourelis, Taimur Sher, Mustaqeem Siddiqi, Rahma Warsame, Sikander Ailawadhi, S. Vincent Rajkumar, Francis Buadi, Ixazomib, Cyclophosphamide, and Dexamethasone (ICd), with or without Daratumumab in Relapsed Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.05.004. May 27, 2026 . 

Overview

Access to newer myeloma therapies remains uneven globally, and fully oral regimens offer practical advantages for people who face barriers to frequent infusion center visits. This phase 2 study evaluated two all-oral or predominantly oral combinations for relapsed myeloma: ixazomib, cyclophosphamide, and dexamethasone (ICd) with and without daratumumab.

Among 33 people treated with ICd, the overall response rate was 73% and 45% achieved at least a very good partial response. Median progression-free survival was 27.1 months at a median follow-up of 27 months, with median overall survival not reached. Among 24 people treated with daratumumab added to ICd, response rates were similar (75% ORR, 54% ≥VGPR) but progression-free survival was longer at 37.7 months after a median follow-up of 41 months, with overall survival also not reached.

The indirect comparison — not a randomized head-to-head — suggests adding daratumumab deepens responses and extends progression-free survival, consistent with daratumumab's established benefit when added to other backbone regimens. Grade 3 or higher hematologic toxicity occurred in approximately 75% of patients in both arms, reflecting the myelosuppressive contribution of cyclophosphamide in a pretreated population.

The results are relevant for settings where intravenous or subcutaneous bispecific antibodies and CAR-T therapy are unavailable or inaccessible, and where an oral proteasome inhibitor-based regimen represents a practical treatment option. The progression-free survival figures compare reasonably with other regimens used at this stage of disease, supporting ICd and daratumumab-ICd as viable options in resource-limited or community settings where treatment delivery flexibility matters.

"Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma"

Source 

Agius, M.P., Song, C., Liu, Q. et al. Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma. Nat Chem Biol (2026). https://doi.org/10.1038/s41589-026-02228-8 May 28, 2026.  

Overview

Transcription factors drive cancer biology but have historically been considered undruggable — their surfaces lack the defined binding pockets that small molecule inhibitors typically require. IRF4 is a transcription factor that myeloma cells depend on for survival, making it an attractive but technically difficult target. This study developed a strategy to overcome that challenge.

Starting from a high-throughput screen, the researchers identified a small molecule called (S)-H1 that binds to IRF4 at the interface where it interacts with SPI1 (also known as PU.1), a partner protein. Binding at this protein-protein interaction site disrupts IRF4 function, but (S)-H1 alone had limited cytotoxic activity — it was a binder rather than a potent inhibitor.

The key step was converting this binder into a PROTAC (proteolysis-targeting chimera) called dIRF4-2, by chemically linking (S)-H1 to a cereblon E3 ligase ligand. PROTACs work by recruiting the cell's own protein degradation machinery to a target protein, marking it for destruction by the proteasome. dIRF4-2 induced selective proteasomal degradation of IRF4 across all myeloma cell lines tested, with strong cytotoxic effects — demonstrating that eliminating the protein entirely is more effective than merely inhibiting its activity at one interaction site.

Beyond the immediate myeloma application, the study establishes a methodological framework: identify a binder at a protein-protein interaction surface, then convert it into a degrader. This approach could be applied to other IRF family members and potentially to other transcription factors that have similarly resisted direct inhibition, opening a broader path to targeting oncoproteins previously considered inaccessible to pharmacological intervention.

"High-Risk Multiple Myeloma: Redefining Risk and Rethinking Therapy"

Source 

Gareth J. Morgan et al. High-Risk Multiple Myeloma: Redefining Risk and Rethinking Therapy. Am Soc Clin Oncol Educ Book 46, e517494(2026). DOI:10.1200/EDBK-26-517494 May 28, 2026.   

Overview

Despite treatment advances that have substantially extended survival in standard-risk myeloma, outcomes for the 15–25% of people with high-risk disease have not improved to the same degree. High-risk myeloma is defined by early treatment resistance and poor survival, and its prevalence increases at each relapse as the disease evolves toward more aggressive biology — making it a problem both at diagnosis and throughout the disease course.

This review provides a framework for understanding and clinically defining high-risk myeloma, with the goal of enabling systematic clinical trial design and personalized treatment selection. Loss of 17p and TP53 mutation are the most established drivers of high-risk biology, but the review argues that high-risk myeloma is not a single entity — it encompasses multiple biological subgroups with distinct molecular underpinnings that are increasingly being characterized separately. Breaking down this heterogeneity is presented as a prerequisite for developing targeted approaches rather than applying uniform high-risk treatment strategies.

The review examines how definitions of high-risk myeloma have evolved, incorporating cytogenetic markers, gene expression profiling, and emerging genomic features beyond the established FISH-based criteria. It then addresses whether current and emerging therapies — including conventional targeted agents and the newer immunotherapies — can overcome the specific resistance mechanisms that define high-risk biology, or whether they merely delay rather than prevent treatment failure.

For people with myeloma who have been told their disease has high-risk features, the central message is that high-risk is not a single prognosis but a collection of biological subtypes, and that matching treatment to specific biology — rather than treating all high-risk disease identically — is the direction the field is moving toward.

"Body mass index and multiple myeloma: a systematic review and dose-response meta-analysis of prospective cohort studies"

Source 

Zahedi, H., Eshaghian, N., Hadizadeh, M. et al. Body mass index and multiple myeloma: a systematic review and dose-response meta-analysis of prospective cohort studies. BMC Cancer (2026). https://doi.org/10.1186/s12885-026-16233-6  May 28, 2026.  

Overview

The relationship between body weight and myeloma risk has been studied across multiple cohorts with inconsistent results. This meta-analysis pooled data from 28 prospective cohort studies — covering 18,923 myeloma cases and 3,926 myeloma deaths across follow-up periods of 8.5 to 38 years — to produce a more reliable estimate of the association between BMI and both myeloma incidence and mortality.

Compared to people with normal weight, those with obesity had a 17% higher risk of developing myeloma (RR 1.17) and a 38% higher risk of dying from it (RR 1.38). Overweight was also associated with elevated risk in both categories, though the effect sizes were smaller. The dose-response analysis found that each 5 kg/m² increase in BMI was associated with a 2% higher myeloma incidence risk and a 3% higher mortality risk — a modest per-unit effect that compounds meaningfully across the BMI range between normal weight and obesity.

Underweight was not significantly associated with either myeloma incidence or mortality, suggesting the relationship is specific to excess rather than insufficient weight.

The stronger association with mortality than incidence is notable and may reflect multiple mechanisms: obesity-related metabolic and inflammatory changes could both increase susceptibility to myeloma and worsen outcomes once disease develops, potentially through effects on treatment tolerability, immune function, or disease biology. Whether weight loss interventions could reduce myeloma risk or improve outcomes in people already diagnosed remains an open question — the observational design of the included studies cannot establish causation or inform whether the association is modifiable.

"Clinical Validation of a QSP Model for ISB 2001, a Trispecific T Cell Engager to Support Optimal FIH Study Design in RRMM Patients"

Source 

Chandralayam Ayyappa Menon, V., Matsuura, T., Holkova, B., Gudi, G.S., Drake, A., Pihlgren, M., van der Graaf, P.H., GN, S., Garton, A., Perro, M., Konto, C. and Pacaud, L. (2026), Clinical Validation of a QSP Model for ISB 2001, a Trispecific T Cell Engager to Support Optimal FIH Study Design in RRMM Patients. Clin Pharmacol Ther. https://doi.org/10.1002/cpt.70319 May 28, 2026. 

Overview

ISB 2001 is a trispecific antibody targeting both CD38 and BCMA on myeloma cells while simultaneously engaging CD3 on T cells — a dual-antigen approach designed to reduce the risk of antigen escape that limits single-target therapies. It is currently in a first-in-human trial (TRIgnite-1) in relapsed or refractory myeloma.

A practical challenge in developing ISB 2001 was that its CD3-binding domain does not cross-react with CD3 in cynomolgus monkeys — the standard preclinical species used to generate pharmacokinetic, toxicity, and efficacy data before human trials. Without a fully cross-reactive animal model, the conventional approach to first-in-human dose selection — the minimum anticipated biological effect level (MABEL) method — would likely produce starting doses too low to show meaningful activity, potentially exposing seriously ill patients to multiple subtherapeutic dose escalation cohorts before reaching an active dose range.

To address this, the researchers developed a quantitative systems pharmacology (QSP) model — a computational approach that integrates known biology of T cell engagement, target expression, drug pharmacokinetics, and tumor dynamics to predict dose-response relationships in humans without requiring animal data. This model informed both the starting dose and the predicted efficacy dose range for TRIgnite-1, enabling a more efficient escalation design.

The model's predictions were then validated against early safety, pharmacokinetic, and anti-myeloma activity data emerging from the ongoing trial, with results showing reasonable concordance. The approach aligns with FDA efforts to reduce animal testing through computational modeling in drug development — a methodological contribution that extends beyond ISB 2001 to the broader challenge of developing T cell engagers whose CD3-binding domains lack cross-reactivity in standard preclinical species.

"A phase I/II study of twice-weekly ixazomib plus pomalidomide and dexamethasone in relapsed and refractory multiple myeloma"

Source 

Nadeem O, Redd RA, Barth PM, Bayliss TJ, Laubach JP, Bianchi G, Mo CC, Reagan JL, Midha S, Sperling AS, Liu Y, Hartley-Brown MA, Chuma MP, Nicholson T, Benjamin EJ, Distaso A, Regan E, Hof AMV, Dahill AJ, Goldbaum R, Mohammadi K, Lewis A, Poda R, Munshi NC, Anderson KC, Ghobrial IM, Richardson PG. A phase I/II study of twice-weekly ixazomib plus pomalidomide and dexamethasone in relapsed and refractory multiple myeloma. Haematologica; https://doi.org/10.3324/haematol.2026.300897 [Early view]. May 28, 2026.  

Overview

Fully oral treatment regimens offer meaningful practical advantages in myeloma — avoiding infusion center visits, reducing treatment burden, and improving access for people who face logistical barriers to frequent clinic attendance. This phase I/II study evaluated a three-drug oral combination of ixazomib (proteasome inhibitor), pomalidomide (immunomodulatory drug), and dexamethasone in 50 people with relapsed or refractory myeloma, nearly all of whom had received prior lenalidomide (98%) and bortezomib (88%).

The recommended phase II dose was established as ixazomib 4 mg plus pomalidomide 4 mg, with dexamethasone on dosing days. Participants received a median of 11 cycles. The overall response rate across all 50 patients was 60%, with 24% achieving at least a very good partial response. Among the 38 people who received the recommended dose, response rate was 65.8% and median progression-free survival was 17.8 months. Three-year overall survival was 80.3% in this group — a notably favorable figure for a relapsed population with prior exposure to both major drug classes, though the relatively small cohort and phase I/II design limit how broadly these numbers generalize.

The most common toxicities were hematologic: neutropenia (76%), thrombocytopenia (70%), and leukopenia (68%), with grade 3/4 rates that are clinically manageable with dose modifications and growth factor support. Fatigue and anemia were also frequent but mostly low grade. Two dose-limiting toxicities occurred during escalation.

The combination is relevant particularly for people with myeloma who are lenalidomide-refractory and need a convenient outpatient regimen, and for settings where intravenous or subcutaneous novel immunotherapies are less accessible.

"Determinants of Clinical Trial Participation and Survival in Multiple Myeloma: A Population-Based Cohort Study from British Columbia"

Source 

Hong Li, Timothy Wong, Arefeh Rouhi, Yasser Abou-Mourad, Hannah Cherniawsky, Shanee Chung, Donna Forrest, Deepesh Lad, Stephen Nantel, Sujaatha Narayanan, Thomas Nevill, Anna Nguyen, Afsaneh Panahi, Melika Bakharzi, Stephen Parkin, Claudia Piechnik, Judith Rodrigo, Claudie Roy, David Sanford, Ryan J. Stubbins, Cynthia Toze, Julia Varghese, Jennifer White, Edward Wong, Heather Sutherland, Kevin Song, Chris Venner, Florian Kuchenbauer, Determinants of Clinical Trial Participation and Survival in Multiple Myeloma: A Population-Based Cohort Study from British Columbia, Leukemia Research, 2026, 108254, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2026.108254. May 28, 2026   

Overview

Clinical trials drive treatment advances in myeloma, but who actually enrolls in them — and whether participation itself confers a survival advantage — has practical implications for both trial design and healthcare equity. This retrospective study examined 599 people with myeloma treated at two British Columbia tertiary centers between 2000 and 2023, of whom 80 (13.4%) participated in at least one trial.

Trial participants were more likely to live closer to the treating center, reside in urban areas, and have better performance status and fewer comorbidities. Age and most socioeconomic measures were not significantly associated with participation — an important finding in a Canadian publicly funded healthcare context, suggesting that financial barriers play less of a role than in systems with more fragmented insurance coverage. The exception was situational vulnerability, a composite measure capturing social instability, which was associated with lower participation.

Trial participants had longer median overall survival than non-participants (121.7 vs 93.9 months, HR 0.69). However, autologous stem cell transplant and performance status were the strongest independent predictors of survival in multivariable analysis — and trial participants were healthier and more likely to receive transplant at baseline. This suggests the apparent survival benefit of trial participation largely reflects selection of fitter patients rather than a direct effect of trial enrollment itself.

The practical conclusions are clear: in this setting, the primary barriers to trial participation were geographic proximity and clinical fitness rather than socioeconomic factors. Expanding trial access would be most effectively addressed by reducing distance and logistical barriers — through decentralized trial designs, satellite enrollment sites, and travel support — and by broadening eligibility criteria to include people with higher comorbidity burden who are currently excluded from most trials.

"Clinical implications of minimal residual disease monitoring in multiple myeloma"

Source 

Yoroidaka, T. Clinical implications of minimal residual disease monitoring in multiple myeloma. Int J Hematol (2026). https://doi.org/10.1007/s12185-026-04229-8 May 28, 2026.   

Overview

This review examines the growing role of minimal residual disease (MRD) testing in multiple myeloma as newer therapies produce deeper and more durable responses. Treatments such as quadruplet induction regimens, CAR T-cell therapies, and bispecific antibodies are enabling many patients to achieve disease levels below the detection limits of traditional blood and urine tests.

The review focuses on the two most widely used MRD detection methods: next-generation sequencing (NGS) and next-generation flow cytometry (NGF). Both techniques can detect very small numbers of remaining myeloma cells and have consistently shown that patients who achieve MRD-negative status experience longer progression-free survival and overall survival than those who remain MRD-positive.

The authors summarize findings from clinical trials in both newly diagnosed and relapsed or refractory myeloma, where high rates of MRD negativity have been reported with newer treatment approaches. They also discuss the emerging concept of MRD-guided therapy, in which treatment decisions are adjusted based on MRD results. This strategy may allow treatment intensification for patients with persistent disease and treatment reduction for patients who achieve deep, sustained responses.

The review highlights several unresolved questions, including the best timing for MRD testing, standardization of testing methods, and how MRD assessment should be incorporated into routine clinical practice. As MRD testing becomes more widely used, it is increasingly being viewed as both a prognostic marker and a tool for personalizing myeloma treatment.
 

"Debulking Chemotherapy Can Overcome Primary Resistance to Teclistamab in Relapsed/Refractory Multiple Myeloma"

Source 

Rintu Sharma, Andree-Anne Pelland, Katherine Lajkosz, Esther Masih-Khan, Harjot Singh Vohra, Sita Bhella, Christine I. Chen, Vishal Kukreti, A. Keith Stewart, Suzanne Trudel, Chloe Yang, Donna E. Reece, Chris Venner, Guido Lancman; Debulking Chemotherapy Can Overcome Primary Resistance to Teclistamab in Relapsed/Refractory Multiple Myeloma. Blood Cancer Discov 1 May 2026; 7 (3): 394–402. https://doi.org/10.1158/2643-3230.BCD-25-0372&nbsp;

Overview

Researchers examined why some patients with multiple myeloma do not respond to teclistamab, a BCMA-targeting bispecific antibody, and explored whether treatment strategies could improve outcomes in these patients.

Using data from two patient cohorts totaling 90 individuals, the investigators identified a group at high risk for primary resistance to teclistamab. This high-risk profile, called Hi-MM, included patients with extramedullary disease, plasma cell leukemia, 50% or greater bone marrow plasma cell involvement, or a recent need for blood transfusions. Patients without these features had response rates ranging from 84% to 96%, compared with only 20% to 40% among patients classified as Hi-MM. They also experienced longer progression-free survival and overall survival.

The study evaluated the use of debulking chemotherapy before teclistamab in 19 patients with high disease burden. After chemotherapy, 79% responded to teclistamab. Responses were seen in all patients whose high-risk features resolved following debulking treatment. Notably, four patients whose disease had failed to respond to a previous BCMA-targeting bispecific antibody achieved deep responses after receiving chemotherapy followed by teclistamab.

The findings suggest that readily identifiable clinical features can help predict which patients are less likely to benefit from teclistamab alone. Reducing disease burden before treatment may improve outcomes and help some patients overcome initial resistance to BCMA-targeted therapy.
 

"MajesTEC-9 Trial Investigators. Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy"

Source 

Touzeau C, Mina R, Quach H, Hungria V, Bhutani D, Chen W, Kumar S, Chaulagain C, Dimopoulos MA, Bahlis NJ, Maral S, van de Donk NWCJ, Schmidt Filho J, Saja K, Teipel R, Ando M, Roeloffzen W, Annibali O, Augustson B, Botta C, Delforge M, Bourgeois E, Buda G, Hus M, Perrot A, Preis M, Beksac M, Pour L, Farmer S, Nunes M, Oriol A, Melchardt T, Hu Y, Flogegård M, Wang D, Pei L, Wroblewski S, Ariës IM, Quijano Cardé NA, Perova T, de Jager T, Yeh TM, Vanquickelberghe V, Shah P, Chastain K, Kobos R, Carson R, Landgren O; MajesTEC-9 Trial Investigators. Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy. N Engl J Med. 2026 May 29. doi: 10.1056/NEJMoa2603870.  

Overview

Researchers compared teclistamab with standard treatment regimens in patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy and whose disease was refractory to lenalidomide. All patients had previously been treated with both lenalidomide and an anti-CD38 monoclonal antibody.

A total of 593 patients were enrolled and randomly assigned to receive either teclistamab or the investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). After a median follow-up of 17.3 months, teclistamab produced substantially better outcomes than the standard regimens.

The estimated progression-free survival rate at 18 months was 69.8% with teclistamab compared with 26.9% with PVd or Kd. Patients receiving teclistamab were also far more likely to achieve deep responses, with 65.9% reaching a complete response or better versus 16.8% in the standard-treatment group. Overall survival was also improved, with estimated 18-month survival rates of 79.2% and 68.6%, respectively.

Side effects were common in both groups. Cytokine release syndrome (CRS) occurred in 66% of patients receiving teclistamab, although most cases were low grade. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 4.1% of patients. Serious infections were more frequent with teclistamab, occurring in 41.6% of patients compared with 29.0% in the PVd or Kd group.

The results show that teclistamab can produce deeper and more durable responses than commonly used standard regimens when used earlier in the relapsed setting, although infection risk remains an important consideration.

 

"Multiplexed Imaging Reveals Immune-Metabolic Niches in Multiple Myeloma Linked to Progression and Bone Disease"

Source 

Ingrid Aass Roseth, Lukas Hatscher, Chiara Schiller, Håkon Skjalg Selland Johnstuen, Tobias S. Slørdahl, Håkon Hov, Denis Schapiro, Therese Standal; Multiplexed Imaging Reveals Immune-Metabolic Niches in Multiple Myeloma Linked to Progression and Bone Disease. Blood Cancer Discov 1 May 2026; 7 (3): 460–478. https://doi.org/10.1158/2643-3230.BCD-25-0334   

Overview

Researchers used advanced imaging technology to examine how myeloma cells are organized within the bone marrow microenvironment in patients with MGUS, smoldering multiple myeloma (SMM), and active multiple myeloma. The goal was to better understand how the location of myeloma cells within the bone marrow influences disease behavior.

The study found that plasma cells located near bone surfaces had biological features associated with a more quiescent, or less active, state. In patients with myeloma-related bone disease, these cells also showed increased expression of IL32, a molecule that may contribute to bone destruction.

Researchers identified two distinct plasma cell microenvironments, or "neighborhoods," within the bone marrow. One, termed **PC OXPHOS**, was characterized by clusters of plasma cells located near blood vessels and showed evidence of oxidative phosphorylation metabolism. The second, **PC MYELOID**, contained plasma cells intermixed with immune cells and displayed a more glycolytic metabolic profile.

The study also found that close spatial interactions between plasma cells and CD4-positive T cells were associated with shorter progression-free survival, independent of other factors. This suggests that the way myeloma cells interact with surrounding immune cells may influence disease outcomes.

The findings highlight that myeloma cells do not behave uniformly throughout the bone marrow. Their location, neighboring cells, and local metabolic environment may all affect disease progression, offering potential new approaches for risk assessment and future therapeutic strategies.

"Clinical Scores to Predict Toxicities and Outcomes in Patients with Multiple Myeloma Undergoing Bispecific T-cell Engager Therapy"

Source 

Jan H. Frenking, Christine Riedhammer, Thomas Hielscher, Christoph Schaefers, Lisa B. Leypoldt, Marie Harzer, David Sedloev, Valentine Landrin, Niklas Kehl, Mirco J. Friedrich, Xiang Zhou, Maximilian Steinhardt, Philipp Weis, Julia Mersi, Johannes Waldschmidt, Niels Weinhold, K. Martin Kortüm, Carsten Müller-Tidow, Hermann Einsele, Sandra Sauer, Katja Weisel, Tim Richardson, Raphael Teipel, Leo Rasche, Marc S. Raab; Clinical Scores to Predict Toxicities and Outcomes in Patients with Multiple Myeloma Undergoing Bispecific T-cell Engager Therapy. Blood Cancer Discov 1 May 2026; 7 (3): 479–495. https://doi.org/10.1158/2643-3230.BCD-25-0062&nbsp;

Overview

Researchers evaluated whether several clinical risk scores could help identify patients with relapsed or refractory multiple myeloma who are at higher risk for complications and poorer outcomes before starting bispecific T-cell engager (TCE) therapy.

The study analyzed two independent groups of patients treated with T-cell engagers, including a discovery cohort of 123 patients and a validation cohort of 155 patients. Researchers examined the performance of the CAR-HEMATOTOX (HTX), Endothelial Activation and Stress Index (EASIX), and modified EASIX (m-EASIX) scores, which have previously been used to assess risk before CAR T-cell therapy.

Patients with an HTX score of 3 or higher or an m-EASIX score above 0.86 were more likely to experience complications during treatment. These patients had higher rates of prolonged hospitalization, fever during step-up dosing, and antibiotic use. They were also more likely to develop low blood counts requiring medical intervention and experienced more severe infections.

In addition to predicting treatment-related complications, these risk scores were associated with lower response rates and shorter progression-free and overall survival. Patients with higher-risk scores generally had poorer outcomes than those with lower scores.

The findings suggest that HTX and m-EASIX may be useful tools for identifying patients who require closer monitoring and supportive care before receiving bispecific antibody therapy. The authors concluded that these readily available clinical scores could help improve risk stratification and treatment planning for patients receiving T-cell engagers.
 

"Development of Fourth-Generation IL-15-Armoured Memory-Like CAR-NK Cells Against Multiple Myeloma: Increased Cell Yield, Superior Transduction, Differential Phenotype, and Enhanced Cytokine Production"

Source 

T.G. Mitsugi, L. Trjano, E. Vidal, I. Ferreira, R.A. Ferreira, N.A. Macedo, Y.M. Amirato, B.Q. Souza, L. Coser, C. Barros, J.R. Silva, J.C. Benincasa, L.C. Zanetti, O.K. Okamoto, N. Hamerschlak, L.N. Kerbauy, DEVELOPMENT OF FOURTH GENERATION IL-15-ARMOURED MEMORY-LIKE CAR-NK CELLS AGAINST MULTIPLE MYELOMA: INCREASED CELL YIELD, SUPERIOR TRANSDUCTION, DIFFERENTIAL PHENOTYPE AND ENHANCED CYTOKINE PRODUCTION., Cytotherapy, Volume 28, Issue 5, Supplement, 2026, 102639, ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2026.102639. May 2026. 

Overview

Researchers developed and tested a fourth-generation anti-BCMA CAR NK-cell therapy designed to improve on existing CAR NK approaches for multiple myeloma. The experimental product combines two strategies: engineering NK cells to produce IL-15 and inducing a memory-like (ML) phenotype, which may enhance persistence, cytokine production, and antitumor activity.

Compared with conventional CAR NK cells, memory-like BCMA-IL15 CAR NK cells achieved substantially higher cell yields during manufacturing and showed better CAR transduction efficiency. These advantages resulted in a greater number of CAR-positive NK cells available by the end of the production process.

The memory-like cells also displayed a distinct phenotype, with a more balanced distribution of CD56+CD16+ and CD56+CD16− NK-cell populations during early expansion. Higher transduction rates were observed in both subsets compared with conventional CAR NK cells.

When tested against the MM1.S multiple myeloma cell line, memory-like BCMA-IL15 CAR NK cells killed tumor cells as effectively as conventional CAR NK cells but produced significantly higher levels of interferon-gamma (IFN-γ), a cytokine involved in antitumor immune responses. Tumor cell killing and TNF-α production were otherwise similar between the two approaches.

The findings suggest that combining IL-15 armoring with a memory-like NK-cell phenotype may improve CAR NK-cell manufacturing efficiency and immune function. These fourth-generation CAR NK cells could represent a potentially more potent and scalable off-the-shelf cellular therapy approach for multiple myeloma.
 

"Elranatamab: Mechanism of Action, Clinical, and Translational Science"

Source 

M.Elmeliegy, A.Viqueira, E.Vandendries, et al., “Elranatamab: Mechanism of Action, Clinical, and Translational Science,” Clinical and Translational Science19, no. 5 (2026): e70554, https://doi.org/10.1111/cts.70554. May 2026. 

Overview

Researchers reviewed the clinical data supporting the approved dosing schedule of elranatamab, a BCMA-targeting bispecific antibody used to treat relapsed or refractory multiple myeloma. Elranatamab works by bringing T cells into direct contact with myeloma cells, triggering T-cell–mediated destruction of the cancer.

To reduce the risk and severity of cytokine release syndrome (CRS), treatment begins with step-up doses before patients receive the full 76 mg weekly dose. Patients who achieve and maintain a response can later transition to dosing every two weeks and eventually every four weeks.

The approved regimen was developed using safety, efficacy, pharmacokinetic, and pharmacodynamic data from the MagnetisMM clinical trial program. In the pivotal MagnetisMM-3 study, which enrolled patients who had not previously received BCMA-targeted therapy, elranatamab produced an overall response rate of 61.0%. A complete response or stringent complete response was achieved by 37.4% of patients.

Responses were often durable. At 30 months, 61.0% of responding patients remained in response. Median progression-free survival was 17.2 months, and median overall survival was 24.6 months.

The most common side effects included infections (71.7%), cytokine release syndrome (58.8%), anemia (53.5%), neutropenia (46.0%), and diarrhea (42.8%). Most CRS events were low grade, with severe CRS occurring in only 0.5% of patients.

The findings support the approved step-up dosing strategy as a way to balance safety and efficacy while achieving deep and durable responses in patients with relapsed or refractory multiple myeloma.
 

"Single-Cell Identification of SPINK2 as a Putative Immune-Suppressive Target in Relapsed/Refractory Multiple Myeloma"

Source 

V.K. Singh, A. KHAN, D. Thakral, S. G, A. Gogia, R. Gupta, SINGLE-CELL IDENTIFICATION OF SPINK2 AS A PUTATIVE IMMUNE-SUPPRESSIVE TARGET IN RELAPSED/REFRACTORY MULTIPLE MYELOMA, Cytotherapy, Volume 28, Issue 5, Supplement, 2026, 102674, ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2026.102674. May 2026. 

Overview

Researchers investigated why natural killer (NK) cells become less effective as multiple myeloma progresses and identified a potential new target that may contribute to immune dysfunction in relapsed or refractory disease.

Using single-cell RNA sequencing and flow cytometry, the researchers analyzed bone marrow samples from healthy individuals, patients with newly diagnosed myeloma, and patients with relapsed or refractory multiple myeloma. They found that NK cells gradually lost their ability to mount effective immune responses as the disease advanced. In patients with relapsed disease, key genes involved in NK-cell killing activity—including PRF1, GNLY, GZMB, and NKG7—were significantly reduced.

One of the most notable findings was the identification of SPINK2, a gene that was consistently overexpressed in relapsed or refractory myeloma. Higher SPINK2 expression was strongly associated with lower NK-cell activity, suggesting that it may contribute to immune suppression within the bone marrow microenvironment.

The researchers also used computational drug-screening methods to evaluate whether SPINK2 could be targeted with small-molecule therapies. Several candidate compounds showed favorable predicted binding characteristics, supporting the feasibility of future drug development efforts.

The findings identify SPINK2 as a potential regulator of NK-cell dysfunction in relapsed or refractory multiple myeloma. Additional laboratory and clinical studies will be needed to determine whether targeting SPINK2.
 

"Enhancing patient education in multiple myeloma – The intersection of cognitive load and socio-emotional adaptation theory"

Source 

Sean N. Halpin, Enhancing patient education in multiple myeloma – The intersection of cognitive load and socio-emotional adaptation theory, Patient Education and Counseling, Volume 146, 2026, 109509, ISSN 0738-3991, https://doi.org/10.1016/j.pec.2026.109509. May 2026. 

Overview

Autologous stem cell transplant involves a complex preparation and recovery process that requires people with myeloma to absorb and act on substantial amounts of medical information, often while managing anxiety about the procedure itself. This qualitative study examined how older adults receiving transplant education actually experience and process that information, using 150 hours of ethnographic observation of nurse-patient education sessions alongside interviews with 35 patients and 7 clinicians over 18 months.

Participants frequently reported anxiety, information overload, and difficulties with health literacy — a combination that contributed to cognitive overload, where the volume and complexity of information exceeded what could be effectively processed and retained. The problem was compounded by the emotional weight of the transplant itself, which competed with cognitive bandwidth needed for learning.

Factors that helped included education tailored to individual comprehension levels rather than delivered as standardized information packages, strong caregiver involvement during education sessions, and clinicians who reinforced key concepts across multiple encounters rather than presenting information once and moving on.

The study's contribution is primarily to transplant education practice rather than disease biology or treatment outcomes. Its findings support restructuring pre-transplant education to account for cognitive load — breaking information into smaller units, prioritizing what people must know to act safely over comprehensive coverage, and building in repetition and checking for understanding. Integrating emotional support alongside information delivery, rather than treating them as separate concerns, emerges as a practical design principle.

The qualitative methodology captures experiential depth that surveys cannot, though the single-center design and relatively small interview sample limit how broadly the findings generalize across different transplant center contexts and patient populations.
 

"Monoclonal Autoimmune Gammopathies"

Source 

Torres, S., Wheeler, S. E., & Shuri MAGa: "Monoclonal Autoimmune Gammopathies." Cancers 2026, 18(11), 1770; https://doi.org/10.3390/cancers18111770

Overview

Monoclonal proteins — the abnormal immunoglobulins produced by clonal plasma cells in MGUS, smoldering myeloma, and active myeloma — have long been treated primarily as disease markers rather than functionally active molecules. This review challenges that assumption, presenting evidence that in a subset of people with plasma cell disorders, the monoclonal protein itself acts as an autoantibody, binding to the body's own tissues and causing organ damage independent of the underlying plasma cell clone's malignant behavior.

The targets of these autoreactive monoclonal proteins span multiple organ systems — neural antigens, insulin, complement components, and others — producing clinical manifestations that can resemble autoimmune, inflammatory, or idiopathic conditions. The authors present pilot data showing antinuclear antibody reactivity in 38% of IgM monoclonal gammopathy sera, suggesting the phenomenon may be more common than currently recognized. The review also highlights a bidirectional relationship: autoimmune conditions can precede and potentially contribute to the development of plasma cell disorders, and plasma cell disorders can trigger autoimmune phenomena, suggesting shared biological ground between these disease categories.

The authors propose the term monoclonal autoimmune gammopathies (MAGa) to describe this clinically distinct subset, arguing that identifying the specific self-antigen targeted by a person's monoclonal protein could inform treatment selection, predict prognosis, and potentially guide development of therapies that address both the clonal process and the autoantibody-mediated damage simultaneously.

For people with MGUS or myeloma who experience unexplained organ dysfunction — particularly neurological, renal, or dermatologic symptoms — MAGa offers a framework for understanding how their monoclonal protein itself, not just the plasma cell clone producing it, may be driving clinical harm..