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 October 2025 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 October 2025)

"Nutritional status indices on the prognosis of patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy"

Source

Xu P, Liu Y, Wang Y, Feng Q, Zhang H, Cheng H, Qi K, Xu K, Li Z. Nutritional status indices on the prognosis of patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy. Front Nutr. 2025 Oct 1;12:1654407. doi: 10.3389/fnut.2025.1654407.  

Overview

This study looked at how a patient’s nutritional status affects outcomes after CAR T-cell therapy for relapsed or refractory multiple myeloma. Researchers reviewed data from 181 patients and used two objective measures—the Controlling Nutritional Status (CONUT) score and the Prognostic Nutritional Index (PNI)—to assess each patient’s nutrition before treatment.

Patients with better nutrition, shown by a low CONUT score or a high PNI, had longer progression-free and overall survival compared to those with poorer nutrition. Although nearly all patients responded to treatment, the level of response was similar across groups. However, patients with healthier nutritional scores recovered their blood counts faster, experienced fewer long-term blood-related side effects, and showed greater CAR T-cell expansion in their bodies. The rates and severity of cytokine release syndrome and neurotoxicity were similar regardless of nutritional status.

Overall, poor nutrition—reflected by a high CONUT or low PNI—was an independent predictor of worse outcomes. The findings suggest that evaluating and potentially improving nutrition before CAR T-cell therapy could play an important role in helping multiple myeloma patients achieve better results.
 

"Current quality of life questionnaires are not relevant for assessing QOL issues in multiple myeloma patients in the era of modern therapies: results from a survey with myeloma patients and myeloma healthcare professionals"

Source

Lecat CSY, Bristogiannis S, Mehta D, Lwin Y, Land J, McCourt O, Dowling E, Correia N, Rabin NK, Xu K, Sive J, Papanikolaou X, Popat R, Lee L, McMillan A, Boyle EM, Yong K, Kyriakou C. Current quality of life questionnaires are not relevant for assessing QOL issues in multiple myeloma patients in the era of modern therapies: results from a survey with myeloma patients and myeloma healthcare professionals. Front Oncol. 2025 Oct 1;15:1656912. doi: 10.3389/fonc.2025.1656912. PMID: 41103964; PMCID: PMC12520875. 

Overview

As treatments help people with multiple myeloma live longer, maintaining quality of life has become just as important as extending survival. Yet, the questionnaires commonly used to measure quality of life were created more than two decades ago. In this survey, 224 patients and 48 healthcare professionals were asked to rate how relevant and important questions from nine established quality of life surveys were.

The results revealed a clear gap between what patients and healthcare providers consider most important. While providers found nearly all questionnaire items relevant, patients identified only some as meaningful—mainly those dealing with physical function, family and social wellbeing, pain, and fatigue.

These findings show that existing tools no longer reflect the real-world experiences of people living with multiple myeloma today. The study emphasizes the need for an updated, patient-centered questionnaire that captures the issues most relevant to modern treatments and everyday life.
 

"Monoclonal Gammopathy of Undetermined Significance"

Source

Rajkumar SV, Kumar S. Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2025 Oct 2;393(13):1315-1326. doi: 10.1056/NEJMra2412716.  

Overview

Monoclonal gammopathy of undetermined significance, or MGUS, is a common condition in which a small number of plasma cells in the bone marrow produce identical antibodies called monoclonal, or M, proteins. It affects about 5% of adults over age 50. MGUS itself is not cancer, but it can lead to serious problems. It is the main precursor to plasma-cell cancers such as multiple myeloma and Waldenström’s macroglobulinemia, and it can also cause organ damage through a group of disorders known as monoclonal gammopathy of clinical significance (MGCS).

In most people, MGUS causes no symptoms because the abnormal proteins do not attack the body. However, in some cases, these proteins can damage tissues or organs. Doctors diagnose MGUS using blood tests that measure M proteins and the ratio of free light chains, and sometimes with bone marrow biopsy. Since biopsy is invasive, it is not needed for people at low risk. MGUS is classified into three types—IgM, non-IgM, and light-chain MGUS—depending on the type of antibody involved.

The risk of MGUS turning into cancer is about 1% per year, but the lifetime risk averages around 11% over 25 years. Certain features raise this risk, including higher M protein levels, abnormal light-chain ratios, and specific antibody subtypes (IgA or IgM). People with all three risk factors have about a 58% chance of progression within 20 years, compared with only 5% for those with none. Genetic factors, reduced normal antibody levels, and a greater number of abnormal plasma cells also increase risk. New research using genomic and immune profiling may soon allow for more precise, individualized risk prediction.

Most people with MGUS do not need treatment, only regular monitoring. Doctors usually repeat blood and protein tests six months after diagnosis and then adjust follow-up frequency based on risk level. The main goal is to detect any progression to cancer or MGCS before serious complications occur. Screening the general population is not recommended, but it may be reasonable for people with a strong family history or those at higher genetic risk, including some Black individuals.

In short, MGUS is common and usually harmless, but because it can progress to life-threatening diseases, careful diagnosis and ongoing monitoring are essential to protect long-term health.
 

"Optimization of a Novel 2 + 2 BCMA × CD3 Bispecific Antibody for Minimized Cytokine Release and Potent Efficacy"

Source

Danqing Wu, Lini Huang, Gaowa Naren, Rui Zhang, Shiyong Gong, Xuan Wu, Chengbin Wu; Optimization of a Novel 2 + 2 BCMA × CD3 Bispecific Antibody for Minimized Cytokine Release and Potent Efficacy. Mol Cancer Ther 1 October 2025; 24 (10): 1600–1610. https://doi.org/10.1158/1535-7163.MCT-24-0846 

Overview

Monoclonal gammopathy of undetermined significance, or MGUS, is a common condition in which a small number of plasma cells IgM monoclonal gammopathy of undetermined significance (IgM MGUS) is a premalignant condition in which plasma cells produce an abnormal IgM antibody. While most cases of MGUS involve IgG or IgA proteins and may progress to multiple myeloma, IgM MGUS usually leads to Waldenström macroglobulinemia (WM)—a slow-growing lymphoma. Rarely, IgM MGUS can progress to a distinct and aggressive form of cancer called IgM multiple myeloma (IgM-MM). Though both WM and IgM-MM produce IgM proteins, they are biologically and clinically different, requiring different treatments.

IgM-MM is extremely rare, making up only about 0.5% to 1% of all myeloma cases. It is currently defined as a symptomatic plasma cell disorder with at least 10% clonal plasma cells in the bone marrow, the presence of IgM monoclonal protein, and either bone lesions or a specific chromosomal change known as t(11;14). This translocation helps distinguish IgM-MM from WM, which arises from earlier-stage lymphoid cells that have not undergone genetic “class switching.” However, this narrow definition can miss patients who have myeloma-like features but lack these specific criteria.

The letter describes a 54-year-old man with severe anemia and high IgM levels who was eventually diagnosed with more than 60% plasma cells in the bone marrow and a rare genetic change, t(14;20). Unlike WM, this translocation is associated with multiple myeloma. Despite lacking bone lesions or t(11;14), his results strongly suggest IgM-MM. The authors note that this is the first reported case of IgM multiple myeloma involving t(14;20), a mutation linked to high-risk disease and poor outcomes in other myeloma types.

This case highlights the need to broaden the diagnostic criteria for IgM-MM beyond the t(11;14) translocation to include other known myeloma-associated abnormalities such as t(4;14), t(6;14), t(14;16), and t(14;20). Doing so could improve diagnosis and ensure patients receive the most appropriate, myeloma-specific treatment rather than being misclassified and treated as having WM.
 

"Advanced Multicolor Flow Cytometry Method for Multiple Myeloma"

Source

Noa Ofir, Ety Rozenberg, Omri Sharabi, Miri Zektser, Ory Rouvio, Roi Gazit, Advanced Multicolor Flow Cytometry Method for Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.09.014. October 1, 2025.  

Overview

Multiple myeloma is a cancer of plasma cells in the bone marrow that remains incurable because of its genetic and cellular complexity. This study introduces a new 14-color flow cytometry (FACS) method designed to more precisely detect and visualize clonal plasma cells in patients with multiple myeloma.

Researchers developed a single-tube test using a stable mix of antibodies to improve consistency and simplify laboratory workflow. The method was tested on bone marrow samples from eight patients. Using advanced data visualization with t-SNE analysis, the team was able to clearly display the clonal diversity of plasma cells in two-dimensional plots. Each patient showed a distinct clonal pattern, revealing substantial heterogeneity both at diagnosis and at relapse.

Overall, this 14-color FACS protocol offers a practical and reliable way to identify and analyze multiple myeloma cell populations with standard lab equipment. By making complex data easier to interpret, it may help doctors tailor treatment strategies and support the development of more targeted therapies for multiple myeloma.
 

"Interdisciplinary Management of Belantamab Mafodotin-Associated Ocular Toxicity in Clinical Practice"

Source

Mattan Arazi, Aya Wattad, Hila Magen, Abraham Avigdor, Nirit Agay, Yoav Berger, Irina S. Barequet, Interdisciplinary Management of Belantamab Mafodotin-Associated Ocular Toxicity in Clinical Practice, The Ocular Surface, 2025, ISSN 1542-0124, https://doi.org/10.1016/j.jtos.2025.09.003. October 1, 2025. 

Overview

Belantamab mafodotin (BLENREP) is an antibody–drug conjugate used to treat relapsed or refractory multiple myeloma, but it can cause corneal damage related to limbal stem cell dysfunction. This study explored how the severity of eye toxicity—measured by the Keratopathy and Visual Acuity (KVA) scale—affects how doctors manage treatment in real-world clinical settings.

Researchers reviewed records of 41 patients treated with belantamab mafodotin between 2019 and 2022 at a tertiary care center. Almost all patients (93%) developed corneal toxicity, typically appearing about four weeks after starting therapy. The first changes in treatment, such as dose adjustments or breaks, occurred around seven weeks. More severe keratopathy led to earlier treatment modifications. After intervention, corneal health tended to worsen during treatment breaks but improved following dose reductions.

Most patients needed some form of treatment adjustment—most often a temporary break, followed by dose reduction or discontinuation. These findings show that eye toxicity is more common in practice than reported in clinical trials. Early and consistent eye monitoring, even at mild stages of keratopathy, is essential to prevent worsening symptoms and protect patients’ vision while maintaining therapy.
 

"Optimization of a Novel 2 + 2 BCMA × CD3 Bispecific Antibody for Minimized Cytokine Release and Potent Efficacy"

Source

Danqing Wu, Lini Huang, Gaowa Naren, Rui Zhang, Shiyong Gong, Xuan Wu, Chengbin Wu; Optimization of a Novel 2 + 2 BCMA × CD3 Bispecific Antibody for Minimized Cytokine Release and Potent Efficacy. Mol Cancer Ther 1 October 2025; 24 (10): 1600–1610. https://doi.org/10.1158/1535-7163.MCT-24-0846  

Overview

Cytokine release syndrome is a major obstacle in using bispecific T-cell engagers to treat multiple myeloma. This study describes the development of a new bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3, designed to maintain strong antitumor activity while reducing cytokine release.

Using a Fabs-in-tandem (FIT) structure, researchers engineered antibodies with different geometries, binding strengths, and valencies to test how these factors affected safety and potency. They found that both CD3 binding strength and the number of binding sites influenced how effectively the antibodies redirected T-cells to kill myeloma cells in the lab. One optimized version—called the CD3^med FIT-Ig—combined medium CD3 affinity with two binding sites for each target. It matched the tumor-killing power of a standard bispecific antibody format but triggered far less cytokine release.

In animal studies using humanized mice and monkeys, the CD3^med FIT-Ig (also known as EMB-06) maintained strong antitumor effects with minimal immune overactivation. These findings suggest that EMB-06 could offer a safer, more balanced approach to bispecific T-cell therapy for multiple myeloma, reducing cytokine-related toxicity without sacrificing efficacy.
 

"Validation of novel low-dose CT methods for quantifying bone marrow in the appendicular skeleton of patients with multiple myeloma: initial results from the [18F]FDG PET/CT sub-study of the Phase 3 GMMG-HD7 Trial"

Source

Sachpekidis, C., Hajiyianni, M., Grözinger, M. et al. Validation of novel low-dose CT methods for quantifying bone marrow in the appendicular skeleton of patients with multiple myeloma: initial results from the [18F]FDG PET/CT sub-study of the Phase 3 GMMG-HD7 Trial. Eur J Nucl Med Mol Imaging (2025). https://doi.org/10.1007/s00259-025-07599-z  October 1, 2025.   

Overview

This study explored new low-dose CT imaging methods to measure bone marrow involvement in the arms and legs of patients with newly diagnosed multiple myeloma. While PET/CT scans are standard for assessing disease activity, the role of CT-detected bone marrow changes in the appendicular skeleton has not been well understood. Researchers aimed to validate two CT-based techniques that could offer a simpler, more standardized way to quantify myeloma-related bone marrow abnormalities.

Seventy-two patients enrolled in a phase 3 clinical trial underwent whole-body PET/CT scans before and after induction therapy. Two CT-based methods—a manual and a semi-automated approach—were used to calculate bone marrow density values, which were then compared with PET scan metrics, lab results, and treatment responses. Both CT techniques showed modest but significant correlations with disease burden, including plasma cell infiltration and β2-microglobulin levels. CT measurements also aligned closely with PET findings such as SUVmax, metabolic tumor volume, and total lesion glycolysis. Patients with higher PET uptake scores had significantly elevated CT values.

After treatment, CT values and PET activity both dropped substantially, reflecting a reduction in disease burden, though CT measures did not differ between patients who were minimal residual disease (MRD)–positive or negative.

The study demonstrates that CT-based methods can complement PET imaging to evaluate bone marrow involvement in multiple myeloma. These standardized, low-dose approaches could strengthen disease monitoring and treatment assessment while using widely available imaging technology.
 

"Investigation of early mortality in the patients with newly diagnosed multiple myeloma: insights from a real-world cohort using J-CHAEGE-MM database"

Source

Tokuhira, M., Nakayama, H., Toyama, K. et al. Investigation of early mortality in the patients with newly diagnosed multiple myeloma: insights from a real-world cohort using J-CHAEGE-MM database. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-04069-y  October 2, 2025. 

Overview

Although new treatments for multiple myeloma—such as proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies—have greatly improved survival, the disease is still not curable. Researchers in Japan analyzed data from the J-CHARGE-MM database to better understand why some patients die early after starting treatment. Out of 461 total deaths, nearly one-third happened within the first year of therapy. The leading cause of death was disease progression, followed by infections like pneumonia and sepsis, which often occurred during the first few months of treatment. Heart-related problems, including heart failure and cardiac amyloidosis, were also common, and some patients died suddenly.

The study found that older age, high levels of C-reactive protein (CRP) or lactate dehydrogenase (LDH), and poor physical condition were strong predictors of early death. These results suggest that early mortality might be reduced by closely monitoring heart health and taking proactive steps to prevent infections, especially in older or frail patients with signs of inflammation or high LDH levels.
 

"Environmental and occupational risk factors associated with multiple myeloma: a multicenter, hospital-based, matched case-control study"

Source

Alnees, M., Abu Hamdeh, N., AbuAlrub, I. et al. Environmental and occupational risk factors associated with multiple myeloma: a multicenter, hospital-based, matched case-control study. BMC Public Health 25, 3308 (2025). https://doi.org/10.1186/s12889-025-24366-9  October 2, 2025. 

Overview

Multiple myeloma (MM) is a blood cancer caused by the abnormal growth of plasma cells, but little is known about how environmental or job-related exposures affect the risk of developing it or patients’ quality of life. A study in the West Bank, Palestine, explored these connections by comparing 227 patients with MM to 176 healthy individuals of similar age and background. Researchers looked at exposure to factors such as radiation, pesticides, organic solvents, and chemicals found in cosmetics, and assessed quality of life using a standardized questionnaire.

The study found that people exposed to cosmetics-related chemicals had almost three times higher odds of developing MM. These patients also reported more disease symptoms and a worse outlook on the future. In contrast, pesticide exposure was unexpectedly linked to fewer symptoms and a more positive outlook, while contact with organic solvents was associated with a poorer sense of future well-being. The findings suggest that certain chemical exposures—especially those from cosmetics and solvents—may increase MM risk and worsen how patients feel about their disease. The researchers call for better occupational health protections and more comprehensive care that addresses both the physical and emotional effects of MM.
 

"Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST"

Source

Maximilian Merz, Nico Gagelmann, Samih Smaili, Sarah Flossdorf, Sandra Sauer, Christof Scheid, Bastian von Tresckow, Gerald Wulf, Katja Weisel, Igor Wolfgang Blau, Monika Engelhardt, Ralph Wäsch, Natalie Schub, Raphael Teipel, Judith Hecker, Johannes Waldschmidt, Britta Besemer, Ben-Niklas Baermann, Simon Call, Leo Hansmann, Francis Ayuketang Ayuk, Marc S. Raab, Hermann Einsele, Uwe Platzbecker, Nicolaus Kröger; Remission conversion drives outcomes after CAR T-cell therapy for multiple myeloma: a registry analysis from the DRST. Blood 2025; 146 (14): 1677–1686. doi: https://doi.org/10.1182/blood.2025028330  October 2, 2025. 

Overview

This real-world study looked at how two CAR T-cell therapies — Abecma® (idecabtagene vicleucel, oride-cel) and Carvykti® (ciltacabtagene autoleucel, or cilta-cel) — perform in patients with relapsed or refractory multiple myeloma who had already received several treatments. Researchers analyzed data from 343 patients in Germany who had been exposed to three major drug classes before receiving one of these cellular therapies.

The results showed that cilta-cel led to better outcomes than ide-cel. Patients treated with cilta-cel had higher overall response rates (94% vs. 82%) and were more likely to reach a complete response (61% vs. 39%). At 10 months, 76% of cilta-cel patients had not seen their disease progress, compared with 47% of those who received ide-cel. Cilta-cel also helped more patients move from a partial response to a complete response, suggesting deeper and longer-lasting remissions.

Both therapies had similar safety profiles. Most patients experienced mild cytokine release syndrome, a common side effect of CAR T therapy. Neurological side effects were more frequent with cilta-cel, but overall death rates unrelated to relapse were about the same between the two groups. These findings align with results from earlier clinical trials and suggest that cilta-cel may offer longer-lasting benefits for some patients. The study highlights the importance of choosing the right CAR T therapy based on each patient’s specific situation to achieve the best outcomes.

 

"DRiving STandard-of-care CAR T cells in real-world Germany"

Source

Mark R. Dowling, Simon J. Harrison; DRiving STandard-of-care CAR T cells in real-world Germany. Blood 2025; 146 (14): 1634–1635. doi: https://doi.org/10.1182/blood.2025029932  October 2, 2025. 

Overview

A new nationwide study from Germany offers the first real-world look at how CAR T-cell therapies for multiple myeloma are performing outside of clinical trials. Researchers analyzed data from the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy, focusing on two BCMA-targeted treatments—idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). Both therapies were originally approved for patients whose myeloma had returned or stopped responding after at least three prior treatments.

The study included more than 340 patients, most of whom received ide-cel because it became available earlier in Germany. Patients had typically undergone six previous lines of treatment and were in their mid-60s. The time from cell collection to infusion was about two months, during which all patients received additional therapy to keep the disease under control—a strategy that appears to improve both safety and effectiveness.

Results showed that both CAR T therapies performed similarly to how they did in clinical trials. At 10 months, progression-free survival was 76% for cilta-cel and 47% for ide-cel. Patients who had better disease control before infusion did significantly better afterward. Side effects were consistent with earlier findings: most patients experienced mild cytokine release syndrome, and neurotoxicity was more common with cilta-cel (25%) than with ide-cel (15%). Importantly, none of the patients experienced the late-onset nerve and motor problems that had been reported in some earlier cilta-cel studies.

After adjusting for differences between the two treatment groups, cilta-cel appeared to offer longer-lasting disease control. Overall, this real-world analysis confirms that CAR T-cell therapy has been successfully integrated into standard care for myeloma in Germany’s universal health care system. It also reinforces the growing understanding that keeping the disease stable before infusion—and treating toxicities early—can lead to better outcomes. As physicians gain more experience and new bridging therapies emerge, real-world results are expected to continue improving.
 

"Characterization and Management of Cytokine Release Syndrome From the MonumenTAL-1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma"

Source

N. W. C. J. van de Donk, A. Chari, T. Martin, et al., “Characterization and Management of Cytokine Release Syndrome From the MonumenTAL-1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma,” Cancer Medicine 14, no. 19 (2025): e71276, https://doi.org/10.1002/cam4.71276.  October 2, 2025. . 

Overview

Cytokine release syndrome (CRS) is a common side effect of immune-based treatments that redirect T cells to attack myeloma cells. This study looked at CRS in patients receiving Talvey® (talquetamab), the first bispecific antibody targeting both GPRC5D and CD3, for relapsed or refractory multiple myeloma. Researchers analyzed patients who received either weekly or every-other-week doses of talquetamab, with step-up dosing to reduce the risk of side effects. Some patients had previously been treated with other T-cell–redirecting therapies, while others had not. All participants received medications like steroids and antihistamines beforehand to help prevent reactions.

Most CRS events happened during the step-up phase of treatment and were mild to moderate (grade 1 or 2). Severe (grade 3) cases were rare. About one in three patients had more than one CRS episode, but those who received the anti-inflammatory drug tocilizumab for their first event were less likely to experience CRS again. Using tocilizumab did not appear to affect how well talquetamab worked against the cancer. The risk and severity of CRS were not linked to patient characteristics such as age or prior treatment history, though certain immune markers showed possible associations.

The study found that CRS with talquetamab behaves much like CRS seen with other T-cell therapies such as teclistamab. These results suggest that doctors can manage talquetamab-related CRS using similar strategies—through careful monitoring, early recognition, and prompt treatment—to ensure patients continue benefiting safely from this therapy

"Deep learning and transformer-based feature fusion of conventional MRI for differentiating spinal osteolytic bone metastases and multiple myeloma"

Source

Haicheng Bian, Na Tian, Yuzhu Zhang, Chuanli Zhou, Xiaona Xia, Sheng Miao, Rongxin Chai, Dapeng Hao, Jiufa Cui, Deep learning and transformer-based feature fusion of conventional MRI for differentiating spinal osteolytic bone metastases and multiple myeloma, European Journal of Radiology, 2025, 112463, ISSN 0720-048X, https://doi.org/10.1016/j.ejrad.2025.112463. October 2, 2025. 

Overview

Distinguishing between spinal bone damage caused by multiple myeloma and that caused by cancer spreading from other parts of the body (osteolytic bone metastases) is difficult because both conditions look similar on scans and cause the same symptoms—such as back pain, nerve problems, and high calcium levels. While a tissue biopsy is the most accurate way to tell them apart, it is invasive and not always possible. This study set out to create a faster, non-invasive, and more reliable way to make this distinction using artificial intelligence (AI) and standard MRI scans.

Researchers analyzed MRI data from 663 patients at two hospitals—342 with bone metastases and 321 with multiple myeloma. The MRIs included three common types of images: T1-weighted, T2-weighted, and fat-suppressed T2-weighted scans. The team used deep learning, a type of AI that can recognize complex patterns in images, to build and compare several diagnostic models. They also tested an advanced “Transformer” model, which can combine information from different MRI sequences to improve accuracy.

Among the single-image models, the fat-suppressed T2 sequence performed best. However, when multiple MRI types were combined using the Transformer method, accuracy improved further. The Transformer model achieved the best overall performance, correctly identifying whether a lesion was due to myeloma or metastasis about 78% of the time. Although the differences between models were not statistically significant, the Transformer-based approach showed better consistency and greater potential clinical benefit.

This study demonstrates that AI models using standard MRI scans—especially those enhanced with Transformer-based image fusion—can accurately and non-invasively distinguish between spinal bone lesions from multiple myeloma and those from metastatic cancer. This approach could help doctors make quicker, safer diagnoses and guide treatment without relying on invasive procedures.
 

"Improvement of revised international staging system risk stratification in patients with newly diagnosed multiple myeloma using a high bone marrow plasma cell percentage: a real-world study in China"

Source

Sun X, Song M, Wang P, Zhang Z, Dai R, Shi J. Improvement of revised international staging system risk stratification in patients with newly diagnosed multiple myeloma using a high bone marrow plasma cell percentage: a real-world study in China. Front Oncol. 2025 Oct 3;15:1627653. doi: 10.3389/fonc.2025.1627653. 

Overview

Multiple myeloma is a cancer of plasma cells that varies widely in how it develops and responds to treatment. One possible indicator of how aggressive the disease may be is the percentage of plasma cells found in the bone marrow (BMPC%). However, the point at which a high BMPC% begins to significantly worsen outcomes has not been clearly defined. This study examined whether BMPC% could help improve current risk models used to predict survival in newly diagnosed multiple myeloma (NDMM).

Researchers analyzed data from 208 patients diagnosed between 2018 and 2023 who received standard treatment. Patients were divided into three groups based on their BMPC%—low, medium, and high—and their survival outcomes were tracked. The study used standard statistical models to compare how BMPC% affected progression-free and overall survival.

The results showed that patients with high BMPC% (≥50%) had much poorer overall survival than those with lower percentages. In fact, high BMPC% increased the risk of death more than fourfold compared with other groups. Among patients already classified as stage II under the Revised International Staging System (R-ISS), those with higher BMPC% had significantly shorter survival times—around 30 months compared to over 50 months or not yet reached for the other groups. These findings were confirmed through external validation.

The study found that a BMPC% of 50% or higher is an important marker of poor prognosis in newly diagnosed multiple myeloma. Adding this measure to the R-ISS system could improve how doctors predict outcomes—especially for patients in stage II, where prognosis has been harder to define accurately.

 

"Subcutaneous daratumumab plus carfilzomib and dexamethasone (D-Kd) versus carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who received previous daratumumab treatment: LYNX study"

Source

Bahlis, N. J., Zonder, J., Karlin, L., Plesner, T., Paris, L., Wrobel, T., … Facon, T. (2025). Subcutaneous daratumumab plus carfilzomib and dexamethasone (D-Kd) versus carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who received previous daratumumab treatment: LYNX study. Leukemia & Lymphoma, 1–12. https://doi.org/10.1080/10428194.2025.2561117  October 3, 2025. 

Overview

Darzalex® (daratumumab) has proven effective for treating relapsed or refractory multiple myeloma, but as more patients now receive this drug early in their treatment, doctors are asking whether it remains effective if used again later. The phase 2 LYNX study explored this question by testing whether retreating patients with daratumumab could improve outcomes.

The study enrolled 88 patients whose myeloma had returned after one to three prior treatments, including at least one that contained daratumumab. Participants were randomly assigned to receive either a combination of daratumumab, carfilzomib, and dexamethasone (D-Kd) or carfilzomib and dexamethasone alone (Kd). The main goal was to see how many patients achieved a very good partial response or better (≥VGPR).

An early analysis showed no meaningful difference between the two groups, and the study was stopped. Final results confirmed that 45.5% of patients in the D-Kd group and 40.9% in the Kd group reached ≥VGPR, showing no significant improvement with daratumumab retreatment. The combination was well tolerated, and no new safety issues were identified.

The LYNX study found that reusing daratumumab after prior exposure did not lead to stronger responses when combined with carfilzomib and dexamethasone. Future research will focus on finding better ways to use daratumumab-based regimens for patients whose myeloma has already been treated with this drug.

 

"Evaluation of cumulative radiation burden and associated risk in smouldering multiple myeloma patients monitored using recurrent whole-body low-dose CT imaging"

Source

Abissi PW, Lymperopoulou G, Agrokostas VP, Koutoulidis V, Grigoropoulos P, Terpos E, Moulopoulos LA, Fiebich M, Seimenis I. Evaluation of cumulative radiation burden and associated risk in smouldering multiple myeloma patients monitored using recurrent whole-body low-dose CT imaging. Phys Med. 2025 Oct 3;138:105173. doi: 10.1016/j.ejmp.2025.105173. Epub ahead of print. 

Overview

This study examined how much radiation exposure patients with smoldering multiple myeloma (SMM) receive from repeated whole-body low-dose CT (WBLDCT) scans, and whether that exposure could increase their risk of developing cancer. WBLDCT is often used to monitor SMM patients for signs that the disease is progressing to active multiple myeloma, but these patients may undergo several scans over time, raising concerns about cumulative radiation effects.

Researchers followed 116 SMM patients who each had between two and seven WBLDCT exams. Using specialized software, they calculated the radiation dose absorbed by different organs and estimated each patient’s lifetime risk of developing radiation-related cancer. They found that radiation exposure was highest in the thyroid, salivary glands, and eyes, with total doses in those organs sometimes exceeding 50 milligrays. The overall effective dose per scan was around 5 to 6 millisieverts, and the highest cumulative dose reached just over 40 millisieverts in patients with the most scans.

Theoretical cancer risks were small. Lung cancer and leukemia represented the highest potential risks, with overall lifetime cancer risk from these scans estimated at about 85 cases per 100,000 women and 58 per 100,000 men. This risk is roughly two orders of magnitude lower than the 10% of SMM patients who naturally progress to active disease.

The study suggests that repeated low-dose CT scans used for SMM monitoring contribute only a very small additional cancer risk. However, researchers recommend optimizing scan protocols to keep doses as low as possible and tailoring surveillance schedules to each patient’s needs, while continuing to study whether early treatment may reduce long-term risks.


 

"PD-1/TIM-3–Expressing Myeloid Cells During the Early Immune Reconstitution in Patients with Multiple Myeloma After High-Dose Chemotherapy"

Source

Serpeninova, P. A., Tyrinova, T. V., Batorov, E. V., Tikhonova, M. A., Aristova, T. A., Batorova, D. S., … Chernykh, E. R. (2025). PD-1/TIM-3–Expressing Myeloid Cells During the Early Immune Reconstitution in Patients with Multiple Myeloma After High-Dose Chemotherapy. Immunological Investigations, 1–23. https://doi.org/10.1080/08820139.2025.2568871  October 4, 2025.  

Overview

Researchers are exploring how the immune system recovers after stem cell transplantation in multiple myeloma and how certain immune “brakes” might influence that process. This study focused on two inhibitory checkpoint receptors, PD-1 and TIM-3, found on monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs)—immune cells that can dampen the body’s defense responses. The goal was to understand how these receptors contribute to early immune recovery after autologous stem cell transplant (auto-HSCT).

Using blood samples from patients, the researchers analyzed the number and activity of these immune cells before and after transplantation. They found that while overall monocyte counts returned to pre-transplant levels, M-MDSCs were significantly more abundant during engraftment—the stage when new blood cells begin to grow. More monocytes showed increased levels of TIM-3, and laboratory tests using cytokines (immune-signaling molecules) further boosted PD-1 and TIM-3 expression.

Higher levels of PD-1 and TIM-3 on monocytes and M-MDSCs were linked to lower lymphocyte counts, suggesting that these checkpoint receptors might suppress immune recovery. TIM-3 expression also correlated with an increase in regulatory T cells, which help control immune activity. After transplantation, monocytes expressing PD-1 or TIM-3 produced more IL-10—an anti-inflammatory cytokine—and less TNFα, which promotes inflammation.

The study suggests that PD-1 and TIM-3 on monocytes and M-MDSCs may play an important role in shaping immune recovery after transplant in multiple myeloma. Targeting these inhibitory pathways could eventually help improve immune balance and recovery in these patients.

 

"Comparison of stem cell mobilization methods in multiple myeloma"

Source

Yutaka Shimazu, Nobuhiro Tsukada, Masaki Maruta, Naoya Mimura, Hiroyuki Takahashi, Shinichi Kako, Yoshinobu Kanda, Akiyoshi Miwa, Emiko Sakaida, Masashi Sawa, Kaichi Nishiwaki, Shuichi Ota, Mitsuhiro Itagaki, Masatoshi Sakurai, Kazunori Imada, Shuichi Shirane, Makoto Yoshimitsu, Junya Kanda, Yoshiko Atsuta, Koji Kawamura, Comparison of stem cell mobilization methods in multiple myeloma, Cytotherapy, 2025, ISSN 1465-3249, https://doi.org/10.1016/j.jcyt.2025.09.011. October 4,2025.  

Overview

Although new drugs have greatly improved outcomes for people with multiple myeloma, autologous stem cell transplant (ASCT) remains an important part of treatment for eligible patients. Traditionally, doctors have used cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) to prepare, or “mobilize,” stem cells before transplant. More recently, the drug plerixafor (PLER) has been used with G-CSF, making the process easier to schedule and often more effective.

In this large real-world study, researchers analyzed 3,319 patients who underwent ASCT between 2019 and 2022. Of these, 743 received cyclophosphamide-based mobilization, and 2,576 were mobilized with G-CSF alone or with PLER. After two years, overall survival was higher for patients in the G-CSF group (93.2%) than for those who received cyclophosphamide (89.7%). Younger age, earlier-stage disease, good physical condition, G-CSF mobilization, and a strong treatment response before transplant were all linked to better survival.

When researchers compared patients with similar backgrounds, the G-CSF group still had a survival advantage, especially among those who hadn’t achieved a complete or very good partial response before transplant. For patients who had already responded well to therapy, both approaches produced similar outcomes.

The findings suggest that G-CSF–based mobilization, with or without plerixafor, may improve survival after transplant—particularly for patients whose disease hasn’t responded deeply before ASCT.


 

"SOHO State of the Art Updates and Next Questions | Treatment of Myeloma Early Relapse –Non CAR-T Cell"

Source

Maria Gavriatopoulou, Sotirios Manganas, Ioannis Ntanasis-Stathopoulos, Meletios-Athanasios Dimopoulos, SOHO State of the Art Updates and Next Questions | Treatment of Myeloma Early Relapse –Non CAR-T Cell, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.10.004. October 4, 2025. 

Overview

As more people with multiple myeloma develop resistance to multiple drug classes after initial treatment, finding effective therapies for early relapse has become more complex. While CAR T-cell therapy has shown powerful results and is now available for some patients at first relapse, its high cost and logistical challenges limit broad access.

This review draws on data from phase 3 clinical trials, subgroup analyses, and treatment guidelines to outline a practical, non–CAR T-cell approach for managing early relapse. The key factor in choosing second-line therapy is whether the disease has become resistant to lenalidomide or anti-CD38 monoclonal antibodies. For patients whose disease remains sensitive to lenalidomide, combinations that include an anti-CD38 antibody with an immunomodulatory drug or a proteasome inhibitor continue to offer strong results. In contrast, patients whose disease is refractory to lenalidomide benefit more from non-lenalidomide regimens. Those whose cancer no longer responds to anti-CD38 therapy must turn to other drug classes.

Because anti-CD38 antibodies are now part of most frontline regimens, resistance to this class is becoming more common. For these patients, newer options such as belantamab mafadotin (which targets BCMA), the exportin-1 inhibitor selinexor, and next-generation proteasome inhibitors are promising. In addition, bispecific antibodies targeting BCMA or GPRC5D—now in clinical trials—may soon provide even more effective treatments for early relapse.

Managing early-relapse myeloma requires personalized care that considers drug resistance, disease behavior, and patient preferences to achieve durable responses with manageable side effects.

"The Role of Radiotherapy for Patients With Multiple Myeloma in the Modern Era: A Real World Single-Centre Experience"

Source

D. Mehta, M. Gabriel, N. Adu-Poku, et al. “The Role of Radiotherapy for Patients With Multiple Myeloma in the Modern Era: A Real World Single-Centre Experience.” eJHaem 6, no. 5 (2025): e70141. https://doi.org/10.1002/jha2.70141 October 4, 2025. 

Overview

As more people with multiple myeloma develop resistance to multiple drug classes after initial treatment, finding effective therapies for early relapse has become more complex. While CAR T-cell therapy has shown powerful results and is now available for some patients at first relapse, its high cost and logistical challenges limit broad access.

This review draws on data from phase 3 clinical trials, subgroup analyses, and treatment guidelines to outline a practical, non–CAR T-cell approach for managing early relapse. The key factor in choosing second-line therapy is whether the disease has become resistant to lenalidomide or anti-CD38 monoclonal antibodies. For patients whose disease remains sensitive to lenalidomide, combinations that include an anti-CD38 antibody with an immunomodulatory drug or a proteasome inhibitor continue to offer strong results. In contrast, patients whose disease is refractory to lenalidomide benefit more from non-lenalidomide regimens. Those whose cancer no longer responds to anti-CD38 therapy must turn to other drug classes.

Because anti-CD38 antibodies are now part of most frontline regimens, resistance to this class is becoming more common. For these patients, newer options such as belantamab mafadotin (which targets BCMA), the exportin-1 inhibitor selinexor, and next-generation proteasome inhibitors are promising. In addition, bispecific antibodies targeting BCMA or GPRC5D—now in clinical trials—may soon provide even more effective treatments for early relapse.

Managing early-relapse myeloma requires personalized care that considers drug resistance, disease behavior, and patient preferences to achieve durable responses with manageable side effects.

"CAR-T cell therapy for multiple myeloma: An update on the current state and future potential"

Source

Prateek Pophali, Jacalyn Rosenblatt, David Avigan, CAR-T cell therapy for multiple myeloma: An update on the current state and future potential, Best Practice & Research Clinical Haematology, 2025, 101659, ISSN 1521-6926, https://doi.org/10.1016/j.beha.2025.101659. October 4, 2025. 

Overview

The treatment landscape for multiple myeloma has advanced rapidly over the past decade, highlighted by the introduction of CAR T-cell therapy. Two CAR-T products targeting B-cell maturation antigen (BCMA) are now FDA approved and have shown remarkable effectiveness in patients with advanced disease, with approvals recently extending to earlier relapses. These therapies can produce dramatic responses, but they come with unique side effects, including cytokine release syndrome, neurotoxicity, low antibody levels, increased infection risk, and low blood counts.

Despite impressive initial results, most patients eventually experience disease progression. This can happen due to factors such as the CAR-T cells losing activity over time, the emergence of cancer cells that no longer express the target antigen, and suppression from the tumor’s microenvironment. Researchers and clinicians are actively working to improve CAR-T therapies by enhancing their durability and reducing side effects. This review examines both approved and investigational CAR-T approaches for multiple myeloma, highlighting the ongoing efforts to optimize this transformative therapy.
 

"Stem cell boost for immune effector cell associated hematotoxicity in multiple myeloma: minimizing long-term complications and expanding post CAR T-cell therapy relapse options"

Source

Mohan, M., & Schinke, C. (2025). Stem cell boost for immune effector cell associated hematotoxicity in multiple myeloma: minimizing long-term complications and expanding post CAR T-cell therapy relapse options. Expert Review of Hematology. https://doi.org/10.1080/17474086.2025.2570335  October 4, 2025. 

Overview

Cytopenia, or low blood cell counts, is one of the most common side effects after BCMA-targeted CAR T-cell therapy for relapsed multiple myeloma. When these blood count problems are severe and last more than 30 days, they are referred to as Immune Effector Cell Associated Hematotoxicity (ICAHT). Prolonged ICAHT is serious because it increases the risk of infections, requires ongoing blood transfusions, and can lead to higher non-relapse mortality.

This review highlights the role of stem cell boost (SCB) as a treatment for prolonged ICAHT. Infusing hematopoietic stem cells into patients with persistent cytopenia can quickly and sustainably restore blood counts, reduce the need for transfusions and growth factors, and does not negatively affect survival outcomes. Risk factors for prolonged cytopenia include multiple prior lines of therapy, previous stem cell transplants, existing cytopenia before CAR-T treatment, and inflammation caused by the therapy itself.

While SCB is highly effective, its use is limited by the availability of stored stem cells, and the high cost of storage makes collecting extra cells challenging. As CAR-T therapy moves into earlier treatment lines, the incidence of prolonged cytopenia may decrease, but long-term data are still limited. For younger patients, collecting an ample number of stem cells upfront is recommended to prepare for possible severe cytopenia or future CAR-T therapies. Overall, SCB offers a valuable approach to managing ICAHT, improving both recovery and quality of life after CAR-T therapy.
 

"PATIENT AND CAREGIVER UNDERSTANDING OF MULTIPLE MYELOMA: A SCOPING REVIEW"

Source

Rachel Hunter, Valerie Jenkins, Lesley Fallowfield, John Jones, Valerie Shilling, PATIENT AND CAREGIVER UNDERSTANDING OF MULTIPLE MYELOMA: A SCOPING REVIEW, European Journal of Oncology Nursing, 2025, 102992, ISSN 1462-3889, https://doi.org/10.1016/j.ejon.2025.102992. October 4, 2025. 

Overview

Understanding multiple myeloma and its treatment can be challenging for patients and caregivers due to the complexity of the disease and the terminology used. This review looked at existing research on how well patients and informal caregivers understand MM diagnosis, prognosis, and treatment, and whether any factors influence that understanding. Researchers examined 16 studies published between 2015 and 2024, including both quantitative and qualitative research, to summarize current knowledge.

The findings suggest that patients generally have a moderate understanding of their disease, but knowledge about specific aspects, such as diagnostic tests, is often poor. There were also mismatches in perceptions of curability, with some patients believing a cure is possible despite being told otherwise by their clinicians. Both patients and caregivers felt that understanding prognosis was important and helpful, yet many reported receiving insufficient information.

The review highlights a significant gap in research focused on patient and caregiver understanding of multiple myeloma. It underscores the need for more studies on how comprehension of prognosis influences treatment decisions and quality of life. Early educational interventions could be valuable in supporting informed decision-making throughout the care pathway.

 

"Immune signatures in older patients with newly diagnosed multiple myeloma are associated with survival outcomes of first-line therapy irrespective of frailty levels"

Source

Bruins, W.S.C., Smits, F., Duetz, C., Nasserinejad, K., Groen, K., Korst, C.L.B.M., de Jonge, A.V., Rentenaar, R., Hageman, T., Cosovic, M., Eken, M., Twickler, I., Homan-Weert, P.M., Verkleij, C.P.M., Frerichs, K., Levin, M.-D., van der Spek, E., Nijhof, I.S., van Kampen, R., van de Donk, N.W.C.J., Zweegman, S. and Mutis, T. (2025), Immune signatures in older patients with newly diagnosed multiple myeloma are associated with survival outcomes of first-line therapy irrespective of frailty levels. HemaSphere, 9: e70210. https://doi.org/10.1002/hem3.70210  October 5, 2025. 

Overview

The treatment of older patients with multiple myeloma has improved with the use of CD38-targeting antibodies, but outcomes still vary widely and are not fully explained by frailty. This study investigated how the immune system influences survival in 89 newly diagnosed patients who were frail or intermediate-fit and treated with daratumumab, ixazomib, and dexamethasone in the HOVON-143 trial. Researchers analyzed lymphoid and myeloid cells in both peripheral blood and bone marrow, comparing immune profiles between frail and intermediate-fit patients. While overall immune composition was similar, frail patients had fewer naive CD4+ and CD8+ T-cells and higher levels of effector memory CD4+ T-cells and CD56bright NK cells.

Among 36 T-cell and NK-cell subsets, nine were strongly linked to progression-free survival and five to overall survival. Four subsets—naive CD8+ T-cells, CD38+CD4+ T-cells, CD56dimCD57+ NK-cells, and effector memory CD8+ T-cells—were associated with both measures, with higher counts of the first three linked to longer survival and elevated effector memory CD8+ T-cells linked to shorter survival. Using these immune markers, the team developed immune-based risk scores for progression-free and overall survival, which predicted outcomes independently of frailty, disease stage, and cytogenetic risk.

These findings highlight that a detailed analysis of the immune system can provide important insights into survival in older, non-fit patients with multiple myeloma. Baseline immune profiles may help identify patients most likely to benefit from first-line therapy and guide more personalized treatment strategies.


 

"Dose delays and treatment interruptions secondary to ocular toxicity from BCMA-directed antibody drug conjugate therapy in relapsed multiple myeloma"

Source

Matthew J Rees, Timothy T Xu, Suheil Albert Atallah-Yunes, Kenneth J C Lim, Sikander Ailawadhi, Ricardo Parrondo, Rafael Fonseca, Peter Leif Bergsagel, Suzanne Hayman, Angela Dispenzieri, Francis Buadi, David Dingli,  RahmaWarsame, Prashant Kapoor, Jithma P. Abeykoon, Morie A Gertz, Eli Muchtar, Taxiarchis Kourelis, Wilson Gonsalves, S. Vincent Rajkumar, Sanjay V Patel, Shaji Kumar, Dose delays and treatment interruptions secondary to ocular toxicity from BCMA-directed antibody drug conjugate therapy in relapsed multiple myeloma, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.10.003. October 5, 2025. 

Overview

BCMA-directed antibody-drug conjugates (ADCs) are a promising treatment for multiple myeloma, but their use has been limited by eye-related side effects. This study examined 111 patients treated with two BCMA-targeted ADCs—belantamab mafodotin (BelMaf) and MEDI2228—between 2019 and 2022. Most patients had heavily pretreated disease, with 87% triple-class refractory and 50% penta-class refractory. Treatments included BelMaf alone, BelMaf in combination therapy, or MEDI2228 alone. Overall response rates were 30% for BelMaf and 44% for MEDI2228.

The study found that each drug caused distinct eye-related toxicities. Keratopathy, including changes in the cornea and reduced visual acuity, was more common with BelMaf (59%), while photophobia and dry eyes were more frequent with MEDI2228 (49%). Four MEDI2228 patients developed mild keratopathy, all linked to dry eyes or light sensitivity. Treatment interruptions and dose adjustments occurred at similar rates for both drugs, and the main reasons for stopping therapy were disease progression or ocular toxicity.

BCMA-directed ADC therapy is effective but often limited by eye-related side effects. BelMaf and MEDI2228 have different patterns of ocular toxicity, highlighting the need for careful monitoring and potential schedule optimization to improve tolerability and outcomes.


 

"A disulfidptosis-related gene signature predicts prognosis and immune-metabolic landscape in multiple myeloma"

Source

Wang L, Wang J, Wang Y, Niu T, Zhao A. A disulfidptosis-related gene signature predicts prognosis and immune-metabolic landscape in multiple myeloma. Br J Haematol. 2025; 00: 1–13. https://doi.org/10.1111/bjh.70189  October 6, 2025. 

Overview

Pomalyst® (pomalidomide) is an important treatment for patients with relapsed or refractory multiple myeloma, but the best drug combinations are still being explored. This study compared two pomalidomide-based regimens in Asian patients: pomalidomide with dexamethasone (PD) and pomalidomide plus Cytoxan® (cyclophosphamide) and dexamethasone (PCD). A total of 122 patients were randomly assigned to either group, with most having received three prior lines of therapy. Pomalidomide and dexamethasone were given in both groups, while the PCD group also received weekly cyclophosphamide.

After a median follow-up of 13.5 months, patients in the PCD group experienced significantly longer progression-free survival, with a median of 10.9 months compared to 5.8 months in the PD group. The risk of disease progression was reduced by more than half with the addition of cyclophosphamide. Both treatment regimens had similar safety profiles, with the most common serious side effects being blood-related toxicities and pneumonia. Three deaths were considered related to treatment.

Adding cyclophosphamide to pomalidomide and dexamethasone offers a meaningful improvement in disease control for Asian patients with relapsed or refractory multiple myeloma, while maintaining a manageable safety profile.

 

"Randomized Phase 3 study of pomalidomide cyclophosphamide dexamethasone versus pomalidomide dexamethasone in relapse or refractory myeloma: an Asian Myeloma Network study (AMN003)"

Source

Kim, J.S., Song, Y., Jen, WY. et al. Randomized Phase 3 study of pomalidomide cyclophosphamide dexamethasone versus pomalidomide dexamethasone in relapse or refractory myeloma: an Asian Myeloma Network study (AMN003). Blood Cancer J. 15, 155 (2025). https://doi.org/10.1038/s41408-025-01356-z  October 6, 2025. 

Overview

Disulfidptosis, a newly identified form of cell death triggered by disulfide stress under low-glucose conditions, may have important implications in multiple myeloma, but its clinical relevance is not yet fully understood. In this study, researchers identified genes linked to disulfidptosis and used them to create a nine-gene risk signature that predicts overall survival in multiple myeloma patients. The model was tested and validated in multiple patient cohorts, showing consistent prognostic accuracy.

High-risk patients identified by this signature had tumors with proliferative activity, higher tumor mutation burden, and an immunosuppressive microenvironment characterized by neutrophils, eosinophils, and exhausted T cells. These patients also showed increased glycolysis and cystine/glutathione metabolism, suggesting a subtype of myeloma that may not respond well to immune checkpoint therapies. Laboratory experiments further confirmed that PLEC, one of the signature genes, mediates actin disulfide cross-linking during metabolic stress.

This disulfidptosis-related gene signature offers a new tool for identifying aggressive multiple myeloma, understanding its molecular and immune landscape, and guiding treatment decisions. It highlights a potential pathway for risk stratification and personalized therapy in patients with high-risk disease.

 

"Pretreatment hemoglobin, myeloma subtype, and induction regimens as independent prognostic factors for survival after autologous stem cell transplantation in multiple myeloma: A retrospective cohort study"

Source

Yong Zhang, Guangzhong Yang, Wen Gao, Wenming Chen, Pretreatment hemoglobin, myeloma subtype, and induction regimens as independent prognostic factors for survival after autologous stem cell transplantation in multiple myeloma: A retrospective cohort study, Transplant Immunology, 2025, 102305, ISSN 0966-3274, https://doi.org/10.1016/j.trim.2025.102305. October 6, 2025. 

Overview

Autologous hematopoietic stem cell transplantation (auto-HSCT) is a key treatment for eligible multiple myeloma patients, but outcomes can vary widely. This study analyzed 350 patients who underwent their first auto-HSCT to identify factors that influence survival. Researchers examined baseline hemoglobin levels, myeloma subtype, bone marrow plasma cell infiltration, and type of induction therapy to determine their impact on progression-free and overall survival.

The results showed that higher baseline hemoglobin (≥10 g/dL), IgG myeloma subtype, and use of a bortezomib-based induction regimen were independently associated with longer progression-free survival. Patients who achieved a deep response, such as complete or very good partial response, after transplantation also had better outcomes. Hemoglobin levels were found to correlate with tumor burden and kidney function, making it a simple and widely available prognostic marker.

Overall, this study highlights that pretreatment hemoglobin, myeloma subtype, and induction regimen type can help predict post-transplant outcomes. These factors can be combined with established markers like ISS stage and cytogenetics to improve risk stratification, guide treatment decisions, and set realistic expectations for patients undergoing auto-HSCT.

 

"Investigation of lncRNA expression in newly diagnosed multiple myeloma reveals a LINC01432-CELF2 axis as an inhibitor of apoptosis"

Source

Mishra, R., Thunuguntla, P., Duraiyan, D. et al. Investigation of lncRNA expression in newly diagnosed multiple myeloma reveals a LINC01432-CELF2 axis as an inhibitor of apoptosis. Oncogenesis 14, 36 (2025). https://doi.org/10.1038/s41389-025-00579-w October 6, 2025. 

Overview

Multiple myeloma is an incurable cancer of plasma cells, with thousands of new cases diagnosed each year in the United States. Despite many available treatments, nearly all patients eventually relapse, and the mechanisms driving disease progression are not fully understood. This study investigated the role of long non-coding RNAs (lncRNAs), a type of RNA that does not code for proteins but can regulate cell behavior, in multiple myeloma progression and treatment response. Researchers analyzed patient samples from newly diagnosed multiple myeloma and compared those with short progression-free survival to those with longer outcomes.

They identified 157 lncRNAs that were more active in patients with shorter progression-free survival and focused on one called LINC01432. Experiments showed that reducing LINC01432 levels triggered cell death and activated immune-related genes, while restoring its expression reversed these effects. LINC01432 works by binding to a protein called CELF2, and together they regulate genes that control immune responses, stress signaling, and cell survival.

Overall, the study highlights LINC01432 as a key regulator of multiple myeloma cell survival and a potential target for therapies aimed at overcoming resistance. Targeting this lncRNA could provide a new approach to improve outcomes in patients with aggressive disease.

 

"Practical guidance on the clinical management of ocular adverse events associated with belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Recommendations from a Japanese expert panel"

Source

Kazutaka Sunami, Tomoaki Fujisaki, Toshinari Funaki, Michiko Ichii, Shigeki Ito, Morio Matsumoto, Koh-ichi Oshima, Kazuhito Suzuki, Teruhito Takakuwa, Practical guidance on the clinical management of ocular adverse events associated with belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Recommendations from a Japanese expert panel, Japanese Journal of Clinical Oncology, 2025;, hyaf148, https://doi.org/10.1093/jjco/hyaf148  October 6, 2025. 

Overview

Multiple myeloma is a serious blood cancer, and treatment options for patients whose disease returns or does not respond to therapy are limited. Belantamab mafodotin, a targeted therapy, has shown improved progression-free survival compared with standard treatments, but it can cause eye-related side effects. To help clinicians use this therapy safely, Japanese experts in hematology, oncology, and ophthalmology developed practical guidelines for managing these ocular adverse events.

The panel focused on four main areas: recognizing eye-related side effects linked to belantamab mafodotin, adjusting treatment doses to manage these effects, promoting collaboration among specialists for optimal care, and ensuring a patient-centered approach to monitoring and management. These guidelines combine evidence from clinical trials with real-world clinical experience, giving Japanese healthcare providers clear recommendations to safely manage eye complications while treating multiple myeloma.

 

"Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses"

Source

Foster, L., Anderson, L.D., Chung, A. et al. Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses. Blood Cancer J. 15, 154 (2025). https://doi.org/10.1038/s41408-025-01355-0 October 6, 2025.

Overview

In the phase 3 AURIGA study, Darzalex® (daratumumab) combined with Revlimid® (lenalidomide), or (D-R), as maintenance therapy improved outcomes for patients with newly diagnosed multiple myeloma who were MRD-positive after transplant. A post hoc analysis examined subgroups with high-risk cytogenetic abnormalities using original, revised, and modified 2024 IMS criteria. Across all high-risk groups, D-R consistently led to higher rates of MRD-negative conversion at 12 months compared with lenalidomide alone, including in patients with ultra-high-risk disease. Trends also suggested improved progression-free survival with D-R across these subgroups. Benefits were observed regardless of age or race, and no new safety concerns were reported in older or Black patients. These findings support D-R maintenance as an effective strategy across diverse risk profiles.


 

"Ablation of CD38 in Multiple Myeloma Cells Leads to an Aggressive Phenotype in a Mouse Xenograft Model"

Source

Michael Riley Dyer, Alexander Zheleznyak, Erin N. Teubner, Julie Prior, Brad Manion, Zhenghan Jing, Amit K. Sharma, Junwei Du, Rui Tang, Mark A Fiala, John F. DiPersio, Deborah Veis, Julie O'Neal, Mikhail Y. Berezin, Monica Shokeen; Ablation of CD38 in Multiple Myeloma Cells Leads to an Aggressive Phenotype in a Mouse Xenograft Model. Blood Adv 2025; bloodadvances.2025017296. doi: https://doi.org/10.1182/bloodadvances.2025017296  October 7, 2025. 

Overview

Research in multiple myeloma (MM) shows that loss of CD38 can drive a more aggressive and treatment-resistant disease. In a study using a CD38 knockout (KO) MM cell line in mice, tumors lacking CD38 caused higher tumor burden, more bone damage, and reduced survival compared to CD38-positive tumors. These KO tumors also led to kidney metastases, increased disease markers in the blood, and elevated pro-inflammatory cytokines in the bone microenvironment. Genetic analysis revealed changes in pathways related to cell adhesion, migration, and cytokine signaling. Findings mirrored those in daratumumab-resistant MM cells, suggesting CD38 loss contributes to resistance and aggressive disease. This work highlights the importance of developing strategies to target CD38-deficient myeloma cells and identifies potential RNA signatures for therapeutic guidance.
 

"Comparison of Patient-Reported Peripheral Neuropathy Among Patients Treated With Elranatamab Versus Real-World Clinical Practice in Triple-Class Refractory Multiple Myeloma"

Source

Charalampos Charalampous et al. Comparison of Patient-Reported Peripheral Neuropathy Among Patients Treated With Elranatamab Versus Real-World Clinical Practice in Triple-Class Refractory Multiple Myeloma. JCO Oncol Adv 2, e2500009(2025). DOI:10.1200/OA-25-00009  October 7, 2025. 

Overview

In the MagnetisMM-3 trial, patients with triple-class refractory multiple myeloma treated with elranatamab reported peripheral neuropathy (PN) symptoms similar to those seen in a real-world cohort receiving standard therapies in the MagnetisMM-14 study. Patient-reported outcomes using the CIPN20 questionnaire showed comparable scores across sensory, motor, and autonomic domains at baseline and over six months, with no clinically meaningful differences between the two groups. These results indicate that elranatamab does not worsen PN symptoms and that its tolerability in terms of neuropathy is similar to commonly used regimens in routine clinical practice, supporting its use for managing heavily pretreated multiple myeloma.
 

"Is surgery for multiple myeloma-related spinal involvement associated with higher blood loss compared to spinal metastases?"

Source

Velde, J., Zijlstra, H., Pierik, R. et al. Is surgery for multiple myeloma-related spinal involvement associated with higher blood loss compared to spinal metastases? Eur Spine J (2025). https://doi.org/10.1007/s00586-025-09294-x October 7, 2025.

Overview

In the MagnetisMM-3 trial, patients with triple-class refractory multiple myeloma treated with elranatamab reported peripheral neuropathy (PN) symptoms similar to those seen in a real-world cohort receiving standard therapies in the MagnetisMM-14 study. Patient-reported outcomes using the CIPN20 questionnaire showed comparable scores across sensory, motor, and autonomic domains at baseline and over six months, with no clinically meaningful differences between the two groups. These results indicate that elranatamab does not worsen PN symptoms and that its tolerability in terms of neuropathy is similar to commonly used regimens in routine clinical practice, supporting its use for managing heavily pretreated multiple myeloma.
 

"Comparison of Patient-Reported Peripheral Neuropathy Among Patients Treated With Elranatamab Versus Real-World Clinical Practice in Triple-Class Refractory Multiple Myeloma"

Source

Charalampos Charalampous et al. Comparison of Patient-Reported Peripheral Neuropathy Among Patients Treated With Elranatamab Versus Real-World Clinical Practice in Triple-Class Refractory Multiple Myeloma. JCO Oncol Adv 2, e2500009(2025). DOI:10.1200/OA-25-00009  October 7, 2025. 

Overview

A recent study examined blood loss during spinal surgery in patients with multiple myeloma (MM) compared with those having spinal metastases (SPM). In a matched analysis of 119 MM and 119 SPM patients, MM patients experienced significantly higher bleeding, with a bleeding index of 5.6 versus 3.9 in SPM patients, and greater estimated blood loss (850 ml vs 600 ml). The bleeding risk in MM was comparable to traditionally hypervascular tumors like hormone-dependent breast cancer and renal cell carcinoma. The study found no significant differences in bleeding risk across different surgical procedures. These findings highlight that MM spinal lesions carry a higher intraoperative bleeding risk than previously recognized, which is important for surgical planning and patient management.
 

"Continuous or fixed carfilzomib, lenalidomide and dexamethasone (krd) for relapsed-refractory multiple myeloma: long-term follow-up from a multicenter, retrospective real-life survey from European myeloma network (emn) Italy"

Source

Conticello, C., Fabro, V.D., Romano, A. et al. Continous or fixed carfilzomib, lenalidomide and dexamethasone (krd) for relapsed-refractory multiple myeloma: long-term follow-up from a multicenter, retrospective real-life survey from European myeloma network (emn) Italy. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06602-9 October 7, 2025. 

Overview

A real-world study in Italy evaluated the safety and effectiveness of continuous versus fixed-cycle KRd (carfilzomib, lenalidomide, dexamethasone) in 356 patients with relapsed/refractory multiple myeloma. While the ASPIRE trial recommends 18 cycles followed by continuous Rd, some centers continued KRd beyond 18 cycles. After a median follow-up of 48.6 months, the overall response rate was 83% with 35% achieving complete responses. Median progression-free survival was 23.1 months, and overall survival was 62.9 months, exceeding ASPIRE trial outcomes. Continuous KRd did not show significant additional benefit in PFS or OS, even though patients in this group had more aggressive disease, and no extra toxicities were observed. These findings support KRd’s effectiveness but do not justify extending carfilzomib beyond 18 cycles routinely.

 

"Reduced ALDH1A1 expression in multiple myeloma cells increases resistance to daratumumab via downregulation of retinoic acid."

Source

Zheng, S., He, J., Song, X. et al. Reduced ALDH1A1 expression in multiple myeloma cells increases resistance to daratumumab via downregulation of retinoic acid. Cell. Mol. Life Sci. 82, 352 (2025). https://doi.org/10.1007/s00018-025-05891-7  October 7, 2025. 

Overview

This study explored the role of ALDH1A1 in relapsed/refractory multiple myeloma (RRMM), particularly its impact on resistance to proteasome inhibitors and sensitivity to the anti-CD38 antibody daratumumab. Researchers found that ALDH1A1 expression increased with chemotherapy resistance but was paradoxically lower in daratumumab-resistant patients. Mechanistically, ALDH1A1 boosts CD38 levels by activating retinoic acid (RA) and the RAR signaling pathway. Knocking down ALDH1A1 in myeloma cells reduced CD38, impaired daratumumab-mediated cell killing, and decreased natural killer cell activity, while RA supplementation restored these effects. In mouse models, ALDH1A1 inhibition weakened daratumumab’s antitumor activity, but RA reversed resistance. These findings suggest ALDH1A1 is a context-dependent regulator, promoting chemotherapy resistance yet enhancing daratumumab efficacy, and could guide strategies to overcome antibody resistance in RRMM.
 

"A plain language summary of the CEPHEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for people with newly diagnosed multiple myeloma who are not expected to receive a stem cell transplant"

Source

Usmani, S. Z., Facon, T., Hungria, V., Bahlis, N. J., Venner, C. P., Braunstein, M., … Zweegman, S. (2025). A plain language summary of the CEPHEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for people with newly diagnosed multiple myeloma who are not expected to receive a stem cell transplant. Future Oncology, 1–24. https://doi.org/10.1080/14796694.2025.2560134  October 7, 2025.  

Overview

The CEPHEUS study evaluated daratumumab combined with bortezomib, lenalidomide, and dexamethasone (D-VRd) versus VRd alone in adults with newly diagnosed multiple myeloma who were not candidates for stem cell transplant. After nearly five years, more participants receiving D-VRd had no detectable myeloma in their bone marrow and were more likely to be alive without disease progression compared to those on VRd. Side effects were generally consistent with known profiles, with some increased risks like infections in the D-VRd group, but no unexpected safety concerns were observed. Overall, the study shows that D-VRd improves treatment response and progression-free survival in this patient population.
 

"Treatment Outcomes of Multiple Myeloma in Developing Countries: A Systematic Review and Meta-Analysis"

Source

Almasri J, Hasan B, Tarakji Z, et al. Treatment Outcomes of Multiple Myeloma in Developing Countries: A Systematic Review and Meta-Analysis. Clinical Hematology International. 2025;7(4):1-20. doi:10.46989/ 001c.144582  October 8, 2025.  

Overview

Treatment results for multiple myeloma can vary widely between countries, especially where medical resources are limited. This study reviewed data from 37 studies conducted across developing regions, including Asia, Africa, Latin America, and Eastern Europe, to understand how treatment access and quality affect outcomes. Researchers found that newer myeloma drugs such as daratumumab, carfilzomib, and pomalidomide were not widely available in these areas.

Patients who received an autologous stem cell transplant (ASCT) lived longer than those treated with standard chemotherapy. On average, 62% of ASCT patients were still alive after up to 12 years of follow-up, and about 44% remained free from disease progression after up to 8 years. Those who received bortezomib-based treatments also had better survival than patients treated with older drugs like thalidomide or alkylating agents.

Overall, the study shows that when advanced treatments like ASCT and newer therapies are available, patients in developing countries can achieve strong outcomes. However, results varied greatly from one region to another, reflecting differences in healthcare systems, access to medicines, and medical expertise. The findings highlight the need to expand access to modern myeloma therapies worldwide to ensure more consistent care and survival for patients everywhere.
 

"Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone"

Source

Luca Bertamini, Cathelijne Fokkema, Paula Rodriguez-Otero, Mark van Duin, Evangelos Terpos, Mattia D'Agostino, Vincent H.J. van der Velden, Niels W.C.J. van de Donk, Michel Delforge, Christoph Driessen, Roman Hajek, Hermann Einsele, Annette Juul Vangsted, Diego Vieyra, Ricardo M Attar, Anna Sitthi-Amorn, Robin Carson, Fredrik Schjesvold, Pawel Robak, Meral Beksac, Andrew Spencer, Annemiek Broijl, Tom Cupedo, Philippe Moreau, Mario Boccadoro, Pieter Sonneveld; Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone. Blood 2025; blood.2025030113. doi: https://doi.org/10.1182/blood.2025030113  October 8, 2025. 

Overview

Circulating tumor cells (CTCs) are cancer cells that break away from the bone marrow and enter the bloodstream, and their presence is linked to higher risk in people newly diagnosed with multiple myeloma. This study examined the role of CTCs in transplant-eligible patients from the Phase 3 PERSEUS trial, which compared two treatment approaches: daratumumab with bortezomib, lenalidomide, and dexamethasone (D-VRd) versus the standard VRd regimen. Both groups also received a stem cell transplant and maintenance therapy.

Among 451 patients tested, 82% had detectable CTCs before starting treatment. Higher levels of CTCs were strongly linked to a greater chance of disease progression, making them an independent marker of poorer outcomes. Patients with low CTC levels responded particularly well to D-VRd, with 88% remaining progression-free after four years, compared to 74% in the VRd group. Across all patients, those with lower CTC levels were also more likely to achieve minimal residual disease (MRD) negativity, meaning no trace of cancer was detectable.

Importantly, adding daratumumab to VRd improved MRD-negativity rates for both high- and low-CTC groups, showing deeper and more sustained responses. The findings confirm that CTC levels at diagnosis are a strong predictor of outcomes, and that D-VRd therapy provides significant benefits across risk groups, helping patients achieve longer remissions and potentially better long-term survival.
 

"Genomics Define Malignant Transformation in Myeloma Precursor Conditions"

Source

Francesco Maura et al. Genomics Define Malignant Transformation in Myeloma Precursor Conditions. J Clin Oncol 0, JCO-25-01733 DOI:10.1200/JCO-25-01733  October 8, 2025.  

Overview

Multiple myeloma always develops from earlier, symptom-free conditions known as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Although these stages don’t cause symptoms, they can eventually progress to full myeloma. Until now, doctors could only diagnose this transition once organ damage occurred, because traditional lab and genetic tests couldn’t clearly separate benign from malignant disease.

This study analyzed genomic data from 374 patients with MGUS or SMM and discovered a new way to identify when these conditions have already become biologically malignant. Researchers introduced two new terms: *genomic MGUS*, for cases unlikely to progress, and *genomic MM*, for those that already share the genetic features of multiple myeloma. They found that most SMM cases are actually “genomic MM,” showing genetic changes similar to full myeloma and a much higher risk of progression, although some patients remained stable for years. In contrast, about 60% of MGUS and 10% of SMM cases had no signs of malignant transformation and did not progress during follow-up.

By combining genomic data with existing risk models, the researchers could more accurately predict which patients would develop myeloma. These results suggest that using genetic profiling to classify MGUS and SMM could transform how doctors assess risk and decide when to begin treatment—potentially allowing earlier and more personalized care.
 

"Cyanidin-3-O-glucoside-mediated reduction of regulatory T cells: a therapeutic strategy for multiple myeloma"

Source

Yip RKH, Er J, Qin L, Nguyen QH, Motyer A, Rimes JS, Light A, Mishi RD, Ling L, Anttila CJA, Tsui E, Amann-Zalcenstein D, Dowling MR, Rogers KL, Bowden R, Chen Y, Harrison SJ, Hawkins ED. Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics. Blood. 2025 Oct 9;146(15):1837-1849. doi: 10.1182/blood.2025028896. PMID: 40643106. 

Overview

Multiple myeloma grows and survives in part because of an immune-suppressing environment in the body. Regulatory T cells, or Tregs, are a major part of that environment, helping the cancer evade the immune system. Anti-CD38 drugs, such as daratumumab, are known to work partly by reducing these Tregs. This study explored whether cyanidin-3-O-glucoside (C3G)—a natural compound found in dark-colored fruits and known to inhibit CD38—could have a similar anti-myeloma effect.

Using mice with multiple myeloma, researchers found that treatment with C3G slowed tumor growth and lowered the number of Tregs in the blood without harming other immune cells like T cells, B cells, or natural killer cells. In lab experiments, C3G also reduced Tregs derived from healthy human blood, even when myeloma cells were present, and its effects increased with higher concentrations.

Genetic analyses showed that C3G’s effects on Tregs were linked to lowering the expression of the *granzyme B* (GZMB) gene and increasing *heme oxygenase 1* (HMOX1), both of which influence immune function. Overall, the findings suggest that C3G may strengthen the immune system’s ability to fight myeloma by reducing Tregs through its inhibition of CD38, pointing to its potential as a new, natural treatment strategy for the disease.
 

"Treatment of transplant-ineligible multiple myeloma."

Source

Jung, J. Treatment of transplant-ineligible multiple myeloma. Blood Res. 60, 53 (2025). https://doi.org/10.1007/s44313-025-00102-5  October 9, 2025. 

Overview

Treatment for multiple myeloma has changed dramatically for patients who are not eligible for stem cell transplant—most often older adults. Decades ago, therapy was limited to melphalan-based chemotherapy, but the introduction of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies has led to more powerful and tolerable combinations. Today, doctors use doublet, triplet, and even quadruple regimens designed not just to prolong survival but also to achieve deep, lasting responses, as measured by minimal residual disease (MRD) negativity.

One key study, SWOG S0777, found that adding bortezomib to lenalidomide and dexamethasone (VRd) improved survival compared with lenalidomide and dexamethasone (Rd) alone. However, benefits were greatest for younger patients, and older adults often needed dose adjustments. A modified version, “RVD lite,” proved to be better tolerated with fewer side effects, such as nerve damage. The introduction of the antibody daratumumab further transformed care. Studies like ALCYONE and MAIA showed that adding daratumumab to standard regimens—either with bortezomib, melphalan, and prednisone (D-VMP) or with Rd (D-Rd)—significantly improved survival and MRD-negativity rates, making D-Rd the preferred treatment for many older patients.

More recently, quadruple combinations have emerged as the new standard for fit, transplant-ineligible patients. Trials such as IMROZ and CEPHEUS showed that adding an anti-CD38 antibody (isatuximab or daratumumab) to VRd produced deeper and longer-lasting remissions than VRd alone, with manageable side effects. These regimens are now FDA-approved for use in patients up to age 80. Other studies, such as BENEFIT and GEM2017FIT, have explored similar four-drug combinations that combine multiple classes of therapy to drive high MRD-negativity rates and improve quality of life.

The field continues to evolve with new therapies on the horizon, including bispecific antibodies and CAR T-cell therapy. Early studies show these treatments can achieve impressive remission rates, even in older patients who cannot undergo transplant. At the same time, managing frailty—how a patient’s overall health affects their ability to tolerate treatment—has become a major focus. Clinical trials have shown that frailty scoring systems can guide treatment choices and predict outcomes. For example, daratumumab-based regimens have been shown to benefit even frail patients, and ongoing research is exploring steroid-sparing approaches to improve tolerability without sacrificing results.

Overall, treatment for transplant-ineligible myeloma has advanced from traditional chemotherapy to highly effective, targeted regimens that improve both survival and quality of life. With the continued development of new antibodies, bispecifics, and CAR T-cell therapies, options for older and frail patients are expected to expand even further, bringing deeper and more durable remissions within reach for a broader range of people.

 

"Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics"

Source

Yip RKH, Er J, Qin L, Nguyen QH, Motyer A, Rimes JS, Light A, Mishi RD, Ling L, Anttila CJA, Tsui E, Amann-Zalcenstein D, Dowling MR, Rogers KL, Bowden R, Chen Y, Harrison SJ, Hawkins ED. Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics. Blood. 2025 Oct 9;146(15):1837-1849. doi: 10.1182/blood.2025028896. PMID: 40643106. 

Overview

Researchers used advanced spatial transcriptomics to study how the bone marrow microenvironment supports the development of multiple myeloma. By mapping the expression of over 5,000 genes in bone marrow biopsy samples from healthy individuals and patients with premalignant or newly diagnosed myeloma, the team created a detailed picture of how plasma cells and surrounding stromal cells interact. They discovered that myeloma plasma cells often form spatially restricted clusters—distinct regions within the bone marrow that differ in cellular composition and molecular activity. Importantly, these microenvironments varied not only between patients but also within individual samples, suggesting that multiple myeloma arises and progresses in diverse, localized bone marrow niches rather than in a single, uniform environment.

 

"Unlocking myeloma's spatial world at the micrometer scale"

Source

Leo Rasche, Niels Weinhold; Unlocking myeloma's spatial world at the micrometer scale. Blood 2025; 146 (15): 1744–1746. doi: https://doi.org/10.1182/blood.2025030205  October 9, 2025. 

Overview

In this commentary, researchers discuss the work of Yip and colleagues, who used spatial transcriptomics to study how multiple myeloma (MM) cells interact with their surroundings in bone marrow biopsies. Their study showed that this advanced technology can be successfully applied to bone marrow samples and revealed that different plasma cell subgroups can shape their local microenvironments in unique ways. For instance, clusters of plasma cells with inflammatory features were often found near areas dense with T cells. The differences between these small tumor neighborhoods were greater than those seen between early disease stages and newly diagnosed MM, suggesting that local tumor behavior—rather than broad changes in the bone marrow—is a key driver of disease progression.

The commentary emphasizes that myeloma is highly complex, with multiple layers of variation across different scales—from microscopic interactions within the bone marrow to large, patient-to-patient differences across regions of the world. As the disease advances, myeloma cells can move beyond the bone marrow, forming focal or soft tissue lesions that differ greatly from the marrow environment. Studies of these lesions have shown that tumor cells and their microenvironments evolve together, supporting the idea that MM is driven by localized ecological interactions rather than uniform biological changes.

Ultimately, the findings highlight how spatial technologies are helping scientists map this heterogeneity across micro, macro, and even molecular scales. By understanding how single cells and their surrounding environments coevolve, researchers hope to uncover why some myeloma cells resist treatment or reemerge after years of dormancy—bringing us closer to predicting and preventing relapse.


 

"Mel200 or BuMel conditioning in myeloma: is there a winner?"

Source

Donna E. Reece; Mel200 or BuMel conditioning in myeloma: is there a winner?. Blood 2025; 146 (15): 1741–1742. doi: https://doi.org/10.1182/blood.2025030399  October 9, 2025. 

Overview

The phase 3 GEM12 trial compared two conditioning regimens—busulfan plus melphalan (BUMEL) versus melphalan alone (MEL200)—in newly diagnosed multiple myeloma patients receiving intensive VRd (bortezomib, lenalidomide, dexamethasone) therapy before and after autologous stem cell transplantation. After a median follow-up of 8.4 years, both groups achieved excellent long-term outcomes, with median progression-free survival (PFS) reaching 89 months for BUMEL and 73 months for MEL200. While the overall PFS difference was not statistically significant, BUMEL showed greater benefit in patients with advanced disease (ISS stage II/III) or high-risk genetic features such as t(14;16) and del(1p). The regimen was well tolerated, achieving one of the longest PFS durations reported in newly diagnosed myeloma.


 

"Laboratory diagnostic in multiple myeloma: Quantification of daratumumab blood levels using isoelectric focusing"

Source

Rieke Reiter, Christoph Mann, Wolfgang Andreas Nockher, Laboratory diagnostic in multiple myeloma: Quantification of daratumumab blood levels using isoelectric focusing, Clinica Chimica Acta, 2025, 120650, ISSN 0009-8981, https://doi.org/10.1016/j.cca.2025.120650. October 9, 2025. 

Overview

This study explored a method to measure blood levels of therapeutic monoclonal antibodies (tmAbs), like daratumumab, used to treat multiple myeloma. The researchers used isoelectric focusing (IEF), a lab technique that can distinguish therapeutic antibodies from the patient’s own proteins. They first tested a series of known daratumumab concentrations in the lab, then analyzed patient blood samples collected between one and five weeks after treatment. Results showed that daratumumab levels stabilize three to four weeks after dosing, but concentrations vary significantly across different treatment phases, including induction, consolidation, and maintenance.

The study concludes that IEF is a reliable method to measure daratumumab and potentially other therapeutic antibodies in the blood, which can help interpret unexpected treatment responses.

 

"High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial"

Source

Juan José Lahuerta, Jesús San-Miguel, Ana Jiménez-Ubieto, Rafael Alonso, Bruno Paiva, Noemí Puig, M. Teresa Cedena, Norma Carmen Gutierrez, María José Calasanz, Manuela Fernández Guijarro, Rafael Ríos Tamayo, Albert Oriol Rocafiguera, María Jesús Blanchard, Estrella Carrillo Cruz, Rafael Martínez-Martínez, Joan Bargay, Ana Sureda Balari, Javier de la Rubia, Miguel Teodoro Hernández García, Valentín Cabañas, Felipe Casado Montero, Luis Palomera Bernal, Yolanda González Montes, Joaquín Martínez-Lopez, Paula Rodriguez-Otero, Isabel Krisnik, José M. Arguiñano, María Esther Gonzalez García, Enrique M. Ocio, Javier de la Cruz, María Victoria Mateos, Laura Rosiñol, Joan Bladé; on behalf of the Spanish Myeloma Group , High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial. Blood 2025; 146 (15): 1747–1758. doi: https://doi.org/10.1182/blood.2025028313  October 9, 2025. 

Overview

In the GEM12 trial, researchers compared two chemotherapy combinations used before stem cell transplantation in people with newly diagnosed multiple myeloma: high-dose melphalan (Mel200) versus busulfan plus melphalan (BuMel). Both regimens were given after an intensive induction therapy known as “reinforced VRD” (bortezomib, lenalidomide, and dexamethasone) and followed by lenalidomide maintenance. The study found that BuMel slightly extended the time before disease progression, especially in patients with more advanced disease (ISS stages II and III) or certain high-risk genetic features, while Mel200 worked better in those with early-stage (ISS I) disease. Overall survival was similar for both groups, and side effects, including secondary cancers, were comparable.

These findings confirm that both conditioning regimens are highly effective when paired with modern induction and maintenance therapy, producing longer progression-free survival than earlier trials. However, the benefit of BuMel may be limited to certain higher-risk subgroups, and the study did not establish a clear reason to replace Mel200 as the standard option. As newer treatments such as daratumumab-based regimens and CAR T-cell therapy continue to redefine first-line care, the role of traditional transplant conditioning may evolve. For now, Mel200 remains the preferred approach for most patients, while BuMel may be considered for select high-risk cases where anti-CD38 therapies are not available.


 

"Machine learning risk stratification strategy for multiple myeloma: Insights from the EMN–HARMONY Alliance platform"

Source

Mosquera Orgueira, A., Gonzalez Perez, M.S., D'Agostino, M., Cairns, D.A., Larocca, A., Palacios, J.J.L., Wester, R., Bertsch, U., Waage, A., Zamagni, E., Pérez Míguez, C., Rojas Martínez, J.A., Mai, E.K., Crucitti, D., Salwender, H., Dall'Olio, D., Castellani, G., Piñeiro Fiel, M., Bringhen, S., Zweegman, S., Cavo, M., Iqbal, S., Hernandez Rivas, J.M., Bruno, B., Cook, G., Kaiser, M.F., Goldschmidt, H., Van De Donk, N.W.C.J., Jackson, G., San-Miguel, J.F., Boccadoro, M., Mateos, M.-V. and Sonneveld, P. (2025), Machine learning risk stratification strategy for multiple myeloma: Insights from the EMN–HARMONY Alliance platform. HemaSphere, 9: e70228. https://doi.org/10.1002/hem3.70228  October 9, 2025. 

Overview

Researchers have developed a new way to predict outcomes in people newly diagnosed with multiple myeloma using machine learning. Traditional systems that classify patients by risk—based on lab results and genetic features—don’t always accurately predict how someone’s disease will progress. In this large study of more than 14,000 patients from 16 clinical trials, scientists used machine learning to analyze many clinical and biological factors at once. They created three prediction models, including one that used just six common lab and genetic markers and another that didn’t require genetic data at all.

The models were tested and validated in multiple datasets and consistently performed better than traditional systems like the ISS and R-ISS. When researchers added information about treatment type and how well patients responded to their first therapy, predictions became even more precise. These machine learning tools can provide more personalized risk estimates, helping doctors and patients make better treatment decisions. A free online version of the calculator is available at [https://taxonomy.harmony-platform.eu/riskcalculator/](https://taxonomy.harmony-platform.eu/riskcalculator/).


 

"Multiple Myeloma Laboratory Diagnostics Made Simple: Practical Insights and Key Recommendations"

Source

Pires, A. M., Barreto, J. P., Caetano, J., Soares, M. J., Geraldes, C., Fernandes, B., Coucelo, M., Chacim, S., Coelho, H., Correia, C., Cruz, A. P., Cunha, M., Cunha, M. R., Cunha, N., Ferraz, P., Freitas, J. G., Henrique, R., Lisboa, S., Lúcio, P., ... on behalf of the Portuguese Multiple Myeloma Group. (2025). Multiple Myeloma Laboratory Diagnostics Made Simple: Practical Insights and Key Recommendations. Journal of Clinical Medicine, 14(19), 7115. https://doi.org/10.3390/jcm14197115 October 9, 2025. 

Overview

Multiple myeloma can look very different from one patient to another, which makes accurate testing and diagnosis especially important. In recent years, major advances in lab testing have helped doctors better understand how the disease works, identify high-risk patients, and choose the right treatments. Even as new, high-tech diagnostic tools are being developed, traditional lab methods still play a crucial role—especially since not every lab has access to the latest technology. However, these standard tests come with their own challenges, such as differences in how results are measured, interpreted, and standardized across labs. This review from the Portuguese Multiple Myeloma Group takes a close look at the conventional lab tests used to diagnose multiple myeloma today, offering a detailed and practical guide to their use in clinical practice.


 

"Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma"

Source

Francesco Di Meo, Francesca Albano, Annamaria Cesarano, Yunfei Wang, Brandon Kale, Kenneth Shain, Ariosto Silva, Noriyoshi Kurihara, Hirofumi Tenshin, David Jellyman, Xiaofei Song, Sasan Ghaffari, Hector Mesa, Ben Creelan, Ciara Freeman, Xiaohong Zhao, Mark B. Meads, Paulo C. Rodriguez, Silvia Marino, Frederick Locke, Patrick Hwu, David Roodman, Jorge Mansilla-Soto, Fabiana Perna, Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma, Cancer Cell, 2025, ISSN 1535-6108, https://doi.org/10.1016/j.ccell.2025.09.007. October 9, 2025. 

Overview

CAR T-cell therapy that targets BCMA has been a major step forward in treating multiple myeloma, but many patients relapse when their cancer cells lose or reduce BCMA expression. This study looked for new targets to overcome that problem. Researchers found that in patients whose tumors had little or no BCMA, another protein called SEMA4A was present at high levels. When SEMA4A was removed from myeloma cells, the cancer grew more slowly, spread less, and caused less bone damage in mice—while also helping the mice live longer. The team then created CAR T cells that target SEMA4A and tested them in the lab. These new CAR T cells expanded well, released the right immune signals, and killed myeloma cells without reacting to normal tissues. In fact, they worked better than standard BCMA CAR T cells against tumors with low BCMA levels and against disease that had started to progress after BCMA therapy. The results pave the way for a phase 1 clinical trial testing SEMA4A-targeted CAR T cells in multiple myeloma.

 

"Analysis of risk factors for major adverse cardiac events in patients with multiple myeloma"

Source

Feng Y, Zhou J, Chen S, Li S, Li T, Gao Y, Wang Q, Xu Y, Mao C, Liu S, Huang J. Analysis of risk factors for major adverse cardiac events in patients with multiple myeloma. Front Cardiovasc Med. 2025 Oct 10;12:1633543. doi: 10.3389/fcvm.2025.1633543.  October 10, 2025. 

Overview

This study looked at which factors increase the risk of serious heart problems—called major adverse cardiovascular events, or MACE—in people with multiple myeloma. Researchers reviewed records from 162 newly diagnosed patients treated at Qingdao University Hospital between 2017 and 2023. They tracked heart-related complications like heart failure, heart attacks, dangerous arrhythmias, and sudden cardiac death during treatment. About one in five patients experienced one of these events. Older age, smoking, advanced myeloma stage (ISS stage III), and treatment with anthracyclines were all linked to a higher risk of heart problems.

The team also tested an existing heart risk scoring system to see how well it worked for these patients. It was able to separate patients into low-, medium-, and high-risk groups, with heart event rates increasing steadily across those groups. However, the score was only moderately accurate at predicting who would have heart issues. Patients who did experience a MACE had shorter progression-free survival, meaning their cancer returned or worsened sooner.

The results show that certain myeloma patients—especially those who are older, smoke, have advanced disease, or receive anthracycline-based therapy—need closer heart monitoring and more personalized treatment plans. The study also highlights the importance of refining current risk tools to better guide cardio-oncology care in multiple myeloma.


 

"Automated radiomics model for prediction of therapy response and minimal residual disease from baseline MRI in multiple myeloma"

Source

Bauer, F., Hajiyianni, M., Weinhold, N. et al. Automated radiomics model for prediction of therapy response and minimal residual disease from baseline MRI in multiple myeloma. Sci Rep 15, 35400 (2025). https://doi.org/10.1038/s41598-025-13165-2  October 10, 2025. 

Overview

This study explored whether advanced MRI-based imaging could help predict how newly diagnosed multiple myeloma patients respond to treatment. Researchers analyzed MRI scans from 118 patients enrolled in the GMMG-HD7 clinical trial, using an automated method called radiomics to extract detailed data from the bone marrow. The goal was to see if this data could forecast treatment response or minimal residual disease (MRD) after initial therapy.

The team used artificial intelligence to automatically map and measure features from MRI images and then trained different computer models to predict outcomes. The best-performing model used only radiomics data and could predict strong treatment responses with moderate accuracy, reaching an area under the curve (AUROC) of 0.70. However, the models were less effective at predicting MRD status, with accuracy levels closer to chance.

Overall, the findings show that radiomics analysis of baseline MRI scans has real promise for identifying which patients are most likely to respond well to therapy—without needing invasive tests. With further refinement and larger studies, this approach could become a useful tool for personalizing multiple myeloma treatment early in the care process.

"Treatment-emergent peripheral neuropathy associated with bortezomib-based frontline regimens for multiple myeloma"

Source

Tan, C., Harper, J. S., Gautam, S., Fu, A. Z., Khare, V., Patel, S., & Kaila, S. (2025). Treatment-emergent peripheral neuropathy associated with bortezomib-based frontline regimens for multiple myeloma. Leukemia & Lymphoma, 1–9. https://doi.org/10.1080/10428194.2025.2560088  October 10, 2025. 

Overview

Bortezomib-based regimens are a common first-line treatment for multiple myeloma, but they often cause nerve damage known as treatment-emergent peripheral neuropathy (TEPN). This side effect can lead to pain, numbness, or tingling in the hands and feet, lowering patients’ quality of life and increasing medical costs. To better understand how often this happens, researchers analyzed data from a large U.S. insurance database, comparing patients who received bortezomib-based therapy with those treated with other regimens.

After carefully matching patients so the two groups were similar in age, sex, and other health factors, the study found that 24% of people treated with bortezomib developed neuropathy compared with only 9% of those on non-bortezomib treatments. The rate of new neuropathy cases was roughly three times higher in the bortezomib group, a difference that was statistically significant.

These findings confirm that bortezomib, while effective against multiple myeloma, carries a much higher risk of nerve-related side effects. Recognizing which treatments cause fewer cases of neuropathy can help doctors choose therapies that better balance disease control with long-term quality of life.

"Management of relapsed multiple myeloma: A British Society of Haematology and UK Myeloma Society guideline"

Source

Jenner M, Boyd K, Choudhuri S, Parrish C, Garg M, Stern S. Management of relapsed multiple myeloma: A British Society of Haematology and UK Myeloma Society guideline. Br J Haematol. 2025; 00: 1–33. https://doi.org/10.1111/bjh.70149  October 10, 2025. 

Overview

These new UK guidelines offer practical direction for treating patients with relapsed or refractory multiple myeloma—those whose disease has returned or stopped responding after at least one prior therapy. The goal is to help healthcare professionals make informed, individualized treatment decisions. The recommendations are meant to guide, not replace, multidisciplinary discussions that take into account each patient’s unique clinical situation, preferences, and the availability or funding of treatments in different parts of the UK.

The guideline was developed using the British Society for Haematology’s standard process and the GRADE system, which rates the strength and quality of evidence behind each recommendation. The evidence base was drawn from an extensive literature review covering studies published since 2000, with updates through late 2023 and 2024. Priority was given to large, high-quality clinical trials, while smaller studies were considered only when stronger data were lacking. The draft was reviewed by multiple professional and patient groups, including the UK Myeloma Society, Myeloma UK, and several BSH committees.

Over the past decade, treatment options for multiple myeloma have multiplied, leading to better outcomes but also more complex decision-making. While many randomized trials exist, few directly compare the wide range of modern combination regimens, making it difficult to define a single best approach. The guideline acknowledges differences in drug access and reimbursement across England, Scotland, Wales, and Northern Ireland, so it focuses on summarizing the best available evidence rather than prescribing a universal treatment sequence.

Ultimately, the message is clear: managing relapsed myeloma requires a personalized strategy. Clinicians should carefully assess disease characteristics, patient health, and prior treatment history to tailor therapy in a way that maximizes both effectiveness and quality of life.

"Association between RDW and in-hospital mortality among multiple myeloma patients: a retrospective investigation of the MIMIC-IV database"

Source

Gao, H., Gao, F., Ma, Y., Mao, Y., & Liu, K. (2025). Association between RDW and in-hospital mortality among multiple myeloma patients: a retrospective investigation of the MIMIC-IV database. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2569906  October 10, 2025 

Overview

This study examined whether a common blood test measure—red cell distribution width (RDW)—can help predict survival for multiple myeloma patients admitted to the intensive care unit. RDW reflects how much red blood cell sizes vary, and higher values often signal inflammation or poor overall health. While RDW has been linked to outcomes in multiple myeloma before, its role in critically ill patients was unclear.

Using data from the large MIMIC-IV hospital database, researchers reviewed records of multiple myeloma patients admitted to the ICU for the first time. They analyzed each patient’s highest RDW value after admission and compared it with their hospital outcomes. After adjusting for multiple health and treatment factors, the results showed that higher RDW levels were strongly and independently associated with a greater risk of dying in the hospital. The analysis also showed that this relationship was linear—the higher the RDW, the higher the risk.

In short, elevated RDW appears to be a reliable warning sign of worse outcomes in multiple myeloma patients needing intensive care. The findings suggest that ICU teams should pay close attention to RDW as a simple, readily available marker to help identify high-risk patients early and guide care decisions.

"Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition"

Source

Takahiro Kamiya, Masahiko Ajiro, Motohiko Oshima, Shuhei Koide, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Akiho Tsuchiya, Satoshi Kaito, Naoki Itokawa, Ryoji Ito, Kiyoshi Yamaguchi, Yoichi Furukawa, Bahityar Rahmutulla, Atsushi Kaneda, Takayuki Shimizu, Noriko Doki, Taku Kikuchi, Nobuhiro Tsukada, Masayuki Yamashita, Shinichiro Okamoto, Akihide Yoshimi, Keisuke Kataoka, Atsushi Iwama; Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-24-0340  October 10, 2025. 

Overview

This study set out to better understand why some multiple myeloma cells resist treatment. Using single-cell RNA sequencing combined with VDJ-targeted sequencing, researchers analyzed highly purified myeloma cells taken directly from patients’ bone marrow. This detailed approach revealed that myeloma cells are not all the same—they vary widely in gene activity, surface markers, and behavior. Among these differences, the team discovered a small group of cells lacking the usual CD138 marker that appeared to drive therapy resistance.

Further experiments showed that these CD138-negative cells had major changes in how their genes were regulated, including abnormal RNA splicing—the process that helps cells turn genes into functional proteins. Using CRISPR gene-editing tools, researchers found that these resistant cells were especially sensitive to drugs or genetic changes that disrupted the splicing process. One splicing-related protein, RBM39, was found to be overactive in resistant cells and played a key role in faulty splicing. When RBM39 was blocked, either genetically or with targeted drugs, the myeloma cells died.

This study uncovered a hidden population of therapy-resistant myeloma cells and showed that their survival depends on abnormal RNA splicing. Targeting this pathway—particularly through RBM39 inhibition—could open up a new way to treat patients whose disease no longer responds to standard therapies.

"Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma"

Source

Li, Q., Ma, C., Zuo, L. et al. Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma. J Transl Med 23, 1079 (2025). https://doi.org/10.1186/s12967-025-07065-2  October 10, 2025. 

Overview

This study investigated the role of DNA polymerase theta (Polθ) in multiple myeloma and its potential as a new treatment target. Polθ is a key enzyme in a backup DNA repair process called microhomology-mediated end joining (MMEJ), which cells use to fix damaged DNA when other repair pathways fail. Because cancer cells often rely on this mechanism to survive genetic stress, the researchers wanted to see whether blocking Polθ could make myeloma cells more vulnerable to treatment.

Analyzing samples from 124 patients, the team found that Polθ levels were much higher in multiple myeloma cells than in normal cells, and that increased expression was linked to more advanced disease and poorer outcomes. Laboratory experiments showed that when Polθ was blocked—either by gene silencing or with a specific inhibitor—myeloma cells became less stable genetically and stopped growing.

The researchers also tested how Polθ interacts with melphalan, a chemotherapy drug commonly used in myeloma. After melphalan exposure, myeloma cells ramped up Polθ activity to repair the DNA damage it caused. But when the Polθ inhibitor was added, the cancer cells could no longer repair their DNA effectively, leading to severe damage, failed cell division, and cell death.

The findings identify Polθ as both a marker of aggressive disease and a potential weak point in myeloma cells. Targeting Polθ—especially in combination with drugs like melphalan—could offer a promising new strategy to overcome treatment resistance and improve patient outcomes.
 

"Predictors of Delayed Responses to Teclistamab in Multiple Myeloma After Initial Non-Response"

Source

Overview

This letter reports the first detailed analysis of multiple myeloma patients who did not respond to teclistamab—a bispecific antibody targeting BCMA—after the first month of treatment. In most trials, responses to these therapies appear around day 30 to 40, which makes this early timepoint important for deciding whether to continue or change treatment. Because bispecific antibodies can cause serious side effects such as infections, immune cell exhaustion, and high treatment costs, identifying patients who are unlikely to benefit from continued therapy is essential.

The authors analyzed real-world data from 351 U.S. patients treated with teclistamab. By day 30, 55% had not achieved at least a partial response. Among those initial non-responders, nearly one in four later showed a delayed response by day 90, while the rest either continued not responding or died. Two key factors predicted who would later respond: having a minimal response (rather than stable or progressive disease) at day 30, and having a higher absolute lymphocyte count (ALC) at that time. Patients with minimal response were much more likely to improve, regardless of ALC. In contrast, patients with progressive disease rarely converted to a response, and those with stable disease plus low ALC had a much lower chance of improvement.

Importantly, the study found that patients who responded late had the same progression-free survival as those who responded early, suggesting that continuing teclistamab beyond day 30 can pay off for selected patients. The results support a simple, two-step framework for decision-making: continue treatment for patients with at least a minimal response or adequate lymphocyte counts, but consider alternative strategies for those with progression or lymphopenia.

The authors acknowledge the limitations of their retrospective design and missing data but emphasize that these findings provide practical guidance for clinicians. Measuring ALC at day 30 could serve as a real-world, accessible marker of immune health to help decide whether to continue or adjust therapy. Future research should refine this approach with more detailed immune profiling to better identify patients likely to benefit from ongoing bispecific antibody treatment despite early non-response.
 

"Infection events in patients with newly diagnosed multiple myeloma with anti-CD38 monoclonal antibody-based first line regimens: A multicentric Italian experience"

Source

Rago, A., Fioritoni, F., Liberatore, C. et al. Infection events in patients with newly diagnosed multiple myeloma with anti-CD38 monoclonal antibody-based first line regimens: A multicentric Italian experience. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06645-y October 11, 2025. 

Overview

A new study looked at how often infections occur in people newly diagnosed with multiple myeloma (NDMM) who are treated with modern drug combinations that include daratumumab (Dara). Infections are a serious problem for people with NDMM and cause nearly half of early deaths, especially in older patients and during the first few months of treatment. While newer therapies—like anti-CD38 antibodies, proteasome inhibitors, and immunomodulatory drugs—have helped patients live longer, they can also make people more likely to get infections.

Researchers from the European Myeloma Network Italy (EMN-I) reviewed the medical records of 472 patients who received Dara-based treatments between 2020 and 2023. About one in three patients (31.3%) had an infection during therapy. When the team compared different treatment combinations, they found no major differences in how often or how severe infections were between groups. Adding Dara during the first phase of treatment did not appear to increase infection risk overall. There was a small trend toward infections happening earlier in the group treated with the D-VTD combination, but this difference was not statistically significant.

The study suggests that while infections remain common in people with NDMM, using Dara as part of initial treatment does not make them more frequent or severe. The authors note that more research is needed to better understand what puts certain patients at higher risk and how preventive treatments might help.
 

"Perspectives on anti-BCMA bispecific antibodies use in multiple myeloma–experience from Asian countries"

Source

Cinnie Soekojo, Shimin Jasmine Chung, Ming-Tao Tsai, Wenming Chen, Jeffrey Huang, Jin Seok Kim, Dong-Gun Lee, Chang Ki Min, Kazuhito Suzuki, Subramanian Swaminathan, Hiroyuki Takamatsu, Daryl Tan, Uday Yanamandra, Chandramouli Nagarajan, Wee Joo Chng, Perspectives on anti-BCMA bispecific antibodies use in multiple myeloma–experience from Asian countries, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.10.005. October 11, 2025. 

Overview

Treatment options for people with relapsed or refractory multiple myeloma—especially those who have already tried many therapies—are rapidly changing thanks to a new class of drugs called bispecific antibodies (BsAbs). These treatments target BCMA, a protein found on myeloma cells, and have brought new hope to patients whose disease no longer responds to standard therapies.

Across Asia, doctors have been using BCMA-targeted BsAbs through clinical trials, compassionate use programs, and early commercial access. While these treatments have shown strong and consistent results, access remains uneven, and doctors face challenges bringing them into everyday practice. Experts from several Asian countries came together to discuss their experiences and found that, while BsAbs are highly effective, questions remain about how long the responses last and how best to manage side effects such as infections and other toxicities.

The group agreed that more research is needed to understand which patients benefit most and how to combine or sequence these treatments for the best results. Their insights will help shape future clinical guidelines and provide practical strategies for doctors to safely and effectively use these powerful new therapies in real-world settings. 

"The Outcomes of Newly Diagnosed Multiple Myeloma Patients With Concurrent or Previous Solid Tumor History"
 

Source

Yaşa Gül Mutlu, Şerife Emre Yüksel, Buse Güleç, İstemi Serin, Eren Arslan Davulcu, Gülçin Miyase Sönmez, Serkan Güven, Süreyya Yiğit Kaya, Senem Maral, Muzaffer Keklik, Ayşe Salihoğlu, Tugba Cetintepe, Güldane Seval Cengiz, Ömür Gökmen Sevindik, THE OUTCOMES OF NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS WITH CONCURRENT OR PREVIOUS SOLID TUMOR HISTORY, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.10.006. October 12, 2025.  

Overview

Patients newly diagnosed with multiple myeloma (NDMM) who also have a history of solid tumors—such as breast, lung, colon, or prostate cancer—often face more complex care decisions. This study looked at 41 people with NDMM who either had another cancer at the same time (synchronous) or had been treated for one in the past (prior). The goal was to understand how having both conditions affects treatment and survival outcomes.

The average patient was 66 years old, and most were men. Among these patients, breast cancer was the most common previous or coexisting tumor, followed by lung, colon, and prostate cancers. The study found that extramedullary disease—when myeloma spreads outside the bone marrow—occurred only in patients whose solid tumor was diagnosed around the same time as their myeloma. These patients were also less likely to undergo stem cell transplantation and were less often prescribed lenalidomide as maintenance therapy, suggesting doctors may have been more cautious due to the dual cancer diagnosis.

Overall, about 17% of patients died from myeloma-related causes, and the median overall survival was four years. There was no significant difference in survival between those with concurrent cancers and those whose solid tumors were diagnosed earlier. The findings suggest that having both myeloma and another cancer can complicate treatment choices, especially when the cancers appear together. The researchers emphasize the importance of close collaboration among specialists and tailored treatment plans. They also recommend that when myeloma spreads outside the bone marrow, doctors should consider the possibility of another underlying cancer.
 

"Total tumor apparent diffusion coefficient histogram analysis of whole-body DWI-MRI for prognostic stratification in patients with R-ISS stage II multiple myeloma"
 

Source

Junde Zhou, Qin Wang, Yanting Liu, Lu Zhang, Jiao Li, Shuo Li, Dong Liu, Jinxia Zhu, Robert Grimm, Alto Stemmer, Shuang Xia, Wenyang Huang, Sheng Xie, Haibo Zhang, Jian Li, Huadan Xue, Zhengyu Jin, Total tumor apparent diffusion coefficient histogram analysis of whole-body DWI-MRI for prognostic stratification in patients with R-ISS stage II multiple myeloma, Magnetic Resonance Imaging, 2025, 110536, ISSN 0730-725X, https://doi.org/10.1016 j.mri.2025.110536. October 14, 2025.   

Overview

This study looked at whether advanced MRI imaging could help predict outcomes for people with stage II multiple myeloma, as classified by the Revised International Staging System (R-ISS II). Researchers focused on a specific MRI measurement called the total tumor apparent diffusion coefficient (ttADC), which reflects how water moves within tumor tissue and can indicate how aggressive the cancer is.

The study reviewed scans from 61 patients who had whole-body MRI before starting treatment. Using special imaging software, the team analyzed each patient’s ttADC values and compared them with overall survival (OS) and progression-free survival (PFS) over an average follow-up period of about six and a half years.

Results showed that patients with higher median ttADC values had a greater risk of death during the study period. Specifically, those with ttADC values at or above 0.620 × 10⁻³ mm²/s were more than twice as likely to die compared to those with lower values. However, ttADC levels did not appear to affect how long patients lived without disease progression.

The findings suggest that ttADC measurements from whole-body MRI could serve as a useful imaging biomarker to help doctors better predict survival in patients with R-ISS II multiple myeloma and refine how these patients are grouped for treatment planning and prognosis.
 

"Efficacy of Bone-Modifying Agents in Preventing Vertebral Complications of Multiple Myeloma: A Systematic Review and Meta-Analysis"

Source

Zsombor T. Gal, Ethan A. Wetzel, Brian V. Nahed, Philip J. Saylor, Joshua A. Hirsch, Ariel E. Marciscano, Noopur S. Raje, Daniel G. Tobert, Andrew J. Yee, Ganesh M. Shankar, Efficacy of Bone-Modifying Agents in Preventing Vertebral Complications of Multiple Myeloma: A Systematic Review and Meta-Analysis, The Spine Journal, 2025, ISSN 1529-9430, https://doi.org/10.1016/j.spinee.2025.10.018. October 14, 2025. 

Overview

Bone disease is one of the most serious complications of multiple myeloma, often leading to painful and disabling spine problems such as vertebral fractures and spinal cord compression. To help prevent these complications, patients are often prescribed bone-strengthening drugs called bone-modifying agents (BMAs). These include bisphosphonates and denosumab. However, it has not been clear how well these treatments actually protect the spine.

In this study, researchers reviewed all available clinical trials to determine how effective BMAs are in reducing the risk of spinal complications in adults with multiple myeloma. After analyzing data from 11 randomized trials, they found that bisphosphonates—especially a drug called zoledronate—significantly lowered the risk of vertebral fractures. Overall, bisphosphonate treatment reduced the chance of fractures by about 28%, and zoledronate was linked to a 64% lower risk compared to no treatment or a placebo.

The review did not include studies on denosumab, and there was not enough data to determine whether BMAs reduce the risk of spinal cord compression. While these results suggest that bisphosphonates, particularly zoledronate, are effective in protecting the spine in clinical trial settings, more research is needed to understand how these benefits translate to real-world patients and to explore the role of other bone-modifying drugs.

 

"Dual targeting of G9a and DNMTs induces antitumor effects in multiple myeloma"

Source

Patrick Nylund, Berta Garrido-Zabala, Stefania Iliana Tziola, Tabassom Mohajershojai, Hanna Berglund, Catharina Muylaert, Lien Ann Van Hemelrijck, Alba Atienza Párraga, Louella Vasquez, Jim Jacob, Eric Bergquist, José Ignacio Martín-Subero, Fredrik Öberg, Torbjörn Karlsson, Marika Nestor, Elke De Bruyne, Antonia Kalushkova, Helena Jernberg Wiklund; Dual targeting of G9a and DNMTs induces antitumor effects in multiple myeloma. Blood Adv 2025; 9 (19): 4825–4841. doi: https://doi.org/10.1182/bloodadvances.2023010571 October 14, 2025. 

Overview

Multiple myeloma remains a difficult disease to treat, even with today’s advanced therapies. This study explored how certain “epigenetic” changes—chemical modifications that turn genes on or off without altering DNA—help myeloma cells grow and resist treatment. Researchers focused on two key enzymes, G9a and DNA methyltransferases (DNMTs), which are both overactive in multiple myeloma and linked to worse patient outcomes.

By studying myeloma cells in the lab, the team found that G9a and DNMTs work together to silence tumor-suppressor genes that would normally help control cancer growth. When both enzymes were blocked with targeted drugs, myeloma cells became less viable and were more likely to die. This dual treatment also lowered the levels of several cancer-promoting proteins, including IRF4, XBP1, and MYC.

The researchers then tested the combination therapy in mice with human myeloma tumors and found that the two drugs—A366 (a G9a inhibitor) and decitabine (a DNMT inhibitor)—worked together to shrink tumors significantly. These findings reveal how G9a and DNMTs cooperate to drive myeloma progression and suggest that blocking both pathways could offer a promising new treatment strategy for multiple myeloma.


 

"Timing Genomic Antigen Loss in Multiple Myeloma Treated with T Cell–Redirecting Immunotherapies"

Source

Marios Papadimitriou, Sungwoo Ahn, Benjamin T. Diamond, Holly Lee, John B. McIntyre, Marietta Truger, Michael A. Durante, Bachisio Ziccheddu, Katalin Osz, Ola Landgren, Leo Rasche, Nizar J. Bahlis, Paola Neri, Francesco Maura; Timing Genomic Antigen Loss in Multiple Myeloma Treated with T Cell–Redirecting Immunotherapies. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-25-0005 October 13, 2025 

Overview

This study explored how multiple myeloma cells develop resistance to advanced immunotherapies such as CAR T-cell therapy and bispecific T-cell engagers, which target proteins like BCMA and GPRC5D on the surface of myeloma cells. Researchers found that resistance often occurs when cancer cells lose these target proteins through genetic changes—a process known as “antigen loss.”

Using whole-genome sequencing, the team determined that these mutations were not present before treatment but developed after patients received CAR T-cell or T-cell engager therapy. Follow-up testing confirmed that these resistance-related mutations appeared shortly before the disease relapsed.

Among newly diagnosed patients, such genetic losses were rare, suggesting that routine genetic screening before treatment may not help predict resistance. However, the findings highlight the need for close monitoring during therapy to detect emerging mutations early and guide future treatment decisions.


 

"Central nervous system myeloma: Pathogenesis, diagnostic challenges, and practical management strategies"

Source

Katodritou, E. and Terpos, E. (2025), Central nervous system myeloma: Pathogenesis, diagnostic challenges, and practical management strategies. HemaSphere, 9: e70213. https://doi.org/10.1002/hem3.70213  October 13, 2025. 

Overview

Central nervous system multiple myeloma (CNS-MM) is a rare and aggressive form of myeloma that spreads to the brain or spinal cord. Because it is uncommon, doctors still know little about its causes, risk factors, and the best ways to treat it. This review highlights the major challenges in diagnosing and managing CNS-MM and offers practical guidance for clinicians caring for patients at risk.

Patients with certain high-risk features—such as advanced-stage myeloma, high LDH levels, or high-risk genetic changes—are more likely to develop CNS involvement. Those with circulating plasma cells, soft-tissue disease, or primary plasma cell leukemia (PCL) are also at elevated risk. For patients showing neurological symptoms, a lumbar puncture and MRI of the brain and spine are recommended to confirm or rule out CNS disease. Early, accurate diagnosis is key to starting effective treatment as soon as possible.

Treatment for CNS-MM is complex and must address both the brain involvement and the underlying myeloma. A combination of systemic therapies that can cross the blood-brain barrier—such as regimens including daratumumab and pomalidomide—is recommended. In certain cases, intrathecal chemotherapy or targeted radiation may be used, especially for patients with localized brain lesions. Emerging therapies, including T-cell receptor (TCR)–based treatments, show promise for patients who do not respond to other approaches.

Despite recent advances in myeloma therapy, CNS-MM continues to carry a poor prognosis. The authors emphasize the urgent need for larger clinical studies and new treatments that can reach the central nervous system more effectively. Understanding who is at highest risk and how to intervene early could eventually improve survival and quality of life for patients facing this difficult complication of multiple myeloma.

 

"European Myeloma Network Group Consensus Statement on the use of next-generation sequencing for prognostic stratification of newly diagnosed multiple myeloma."

Source

Bolli, N., D'Agostino, M., Bagratuni, T., Boccadoro, M., Cavo, M., Driessen, C., Einsele, H., Engelhardt, M., Gay, F., Gutiérrez, N.C., Hájek, R., Holien, T., João, C., Kaiser, M., Kortüm, K.M., Leypoldt, L., Moreau, P., Musto, P., Ocio, E.M., Raab, M.S., Rasche, L., Schjesvold, F., Sevcikova, T., Terpos, E., Touzeau, C., Van de Donk, N.W.C.J., van Duin, M., Weisel, K., Zamagni, E., Cupedo, T., Sonneveld, P. and Terragna, C. (2025), European Myeloma Network Group Consensus Statement on the use of next-generation sequencing for prognostic stratification of newly diagnosed multiple myeloma. HemaSphere, 9: e70216. https://doi.org/10.1002/hem3.70216  October 13, 2025. 

Overview

As scientists learn more about the genetic factors that influence multiple myeloma, they are exploring new tools to better predict outcomes and guide treatment. This paper from the European Myeloma Network (EMN) examined whether next-generation sequencing (NGS)—a powerful method that can analyze many genes at once—could complement or eventually replace the standard genetic test known as fluorescence in situ hybridization (FISH), which is currently used at diagnosis.

Through a structured consensus process, clinical and laboratory experts reviewed the latest research and technology to create practical recommendations for using NGS in myeloma care. They concluded that while NGS offers great promise for identifying important genetic markers and refining risk assessment, it should currently be used alongside, not instead of, FISH.

The panel recommended offering NGS testing to patients who are fit enough to receive modern, intensive therapies such as triplet or quadruplet regimens. They also advised repeating NGS at relapse in the future, especially as new targeted drugs become available that rely on genetic information to guide treatment.

Although NGS can provide a more complete genetic picture than FISH, challenges like cost, test availability, and integration into clinical workflows remain. This consensus serves as an important step toward making NGS a standard part of multiple myeloma diagnosis and treatment planning.

 

"Updated guidelines in the treatment of myeloma bone disease in 2025: consensus statement by the Medical and Scientific advisory group of Australia (MSAG) to Myeloma Australia"

Source

Yong, A., Vandyke, K., Augustson, B., McCaughan, G., Talaulikar, D., Szabo, F., … Lee, C. H. (2025). Updated guidelines in the treatment of myeloma bone disease in 2025: consensus statement by the Medical and Scientific advisory group of Australia (MSAG) to myeloma australia. Expert Review of Hematology. https://doi.org/10.1080/17474086.2025.2574716. October 13, 2025. 

Overview

Bone disease is one of the most common and serious complications of multiple myeloma, often leading to painful bone damage and fractures. For years, doctors have used drugs called bisphosphonates—such as zoledronic acid and pamidronate—to prevent and treat this bone destruction.

This review analyzed nearly 30 years of research, focusing on high-quality clinical trials that compared different bone-protective treatments in multiple myeloma. Based on the findings, experts now recommend that most patients receive bisphosphonate therapy for about two years, with longer dosing intervals if the disease remains stable.

The review also highlights denosumab, a newer bone-protective drug that works differently from bisphosphonates. Denosumab blocks a protein called RANKL, which drives bone breakdown, and has been shown to be just as effective as zoledronic acid. It may be a better option for patients with kidney problems, since it is not cleared through the kidneys.

Looking ahead, researchers are studying how bone turnover markers—measurements of bone activity—could help doctors tailor treatment more precisely. They are also exploring new therapies that stimulate bone formation, which could further protect and strengthen bones in people living with multiple myeloma.

 

"Targeting Siglec–sialic acid checkpoint to reverse immune dysfunction mediated by plasmacytoid dendritic cells in myeloma"

Source

Arghya Ray, Leutz Buon, Xueping Wan, Ting Du, Yan Song, Sindhu C. Pillai, Md Abu Musa, Teng Fang, Minxing Wang, Kenneth C. Anderson; Targeting Siglec–sialic acid checkpoint to reverse immune dysfunction mediated by plasmacytoid dendritic cells in myeloma. Blood Adv 2025; 9 (19): 5085–5090. doi: https://doi.org/10.1182/bloodadvances.2025015980  October 14, 2025. 

Overview

Researchers have discovered a new way that immune cells may help multiple myeloma (MM) survive and resist treatment—and a possible strategy to reverse it. In this study, scientists examined bone marrow samples from patients with relapsed or refractory myeloma and found that certain immune cells called plasmacytoid dendritic cells (pDCs) were behaving abnormally. These cells normally help activate the immune system, but in myeloma, they appear to support tumor growth instead.

Using advanced single-cell RNA sequencing, the team found that myeloma-related pDCs showed high activity in a process called **sialylation**, where sugar molecules (sialic acids) attach to proteins on the cell surface. This process helps tumor cells hide from the immune system, acting like an “off switch” for immune attack—similar to how PD-1 and PD-L1 work in other cancers. The researchers also identified a key molecule, **Siglec-6**, that is highly active on these pDCs in myeloma.

When they used drugs to block the sialylation pathway or to target Siglec-6 directly, the immune system “woke up.” The pDCs became more active, T cells began attacking cancer cells again, and the number of myeloma cells dropped in lab experiments. Blocking Siglec-6 also restored the activity of natural killer (NK) cells—another important type of immune cell that fights cancer.

These findings suggest that **targeting the Siglec/sialic acid pathway** could be a promising new way to boost the immune system in multiple myeloma. While this research is still in early stages, it offers hope for future therapies that could help overcome immune suppression and improve treatment response in patients with relapsed or resistant myeloma.  

"Joint modeling of progression-free survival and patient-reported outcomes to evaluate the association between disease progression and symptoms among patients with relapsed/refractory multiple myeloma"

Source

Knop, S., Einsele, H., Dhanda, D. et al. Joint modeling of progression-free survival and patient-reported outcomes to evaluate the association between disease progression and symptoms among patients with relapsed/refractory multiple myeloma. J Patient Rep Outcomes 9, 118 (2025). https://doi.org/10.1186/s41687-025-00943-9 October 14, 2025. 

Overview

This study explored whether worsening symptoms reported by patients with relapsed or refractory multiple myeloma (RRMM) could predict shorter progression-free survival (PFS). Researchers focused on pain and fatigue—the two most common symptoms affecting patients—using data from seven RRMM clinical trials.

By linking changes in patient-reported quality-of-life scores to disease outcomes, the study found that increases in pain and fatigue scores were consistently associated with a higher risk of disease progression or death. Specifically, worsening symptoms were tied to about a 10% greater hazard of progression events across trials.

These findings suggest that patient-reported pain and fatigue may serve as early indicators of disease worsening in RRMM, reinforcing the importance of monitoring symptoms alongside traditional clinical measures.
 

"Long non-coding RNA FEZF1-AS1 suppresses ferroptosis in multiple myeloma cells through KIAA1429-mediated m6A modification"

Source

Su, Q., Liu, W., Wang, P. et al. Long non-coding RNA FEZF1-AS1 suppresses ferroptosis in multiple myeloma cells through KIAA1429-mediated m6A modification. Human Cell 38, 178 (2025). https://doi.org/10.1007/s13577-025-01274-z  October 14, 2025. 

Overview

This study examined how the long non-coding RNA FEZF1-AS1 helps multiple myeloma (MM) cells avoid a type of cell death called ferroptosis, which is triggered by iron and oxidative stress. Researchers found that FEZF1-AS1 is highly active in MM cells and works through a molecular chain involving several proteins—IGF2BP3, KIAA1429 (VIRMA), and OTUB1—to maintain cell survival.

Specifically, FEZF1-AS1 binds to IGF2BP3, which stabilizes KIAA1429. KIAA1429 then modifies OTUB1 through m6A RNA methylation, increasing its expression. OTUB1, in turn, prevents ferroptosis by stabilizing SLC7A11, a key protein that blocks oxidative damage.

When FEZF1-AS1 was silenced, MM cells became less viable and more prone to ferroptosis. However, restoring KIAA1429 or OTUB1 reversed this effect. These findings suggest that the FEZF1-AS1/KIAA1429/OTUB1 pathway plays a crucial role in MM cell survival and could serve as a potential therapeutic target.

"A First-In-Human Phase 1 Study of a Novel BCMA×CD3 Bispecific T Cell Engager EMB-06 in Relapsed or Refractory Multiple Myeloma"

Source

P. T. Tan, L. Bao, Q. Yin, et al., “A First-In-Human Phase 1 Study of a Novel BCMA×CD3 Bispecific T Cell Engager EMB-06 in Relapsed or Refractory Multiple Myeloma,” American Journal of Hematology (2025): 1–4, https://doi.org/10.1002/ajh.70115.  October 14, 2025. 

Overview

This early-phase study evaluated EMB-06, a novel BCMA-targeted therapy, in patients with relapsed or refractory multiple myeloma (RRMM) who had previously received proteasome inhibitors and immunomodulatory drugs. EMB-06 is designed to engage T cells against myeloma cells while reducing the risk of cytokine release syndrome (CRS) and neurotoxicity, two common side effects of other BCMA therapies. In this Phase 1 trial, 40 patients received weekly EMB-06 infusions across a range of doses, with careful monitoring for safety and response.

The treatment was generally well tolerated. CRS occurred in 25% of patients and was mild (Grade 1–2) and fully resolved; no neurotoxicity events were observed. The most common side effects were cytopenias (low blood counts) and infections, which were managed with supportive care, including immunoglobulin supplementation when needed. Only one patient experienced a severe dose-limiting toxicity.

EMB-06 showed promising anti-myeloma activity. Across all patients, the overall response rate (ORR) was 39.5%, with responses appearing as early as the lowest tested doses. At higher doses (120–300 mg), nearly all patients responded, including several achieving minimal residual disease (MRD)–negative complete responses. Responses were durable, deepened over time, and persisted even when treatment was interrupted for several months.

Pharmacokinetic analyses showed predictable, dose-proportional drug behavior, and only a small number of patients developed anti-drug antibodies, which did not affect treatment activity. Biomarker analyses demonstrated that responders experienced substantial reductions in peripheral B cells and serum IgG levels, suggesting that EMB-06 effectively targets both short- and long-lived plasma cells.

Overall, EMB-06 offers a potentially safer and highly effective BCMA-targeted therapy option for RRMM. The study supports further investigation of higher doses and flexible, response-guided dosing strategies, which could maintain efficacy while minimizing risks and improving convenience for patients. These results also suggest potential applications beyond myeloma, including B-cell– or plasma cell–related autoimmune diseases.
 

"Combining IMWG GA and hematopoietic score to optimize the evaluation of dynamic chemotherapy tolerance in multiple myeloma"

Source

Chen, Y., He, F., Chen, Y., He, Z., Wu, D., An, H., … Zheng, Y. (2025). Combining IMWG GA and hematopoietic score to optimize the evaluation of dynamic chemotherapy tolerance in multiple myeloma. Annals of Medicine, 57(1). https://doi.org/10.1080/07853890.2025.2558127  October 14, 2025. 

Overview

In multiple myeloma (MM), how well patients tolerate chemotherapy can strongly influence treatment outcomes, particularly for older or frail individuals. Standard frailty assessments, like the International Myeloma Working Group Geriatric Assessment (IMWG GA), provide a snapshot at diagnosis but may not fully capture changes over time. This study looked at 111 newly diagnosed MM patients to compare traditional static frailty evaluations with a dynamic, ongoing approach that also included the Hematopoietic Score (HS), which focuses on blood-related risk factors.

The analysis showed that chemotherapy tolerance and frailty status often changed during treatment. Static assessments alone were limited in predicting which patients would experience side effects, while the dynamic evaluation using both IMWG GA and HS better identified those at higher risk. The IMWG GA was particularly useful for predicting overall and non-blood-related toxicities, whereas the HS was strong at predicting blood-related side effects. By combining the two tools into a single Hemo-IMWG GA model, clinicians achieved improved prediction of treatment-related toxicity, especially hematological complications.

These findings suggest that a dynamic, integrated assessment approach can provide a more accurate understanding of a patient’s ability to tolerate chemotherapy. Using the Hemo-IMWG GA model could help doctors tailor treatment plans, minimize serious side effects, and make more informed, personalized decisions for patients with MM.  

"The efficacy of teclistamab in patients with multiple myeloma and secondary plasma cell leukemia"

Source

Asis Shrestha, Sharmilan Thanendrarajan, Aishee Bag, Binod Dhakal, Maurizio Zangari, Samer Al-Hadidi, Frits van Rhee, Anita D’Souza, Nishi Shah, Mansi R. Shah, Meera Mohan, Carolina Schinke; The efficacy of teclistamab in patients with multiple myeloma and secondary plasma cell leukemia. Blood Adv 2025; 9 (19): 4806–4809. doi: https://doi.org/10.1182/bloodadvances.2025016695  October 14, 2025. 

Overview

Plasma cell leukemia (PCL) is a rare and aggressive form of multiple myeloma (MM) marked by ≥5% circulating plasma cells (CPCs). Secondary PCL (sPCL), which arises from relapsed or refractory MM, carries an especially poor prognosis, with median progression-free survival (PFS) of only 2–3 months even with modern therapies. While BCMA-targeted T-cell–redirecting therapies, including bispecific antibodies and CAR-T cells, have shown high response rates in relapsed MM, patients with sPCL have largely been excluded from clinical trials.

This study reports the first experience of teclistamab, a BCMA×CD3 bispecific antibody, in 16 patients with sPCL across three U.S. academic centers. Most patients had heavily pretreated, high-risk disease, with a median of 4.5 prior therapy lines; 93% were triple-class refractory and 62% penta-refractory. Teclistamab treatment was generally well tolerated: grade 1–2 cytokine release syndrome (CRS) occurred in 56% of patients, and no grade 3–4 CRS events were observed; immune cell–associated neurotoxicity syndrome occurred in 2 patients.

Efficacy was limited, with an overall response rate (ORR) of 31%. Only one patient achieved a complete response, and four achieved partial responses. Responders had a median PFS of 4.6 months, whereas nonresponders had extremely short PFS (18 days) and overall survival (1.13 months). Prior exposure to BCMA-targeted therapy did not result in responses, and baseline lymphocyte counts or CPC percentages were not predictive of outcomes.

These findings highlight the exceptional challenge of treating sPCL. While teclistamab can induce responses in some patients, the depth and durability of these responses remain limited, and long-term disease control is difficult to achieve. The poor outcomes underscore the need for novel therapeutic strategies and further research into the molecular mechanisms driving sPCL to improve patient prognosis.  

"Diagnostic sequencing identifies high-risk markers and mechanisms of resistance to guide immunotherapy selection"

Source

Parvathi Sudha, Phillip Pham, Wen Niu, Enze Liu, Lin Wang, Gillian Truong, Cameron Ligocki, Ramzi Al-Azzawi, Mallini Surapenini, Steven Bray, Francesco Vetrini, Magdalena Czader, Marwan Tayeh, Kelvin P Lee, Rafat Abonour, Attaya Suvannasankha, Brian A Walker; Diagnostic sequencing identifies high-risk markers and mechanisms of resistance to guide immunotherapy selection.. Blood Adv 2025; bloodadvances.2025017721. doi: https://doi.org/10.1182/bloodadvances.2025017721 October 15, 2025. 

Overview

This study highlights the value of next-generation sequencing (NGS) in multiple myeloma (MM) for both risk stratification and guiding precision therapy. A single-center cohort of 134 CD138+ bone marrow samples—including smoldering MM (n=11), newly diagnosed MM (n=38), and relapsed MM (n=79)—was analyzed using a targeted sequencing panel.

High-risk cytogenetic markers, such as t(4;14), t(14;16), t(14;20), 1q gain/amplification, CDKN2C deletion, and TP53 alterations, were detected in 15% of newly diagnosed patients. At relapse, 24.3% of patients previously treated with immunomodulatory drugs (IMiDs) showed alterations in the cereblon degradation pathway. Deletions of 4p (CD38) were enriched in patients exposed to anti-CD38 therapy (mostly monoallelic, P=0.03), and BCMA (TNFRSF17) deletions or mutations were observed in patients treated with anti-BCMA regimens, prompting treatment modifications.

These results demonstrate that NGS can identify both high-risk features and evolving resistance mechanisms, supporting personalized treatment sequencing. Integrating NGS into routine clinical practice allows clinicians to monitor genetic changes over time, optimize therapy choices, and potentially overcome treatment resistance in MM.  

"Soluble B-cell Maturation Antigen in Multiple Myeloma and Correlation With Response to Therapy"

Source

Saha, Souvik, Kakati, Prankrishna, Singh, Kulwant, Singh, Manish Kumar, Rahman, Khaliqur, Yadav, Sanjeev, Chandra, Dinesh, Gupta, Ruchi, Kashyap, Rajesh, Soluble B-cell Maturation Antigen in Multiple Myeloma and Correlation With Response to Therapy, Advances in Hematology, 2025, 6664621, 7 pages, 2025. https://doi.org/10.1155/ah/6664621  October 15, 2025. 

Overview

This prospective longitudinal study evaluated serum-soluble BCMA (sBCMA) as a biomarker in newly diagnosed multiple myeloma (MM) patients. Conducted between March 2023 and July 2024, the study measured sBCMA levels at baseline and during follow-up to assess correlations with disease characteristics and therapy response.

Baseline sBCMA levels were higher in patients with anemia, hypercalcemia, and high-risk cytogenetics, and showed trends correlating with bone marrow plasma cell percentage, β2-microglobulin, and thrombocytopenia. Significant associations were observed between sBCMA levels and both ISS and R-ISS staging. During treatment, declines in sBCMA closely mirrored reductions in M-protein and aligned with conventional IMWG response criteria.

The findings suggest that sBCMA is a valuable biomarker for monitoring tumor burden and therapy response, particularly in patients with renal impairment or nonsecretory myeloma, offering a practical complement to traditional disease monitoring methods.
This study highlights the value of next-generation sequencing (NGS) in multiple myeloma (MM) for both risk stratification and guiding precision therapy. A single-center cohort of 134 CD138+ bone marrow samples—including smoldering MM (n=11), newly diagnosed MM (n=38), and relapsed MM (n=79)—was analyzed using a targeted sequencing panel.

High-risk cytogenetic markers, such as t(4;14), t(14;16), t(14;20), 1q gain/amplification, CDKN2C deletion, and TP53 alterations, were detected in 15% of newly diagnosed patients. At relapse, 24.3% of patients previously treated with immunomodulatory drugs (IMiDs) showed alterations in the cereblon degradation pathway. Deletions of 4p (CD38) were enriched in patients exposed to anti-CD38 therapy (mostly monoallelic, P=0.03), and BCMA (TNFRSF17) deletions or mutations were observed in patients treated with anti-BCMA regimens, prompting treatment modifications.

These results demonstrate that NGS can identify both high-risk features and evolving resistance mechanisms, supporting personalized treatment sequencing. Integrating NGS into routine clinical practice allows clinicians to monitor genetic changes over time, optimize therapy choices, and potentially overcome treatment resistance in MM.  

"Soluble B-cell Maturation Antigen in Multiple Myeloma and Correlation With Response to Therapy"

Source

Saha, Souvik, Kakati, Prankrishna, Singh, Kulwant, Singh, Manish Kumar, Rahman, Khaliqur, Yadav, Sanjeev, Chandra, Dinesh, Gupta, Ruchi, Kashyap, Rajesh, Soluble B-cell Maturation Antigen in Multiple Myeloma and Correlation With Response to Therapy, Advances in Hematology, 2025, 6664621, 7 pages, 2025. https://doi.org/10.1155/ah/6664621  October 15, 2025. 

Overview

This prospective longitudinal study evaluated serum-soluble BCMA (sBCMA) as a biomarker in newly diagnosed multiple myeloma (MM) patients. Conducted between March 2023 and July 2024, the study measured sBCMA levels at baseline and during follow-up to assess correlations with disease characteristics and therapy response.

Baseline sBCMA levels were higher in patients with anemia, hypercalcemia, and high-risk cytogenetics, and showed trends correlating with bone marrow plasma cell percentage, β2-microglobulin, and thrombocytopenia. Significant associations were observed between sBCMA levels and both ISS and R-ISS staging. During treatment, declines in sBCMA closely mirrored reductions in M-protein and aligned with conventional IMWG response criteria.

The findings suggest that sBCMA is a valuable biomarker for monitoring tumor burden and therapy response, particularly in patients with renal impairment or nonsecretory myeloma, offering a practical complement to traditional disease monitoring methods.
 

"Belantamab mafodotin for the treatment of multiple myeloma"

Source

Oriol, A., Ibarra, G., Loscos, J., & Abril, L. (2025). Belantamab mafodotin for the treatment of multiple myeloma. Expert Opinion on Biological Therapy. https://doi.org/10.1080/14712598.2025.2576502  October 15, 2025. 

Overview

This review summarizes the emerging role of belantamab mafodotin, a BCMA-directed antibody–drug conjugate (ADC), in multiple myeloma (MM) treatment. With frontline combinatorial therapies improving outcomes, there is a growing need for accessible alternatives at relapse, especially for patients ineligible for CAR-T therapy. Belantamab mafodotin has demonstrated efficacy both as monotherapy and in combination with proteasome inhibitors or immunomodulators, providing an “off-the-shelf” option with a distinct mechanism of action.

Approved in the UK (April 2025) and EU (July 2025) for second-line therapy, belantamab mafodotin offers advantages over CAR-Ts and T-cell engagers, including lower infection risk and broader availability. Its primary adverse event, ocular keratopathy, is manageable with monitoring and dose adjustments. Current evidence and ongoing trials suggest that belantamab mafodotin can be safely integrated into treatment regimens, particularly for frail patients, and may play an increasing role in both relapsed and frontline MM therapy.
 

"A feasibility study of [18F] FDG PET/CT radiomics in predicting high-risk cytogenetic abnormalities in multiple myeloma"

Source

Chen, H., Han, J., Huang, H. et al. A feasibility study of [18F] FDG PET/CT radiomics in predicting high-risk cytogenetic abnormalities in multiple myeloma. EJNMMI Res 15, 131 (2025). https://doi.org/10.1186/s13550-025-01321-8  October 15, 2025. 

Overview

This review highlights long-term survival (LTS) in multiple myeloma (MM), defined as surviving ≥10 years after a single line of therapy, an increasingly observed outcome due to advances in treatment. Proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, autologous stem cell transplantation, and novel immunotherapies have transformed MM care, yet only a subset of patients achieves durable disease control, underscoring the role of both tumor-intrinsic and immune-mediated mechanisms.

Evidence suggests that the immune bone marrow environment (IBME) is a key determinant of LTS, with enhanced T-cell function, increased natural killer cell activity, and reduced immunosuppressive myeloid populations supporting long-term disease control. Therapeutic strategies such as CAR-T cells and bispecific antibodies have primarily benefited standard-risk patients, but understanding immune adaptations in LTS offers a roadmap for next-generation therapies. Future studies integrating genomic and immune profiling, alongside IBME modulation, may enable sustained remission and functional cures in MM.
 

"Molecular and immunological determinants of long-term survival in multiple myeloma"

Source

Khanmi Kasomva, Kritika Yadav, Siegfried Janz, Binod Dhakal, Sridhar Rao; Molecular and immunological determinants of long-term survival in multiple myeloma. Blood Adv 2025; 9 (20): 5134–5147. doi: https://doi.org/10.1182/bloodadvances.2025016829  October 15, 2025. 

Overview

This study evaluates a non-invasive radiomics approach using pretreatment [¹⁸F]FDG PET/CT imaging to predict high-risk cytogenetic abnormalities (HRCAs) in newly diagnosed multiple myeloma (MM). A Decision Tree model analyzing PET-active lesion features demonstrated the best performance (AUC = 0.89), outperforming conventional PET metrics (AUC = 0.84) and clinical models (AUC = 0.74). SHapley Additive exPlanations (SHAP) analysis highlighted PET-derived features as key predictors.

The model effectively stratified patients into high- and low-risk groups, with the high-risk cohort showing significantly worse progression-free survival (24.5 vs. 29 months, p = 0.036) and overall survival (33.5 vs. 50 months, p = 0.002). These findings suggest PET/CT radiomics could serve as a non-invasive biomarker to predict cytogenetic risk and guide prognosis-driven treatment decisions. Large-scale, multi-center prospective studies are needed to validate its role in personalized MM therapy.
 

"The Causal Relationship between Lipid Metabolites and Multiple Myeloma Risk: A Mendelian Randomization Study"

Source

Tao J, Wang L, Gu Z. The Causal Relationship between Lipid Metabolites and Multiple Myeloma Risk: A Mendelian Randomization Study. Acta Haematol. 2025 Oct 16:1-14. doi: 10.1159/000548566. Epub ahead of print. 

Overview

This Mendelian randomization study investigated the potential causal relationship between lipid metabolites and multiple myeloma (MM) risk using genetic data from 7,824 Europeans for metabolites and 601 MM cases with 372,016 controls from the UK Biobank. Among 121 metabolites analyzed, nominal associations suggested that 1-docosahexaenoyl-glycerophosphocholine, tetradecanedioate, and X-12990-docosapentaenoic acid were linked to increased MM risk, whereas palmitoleate showed a nominal inverse association.

However, none of these associations remained statistically significant after false discovery rate correction, and sensitivity analyses supported the robustness of these nominal findings. These results indicate potential metabolic pathways involved in MM pathogenesis, but further studies are needed before these metabolites can be considered as clinical biomarkers or therapeutic targets.
 

"Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response"

Source

Anna Maria Corsale, Mojtaba Shekarkar Azgomi, Emilia Gigliotta, Marta Di Simone, Paola Pacelli, Francesca Cioffi, Elena Bestoso, Donatella Raspadori, Alessandro Gozzetti, Antonio Solimando, Paula Tabares, Andreas Beilhack, Maria Speciale, Giusy Corsale, Miriam Sciortino, Cristina Aquilina, Fulvio Brucato, Michele Cea, Renato Zambello, Francesca Garofano, Marta Biondo, Francesca Buffa, Nadia Caccamo, Francesco Dieli, Serena Meraviglia, Sergio Siragusa, Cirino Botta, Bone marrow immune cell composition reflects multiple myeloma progression and affects treatment response, Blood Neoplasia, 2025, 100174, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2025.100174. October 16, 2025. 

Overview

This study analyzed bone marrow (BM) immune cell composition across 159 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), using the semi-automated FlowCT platform. Disease progression was associated with decreased granulocyte-to-lymphocyte (GLR) and granulocyte-to-T lymphocyte (GTL) ratios and increased T lymphocytes. Higher baseline GLR and GTL ratios correlated with longer progression-free survival (PFS), particularly in patients receiving daratumumab-based therapy. Mechanistically, autologous BM granulocytes enhanced daratumumab-mediated cytotoxicity against primary plasma cells, revealing a novel granulocyte-dependent mechanism. These findings highlight the prognostic importance of BM immune composition in MM and its potential to guide treatment strategies.
 

"Equal survival for Black Americans with multiple myeloma when appropriately matched to White Americans"

Source

Mery, D.E., Tricot, G., Al Hadidi, S. et al. Equal survival for Black Americans with multiple myeloma when appropriately matched to White Americans. Blood Cancer J. 15, 164 (2025). https://doi.org/10.1038/s41408-025-01379-6 October 16, 2025 

Overview

This study examined racial disparities in multiple myeloma (MM) outcomes by analyzing 1,827 newly diagnosed MM patients at the University of Arkansas for Medical Sciences, including 171 Black Americans (BA) and 1,656 White Americans (WA). Using strict inclusion criteria and propensity score matching to align BA and WA patients on age, sex, molecular risk (GEP70), disease burden (PET/MRI), transplant type, and maintenance therapy, the analysis aimed to isolate the effect of race under equitable treatment conditions. Baseline clinical characteristics were largely comparable, though BA were more often obese and had lower hemoglobin. After matching, overall survival (OS) and event-free survival (EFS) were similar between BA and WA (median OS: 11.78 vs. 12.97 years; median EFS: 6.84 vs. 5.92 years). These results indicate that when access to care and treatment are equal, racial disparities in MM outcomes are negligible. The findings highlight the importance of equitable treatment, advanced diagnostics, and precise risk stratification, and suggest that observed racial differences in broader populations may reflect systemic healthcare inequities rather than intrinsic biological differences.

"Sex-specific dysregulation of exosomal non-coding RNAs drives multiple myeloma progression"

Source

Kodandaram Pillarisetti, Danlin Yang, Leopoldo Luistro, Jianhong Yao, Melissa Smith, Peter Vulfson, James Testa, Randolph Ponticiello, Scott R Brodeur, Bradley Heidrich, Kathryn Packman, Sanjaya Singh, Ricardo M Attar, Yusri A Elsayed, Ulrike Philippar; Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models. Blood 2025; blood.2025030027. doi: https://doi.org/10.1182/blood.2025030027  October 16, 2025. 

Overview

This study explored sex-specific differences in multiple myeloma (MM) by analyzing exosomal non-coding RNAs (ncRNAs) from patients and MM cell lines. Researchers found distinct expression patterns of lncRNAs and miRNAs between males and females across clinical contexts including newly diagnosed, relapsed, and hyperdiploid versus non-hyperdiploid disease. These ncRNAs were linked to key biological processes such as cell proliferation, apoptosis, and gene regulation. The study identified a panel of sex-specific ncRNAs affecting mRNA regulation and MM-associated pathways, highlighting how exosomal profiling can sensitively detect transcriptomic alterations. These findings suggest that sex-specific ncRNA dysregulation may influence MM progression and therapy response, emphasizing the potential for personalized, sex-tailored therapeutic strategies.
 

"Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models"

Source

Kodandaram Pillarisetti, Danlin Yang, Leopoldo Luistro, Jianhong Yao, Melissa Smith, Peter Vulfson, James Testa, Randolph Ponticiello, Scott R Brodeur, Bradley Heidrich, Kathryn Packman, Sanjaya Singh, Ricardo M Attar, Yusri A Elsayed, Ulrike Philippar; Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models. Blood 2025; blood.2025030027. doi: https://doi.org/10.1182/blood.2025030027  October 16, 2025. 

Overview

This study investigated ramantamig (JNJ-79635322), a trispecific T-cell–engaging antibody designed for multiple myeloma (MM), which targets BCMA and GPRC5D, antigens highly expressed on malignant plasma cells. By recognizing dual antigens, ramantamig enhances tumor binding, potentially improving depletion of heterogeneous MM clones and reducing antigen-loss–mediated resistance. In preclinical studies, it showed potent cytotoxicity at sub-nanomolar concentrations, activated T cells, and effectively depleted malignant plasma cells in MM cell lines, patient samples ex vivo, and healthy blood co-cultures. In murine xenograft models, ramantamig demonstrated strong antitumor activity in both tumor prevention and regression settings. These findings highlight its selective, clonal-depleting potential and support ongoing Phase 1 trials assessing its ability to produce durable responses in relapsed/refractory MM (NCT05652335, NCT06768489).
 

"Impact of Body Mass Index on Anti-BCMA Chimeric Antigen Receptor T Cell Therapy Outcomes in Multiple Myeloma"

Source

Ruth Choa, Kevin Miller, Advait Joshi, Cole Minsky, Samuel S. Han, Alexis Barselau, Andrew Yee, Andrew Branagan, Benjamin Puliafito, Matthew Frigault, Noopur Raje, Diana Cirstea, Impact of Body Mass Index on Anti-BCMA Chimeric Antigen Receptor T Cell Therapy Outcomes in Multiple Myeloma, Blood Immunology & Cellular Therapy, 2025,100015, ISSN 3050-5976, https://doi.org/10.1016/j.bict.2025.100015. October 16, 2025. 

Overview

This study examined the impact of body mass index (BMI) on outcomes of anti-BCMA CAR-T therapy in relapsed/refractory multiple myeloma (MM) patients treated at Massachusetts General Hospital (2016–2023). Analysis revealed a U-shaped relationship between BMI and survival: overweight patients (BMI 25–29.9 kg/m²) had worse 12-month progression-free survival (28.8%) and overall survival (61.4%) compared with normal weight (PFS 51.9%, OS 82.9%) and obese patients (PFS 62.6%, OS 84.2%). Complete response rates were lower in overweight patients, though not statistically significant. Incidents of cytokine release syndrome (CRS) and ICANS were similar across BMI groups. These findings suggest BMI is a nonlinear determinant of CAR-T efficacy in MM and highlight the need for mechanistic studies to understand modifiable biological factors underlying this observation.
 

"Assumptions Matter: The Long-Term Cost Analysis of IsaVRd vs DVRd"

Source

Lin F, Petitjean A, Sasane M. Assumptions Matter: The Long-Term Cost Analysis of IsaVRd vs DVRd. J Health Econ Outcomes Res. 2025 Oct 17;12(2):145-146. doi: 10.36469/001c.145075.  . 

Overview

This letter critiques the drug acquisition cost (DAC) analysis by Gupta-Werner et al comparing DVRd (daratumumab + VRd) versus IsaVRd (isatuximab + VRd) in frontline therapy for transplant-ineligible newly diagnosed multiple myeloma (NDMM) in the U.S. The authors highlight key methodological issues: inflated assumptions of patient weight, dose rounding that favors daratumumab, a limited 2-year time horizon, and omission of relative dose intensity (RDI).

By adjusting these factors—using accurate patient weights, rounding isatuximab doses within HOPA guidelines, incorporating RDI, and extending the analysis beyond two years—IsaVRd was shown to be more cost-effective, with cumulative savings increasing over time. Additionally, the adoption of a 30-minute isatuximab infusion reduces administration costs by 42–52% versus standard infusion, further enhancing its economic advantage.

The analysis concludes that when methodological limitations are corrected, IsaVRd provides a more economically favorable frontline option for transplant-ineligible NDMM patients, emphasizing the need for comprehensive, real-world-informed cost evaluations.

"GPRC5D-targeted CAR T-cell therapy (CT071) in patients with relapsed or refractory multiple myeloma: a first-in-human, single-centre, single-arm, phase 1 trial"

Source

Jin L, Gu S, Ruan Q, Lu J, Qiang W, He H, Fan X, Liu J, Guo P, Meng X, Rajakumaraswamy N, Chen D, Li Z, Du J. GPRC5D-targeted CAR T-cell therapy (CT071) in patients with relapsed or refractory multiple myeloma: a first-in-human, single-centre, single-arm, phase 1 trial. Lancet Haematol. 2025 Oct;12(10):e798-e807. doi: 10.1016/S2352-3026(25)00176-0. 

Overview

This first-in-human, phase 1 study evaluated CT071, a fully human CAR T-cell therapy targeting GPRC5D, in 20 patients with relapsed or refractory multiple myeloma at Shanghai Changzheng Hospital. Patients had received ≥3 prior lines of therapy or were double-class refractory. CT071 showed a favorable safety profile: no dose-limiting toxicities, mostly grade 1–2 cytokine release syndrome (60%), and manageable hematologic toxicities; one patient experienced grade 3 neurotoxicity. The efficacy was notable, with a 100% overall response rate and 50% achieving complete response or better. These results support further clinical development of CT071 in heavily pretreated multiple myeloma patients. 

"Phase I clinical study of humanized BCMA-single-domain antibodies targeting CAR-T in patients with relapsed or refractory multiple myeloma"

Source

Gaofeng Zheng, Ruyi Xu, Heng Mei, Xiaoyan Han, Donghua He, Yanling Weng, Cheng Wen, Zhuoxiao Cao, Zhen Cai. Phase I clinical study of humanized BCMA-single-domain antibodies targeting CAR-T in patients with relapsed or refractory multiple myeloma, Cancer Biology & Medicine Oct 2025, 20240581; DOI: 10.20892/j.issn.2095-3941.2024.0581.  October 17, 2025. 

Overview

This study reviews the rationale and early clinical development of BCMA-targeted CAR-T therapy for relapsed or refractory multiple myeloma (RRMM). BCMA is highly expressed on malignant plasma cells, making it an ideal target for CAR-T therapy. Preclinical studies demonstrated potent cytotoxicity of BCMA CAR-T against MM cell lines and effective tumor clearance in xenograft models.

A phase I clinical trial in China (NCT05346198) evaluated the safety and efficacy of single-domain BCMA CAR-T cells using dose escalation and expansion designs, establishing a recommended dose for further studies. While BCMA CAR-T can induce remission in RRMM, responses are often temporary, prompting ongoing trials to improve durability and persistence. These findings support BCMA CAR-T as a promising therapeutic approach for heavily pretreated MM patients.

"Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis"

Source

Żyłka, K., Łuczak, M., Kostrzewska-Poczekaj, M. et al. Carfilzomib resistance in multiple myeloma: A comparative metabolomic analysis. J Appl Genetics (2025). https://doi.org/10.1007/s13353-025-01022-x  October 17, 2025. 

Overview

This study investigates metabolic alterations associated with carfilzomib resistance in multiple myeloma (MM). Using global metabolomic profiling, researchers compared carfilzomib-sensitive MM cell lines with their resistant counterparts, revealing increased amino acid levels, decreased fatty acids, enhanced glucose-6-phosphate oxidation, and reduced lipid accumulation in resistant cells. Bioinformatic analysis identified PML, ARNT D-glucose, and UPC1 as potential upstream regulators of these metabolic changes. These findings provide one of the first metabolomic characterizations of carfilzomib-resistant MM, offering insights into mechanisms of drug resistance and potential therapeutic targets.

"ID2 suppresses multiple myeloma cell proliferation by repressing the activity of the transcription factor TCF3"

Source

Mariateresa Fulciniti, Yao Yao, Tommaso Perini, Jessica Fong Ng, Anaïs Schavgoulidze, Shuhui Deng, Jian Cui, Jessica Encinas Mayoral, Francesco Ladisa, Ryan M. Young, Charles B. Epstein, Cassandra M. White, Christopher J. Ott, Annamaria Gulla, Shannon M. Matulis, Adam S. Sperling, Eugenio Morelli, Lawrence H. Boise, Moritz Binder, Raphael Szalat, Mehmet K. Samur, Kenneth C. Anderson, Nikhil C. Munshi; ID2 suppresses multiple myeloma cell proliferation by repressing the activity of the transcription factor TCF3. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-25-0048  October 17, 2025. 

Overview

This study uncovers a tumor-suppressive role for ID2 in multiple myeloma (MM). Using gain-of-function screens, researchers found that ID2 is downregulated in MM cells, which increases activity of the transcription factor TCF3 (E2A), promoting cell proliferation. Overexpression of ID2 reduced TCF3 DNA binding, causing cell-cycle arrest. The bone marrow microenvironment further decreases ID2 via IL-6, enhancing TCF3 activity and illustrating how tumor-microenvironment interactions drive MM cell growth.

"Endothelial activation and stress index (EASIX) to predict engraftment syndrome after autologous hematopoietic cell transplantation in patients with multiple myeloma. A single-center experience"

Source

Tolosa-Ridao, C., Cid, J., Rodríguez-Lobato, L. G., Charry, P., Mateos, J. M., Moreno-Castaño, A. B., … Salas, M. Q. (2025). Endothelial activation and stress index (EASIX) to predict engraftment syndrome after autologous hematopoietic cell transplantation in patients with multiple myeloma. A single-center experience. Leukemia & Lymphoma, 1–9. https://doi.org/10.1080/10428194.2025.2556179  October 17, 2025. 

Overview

This study highlights the use of the Endothelial Activation and Stress Index (EASIX) to predict engraftment syndrome (ES) in multiple myeloma patients undergoing at-home autologous hematopoietic cell transplantation (auto-HCT). Among 187 patients, ES occurred in 16.6% but resolved with treatment, rarely requiring hospitalization. Higher post-apheresis EASIX and any-grade mucositis were significantly associated with ES, and an EASIX cutoff ≥0.9 may identify high-risk patients. These findings support EASIX-guided risk stratification to optimize ES management and improve patient outcomes in home-based transplant settings.

"Daratumumab in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials"

Source

Wang, C., Xu, Z., Jiang, M., Chen, Y., & Lan, Y. (2025). Daratumumab in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials. Cancers, 17(20), 3349. https://doi.org/10.3390/cancers17203349  October 17, 2025. 

Overview

This meta-analysis evaluated daratumumab-based regimens in transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM) across six randomized controlled trials involving 2,478 patients. Daratumumab significantly improved progression-free survival (HR = 0.544), overall survival (HR = 0.693), and MRD negativity, including a four-fold increase in sustained MRD negativity (≥12 months). However, these regimens were associated with higher rates of serious and grade 3/4 adverse events, including neutropenia, lymphopenia, infections, pneumonia, and fatal events. Overall, daratumumab-based therapy offers enhanced efficacy as first-line treatment, but requires careful patient selection and proactive management of toxicities to optimize outcomes in this vulnerable population.

"How should we choose optimal salvage treatments following BCMA-directed CAR T-cell therapy?"

Source

Suresh, A., Pan, D., Lipof, J., Kumar, A., Arora, S., Sayre, P., … Chung, A. (2025). How should we choose optimal salvage treatments following BCMA-directed CAR T-cell therapy? Immunotherapy, 1–14. https://doi.org/10.1080/1750743X.2025.2571392  October 17, 2025. 

Overview

This review focuses on salvage therapies for relapsed/refractory multiple myeloma (RRMM) following BCMA-directed CAR-T therapy. Although BCMA CAR-T has transformed RRMM treatment, most patients eventually relapse, and resistance mechanisms remain a major challenge. The article summarizes the current salvage treatment options, the evidence supporting their use, and explores potential sequencing strategies aimed at maximizing clinical outcomes. It highlights the need for guidance on optimal therapy sequencing in this difficult-to-treat population.

"Cardiovascular complications and their association with short- and long-term outcomes in patients with multiple myeloma undergoing chimeric antigen receptor T-cell therapy"

Source

Itzhaki Ben Zadok O, Simitsis P, Jacobson C, Nadeem O, Frigault MJ, Raje N, et al. Cardiovascular complications and their association with short- and long-term outcomes in patients with multiple myeloma undergoing chimeric antigen receptor T-cell therapy. Br J Haematol. 2025; 00: 1–11. https://doi.org/10.1111/bjh.70216  October 19, 2025. 

Overview

This study examines cardiovascular (CV) events in multiple myeloma (MM) patients treated with CAR-T therapy. Among 256 patients, 11.7% experienced in-hospital CV events, mainly atrial arrhythmias and new left ventricular dysfunction, with most LV dysfunction resolving. Risk factors included age >65, prior atrial fibrillation, antiplatelet use, and higher grades of cytokine release syndrome or neurotoxicity. Post-discharge CV events were less frequent (7.8%) but were associated with higher all-cause mortality. The findings highlight that in-hospital CV events are generally reversible and not fatal, whereas post-discharge CV events, though rare, indicate poorer survival.

"DNA Damage Response and Redox Status in the Resistance of Multiple Myeloma Cells to Genotoxic Treatment"

Source

Malamos, P., Papanikolaou, C., Deligianni, E., Mavroeidi, D., Koutoulogenis, K., Gavriatopoulou, M., Terpos, E., & Souliotis, V. L. (2025). DNA Damage Response and Redox Status in the Resistance of Multiple Myeloma Cells to Genotoxic Treatment. International Journal of Molecular Sciences, 26(20), 10171. https://doi.org/10.3390/ijms262010171  October 19, 2025. 

Overview

This study investigates how DNA damage response (DDR) parameters and redox status influence sensitivity to genotoxic treatments in multiple myeloma (MM) cells. By analyzing 11 MM cell lines and a healthy B lymphoblastoid line, the authors found that cell lines with higher apoptosis rates exhibited more baseline DNA damage, lower GSH/GSSG ratios, increased apurinic/apyrimidinic sites, reduced DNA repair capacity, and condensed chromatin. These findings suggest that DDR and redox biomarkers may predict MM cell sensitivity to DNA-damaging agents like melphalan and could inform future personalized treatment strategies.

"How Does Age at Diagnosis Influence Multiple Myeloma Survival?"

Source

Lawanson, M. O., Griffin, E., Berleant, D., Farmer, P., Hodge, R., Schinke, C., Ashby, C., & Bauer, M. A. (2025). How Does Age at Diagnosis Influence Multiple Myeloma Survival? Empirical Evidence. Healthcare, 13(20), 2637. https://doi.org/10.3390/healthcare13202637  October 20, 2025 

Overview

This study examines the impact of age at diagnosis on survival in multiple myeloma (MM) patients using data from the University of Arkansas Myeloma Center Database. Analysis showed that younger patients had better survival, with the oldest group (>70) facing a 3.3-fold higher risk of death compared to younger patients. Non-linear modeling confirmed that age strongly predicts survival, highlighting the critical role of age as a key prognostic factor in MM outcomes.

"Correlation of blood transfusion to progression-free survival and overall survival in multiple myeloma patients undergoing chemotherapy"

Source

Sourav Chowdhury, Sudipta Sekhar Das, Anupam Chakrapani, Debmalya Bhattacharyya, Sourav Mukherjee, Correlation of blood transfusion to progression-free survival and overall survival in multiple myeloma patients undergoing chemotherapy, Transfusion and Apheresis Science, 2025, 104266, ISSN 1473-0502, https://doi.org/10.1016/j.transci.2025.104266. October 20, 2025.  

Overview

This study investigated the impact of blood transfusion on outcomes in multiple myeloma (MM) patients undergoing chemotherapy at a tertiary center in India. Patients receiving ≥5 transfusions had higher disease stage (RISS), more relapses, and required more chemotherapy regimens. Higher transfusion burden was associated with shorter progression-free and overall survival, suggesting that frequent transfusions may serve as a negative prognostic factor in MM.

"Optimizing autologous hematopoietic stem cell transplantation for multiple myeloma: early step-down ward versus HEPA-filtered rooms – a practical approach for resource-limited settings"

Source

Chutima Kunacheewa, Sukanpuk Niwatkittipon, Suparat Atakulreka, Nawapotch Donsakul, Smith Kungwankiattichai, Ekapun Karoopongse, Jane Jianthanakanon, Narupon Sonsak, Pongthep Vittayawacharin, Utairat Meeudompong, Natchanon Sathapanapitagkit, Kamolchanok Kulchutisin, Weerapat Owattanapanich, Optimizing autologous hematopoietic stem cell transplantation for multiple myeloma: early step-down ward versus HEPA-filtered roomS – a practical approach for resource-limited settings, Transplantation and Cellular Therapy, 2025, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2025.10.018. October 20, 2025.   

Overview

This study evaluated an early step-down ward model for outpatient autologous stem cell transplantation (ASCT) in multiple myeloma patients in Thailand, where HEPA-filtered room availability is limited. Comparing 138 patients in the step-down group with 114 pre-step-down patients, infection rates, treatment-related mortality (0% at 30 and 100 days), and engraftment outcomes were comparable. The model increased the annual ASCT capacity without compromising safety, suggesting it is a feasible and effective approach to expand access to ASCT in resource-limited settings.

"New Zealand multiple myeloma patients demonstrate inferior outcomes when compared to Australian counterparts – a retrospective cohort study from the Myeloma and Related Diseases Registry (MRDR)"

Source

Jian Li, Yayehirad Melsew, Cameron Wellard, Elizabeth M Moore, P. Joy Ho, Hang Quach, Simon J Harrison, Rajeev Rajagopal, Bradley Augustson, Erica M Wood, Andrew Spencer, New Zealand multiple myeloma patients demonstrate inferior outcomes when compared to Australian counterparts – a retrospective cohort study from the Myeloma and Related Diseases Registry (MRDR)., Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.10.013. October 20, 2025. 

Overview

This retrospective cohort study of 5,031 multiple myeloma patients in Australia and New Zealand found that New Zealand patients had significantly shorter median overall survival (65.3 vs. 79.8 months) despite generally similar clinical characteristics. Inferior survival was linked to lower rates of autologous stem cell transplant (ASCT), less frequent use of frontline proteasome inhibitor–IMID combinations, and reduced anti-CD38 therapy at first relapse. The findings highlight healthcare access disparities and the need for system-level improvements in treatment delivery to improve outcomes in New Zealand.

"Epidemiological Trends and Disease Burden of Multiple Myeloma in the Middle-Aged and Elderly Population: A Global Study from 1990 to 2021"

Source

Chen, Y., Jiang, Y., Xu, Y., Ma, Y., Yao, W., Wang, H., … Lang, H. (2025). Epidemiological Trends and Disease Burden of Multiple Myeloma in the Middle-Aged and Elderly Population: A Global Study from 1990 to 2021. Cancer Investigation, 1–19. https://doi.org/10.1080/07357907.2025.2573084  October 20, 2025.  

Overview

This global analysis of multiple myeloma (MM) from 1990 to 2021 found that cases, deaths, and disability-adjusted life years (DALYs) doubled among adults over 55, with the highest burden in those aged 65–74. Age-standardized incidence, mortality, and DALYs increased worldwide, especially in intermediate socio-demographic index regions, with the USA contributing 20% of the global burden. Projections suggest a potential decline by 2050, highlighting the need for targeted strategies to improve outcomes in older adults.

"Prognostic potential of albumin to fibrinogen ratio in multiple myeloma patients"

Source

Carlisi, M., Presti, R.L., Pirrera, A. et al. Prognostic potential of albumin to fibrinogen ratio in multiple myeloma patients. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06630-5  October 20, 2025. 

Overview

This study found that the albumin/fibrinogen ratio—an inexpensive and easy-to-measure blood marker—was linked to several prognostic factors in newly diagnosed multiple myeloma and differed clearly between patients who survived and those who did not. These early results suggest it may serve as an additional biomarker to help assess prognosis in myeloma.
 

"Correlation of blood transfusion to progression-free survival and overall survival in multiple myeloma patients undergoing chemotherapy"

Source

Chowdhury S, Das SS, Chakrapani A, Bhattacharyya D, Mukherjee S. Correlation of blood transfusion to progression-free survival and overall survival in multiple myeloma patients undergoing chemotherapy. Transfus Apher Sci. 2025 Oct 20;64(6):104266. doi: 10.1016/j.transci.2025.104266. Epub ahead of print. October 20, 2025. 

Overview

This study found that multiple myeloma patients who needed five or more blood transfusions during treatment had more advanced disease and shorter progression-free and overall survival. The results suggest that a high transfusion burden may be an important warning sign of poorer outcomes in myeloma.

 

"Chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel therapy"

Source

Korenkov, M., Liebaert, J., Yousefian, S. et al. Chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel therapy. Blood Cancer J. 15, 168 (2025). https://doi.org/10.1038/s41408-025-01384-9  October 20, 2025. 

Overview

Two patients developed a rare but severe nerve disorder called CIDP after receiving the BCMA-directed CAR-T therapy cilta-cel. The cases suggest this complication may be driven not by CAR-T cells themselves but by an abnormal surge of other autoreactive T-cells, highlighting the need for rapid diagnosis and early T-cell-depleting treatment when such delayed neurotoxicity occurs.

 

"Prospective systematic classification of causes of death in the course of multiple myeloma"

Source

Jin, J.x., Besemer, B., Yilmaz, B. et al. Prospective systematic classification of causes of death in the course of multiple myeloma. Blood Cancer J. 15, 167 (2025). https://doi.org/10.1038/s41408-025-01380-z  October 20, 2025. 

Overview

Multiple myeloma treatments have improved survival over the past decade, but most patients in this large German study still died from the disease itself or from infections. The findings show that therapy-related risks—including infections, second cancers, and the major impact of COVID-19—continue to shape outcomes, highlighting the need for strong infection prevention and careful monitoring throughout treatment.

 

"Epidemiological landscape of early-onset multiple myeloma: global burden, temporal trends, cross-country inequality, and projections to 2045"

Source

Zhang, H., Li, M., Zhao, L., Wang, L., & Geng, J. (2025). Epidemiological landscape of early-onset multiple myeloma: global burden, temporal trends, cross-country inequality, and projections to 2045. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2576308  October 21, 2025. 

Overview

Early-onset multiple myeloma (MM) refers to myeloma diagnosed before age 50. This study looked at how common early-onset MM is around the world and how it has changed over time.

Researchers used data collected from 1990 to 2021 and found that cases of early-onset MM have risen sharply. During that period, the number of new cases went up by 142%, and the number of people living with the disease nearly doubled. The overall impact of the disease—measured by disability-adjusted life years (DALYs)—also increased by more than 100%. These rises were faster than the increases seen in older adults with myeloma.

In 2021, early-onset MM was more common in men and in countries with higher levels of income, education, and life expectancy. While differences between countries are starting to narrow, the burden remains uneven. The study also showed that in many high-income countries, changes in disease patterns helped reduce some of the increase, but not enough to stop overall growth.

Looking ahead to 2045, researchers expect early-onset MM to keep increasing worldwide.

Overall, this study highlights that early-onset MM is becoming a growing global concern. Health systems will need focused plans and resources to support younger patients and address differences across regions.

 

"Single-cell transcriptomics identifies PDIA4 as a marker of progression and therapeutic vulnerability in multiple myeloma"

Source

Yu, W., Zhan, J., Wang, Y. et al. Single-cell transcriptomics identifies PDIA4 as a marker of progression and therapeutic vulnerability in multiple myeloma. J Transl Med 23, 1136 (2025). https://doi.org/10.1186/s12967-025-07098-7  October 21, 2025. 

Overview

This study looked at how certain genes help multiple myeloma (MM) cells grow, survive, and resist treatment. While the genetic changes in MM are well known, scientists still don’t fully understand how abnormal plasma cells keep themselves alive over time.

Researchers combined single-cell RNA sequencing data from healthy donors and people with MGUS, smoldering myeloma, and newly diagnosed myeloma. This allowed them to track how plasma cells change as the disease progresses. They found that a gene called PDIA4 becomes more active in the later stages of plasma cell development.

They then studied PDIA4 in patient data and in lab models. Patients with higher levels of PDIA4 had worse overall survival. When scientists removed PDIA4 from MM cells, the cancer cells stopped growing as well, got stuck in an early phase of the cell cycle, and became more sensitive to the drug bortezomib. In mouse models, blocking PDIA4 also slowed tumor growth.

Overall, the study suggests that PDIA4 helps myeloma cells manage stress inside the cell and supports their survival. Targeting PDIA4 could make treatments like proteasome inhibitors work better and may help overcome drug resistance in multiple myeloma.

This study looked at how certain genes help multiple myeloma (MM) cells grow, survive, and resist treatment. While the genetic changes in MM are well known, scientists still don’t fully understand how abnormal plasma cells keep themselves alive over time.

Researchers combined single-cell RNA sequencing data from healthy donors and people with MGUS, smoldering myeloma, and newly diagnosed myeloma. This allowed them to track how plasma cells change as the disease progresses. They found that a gene called **PDIA4** becomes more active in the later stages of plasma cell development.

They then studied PDIA4 in patient data and in lab models. Patients with higher levels of PDIA4 had worse overall survival. When scientists removed PDIA4 from MM cells, the cancer cells stopped growing as well, got stuck in an early phase of the cell cycle, and became more sensitive to the drug bortezomib. In mouse models, blocking PDIA4 also slowed tumor growth.

Overall, the study suggests that PDIA4 helps myeloma cells manage stress inside the cell and supports their survival. Targeting PDIA4 could make treatments like proteasome inhibitors work better and may help overcome drug resistance in multiple myeloma.

 

"Single-cell and bulk transcriptomics uncovers PRKD2-driven tumor stemness and progression in multiple myeloma"

Source

Zhang, G., Cao, S., Geng, C. et al. Single-cell and bulk transcriptomics uncovers PRKD2-driven tumor stemness and progression in multiple myeloma. Sci Rep 15, 36723 (2025). https://doi.org/10.1038/s41598-025-20615-4  October 21, 2025.  

Overview

This study looked at why multiple myeloma (MM) becomes aggressive and hard to treat, especially when it relapses or stops responding to therapy. Researchers focused on a gene called PRKD2, which may help myeloma cells grow, avoid the immune system, and resist treatment.

They analyzed large datasets from patient samples at diagnosis, relapse, and from people with poor survival outcomes. PRKD2 was the only gene consistently increased across all these groups. Higher PRKD2 levels were linked to more advanced disease, more stem-like cancer cells, and much lower 5-year survival.

In lab studies, lowering PRKD2 levels made myeloma cells grow more slowly and made it easier for the immune system to recognize them. Increasing PRKD2 had the opposite effect and pushed immune cells called macrophages into a tumor-supporting state.

The team also studied how PRKD2 affects treatment response. They found that cells with high PRKD2 were more sensitive to axitinib, a drug that blocks VEGFR and PDGFR pathways. In experiments, axitinib caused more cell death in PRKD2-high cells and reversed the growth advantage created by PRKD2 overexpression.

Overall, the study suggests that PRKD2 drives more aggressive, treatment-resistant myeloma—but it also creates a weakness. Drugs like axitinib, possibly combined with proteasome inhibitors, may be especially effective for patients with high PRKD2 levels.

 

"Single-cell and bulk transcriptomics uncovers PRKD2-driven tumor stemness and progression in multiple myeloma"

Source

Chalopin, T., Cellerin, E., Demarquette, H. et al. Debulking strategy prior to anti-BCMA/CD3 bispecific antibodies in extramedullary and/or high tumor burden RRMM: a retrospective cohort study. Blood Cancer J. 15, 174 (2025). https://doi.org/10.1038/s41408-025-01365-y  October 21, 2025.   

Overview

This letter describes a study looking at whether giving chemotherapy first—before starting anti-BCMA bispecific antibody (BsAb) therapy—can help improve treatment results for people with relapsed or refractory multiple myeloma (RRMM), especially those with extramedullary disease (EMD) or high-risk genetic features, who usually have poorer outcomes.

Researchers reviewed medical records from 44 patients treated at 14 centers in France. All patients received a cycle of standard chemotherapy to “debulk” or reduce the amount of cancer before beginning BsAb therapy like teclistamab or elranatamab. Most patients had aggressive disease, with many having EMD or high-risk cytogenetics.

Safety:
Even after chemotherapy, BsAb treatment was generally safe. Side effects like cytokine release syndrome (CRS) and ICANS were mostly mild, and serious infections occurred at rates similar to past BsAb studies.

Effectiveness:
The early response to BsAb therapy was encouraging.

After the first cycle, 64% of patients responded.

By cycle 6, the response rate rose to 87%.

Patients with high-risk genetics and those with EMD also showed improvement, though results were still better for patients without EMD.

Overall, patients had a median progression-free survival (PFS) of about 10 months, similar to what has been seen in major BsAb clinical trials. For patients with EMD—who usually do much worse—PFS was longer than expected based on previous real-world data.

The authors suggest that chemotherapy may help BsAb therapy work better by lowering tumor burden and improving the immune environment, making it easier for T cells to attack cancer cells.

While the results are promising, the study was small and retrospective, which means more research is needed. The authors recommend future clinical trials to confirm whether using chemotherapy before BsAb therapy can reliably improve outcomes for high-risk myeloma patients.

 

"Novel proteomic characterization of multiple myeloma bone marrow interstitial fluid links prognosis to coagulation pathways"

Source

Cutler, S., Trottier, A.M., Liwski, R. et al. Novel proteomic characterization of multiple myeloma bone marrow interstitial fluid links prognosis to coagulation pathways. Clin Proteom 22, 40 (2025). https://doi.org/10.1186/s12014-025-09560-6  October 21, 2025. 

Overview

This study explored whether proteins found in bone marrow fluid can help doctors better predict outcomes for people with multiple myeloma (MM). While MM has been well studied at the DNA and RNA level, much less is known about its “proteome”—the full set of proteins active in the disease. Because proteins reflect what the cancer cells are actually doing, they may offer new clues about disease behavior.

Researchers used advanced mass spectrometry to analyze bone marrow interstitial fluid from patients with MM and its precursor conditions. They were able to measure more than 11,000 proteins, making this one of the deepest proteomic studies of MM to date.

They found 194 proteins that were linked to overall survival. Many of these proteins were involved in blood clotting (coagulation). When the researchers grouped newly diagnosed patients based on the levels of these coagulation-related proteins, they discovered three distinct risk groups. Patients with low levels of these proteins had significantly worse survival, regardless of their age, treatment type, or disease stage.

The study suggests that protein-based testing—especially looking at clotting-related proteins—may help identify which patients are at higher risk. This could lead to better risk stratification and more personalized treatment planning in multiple myeloma. More research is needed to confirm these findings.

 

"Fully Human anti-GPRC5D CAR T-Cell Therapy RD118 Induces Durable Remissions in Relapsed/Refractory Multiple Myeloma"

Source

Mengmeng Pan, Di Wang, Jie Xu, Shiwei Jin, Yan Wang, Yi Tao, Yuanfang Liu, Wanyan Ouyang, Xiangqin Weng, Hongmei Yi, Yu Huang, Xinmei Cao, Shuhua Li, Fuyuan Zhang, Weiping Zhang, Chunrui Li, Jian-Qing Mi; Fully Human anti-GPRC5D CAR T-Cell Therapy RD118 Induces Durable Remissions in Relapsed/Refractory Multiple Myeloma. Blood 2025; blood.2025030559. doi: https://doi.org/10.1182/blood.2025030559  October 21, 2025. 

Overview

This study looked at a new CAR T-cell therapy called RD118, which targets a protein on myeloma cells known as GPRC5D. This approach is especially important for people whose disease has returned after BCMA-directed CAR T-cell therapy. In this early trial, 18 heavily pretreated patients—including one with a history of plasma cell leukemia—received a single dose of RD118.

The results were very promising. Overall, 94% of patients responded to the treatment, and more than 70% achieved a complete response, meaning no signs of active disease. Even among those who had previously received BCMA-directed CAR T-cell therapy, the response rate remained high at nearly 86%. The treatment also provided durable disease control. Median progression-free survival was 18.2 months, and after one year, more than 80% of patients had not relapsed, while over 93% were still alive.

Side effects were manageable. Most patients experienced cytokine release syndrome, but it was usually mild. Only one patient developed more serious neurological symptoms, which resolved within three days. No treatment-related deaths occurred. Overall, RD118 appears to be a highly effective and safe new CAR T-cell option for people with hard-to-treat multiple myeloma, and further studies are needed to confirm these encouraging results.

 

"Circulating tumor cells by Next Generation Flow Cytometry as a new prognostic biomarker for patients with asymptomatic monoclonal gammopathies"

Source

Kastritis, E., Malandrakis, P., Kostopoulos, I.V. et al. Circulating tumor cells by Next Generation Flow Cytometry as a new prognostic biomarker for patients with asymptomatic monoclonal gammopathies. Blood Cancer J. 15, 170 (2025). https://doi.org/10.1038/s41408-025-01369-8   October 21, 2025. 

Overview

Researchers looked at whether circulating tumor cells (CTCs)—myeloma cells that can be found in the bloodstream—can help predict which people with MGUS or smoldering myeloma are more likely to progress to active myeloma. They followed 253 patients who had been diagnosed since 2016 and tested their blood using a very sensitive method called next-generation flow cytometry. About 40% of patients had detectable CTCs at diagnosis, and these patients tended to have other signs of higher disease activity, such as more bone marrow involvement, higher M-protein levels, and more abnormal light chain ratios.

After a median of two years of follow-up, 23 patients had progressed to symptomatic myeloma. People with detectable CTCs had a higher risk of progression than those without them. This was true for the overall group and for patients with smoldering myeloma specifically. The researchers also found that even very low levels of CTCs—above a cutoff of 0.0014%—were linked to a higher chance of progressing. A higher cutoff used in past studies did not work as well in this group, likely because most patients in this study had MGUS or lower-risk smoldering disease.

The findings suggest that measuring CTCs in the blood may offer a helpful, non-invasive way to identify patients who are more likely to develop active myeloma. CTCs may reflect more than just tumor amount; they may also signal biological changes that drive the disease forward. Detecting CTCs in MGUS could help identify people who need closer monitoring, while the absence of CTCs in smoldering myeloma might point to a slower-moving condition.

Overall, this study supports using CTC testing as part of risk assessment in early disease states, but longer follow-up and larger studies are needed—especially in MGUS—to determine how best to use this information in day-to-day care.

 

"Abstract A098: Nuvisertib shows single-agent anti-tumor activity in multiple myeloma nonclinical models"

Source

Zakir Khan, Stacy Behare, Mingjie Li, Jason M. Foulks, Steven L. Warner, James R. Berenson; Abstract A098: Nuvisertib shows single-agent anti-tumor activity in multiple myeloma nonclinical models. Mol Cancer Ther 1 October 2025; 24 (10_Supplement): A098. https://doi.org/10.1158/1535-7163.TARG-25-A098  October 22, 2025.  

Overview

Researchers tested a drug called nuvisertib, which blocks an enzyme known as PIM-1, to see whether it could help treat multiple myeloma. PIM-1 is often more active in blood cancers and can help cancer cells grow and resist treatment. Nuvisertib is already being studied in people with another bone marrow disease, but until now, it had not been tested in myeloma models.

In lab studies using myeloma cells from patients, nuvisertib was able to kill cancer cells in a dose-dependent way, meaning higher doses led to stronger effects. Its activity was similar to several drugs already used to treat myeloma. When nuvisertib was combined with standard treatments, the cancer-killing effect increased, especially in samples from patients whose disease had come back or become resistant. Cells from patients in complete remission were less sensitive, suggesting the drug may be most useful for harder-to-treat disease.

The drug was also tested in mouse models implanted with human myeloma tumors. In these animals, nuvisertib slowed tumor growth and reduced tumor size compared with untreated mice. Tumor weights at the end of the study were also significantly lower in the treated group.

Overall, these early results suggest that nuvisertib may have real potential as a new treatment option for multiple myeloma, either on its own or combined with other therapies. More research is needed to confirm how it works in different types of myeloma and whether it can improve outcomes in future clinical trials.

 

"Abstract B106: NASH as a Silent Threat: Impaired Survival in Relapsed/Refractory Myeloma Patients Treated with Teclistamab"

Source

Allen Seylani, Kayvon Sanjasaz, Assal Sadighian; Abstract B106: NASH as a Silent Threat: Impaired Survival in Relapsed/Refractory Myeloma Patients Treated with Teclistamab. Mol Cancer Ther 1 October 2025; 24 (10_Supplement): B106. https://doi.org/10.1158/1535-7163.TARG-25-B106  October 22, 2025 

Overview

Teclistamab is an approved treatment for people with relapsed or refractory multiple myeloma who have already received several other therapies. It works by bringing T cells directly to myeloma cells so they can attack them. While effective, the drug can sometimes affect the liver, causing changes in liver enzymes or, in rare cases, more serious liver problems.

In this study, researchers looked at whether people with a liver condition called nonalcoholic steatohepatitis (NASH) had different long-term outcomes when treated with teclistamab. They reviewed real-world medical records and compared patients who had NASH to those who did not. Only a small number of patients had NASH, but the differences were striking: five years after starting treatment, survival was much lower in the NASH group. These patients also had bigger increases in liver enzymes and bilirubin levels within the first three months of treatment, suggesting more strain on the liver.

The study suggests that people with NASH may be more vulnerable to liver-related side effects from teclistamab. Because teclistamab activates the immune system, it can trigger inflammation that may further tax a liver already affected by NASH. The findings highlight the importance of close monitoring and early management of liver issues in patients with preexisting liver disease who receive this therapy.

 

"Abstract C009: Development of an innovative anticancer drug TBP1901, an injectable prodrug of curcumin, for the treatment of multiple myeloma"

Source

Hideaki Kakeya, Tomoyuki Abe, Yoshihito Horisawa, Osamu Kikuchi, Hitomi Ozawa-Umeta, Atsuhiro Kishimoto, Yasuhiro Katsuura, Atsushi Imaizumi, Tadashi Hashimoto, Kotaro Shirakawa, Akifumi Takaori-Kondo, Kosuke Yusa, Tadashi Asakura, Masashi Kanai; Abstract C009: Development of an innovative anticancer drug TBP1901, an injectable prodrug of curcumin, for the treatment of multiple myeloma. Mol Cancer Ther 1 October 2025; 24 (10_Supplement): C009. https://doi.org/10.1158/1535-7163.TARG-25-C009  October 22, 2025. 

Overview

Researchers are exploring new ways to use curcumin, a natural compound from turmeric, to treat multiple myeloma, especially in cases resistant to standard therapy like bortezomib. Curcumin has shown promise in lab studies for slowing cancer cell growth, affecting pathways like NF-κB and increasing reactive oxygen species (ROS), but its use in patients has been limited because it is poorly absorbed and unstable in the body. To overcome this, scientists developed TBP1901, a water-soluble injectable prodrug that converts into active curcumin in the body with higher availability.

In preclinical studies, TBP1901 was given to mice with multiple myeloma tumors resistant to bortezomib. The drug itself had little effect in lab-grown cells, but once converted to curcumin in the body—especially in the bone marrow—it showed strong anti-myeloma activity and low toxicity. The conversion depended on an enzyme called β-glucuronidase (GUSB), which activates TBP1901 into curcumin. Further analysis using a genome-wide CRISPR-Cas9 screen identified that curcumin’s effects mainly target the NF-κB signaling pathway and mitochondrial function, causing ROS production that contributes to killing myeloma cells.

These findings suggest that TBP1901 could be a promising new therapy for multiple myeloma, including drug-resistant forms, by delivering curcumin directly to the tumor site in an active form and targeting key cancer survival pathways.

 

"Targeting Wnt/β-catenin signaling enhances the efficacy of anti-CD38 immunotherapy in multiple myeloma"

Source

Li H, Chen Y, Gregorova M, Yang T, Zhang X, Yu X, Wang Z, Hua H, Ye L, Qi X, Spaargaren M, Pals ST, Ren Z. Targeting Wnt/β-catenin signaling enhances the efficacy of anti-CD38 immunotherapy in multiple myeloma. Neoplasia. 2025 Oct 23;70:101242. doi: 10.1016/j.neo.2025.101242. Epub ahead of print. 

Overview

Researchers are exploring ways to make existing multiple myeloma treatments more effective by targeting key cell signaling pathways. In multiple myeloma, the Wnt/β-catenin pathway is often overactive and helps cancer cells grow. Another pathway, STAT3, regulates the expression of CD38, a protein targeted by antibody therapies like daratumumab. This study investigated whether blocking Wnt signaling could improve the effectiveness of anti-CD38 treatment.

Using lab-grown myeloma cells and patient-derived samples, scientists inhibited Wnt signaling through genetic methods and chemical inhibitors. They found that blocking Wnt reduced STAT3 activity, which in turn increased CD38 levels on myeloma cells. Higher CD38 expression made the cancer cells more sensitive to daratumumab, improving the drug’s ability to kill tumor cells. These results were confirmed in mouse models, where combining a Wnt inhibitor with daratumumab significantly enhanced anti-myeloma effects compared to daratumumab alone.

The study suggests that targeting Wnt signaling could be a promising strategy to boost the effectiveness of existing anti-CD38 therapies. Combining Wnt inhibitors with daratumumab may help patients with multiple myeloma achieve better treatment responses.

 

"Tandem autologous stem cell transplant in multiple myeloma patients with minimal residual disease: an explorative study"

Source

Oh, S., Park, SS., Lee, J.Y. et al. Tandem autologous stem cell transplant in multiple myeloma patients with minimal residual disease: an explorative study. Blood Res. 60, 54 (2025). https://doi.org/10.1007/s44313-025-00101-6  October 23, 2025.  

Overview

This study looked at how tandem autologous stem cell transplantation (tASCT) affects disease burden in patients with high-risk multiple myeloma. Minimal residual disease (MRD), which measures the small number of myeloma cells that remain after treatment, was used to track responses. Researchers analyzed 28 patients who were MRD-positive before undergoing two stem cell transplants within a year. Patients were grouped based on how much their MRD levels dropped after tASCT, with one group achieving extensive clearance (≥50% reduction) and the other showing modest clearance (<50% reduction).

Overall, MRD levels fell from an average of 0.111% before tASCT to 0.056% after treatment. Three patients became MRD-negative, 20 had reductions without reaching negativity, and five had increases. Patients with extensive MRD clearance saw a dramatic drop in MRD (from 0.152% to 0.017%) and experienced longer progression-free survival—about 38 months compared with 16 months for those with modest clearance. Overall survival was similar between groups.

The findings suggest that tASCT can provide meaningful benefit for patients with MRD-positive multiple myeloma, especially when it leads to a large reduction in residual disease. This supports the use of tASCT as a valuable treatment strategy after an initial transplant for patients with detectable MRD.

 

"Sequential targeting in multiple myeloma: talquetamab, a GPRC5D bispecific antibody, as a bridge to BCMA CAR-T therapy"

Source

Binod Dhakal, Othman S. Akhtar, David Fandrei, Alexandria Jensen, Rahul Banerjee, Darren Pan, Shambavi Richard, Reed Friend, Matthew Rees, Patrick Costello, Mariola Vazquez Martinez, Oren Pasvolsky, Charlotte Wagner, James A. Davis, Omar Castaneda Puglianini, Ran Reshef, Aimaz Afrough, Danai Dima, Manisha Bhutani, Omar Nadeem, Ricardo Parrondo, Ciara Freeman, Lekha Mikkilineni, Shahzad Raza, Larry D. Anderson Jr, Prashant Kapoor, Hitomi Hosoya, Saurabh Chhabra, Ariel Grajales-Cruz, Mahmoud Gaballa, Shonali Midha, Melissa Alsina, Douglas Sborov, Krina Patel, Yi Lin, Christopher Ferreri, Nico Gagelmann, Anupama Kumar, Doris Hansen, Andrew Cowan, Luciano J. Costa, Maximilian Merz, Surbhi Sidana; Sequential targeting in multiple myeloma: talquetamab, a GPRC5D bispecific antibody, as a bridge to BCMA CAR-T therapy. Blood 2025; 146 (17): 2063–2072. doi: https://doi.org/10.1182/blood.2025029773  October 23, 2025. 

Overview

This study looked at using talquetamab, a bispecific antibody targeting GPRC5D, as a temporary treatment for patients with relapsed or refractory multiple myeloma while they waited for CAR-T therapy. CAR-T treatments like ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) have transformed outcomes for these patients, but manufacturing the CAR-T cells can take six to eight weeks, during which disease can progress. Researchers analyzed 134 patients across 20 centers who received talquetamab before CAR-T therapy. Most patients (119) were able to proceed to CAR-T, while 15 did not due to disease progression, manufacturing issues, or personal decisions. Patients had a median age of 65 and had tried a median of five prior therapies, with most being ineligible for prior CAR-T clinical trials.

Talquetamab was given for a median of 23 days and was generally well tolerated. There were no severe cases of cytokine release syndrome (CRS), and only a few serious immune side effects were reported. Common mild side effects included mouth, skin, and nail issues, most of which resolved. The antibody achieved a 71% response rate, and after CAR-T therapy, 88% of patients responded, with 54% achieving complete responses. Toxicities after CAR-T were mostly low-grade, though a few serious infections and rare events like facial palsy and one case of acute myeloid leukemia occurred.

The study suggests that using talquetamab as a bridging therapy is safe and effective, allowing most patients, including those with difficult-to-treat disease, to successfully proceed to BCMA-directed CAR-T therapy while maintaining disease control.

 

"Designing a strong bridge to CAR-T cells with bispecifics"

Source

Francesca Gay, Mattia D’Agostino; Designing a strong bridge to CAR-T cells with bispecifics. Blood 2025; 146 (17): 2012–2014. doi: https://doi.org/10.1182/blood.2025030525  October 23, 2025. 

Overview

This study looked at using talquetamab, a bispecific antibody targeting GPRC5D, as a bridging therapy for patients with relapsed or refractory multiple myeloma while they waited for CAR-T treatments targeting BCMA, such as idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). While CAR-T therapies have shown unprecedented responses, their manufacturing can take six to eight weeks, during which patients with aggressive, heavily treated disease risk progression or death. Bridging therapy helps control the disease during this waiting period, lowers disease burden before CAR-T infusion, and may reduce treatment-related toxicities. An ideal bridging therapy works quickly, reduces tumor burden, does not interfere with CAR-T effectiveness, and avoids adding severe side effects.

Talquetamab has emerged as a promising option because it targets GPRC5D rather than BCMA, acts quickly, and shows high response rates even in heavily pretreated patients. In the study of 134 patients, talquetamab was given for a median of 23 days, achieving a 71% response rate, with 40% achieving very good partial response or better. Severe side effects were rare, with no grade 3 or higher cytokine release syndrome and only 2% grade 3 neurotoxicity. Mild side effects, including mouth, skin, and nail changes and weight loss, were common but mostly resolved.

Following talquetamab, 89% of patients were able to receive CAR-T therapy. Among those who did not, most had disease progression or manufacturing failure. For patients who proceeded to CAR-T, the overall response rate was 88%, with 71% achieving very good partial response or better, and responses deepened over time. Low-grade CAR-T toxicities were common, but severe events were rare, and infections were minimal. Extramedullary disease was the main factor associated with poorer outcomes. The short duration of talquetamab therapy may allow for retreatment with anti-GPRC5D therapies if relapse occurs after CAR-T, as longer continuous therapy can lead to loss of GPRC5D expression.

Overall, this real-world study supports the safety and effectiveness of using talquetamab as a bridging therapy before CAR-T, showing that sequential treatment with bispecific antibodies followed by CAR-T is feasible and may optimize outcomes for patients with relapsed or refractory multiple myeloma.

 

"From Imaging to Insight: The Expanding Role of F-18 FDG PET/CT in Multiple Myeloma"

Source

Cho, H.J., Hong, C. From Imaging to Insight: The Expanding Role of F-18 FDG PET/CT in Multiple Myeloma. Nucl Med Mol Imaging (2025). https://doi.org/10.1007/s13139-025-00957-7  October 23, 2025. 

Overview

Recent guidelines from the Korean Multiple Myeloma Working Party (KMMWP) highlight the growing importance of advanced imaging in managing newly diagnosed multiple myeloma (MM). Both F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and magnetic resonance imaging (MRI) provide valuable information for prognosis and treatment planning. While standard low-dose whole-body CT is highly effective for detecting bone destruction, it is less able to capture infiltrative disease in the bone marrow, which reflects tumor burden and disease activity. MRI and FDG PET/CT are recommended to fill this gap, with MRI being particularly sensitive for detecting focal and diffuse lesions and FDG PET/CT offering superior specificity and the ability to assess lesion viability and extramedullary disease.

Meta-analyses confirm that both imaging methods have significant prognostic value. Multiple focal lesions on either modality are linked to worse outcomes, although the threshold for concern differs—PET/CT studies often cite more than three lesions, while MRI studies suggest seven to twenty-five. MRI tends to detect more lesions, whereas PET/CT better reflects disease activity, making it especially useful for guiding decisions about salvage therapy. PET/CT also shows faster lesion resolution after treatment compared with MRI, and normalization of PET/CT findings has been strongly associated with improved progression-free and overall survival. This correlation extends to minimal residual disease in the bone marrow, which is a key goal of therapy.

Despite these advantages, challenges remain in using PET/CT routinely. There is no universally accepted standard for interpreting results, though scoring systems like IMPeTUs offer a promising framework. False-negative results can occur in about 10% of patients due to low expression of FDG-retaining enzymes, prompting research into alternative tracers. The timing and frequency of follow-up PET/CT scans are also not standardized, and while post-treatment PET/CT negativity predicts better outcomes, isolated PET abnormalities without biochemical relapse are not enough to start salvage therapy.

Overall, both PET/CT and MRI are valuable noninvasive tools that provide prognostic insights and help guide treatment decisions in MM. FDG PET/CT, in particular, is increasingly recognized for monitoring response and identifying high-risk disease features. Guidelines from the KMMWP and recent meta-analyses support their use in routine clinical practice, although further research is needed to clarify optimal follow-up strategies and integrate imaging findings into daily management.

 

"Identification of Copy Number Alterations From Shallow Whole-Genome Sequencing in Multiple Myeloma"

Source

Li, Jiali, Shaobing Gao, Zhenling Li, et al. 2025. “Identification of Copy Number Alterations From Shallow Whole-Genome Sequencing in Multiple Myeloma,” Hematological Oncology: e70150. https://doi.org/10.1002/hon.70150.  October 23, 2025. 

Overview

A recent study explored a new approach for understanding the genetic changes in multiple myeloma (MM) using a technology called LeukoPrint, which employs shallow whole-genome sequencing (sWGS) to detect copy number alterations (CNAs) across the entire genome without requiring cell culture. In MM, prognosis and treatment decisions often rely on identifying CNAs, but traditional methods like karyotyping and FISH are limited because plasma cells are few and divide slowly. In this study of 128 patients, LeukoPrint detected CNAs in 75% of cases, significantly outperforming karyotyping (8%) and FISH (44%). This approach also provided new genetic information and led to changes in prognostic classification for about 20% of patients according to mSMART guidelines.

Hyperdiploidy, an abnormal increase in chromosome number, was the most common CNA observed, present in nearly 40% of patients. LeukoPrint also showed a high agreement (over 90%) between bone marrow and peripheral blood samples, suggesting it could be used as a less invasive method for monitoring disease. The study highlights LeukoPrint as an automated, convenient, and cost-effective tool that complements traditional genetic tests. By detecting CNAs that might be missed by other methods and improving prognostic accuracy, LeukoPrint could help clinicians better tailor treatment strategies for patients with MM.

 

"Rapid PET/MRI to Assess Multiple Myeloma Using T2-Weighted Imaging With Uniform Fat Suppression. Journal of Computer Assisted Tomography"

Source

van der Heijden, Rianne A. MD, PhD, Schmidt, Timothy M. MD, Mao, Lu PhD, Callander, Natallie S. MD; Hernando, Diego PhD; Reeder, Scott B. MD, PhD; Pirasteh, Ali MD. Rapid PET/MRI to Assess Multiple Myeloma Using T2-Weighted Imaging With Uniform Fat Suppression. Journal of Computer Assisted Tomography ():10.1097/RCT.0000000000001811, October 23, 2025. | DOI: 10.1097/RCT.0000000000001811  October 23, 2025. 

Overview

A recent study evaluated a faster MRI technique, called rapid whole-body T2-weighted MRI with fat suppression (T2-FS), for detecting multiple myeloma lesions and compared it with diffusion-weighted imaging (DWI) and FDG PET scans. Traditional whole-body DWI can take a long time and may have imaging artifacts, while T2-FS offers shorter exam times without compromising image quality. In this study, 31 patients with multiple myeloma underwent PET/MRI exams, and the accuracy of each imaging method was compared using a reference standard.

The results showed that T2-FS was significantly more sensitive in detecting individual lesions than both DWI (91.9% vs. 66.7%) and PET (91.9% vs. 44.4%). On a per-patient basis, T2-FS identified all 21 patients with disease, while DWI and PET each detected about 86%. Adding DWI to T2-FS did not change patient management, while adding PET altered care in three patients. Overall, T2-FS proved to be faster and more sensitive than DWI, and it may serve as a practical first-line imaging tool for multiple myeloma. The study suggests that larger prospective studies are needed to confirm these findings and further define the role of T2-FS in clinical practice.

 

"Infection Prophylaxis with Intravenous Immunoglobulin in Multiple Myeloma Patients Treated with Teclistamab"

Source

Michael Sheu, Sofia Molina Garcia, Meera Patel, Ali Mushtaq, Thomas Rust, Muhammad Anns Asif, Faiz Anwer, Aneela Majeed; Infection Prophylaxis with Intravenous Immunoglobulin in Multiple Myeloma Patients Treated with Teclistamab. Oncology 2025; https://doi.org/10.1159/000548964  October 23, 2025. 

Overview

A recent study looked at whether giving intravenous immunoglobulin (IVIG) could help prevent serious infections in multiple myeloma patients receiving Teclistamab, a B-cell maturation antigen-targeting bispecific antibody. Teclistamab is effective against myeloma but can increase the risk of infections because it affects normal antibody production and weakens the immune system. Researchers reviewed 44 patients treated at Taussig Cancer Center and compared infection-related hospitalizations when patients were on IVIG versus off IVIG.

During the study period, 19 infections requiring hospitalization occurred among 17 patients. Only 5 infections happened during 4,378 patient-days on IVIG, compared with 14 infections over 4,619 patient-days when patients were not receiving IVIG. This corresponded to an infection incidence rate more than twice as high in the off-IVIG period, showing a statistically significant reduction in infections while on IVIG. The study suggests that IVIG can effectively lower the risk of serious infections in patients receiving Teclistamab, offering a practical way to protect this vulnerable population while on therapy.

 

"Updated recommendations for diagnosis and treatment of multiple myeloma in Switzerland"

Source

Bertschinger M, Auner HW, Ballova V, De Ramon Ortiz C, Driessen C, Gerull S, Heim D, Jeker B, Lerch E, Müller R, Pabst T, Samaras P, Schmidt A, Taverna C, Zander T, Mey U, Renner C. Updated recommendations for diagnosis and treatment of multiple myeloma in Switzerland. Swiss Med Wkly. 2025 Oct 23;155:4252. doi: 10.57187/s.4252.  October 23, 2025.  

Overview

"Since the last update of the Swiss recommendations for the diagnosis and treatment of multiple myeloma in 2019, the therapeutic landscape has evolved significantly, with the development of new monoclonal antibodies, novel combination therapies, and the introduction of T-cell-redirecting treatments such as bispecific antibodies and CAR T-cell therapy. This article summarises the current diagnostic procedures and therapeutic recommendations in Switzerland."

 

"PET in myeloma redefined: a comparative imaging study with FDG and fluorocholine PET/CT"

Source

Kaya, G., Akin, S., Buyukasik, Y. et al. PET in myeloma redefined: a comparative imaging study with FDG and fluorocholine PET/CT. Eur J Nucl Med Mol Imaging (2025). https://doi.org/10.1007/s00259-025-07624-1  October 23, 2025. 

Overview

A recent study compared two PET/CT imaging methods—^18F-fluorodeoxyglucose (FDG) and ^18F-fluorocholine (FCH)—to see which better detects active multiple myeloma. FDG-PET/CT, the standard imaging approach, can miss disease in some patients because multiple myeloma cells vary in their uptake of glucose. FCH-PET/CT, which highlights areas of increased membrane phospholipid synthesis, was tested as an alternative. The study included 35 adults, 19 at initial diagnosis and 16 at restaging, who had both scans within four weeks.

FDG detected active myeloma in only 49% of patients, while FCH identified disease in 91%, showing much higher sensitivity. FCH also revealed more hypermetabolic foci and its uptake correlated with lab markers such as bone marrow plasma cell infiltration, hemoglobin, and albumin, whereas FDG did not show these associations. These findings suggest that FCH-PET/CT more accurately reflects disease burden, particularly in bone marrow-rich regions, making it a useful tool for staging, evaluating residual disease, and monitoring treatment response in multiple myeloma.

 

"Carfilzomib, pomalidomide, and dexamethasone for multiple myeloma after carfilzomib, lenalidomide, and dexamethasone"

Source

Yi, J.H., Park, SS., Min, CK. et al. Carfilzomib, pomalidomide, and dexamethasone for multiple myeloma after carfilzomib, lenalidomide, and dexamethasone. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-04087-w  October 24, 2025. 

Overview

A recent phase II study explored a new treatment approach for patients with relapsed or refractory multiple myeloma (RRMM) who had already received standard therapy with carfilzomib, lenalidomide, and dexamethasone (KRD). Since many patients relapse during follow-up maintenance with lenalidomide and dexamethasone, researchers tested a regimen combining carfilzomib, pomalidomide, and dexamethasone (KPD), aiming to overcome lenalidomide resistance while keeping carfilzomib for patients still sensitive to it. The study enrolled 12 patients with measurable disease who had previously completed at least 12 cycles of KRD and six cycles of maintenance therapy.

Patients received carfilzomib on days 1, 8, and 15, pomalidomide for 21 days, and weekly dexamethasone every 28 days. The overall response rate was 75%, with three patients achieving complete response, four very good partial responses, and two partial responses. The median progression-free survival was 17.2 months. The most common severe blood-related side effects included neutropenia, thrombocytopenia, and anemia. Despite early study closure due to slow enrollment, the findings suggest that KPD is a feasible and active option for patients with lenalidomide-refractory but carfilzomib-sensitive multiple myeloma.

 

"Risk stratification and early intervention in smoldering multiple myeloma"

Source

Sra, M. S., & Kumar, S. (2025). Risk stratification and early intervention in smoldering multiple myeloma. Leukemia & Lymphoma, 1–9. https://doi.org/10.1080/10428194.2025.2576562  October 24, 2025. 

Overview

Smoldering multiple myeloma (SMM) is an early, asymptomatic form of multiple myeloma with varying risks of progression to active disease. Some patients have a higher likelihood of developing full-blown myeloma, and several validated risk models help identify those at greatest risk. Current guidelines suggest that high-risk patients may benefit from early treatment, typically with lenalidomide alone or combined with dexamethasone, or by enrolling in clinical trials. Recent studies also show that daratumumab, used as a single agent, can significantly delay the progression to multiple myeloma. However, questions remain about the long-term impact of treating SMM early, including effects on overall survival, quality of life, and whether the benefits outweigh the risks in this generally asymptomatic population. This review summarizes the main risk models, key clinical trial evidence, and ongoing research shaping prevention strategies for SMM.

 

"Parameters Associated With Renal Recovery and Survival in Myeloma Patients With Acute Renal Failure to Cast Nephropathy"

Source

H. Ludwig, M. A. Dimopoulos, E. Terpos, et al., “Parameters Associated With Renal Recovery and Survival in Myeloma Patients With Acute Renal Failure to Cast Nephropathy,” American Journal of Hematology (2025): 1–14, https://doi.org/10.1002/ajh.70104.  October 24, 2025. 

Overview

Acute kidney failure caused by cast nephropathy (CAN) is a serious complication in multiple myeloma (MM) that can affect survival and treatment outcomes. This study looked at newly diagnosed MM patients with CAN-related kidney failure to identify factors linked to kidney recovery and overall survival, and to validate the International Myeloma Working Group (IMWG) criteria for renal response. Among 354 patients studied, most had very high levels of free light chains (FLCs) at diagnosis, which decreased below 500 mg/L in about two-thirds of patients after treatment. Using IMWG criteria, roughly one-third achieved a complete renal response, while others had partial or minimal improvement. Kidney function, measured by eGFR, improved to normal or near-normal levels in about one-third of patients, with varying degrees of recovery in the rest. Better kidney outcomes were associated with lower baseline FLC levels, IgG kappa type, initial kidney function, and overall health status. Survival was influenced by age, response to myeloma therapy, kidney function, cytogenetic risk, and calcium levels. Of patients who needed dialysis at the start, nearly 60% were able to stop dialysis during therapy. Treatments including bortezomib and effective reduction of FLCs were linked to better kidney recovery and longer survival. These findings support the use of IMWG renal response criteria and highlight the importance of rapid, effective myeloma therapy in patients with kidney complications.

 

"Using RNA-seq for detecting MRD in multiple myeloma: high sensitivity and prognostic value"

Source

Ren, Y., Liu, M., Fang, J. et al. Using RNA-seq for detecting MRD in multiple myeloma: high sensitivity and prognostic value. Cancer Gene Ther (2025). https://doi.org/10.1038/s41417-025-00973-x  October 24, 2025. 

Overview

Minimal residual disease (MRD) is an important prognostic marker in multiple myeloma (MM), but standard DNA-based NGS methods can miss detections due to somatic hypermutation (SHM). This study compared RNA sequencing (RNA-seq) with targeted IGH-CDR3 DNA-NGS for MRD monitoring. Analyzing 125 samples from 35 MM patients, RNA-seq detected clonal immunoglobulin sequences in all bone marrow and peripheral blood samples with high sensitivity (10⁻⁶), outperforming targeted NGS, which missed some cases, especially those with higher SHM rates. Clonal immunoglobulin expression was higher in MM than in B-ALL, and MRD-negative peripheral blood samples identified by RNA-seq correlated with better survival. These findings suggest that RNA-seq is a more sensitive and informative method for MRD monitoring in MM, allowing better prognosis prediction and detailed assessment of clonal immunoglobulin gene expression.

 

"35 years of academic trials focusing on high-dose therapy and autologous stem cell transplantation: the Intergroupe Francophone du Myélome (IFM) experience"

Source

Moreau, P., Hulin, C., Talbot, A. et al. 35 years of academic trials focusing on high-dose therapy and autologous stem cell transplantation: the Intergroupe Francophone du Myélome (IFM) experience. Blood Cancer J. 15, 177 (2025). https://doi.org/10.1038/s41408-025-01387-6  October 24, 2025. 

Overview

Minimal residual disease (MRD) is an important prognostic marker in multiple myeloma (MM), but standard DNA-based NGS Frontline high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for transplant-eligible multiple myeloma (MM) patients in 2025. Current strategies include induction with quadruplet regimens when possible and lenalidomide maintenance until progression. These approaches, developed through decades of phase 3 trials by academic groups, have extended median overall survival from approximately 5 years in the 1990s to over 15 years today. The French myeloma cooperative group, Intergroupe Francophone du Myélome (IFM), has played a key role in advancing treatment in the newly diagnosed, transplant-eligible setting.

 

"Hypoalbuminemia: a new risk factor for progression in patients with monoclonal gammopathy of uncertain significance"

Source

Alejo, E., González-Calle, V., Blázquez, P. et al. Hypoalbuminemia: a new risk factor for progression in patients with monoclonal gammopathy of uncertain significance. Blood Cancer J. 15, 179 (2025). https://doi.org/10.1038/s41408-025-01371-0  October 24, 2025. 

Overview

Hypoalbuminemia may be an important prognostic marker in monoclonal gammopathy of uncertain significance (MGUS). In a retrospective study of 838 MGUS patients, low albumin (≤3.5 g/dL) was associated with older age, male sex, IgA subtype, lower hemoglobin, and higher creatinine. Both hypoalbuminemia and serum M protein ≥1.5 g/dL independently predicted progression to multiple myeloma. Incorporating hypoalbuminemia into existing risk models improved identification of intermediate-risk patients, suggesting it could enhance prognostic stratification and inform clinical management if validated in future studies.

 

"Structure-based prediction reveals a difference in the binding mode of anti-BCMA antibodies to BCMA and soluble BCMA"

Source

Kikuchi, J., Osada, N., Matsuoka, S. et al. Structure-based prediction reveals a difference in the binding mode of anti-BCMA antibodies to BCMA and soluble BCMA. Leukemia (2025). https://doi.org/10.1038/s41375-025-02792-3  October 24, 2025. 

Overview

B-cell maturation antigen (BCMA)–targeted therapies have improved outcomes for relapsed and refractory multiple myeloma (RRMM), including patients with triple-class refractory disease. However, treatment efficacy can be limited by antigen escape and the neutralizing effects of soluble BCMA (sBCMA). This study compared three BCMA antibodies—teclistamab (Tec), elranatamab (Elra), and belantamab—using structural analysis and in vitro experiments. Results showed that Tec maintained binding to myeloma cells even in the presence of sBCMA, whereas Elra binding was significantly inhibited by sBCMA, indicating greater susceptibility to the sBCMA sink effect. These findings suggest differences in how BCMA antibodies are affected by sBCMA and highlight Tec’s potential advantage in overcoming this resistance mechanism

 

"Bone disease burden does not impact overall survival in newly diagnosed patients with multiple myeloma − a single center, retrospective imaging analysis on 119 patients"

Source

Evangelos Terpos, Vassilis Koutoulidis, Ioannis Ntanasis-Stathopoulos, Stylianos Mavropoulos-Papoudas, Maria Douka, Maria Gavriatopoulou, Panagiotis Malandrakis, Vasiliki Spiliopoulou, Foteini Theodorakakou, Despina Fotiou, Magdalini Migkou, Nikolaos Kanellias, Evangelos Eleutherakis-Papaiakovou, Efstathios Kastritis, Lia-Angela Moulopoulos, Meletios A Dimopoulos, Bone disease burden does not impact overall survival in newly diagnosed patients with multiple myeloma − a single center, retrospective imaging analysis on 119 patients, Journal of Bone Oncology, 2025, 100720, ISSN 2212-1374, https://doi.org/10.1016/j.jbo.2025.100720. October 25, 2025. 

Overview

Vertebral compression fractures (VCFs) on whole-body low-dose CT (WBLDCT) at diagnosis correlate with shorter progression-free and overall survival in multiple myeloma (MM) in univariate analysis, but they are not independent prognostic markers after adjusting for clinical factors. Other imaging features, including lesion count, cortical destruction, and appendicular skeleton medullary cavity patterns, were also not predictive. These results suggest that, with modern anti-myeloma therapies, baseline bone disease burden may have limited impact on prognosis.

 

"CD70-Targeting CAR-NK Cells Overcome BCMA Downregulation and Improve Survival in High-Risk Multiple Myeloma Models"

Source

Paul Lin, Sunil Acharya, Francia Reyes-Silva, Rafet Basar, Nadima Uprety, Luz Yurany. Moreno Rueda, Pei Lin, April L. Gilbert, Pinaki P. Banerjee, Dexing Fang, Chenyu Zhang, Ana Karen. Nunez Cortes, Luciana Melo Garcia, May Daher, Luis Muniz-Feliciano, Gary M. Deyter, Vernikka Woods, Seema Rawal, Ping Li, Corry M. Jones, Rejeena Shrestha, Muzaffar H. Qazilbash, Krina K. Patel, Hans C. Lee, Richard E. Champlin, David Marin, Elizabeth J. Shpall, Robert Z. Orlowski, Katayoun Rezvani; CD70-Targeting CAR-NK Cells Overcome BCMA Downregulation and Improve Survival in High-Risk Multiple Myeloma Models. Blood Cancer Discov 2025; https://doi.org/10.1158/2643-3230.BCD-25-0130  October 27, 2025.  

Overview

CD70 is highly expressed in high-risk multiple myeloma (MM) and is associated with poor survival. Preclinical studies show that natural killer (NK) cells engineered with a CD70-targeting CAR incorporating CD27 and IL-15 effectively kill CD70+ MM cells, including BCMA-resistant models. These findings establish CD70 as a promising therapeutic target, supporting ongoing clinical trials of CD70-directed CAR-NK therapy in relapsed MM.

 

"Epigenetic modifications of the PHOX2A and CDH2 genes expression– new insights into the pathogenesis of multiple myeloma"

Source

Łuczkowska, K., Brzosko, M., Stodolak, P. et al. Epigenetic modifications of the PHOX2A and CDH2 genes expression– new insights into the pathogenesis of multiple myeloma. BMC Cancer 25, 1653 (2025). https://doi.org/10.1186/s12885-025-15030-x  October 27, 2025.  

Overview

Epigenetic analysis of multiple myeloma (MM) and precursor MGUS revealed that decreased methylation and increased expression of the oncogenic genes PHOX2A and CDH2 are associated with MM progression and poor prognosis. Additionally, specific miRNAs (miR-208b-3p and miR-320c) were upregulated in MGUS and may inhibit these genes. These findings suggest that targeting epigenetic changes or monitoring circulating miRNAs could inform prognosis and guide novel therapeutic strategies in MM.

 

"The prognostic value of POD24 for multiple myeloma: a comprehensive analysis based on traditional statistics and machine learning"

Source

Zhang, Q., Wang, Y., Chen, Q. et al. The prognostic value of POD24 for multiple myeloma: a comprehensive analysis based on traditional statistics and machine learning. BMC Cancer 25, 1652 (2025). https://doi.org/10.1186/s12885-025-15089-6  October 27, 2025. 

Overview

Early disease progression within 24 months (POD24) strongly predicts poorer overall survival in multiple myeloma. Both traditional statistical analyses and machine learning—including artificial neural networks (ANN) with SHAP interpretation—confirmed POD24 as the most influential predictor of mortality, highlighting its potential as a key factor in risk stratification and prognostic modeling.

 

"Machine learning reveals distinct T-cell receptor clusters in plasma cell dyscrasias compared to healthy controls"

Source

Coffey DG, Zhang Y, Hill E, Cross F Jr, Philip R, Theoret MR, Landgren O, Baines AC, Kazandjian D. Machine learning reveals distinct T-cell receptor clusters in plasma cell dyscrasias compared to healthy controls. PLoS One. 2025 Oct 27;20(10):e0334053. doi: 10.1371/journal.pone.0334053.  

Overview

T-cell receptor (TCR) repertoire diversity does not differ significantly between healthy individuals and patients with MGUS, SMM, or newly diagnosed multiple myeloma, nor does it correlate with treatment response. However, machine learning revealed distinct TCR clusters with unique amino acid properties in plasma cell dyscrasias, suggesting shared antigen-specific immune signatures that may have prognostic or functional relevance and warrant further study.

 

"Resolving Daratumumab-Induced Serologic Interference: A Modified Low-Concentration DTT Protocol in Multiple Myeloma Patients in Eastern India"

Source

Das, S.S., Mukherjee, S., Chowdhury, S. et al. Resolving Daratumumab-Induced Serologic Interference: A Modified Low-Concentration DTT Protocol in Multiple Myeloma Patients in Eastern India. Indian J Hematol Blood Transfus (2025). https://doi.org/10.1007/s12288-025-02174-w  October 27, 2025.  

Overview

Daratumumab (DARA) causes pan-reactivity in antibody screens and crossmatch incompatibility in multiple myeloma patients, complicating transfusions. A modified low-concentration DTT protocol effectively resolves this interference, restoring crossmatch compatibility in 97.7% of cases, allowing safe and efficient transfusion while preserving red cell integrity.
 

"Impact of body mass index on the prognosis of patients with newly diagnosed Multiple Myeloma"

Source

Kevin D Arnold, Krystle L Ong, Gayathri Ravi, Meredith C Wessel, Faith E. Davies, Luciano J. Costa, Ananya Deshpande, Gareth J. Morgan, Brenda M Birmann, Elizabeth E Brown; Impact of body mass index on the prognosis of patients with newly diagnosed Multiple Myeloma. Blood Adv 2025; bloodadvances.2025018024. doi: https://doi.org/10.1182/bloodadvances.2025018024  October 28, 2025.   

Overview

In newly diagnosed multiple myeloma patients, extremes of BMI are linked to worse outcomes, with severe obesity (BMI ≥ 35 kg/m²) associated with the highest risk of disease progression and mortality. These results underscore the potential importance of weight management to improve prognosis across patient populations.
 

"A Post-Market Economic Evaluation of Bortezomib, Lenalidomide and Dexamethasone Versus Pre-funding Standard of Care for Newly Diagnosed Multiple Myeloma Using Registry Data"

Source

Irving, A., Petrie, D., Harris, A. et al. A Post-Market Economic Evaluation of Bortezomib, Lenalidomide and Dexamethasone Versus Pre-funding Standard of Care for Newly Diagnosed Multiple Myeloma Using Registry Data. PharmacoEconomics (2025). https://doi.org/10.1007/s40273-025-01554-4  October 29, 2025.    

Overview

A real-world economic analysis in Australia found that funding bortezomib, lenalidomide, and dexamethasone (VRd) for newly diagnosed multiple myeloma produced only modest gains in quality-adjusted life-years at substantial incremental cost, falling short of conventional cost-effectiveness thresholds. These findings emphasize the value of post-market evaluations in guiding healthcare resource allocation.
 

"Long-term Follow-up of Zevor-cel in Patients with Relapsed/Refractory Multiple Myeloma"

Source

Chengcheng Fu, Wenming Chen, Zhen Cai, Lingzhi Yan, Huijuan Wang, Jingjing Shang, Yin Wu, Shuang Yan, Wen Gao, Xiaolan Shi, Xiaoyan Han, Fang Tang, Gaofeng Zheng, Yanling Wen, Xingxing Meng, Daijing Yuan, Huamao Wang, Zonghai Li; Long term Follow-up of Zevor-cel in Patients with Relapsed/Refractory Multiple Myeloma. Blood Adv 2025; bloodadvances.2025017365. doi: https://doi.org/10.1182/bloodadvances.2025017365  October 29, 2025. 

Overview

Long-term follow-up from the phase 1 LUMMICAR Study 1 shows that zevorcabtagene autoleucel (zevor-cel), a fully human BCMA-directed CAR T therapy, produces high response rates and durable remissions in relapsed/refractory multiple myeloma. With over four years of median follow-up, zevor-cel demonstrated a manageable safety profile and sustained overall survival, supporting its promising efficacy in heavily pretreated patients.
 

"Mezigdomide for multiple myeloma: a focus on phase 2 trial data. Expert Opinion on Emerging Drugs"

Source

Mo, C. C., Liu, Y., Nadeem, O., Midha, S., Laubach, J. P., Salman, T. J., … Richardson, P. G. (2025). Mezigdomide for multiple myeloma: a focus on phase 2 trial data. Expert Opinion on Emerging Drugs. https://doi.org/10.1080/14728214.2025.2575570  October 29, 2025.  

Overview

Mezigdomide, a next-generation cereblon E3 ligase modulator, shows promising preclinical and early-phase clinical activity in relapsed/refractory multiple myeloma, including triple-class-refractory disease. With higher cereblon binding and greater substrate degradation than traditional immunomodulatory drugs, mezigdomide demonstrates potential synergy with standard therapies and is under investigation in combination regimens to improve outcomes across difficult-to-treat patient populations.
 

"Targeting of SKP2 to combat drug resistance in multiple myeloma"

Source

Faruq, O., Ngo, J., Iyer, D. et al. Targeting of SKP2 to combat drug resistance in multiple myeloma. Sci Rep 15, 37838 (2025). https://doi.org/10.1038/s41598-025-21719-7  October 29, 2025.  

Overview

SKP2, a key component of the SCF-SKP2 ubiquitin ligase complex, is increasingly expressed as multiple myeloma progresses and contributes to drug resistance. Preclinical studies show that SKP2 inhibition with SkpinC1 suppresses STAT3 signaling and oncogenic proteins like c-MYC and c-MAF, impairs myeloma cell growth, induces apoptosis, and enhances sensitivity to bortezomib, highlighting SKP2 as a promising therapeutic target in overcoming drug resistance in MM.
 

"Bispecific antibodies in multiple myeloma: maximizing potential through rational combination therapies"

Xiang Zhou, Johannes M. Waldschmidt, Hermann Einsele, Bispecific antibodies in multiple myeloma: maximizing potential through rational combination therapies, Blood Reviews, 2025, 101342, ISSN 0268-960X, https://doi.org/10.1016/j.blre.2025.101342. October 30, 2025.  

Overview

Bispecific antibodies are transforming multiple myeloma treatment by engaging T cells to target tumor antigens. Approved agents such as teclistamab, elranatamab, linvoseltamab (BCMA×CD3), and talquetamab (GPRC5D×CD3) show high response rates in relapsed/refractory MM, while next-generation constructs and agents targeting FcRH5 are under investigation. Challenges like antigen loss, T-cell dysfunction, and soluble BCMA are being addressed through combination strategies and dual-targeting approaches. Early frontline studies suggest bispecific antibodies may deepen responses and achieve MRD negativity, offering a scalable, off-the-shelf alternative to CAR-T therapy with potential for long-term disease control.
 

"Targeting lncRNA MALAT1 attenuates lenalidomide resistance via CD38 epigenetic modulation, oxidative stress–mediated cell death, and remodeling of the pro-tumor microenvironment in multiple myeloma"

Chang, WH., Liao, WT., Yeh, TJ. et al. Targeting lncRNA MALAT1 attenuates lenalidomide resistance via CD38 epigenetic modulation, oxidative stress–mediated cell death, and remodeling of the pro-tumor microenvironment in multiple myeloma. J Transl Med 23, 1199 (2025). https://doi.org/10.1186/s12967-025-07252-1  October 30, 2025. 

Overview

MALAT1, an oncogenic long non-coding RNA, drives drug resistance in multiple myeloma by epigenetically regulating CD38, reprogramming metabolism, and shaping a tumor-supportive bone marrow environment. In lenalidomide-resistant MM cells and patient samples, MALAT1 knockdown reduced CD38, impaired mitochondrial function, decreased OXPHOS and ATP, and increased ROS, while lowering pro-tumorigenic cytokines. Combining anti-MALAT1 antisense oligonucleotides with standard therapies enhanced cytotoxicity, highlighting MALAT1 as a promising target to overcome drug resistance and improve therapeutic response in multiple myeloma.
 

"AI-Quantified ¹¹C-MET PET/CT bone marrow metabolic activity for prognostic assessment in newly diagnosed multiple myeloma"

Ye, Z., Lv, J., Wu, X. et al. AI-Quantified ¹¹C-MET PET/CT bone marrow metabolic activity for prognostic assessment in newly diagnosed multiple myeloma. Eur J Nucl Med Mol Imaging (2025). https://doi.org/10.1007/s00259-025-07594-4  October 30, 2025. 

Overview

An AI algorithm can accurately quantify whole-skeleton bone marrow metabolic activity on ¹¹C-methionine PET/CT in newly diagnosed multiple myeloma, generating metabolic tumor volume (MTV) and total lesion methionine uptake (TLMU) metrics that correlate with bone marrow plasma cell percentage, serum β₂-microglobulin, and disease stage. These AI-derived ¹¹C-MET measures independently predicted progression-free survival and outperformed ¹⁸F-FDG PET/CT parameters, suggesting their potential as objective biomarkers to improve risk stratification and prognostic assessment in multiple myeloma.
 

"Improved survival in multiple myeloma following prior detection of precursor conditions: a nationwide real-world study"

Choi, S., Park, SS., Lee, C.H. et al. Improved survival in multiple myeloma following prior detection of precursor conditions: a nationwide real-world study. Blood Cancer J. 15, 185 (2025). https://doi.org/10.1038/s41408-025-01395-6  October 30, 2025. 

Overview

A nationwide Korean population-based study shows that patients whose multiple myeloma (MM) was preceded by MGUS or smoldering MM (SMM) experience significantly better overall survival than those diagnosed de novo, even when therapy begins only at symptomatic progression. After adjusting for demographics, comorbidities, and treatment intensity, patients progressing from MGUS or SMM had weighted hazard ratios of 0.53 and 0.83, respectively, versus de novo MM, suggesting that early detection and structured surveillance of precursor conditions may identify biologically more indolent disease, enable timely intervention, and improve survival outcomes.