A summary of some notable key multiple myeloma research from March-April 2026  

Scope and Methodology   
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals March-April 2026. Content was developed by the International Myeloma Foundation medical editorial team using various medical abstracts on new guidelines, recommendations, reviews, letters to the editor, correspondence, and the latest results of ongoing clinical trials. It is intended for patients, care partners, and oncology professionals. This blog article was medically reviewed by Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, on April 29, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.   

Guidelines and Recommendations

Choosing Wisely in First Relapse of Multiple Myeloma: Expert Insights on Treatment Selection — Clinical Lymphoma Myeloma and Leukemia (March 2026)

What is the purpose of the study? 
To evaluate treatment strategies for patients with multiple myeloma at first relapse, focusing on how prior therapies, patient characteristics, and emerging options influence optimal treatment selection; and to assess the role and sequencing of novel therapies, including CAR-T and BCMA-targeting agents, to improve outcomes and preserve long-term treatment effectiveness.

Summary 
After initial therapy, most patients with newly diagnosed multiple myeloma (NDMM) eventually relapse and need second-line treatment. Choosing therapy at first relapse depends on prior drug exposure, disease characteristics, patient health, and future options like CAR-T therapy or bispecific T-cell engagers (TCEs). Standard options include anti-CD38 monoclonal antibody (mAb)–based regimens, proteasome inhibitors (PIs), and immunomodulatory drugs (IMiDs), but resistance can limit their effectiveness. Cell therapies such as autologous stem cell transplant (ASCT) and CAR-T therapy (e.g., cilta-cel) offer durable responses, with CAR-T showing significant progression-free and overall survival benefits in lenalidomide-refractory patients. New BCMA-targeting therapies, including antibody-drug conjugates (belantamab mafodotin) and TCEs (teclistamab, talquetamab), are expanding options but carry unique side effects, such as ocular toxicity or infections, and treatment sequencing is critical to maintain efficacy.

Key points

• First relapse therapy: Should consider prior drug exposure, cytogenetics, comorbidities, and response duration. 
• Anti-CD38 mAbs: Effective for anti-CD38–naive or exposed patients; triple-class refractory disease needs novel targets like BCMA. 
• Cell therapies: ASCT and CAR-T (cilta-cel) improve survival; CAR-T requires early referral and bridging therapy. 
• Cilta-cel (CAR-T): Phase 3 CARTITUDE-4 showed median PFS not reached vs 11.8 months for standard care; OS at 30 months 76.4% vs 63.8%. Side effects: cytokine release syndrome (76%), neurologic events (20%), infections. 
• BCMA-targeting therapies: Belantamab mafodotin (DREAMM-7 & 8) improves PFS but has ocular toxicity; TCEs like teclistamab show high response rates (≥CR 54.5%) with infection risks. 
• Treatment sequencing: Crucial to preserve T-cell fitness for CAR-T and avoid cross-resistance between BCMA therapies. 
• High-risk patients: Immediate treatment plus early CAR-T referral recommended; standard-risk may delay CAR-T but can benefit from longer treatment-free periods.

Why these insights matter 
Selecting treatment at first relapse in MM is increasingly complex and requires individualized decisions based on prior therapy, disease risk, and patient health. Anti-CD38 mAbs, PIs, and IMiDs remain foundational, but CAR-T therapy (cilta-cel) offers transformative survival benefits and should be considered early. Emerging BCMA-targeting therapies expand options but require careful sequencing and monitoring for toxicity. Early referral to CAR-T centers and strategic use of holding and bridging therapy optimize patient outcomes. Multidisciplinary collaboration ensures access to the most effective therapies at the right time in the disease course.

Reference: 
Samer Al Hadidi, Caitlin Costello, Luciano J. Costa, Binod Dhakal, Peter Georges, Ajeet Gajra, Yi Lin, Ranjana S Bhargava, Agne Paner-Straseviciute, Ravi Vij, Choosing Wisely in First Relapse of Multiple Myeloma: Expert Insights on Treatment Selection, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.009.

 
Revised Recommendations for Restarting Teclistamab Following Dose Delays: Insights from the MajesTEC-1 Study on Clinical Safety, and from Simulated Pharmacokinetics and Cytokine Dynamics — Targeted Oncology (March 2026)

What is the purpose of the study? 
To determine safe and effective strategies for restarting teclistamab after treatment delays in patients with relapsed/refractory multiple myeloma (RRMM); and to guide recommendations on whether step-up doses (SUDs) should be repeated, pharmacokinetic modeling and data from the MajesTEC-1 clinical trial were used.

Summary  
Using modeling simulations and retrospective analysis from the MajesTEC-1 trial, researchers evaluated how treatment delays affect teclistamab drug levels and the risk of cytokine release syndrome (CRS). Results showed that drug levels after delays of up to 62 days and 111 days were comparable to levels seen after step-up doses, while predicted cytokine peaks were lower than during initial treatment. Clinical data confirmed a low incidence of CRS (3.3%, all grade 1–2) in patients restarting therapy after delays longer than 28 days. Based on these findings, restarting teclistamab without repeating SUDs is safe for shorter delays, with partial or full SUD repetition recommended only for longer interruptions.

Key points 
• Drug: Teclistamab (BCMA × CD3 bispecific antibody for RRMM)  
• Study approach: Population pharmacokinetic (PK) and quantitative systems pharmacology (QSP) modeling + retrospective MajesTEC-1 data  
• Key findings (Drug levels):  
    - Comparable to SUD2 levels after ~62 days delay  
    - Comparable to SUD1 levels after ~111 days delay  
• Safety (CRS):  
    - Low incidence after restart: 3.3% (2/61 patients)  
    - All CRS events were mild (grade 1–2)  
• Cytokine modeling: Predicted lower cytokine peaks at restart vs initial dosing  

• Restart recommendations:  
   - ≤ 62 days: resume without repeat SUD  
   - 63–111 days: restart at second SUD  
   - 111 days: repeat both SUDs before full dosing

• Clinical relevance: Supports updated, more flexible dosing guidelines after interruptions  

Why these recommendations matter  
This study shows that teclistamab can be safely restarted after treatment delays with a very low risk of CRS, supported by both modeling and clinical data from MajesTEC-1. The findings provide clear, evidence-based guidance on when step-up dosing should be repeated, allowing greater flexibility in patient care. Overall, these recommendations help optimize safety while maintaining treatment effectiveness in RRMM patients.

Reference: 
Cardé, N.A.Q., Niu, J., Guo, Y. et al. Revised Recommendations for Restarting Teclistamab Following Dose Delays: Insights from the MajesTEC-1 Study on Clinical Safety, and from Simulated Pharmacokinetics and Cytokine Dynamics. Targ Oncol (2026). https://doi.org/10.1007/s11523-026-01205-4

Review

Mapping the Landscape of Quality of Life in Smoldering Multiple Myeloma Clinical Trials: A Systematic Review — Clinical Lymphoma Myeloma and Leukemia (March 2026)

What is the purpose of the review? 
To evaluate how health-related quality of life (HRQoL) is measured and reported in clinical trials of treatments for smoldering multiple myeloma (SMM); and to understand whether early treatment improves patients’ quality of life and to identify gaps in current research. Ultimately, the review seeks to highlight the need for better inclusion of HRQoL data to support more patient-centered treatment decisions.

Summary  
Smoldering multiple myeloma (SMM) is an early stage of multiple myeloma with a higher risk of progressing to active disease, especially in high-risk patients. Recent research is shifting toward early treatment to delay or prevent progression, but its impact on health-related quality of life (HRQoL) is not well understood. This systematic review found that only a few clinical trials, including AQUILA and ECOG-ACRIN, assessed HRQoL, and both reported improvements that appeared to depend on the specific treatment used. However, most studies did not include HRQoL outcomes, highlighting a major gap in patient-centered research. Better and more consistent measurement of HRQoL is needed to guide treatment decisions.

Key points 
• Smoldering multiple myeloma (SMM): precursor to active multiple myeloma, with high progression risk in some patients 
• Shift from observation to early treatment strategies to delay/prevent progression 
• HRQoL (health-related quality of life) is an important but underreported outcome 
• Only 4 randomized trials assessed HRQoL; only 2 provided detailed data 
• AQUILA and ECOG-ACRIN trials showed improvements in HRQoL 
• HRQoL benefits appear treatment-specific 
• Most trials did not include HRQoL, representing a major evidence gap 
• Lack of HRQoL data is both a methodological and ethical concern 
• Need for routine inclusion of HRQoL in future clinical trials

Why this review matters 
This review highlights a growing shift toward early treatment in smoldering multiple myeloma, particularly for high-risk patients. While some trials, such as AQUILA and ECOG-ACRIN, suggest that treatment can improve quality of life, overall evidence remains limited. The lack of consistent HRQoL reporting in most studies is a significant gap that affects both research quality and patient care. Incorporating HRQoL as a standard outcome is essential for understanding the full impact of treatment. Doing so will support more balanced, patient-centered decisions as treatment strategies continue to evolve.

Reference: 
Gómez-Almaguer David, Saldaña-Vázquez Roxana, Tarín-Arzaga Luz, Herrera-Rojas Miguel Angel, Vázquez-Mellado de Larracoechea Alberto, Cantú-Rodríguez Olga Graciela, Gutiérrez-Aguirre Cesar Homero, Jaime-Pérez José Carlos, "Mapping the Landscape of Quality of Life in Smoldering Multiple Myeloma Clinical Trials: A Systematic Review", Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.006.

Early intervention for high-risk smoldering multiple myeloma (SMM) — Cochrane Database of Systematic Review (March 2026)

What is the purpose of the review? 
To evaluate whether early treatment improves outcomes compared with observation in patients with high-risk smoldering multiple myeloma (SMM); and to assess the benefits and harms of interventions such as daratumumab, lenalidomide, thalidomide, melphalan-prednisone, and siltuximab.

Summary  
This systematic review included seven randomized controlled trials (1,096 patients) comparing early intervention versus observation or placebo in high-risk SMM. Early treatment with the monoclonal antibody daratumumab showed a potential reduction in progression or death (HR 0.49) and mortality (HR 0.52), although the certainty of evidence was low and adverse event risks were unclear. Results for immunomodulatory drugs such as lenalidomide and thalidomide were inconsistent, with no clear benefit in progression-free survival (PFS), overall survival (OS), or quality of life. Evidence for siltuximab (cytokine inhibitor) and melphalan-prednisone (alkylating therapy) was very limited and uncertain. Overall, while some early intervention strategies show promise, the evidence remains insufficient and variable across treatments.

Key points 
• High-risk SMM is an intermediate stage before symptomatic multiple myeloma. 
• Daratumumab may reduce disease progression (HR 0.49) and mortality (HR 0.52), but evidence is low certainty. 
• Immunomodulatory agents (lenalidomide, thalidomide) show inconsistent and uncertain benefits. 
• Limited and very uncertain evidence for siltuximab and melphalan-prednisone. 
• Adverse event risks with early treatment remain unclear. 
• Decision-making should be individualized with careful risk–benefit assessment.

Why this review matters  
Early intervention in high-risk SMM, particularly with daratumumab, may delay disease progression and potentially improve survival, but the certainty of evidence is limited. Other treatments, including lenalidomide and thalidomide, have shown inconsistent results and do not clearly improve outcomes. Evidence supporting older or less commonly used therapies such as siltuximab and melphalan-prednisone is insufficient. The potential for adverse effects adds uncertainty to early treatment decisions. Therefore, management of high-risk SMM should involve individualized assessment and shared decision-making until stronger evidence becomes available.

Reference: 
Chen PH, Jhou HJ, Ho CL, Huang HL, Lee CH. Early intervention for high-risk smoldering multiple myeloma (SMM). Cochrane Database Syst Rev. 2026 Mar 18;3:CD015494. doi: 10.1002/14651858.CD015494.pub2.  

The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma — European Journal of Haematology (March 2026)

What is the purpose of the review? 
To examine how the tumor microenvironment (TME) influences the effectiveness of T-cell-redirecting bispecific antibodies (BsAbs) in multiple myeloma (MM); and to identify mechanisms of resistance and highlight emerging strategies, including combination therapies and trispecific antibodies, to improve patient outcomes.

Summary  
MM remains largely incurable despite advances such as BsAbs and CAR-T cell therapies, which can produce deep responses in relapsed/refractory disease. However, many patients relapse due to limited durability of response and treatment-related toxicities. The tumor microenvironment plays a key role in reducing treatment effectiveness by suppressing immune responses through regulatory T cells, myeloid-derived suppressor cells, inhibitory cytokines (e.g., TGF-β, IL-6), and metabolic constraints, leading to T-cell exhaustion. Resistance mechanisms such as antigen escape and impaired T-cell fitness further limit long-term outcomes. Emerging approaches, including trispecific antibodies (e.g., JNJ-5322, HPN217), immunomodulatory drugs like iberdomide, and combination regimens studied in trials such as MonumenTAL-3, aim to enhance T-cell function and overcome these barriers.

Key points 
• MM is a clonal plasma cell malignancy that remains largely incurable.  
• BsAbs and CAR-T therapies show strong initial responses but are limited by relapse and toxicity.  
• The tumor microenvironment suppresses immune activity via:  
     - Regulatory T cells (Tregs)  
     - Myeloid-derived suppressor cells (MDSCs)  
     - Cytokines such as IL-6 and TGF-β  
     - Hypoxia and metabolic constraints  
• Chronic CD3 stimulation contributes to T-cell exhaustion and reduced efficacy.  
• Resistance mechanisms include antigen escape and impaired T-cell persistence.  
• Trispecific antibodies (e.g., JNJ-5322, HPN217) enhance co-stimulation and dual-antigen targeting.  
• Combination strategies (e.g., talquetamab + daratumumab ± pomalidomide in MonumenTAL-3) aim to reshape the TME and improve outcomes.  

Why this review matters  
The tumor microenvironment in MM is an active driver of resistance to bispecific antibody therapies, limiting their durability and effectiveness. Immunosuppressive cells, inhibitory cytokines, and metabolic factors contribute to T-cell dysfunction and disease progression. Understanding these mechanisms has led to new therapeutic strategies, including combination regimens, checkpoint inhibition, and next-generation trispecific antibodies designed to enhance immune activation and prevent antigen escape. These approaches aim to improve the depth and duration of responses while maintaining safety. Ultimately, targeting and reshaping the tumor microenvironment may significantly advance treatment outcomes for patients with relapsed or refractory MM.

Reference: 
S.Barachini, R.Cassano Cassano, F.Ronca, I.Petrini, S.Galimberti, and G.Buda, “The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma,” European Journal of Haematology (2026): 1–19, https://doi.org/10.1111/ejh.70168.

The Role of Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma With Renal Impairment: A Systematic Review — American Journal of Hematology (April 2026)

What is the purpose of the review? 
To systematically review clinical trials and real-world data and evaluate the safety and effectiveness of bispecific antibodies (BsAbs) in patients with relapsed/refractory multiple myeloma (RRMM) who have renal impairment (RI). It aims to determine whether outcomes differ between patients with and without impaired kidney function.

Summary  
Across 11 studies (three pivotal studies and eight real-world cohorts with 1,117 patients), BsAbs such as teclistamab and talquetamab showed similar overall response rates (ORR), progression-free survival (PFS), and overall survival (OS) in patients with and without renal impairment. Safety outcomes were comparable, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and most hematologic toxicities. However, thrombocytopenia occurred more frequently in patients with RI. These findings suggest that BsAbs remain effective and generally well tolerated even in patients with moderate to severe renal dysfunction, including some who are on dialysis.

Key points 
• Renal impairment (estimated glomerular filtration rate <60 mL/min) is common and high-risk in RRMM. 
• 11 studies (3 clinical trials, 8 real-world cohorts) with 1,117 patients were analyzed. 
• BsAbs (e.g., teclistamab, talquetamab) showed comparable efficacy (ORR, PFS, OS) in patients with and without RI. 
• Safety profiles were similar across renal function groups: 
 - No increase in CRS or ICANS 
 - Similar infection and hematologic toxicity rates 
• Thrombocytopenia was more frequent in patients with RI. 
• Pharmacokinetics of BsAbs (non-renal clearance) likely explain consistent outcomes. 
• Evidence supports use even in severe RI or dialysis, though data remain limited.

Why this review matters 
Bispecific antibodies demonstrate strong and consistent efficacy in RRMM patients regardless of renal function, with no meaningful reduction in treatment benefit in those with renal impairment. Their safety profile is largely comparable across groups, aside from a higher risk of thrombocytopenia in patients with RI. These results support broader use of BsAbs in clinical practice, while highlighting the need for more prospective studies in patients with severe renal dysfunction or dialysis dependence.

Reference: 
I.Ntanasis-Stathopoulos, S.Manganas, C.Filippatos, et al., “The Role of Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma With Renal Impairment: A Systematic Review,” American Journal of Hematology (2026): 1–10, https://doi.org/10.1002/ajh.70312.

Resistance to BCMA-Directed CAR T-Cell Therapy in Multiple Myeloma: Biology, Clinical Patterns, and Strategies to Overcome Treatment Failure — Clinical Lymphoma Myeloma and Leukemia (April 2026)

What is the purpose of the study? 
To delve into the reasons why myeloma patients relapse after BCMA-directed CAR T-cell therapy, despite high initial response rates; and to propose a unified framework linking resistance mechanisms to clinical relapse patterns and highlights strategies to overcome treatment failure.

Summary  
BCMA-directed CAR T-cell therapies, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), produce high response rates (up to 97–98%) and improved progression-free survival in relapsed/refractory multiple myeloma (RRMM). However, most patients eventually relapse due to multiple resistance mechanisms, including loss or reduction of the BCMA target, tumor evolution, CAR T-cell dysfunction, and an immunosuppressive bone marrow environment. The review outlines emerging solutions such as dual-target CAR T cells, improved CAR T-cell design, and combination or alternative antigen-targeted therapies to achieve more durable remissions.

Key points 
• Therapies discussed: BCMA-directed CAR T-cell therapy and approved CAR T: ide-cel, cilta-cel  

• Efficacy data:  
 - ide-cel (KarMMa trial):Overall response rate (ORR):73%; Complete response CR):33%;Median PFS:8.6 months;Median OS: 24.8 months  
 - cilta-cel (CARTITUDE-1):ORR: 97–98%;Stringent CR:~80%;; Median PFS: ~34–35 months  

• Randomized trial outcomes:  
 - KarMMa-3: PFS 13.3 vs 4.4 months (CAR T vs standard care)  
 - CARTITUDE-4: 74% reduction in progression/death risk; 12-month PFS 76% vs 49%  

• Major resistance mechanisms:  
 - Antigen-dependent:BCMA loss (genetic deletion, mutation);Downregulation (shedding, trogocytosis)  
 - Antigen-independent: Tumor clonal evolution; Lineage plasticity  
 - CAR T-cell limitations:Poor expansion;Early exhaustion;Limited persistence  
 - Tumor microenvironment: Immunosuppressive cells (regulatory T cells, MDSCs); Inhibitory cytokines; Bone marrow “sanctuary sites”  

• Clinical challenges:  
 - Most patients relapse within 12–18 months  
 - Only ~1/3 remain progression-free at 5 years (cilta-cel data)  

• Emerging strategies:  
 - Dual-target CAR T-cell therapies  
 - Enhanced CAR T-cell engineering (better persistence/fitness)  
 - Combination therapies to increase antigen expression  
 - Alternative targets (e.g., non-BCMA antigens)  

Why this study matters 
BCMA-directed CAR T-cell therapy has significantly improved outcomes in multiple myeloma, but relapse remains common due to complex and multifactorial resistance mechanisms. Understanding these mechanisms—ranging from tumor adaptation to immune and cellular limitations—is critical for improving long-term outcomes. Emerging next-generation therapies and combination approaches offer promising strategies to achieve deeper and more durable remissions.

Reference: 
Mohammad Ahsen Soomro, Mohamed Ahmed, Al Ola Abdallah, Nausheen Ahmed, Jeries Kort, Resistance to BCMA-Directed CAR T-Cell Therapy in Multiple Myeloma: Biology, Clinical Patterns, and Strategies to Overcome Treatment Failure, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.04.004.

Biochemical bone biomarkers in plasma cell dyscrasias for the British Journal of Haematology — British Journal of Haematology (April 2026)

What is the purpose of the review? 
To evaluate the clinical role of bone turnover markers (BTMs) in multiple myeloma (MM) and related plasma cell disorders, including MGUS and smoldering MM; and to focus on their utility in disease detection, prognosis, monitoring progression, and assessing treatment response.

Summary  
Bone turnover markers reflect the imbalance between bone resorption and formation in MM, with markers such as CTX, ICTP, and u-DPD indicating osteoclastic activity, while B-ALP and P1NP reflect osteoblastic function. Evidence shows that some BTMs correlate with disease burden, early progression, skeletal-related events, and response to therapies like bortezomib, carfilzomib, and daratumumab (e.g., REBUILD trial), but their routine clinical use is limited by variability, renal impairment, and lack of standardization. Emerging biomarkers (e.g., periostin, GDF-15, DKK-1) and trials like Z-MARK highlight future potential, though imaging remains the diagnostic standard.

Key points 
• MM bone disease results from increased osteoclast activity and reduced osteoblast function, causing osteolytic lesions. 
• BTMs are non-invasive tools for assessing bone metabolism and may aid in: 
 - Disease classification (MGUS → SMM → MM) 
 - Monitoring progression and relapse 
 - Evaluating treatment response 
• Resorption markers (CTX, ICTP, u-DPD) generally have better diagnostic and prognostic value than formation markers. 
• Some BTMs (e.g., ICTP, CTX) correlate with fracture risk, skeletal disease burden, and early relapse. 
• Therapies influence BTMs: 
 - Bortezomib / carfilzomib → increase bone formation markers 
 - Daratumumab (REBUILD trial) → promotes bone formation and reduces inhibitors 
 - Bisphosphonates (e.g., zoledronic acid, Z-MARK trial) → reduce bone resorption markers 
• Limitations: 
 - High biological variability 
 - Lack of standardized assays and cut-offs 
 - Influence of renal function 
• Imaging (CT, PET-CT, MRI) remains the gold standard for diagnosis and monitoring. 
• Emerging biomarkers and multi-marker approaches may improve risk stratification and personalized care in the future.

Why this review matters 
BTMs provide valuable insight into bone metabolism and disease activity in multiple myeloma but are not yet reliable enough for routine clinical use due to variability and lack of standardization. They are best considered complementary tools alongside imaging for monitoring bone disease and treatment response. Future research focusing on standardization, validation, and integration with clinical and imaging data may enable BTMs to play a key role in personalized management of myeloma-related bone disease.

Reference: 
Nador G, Vijjhalwar R, Javaid MK, Edwards CM, Ramasamy K. Biochemical bone biomarkers in plasma cell dyscrasias for the British Journal of Haematology. Br J Haematol. 2026;00:1–15. https://doi.org/10.1111/bjh.70467

Research  
 

Elranatamab Versus Teclistamab in Relapsed and Refractory Multiple Myeloma: A Real-World Propensity Score-Matched Study — Targeted Oncology (March 2026)

What is the purpose of the study? 
To compare two treatments, elranatamab and teclistamab, in patients with relapsed or refractory multiple myeloma; and to focus on how long patients could go before needing another treatment, how long they lived, and what side effects they experienced in real-world clinical practice.

Summary  
This real-world study compared two BCMA-targeting bispecific antibodies, elranatamab and teclistamab, in patients with relapsed/refractory multiple myeloma (RRMM). Results showed similar effectiveness, with no significant differences in time to next treatment (11.0 vs 12.3 months) or 3-year overall survival (58.8% vs 59.7%). However, teclistamab showed longer disease control in certain high-risk patients, such as those with low platelet counts or heavily pretreated disease. The safety profiles differed: teclistamab had more severe neutropenia (84.6% vs 74.5%), while elranatamab had higher rates of cytokine release syndrome (45.2% vs 27.1%). Overall, both treatments are effective options, but choice of therapy may depend on patient-specific risks and side effects.

Key points 
• Study design: multinational, real-world retrospective cohort using TriNetX database 
• Population: 188 patients per group after matching, all with RRMM 
• Effectiveness: 
 - Time to next treatment: 11.0 months (elranatamab) vs 12.3 months (teclistamab) (no significant difference) 
 - 3-year overall survival: 58.8% vs 59.7% (similar outcomes)

• Subgroup findings: 
 - Teclistamab showed longer benefit in patients with thrombocytopenia and >5 prior treatments

•Safety differences: 
- Grade ≥3 neutropenia: higher with teclistamab (84.6% vs 74.5%) 
- Cytokine release syndrome (CRS): higher with elranatamab (45.2% vs 27.1%) 
- ICANS and infection rates: similar between groups

• Findings consistent with clinical trials: MagnetisMM-1 (elranatamab) and MajesTEC-1 (teclistamab) 
• Both drugs cause immune suppression → need for infection monitoring and prophylaxis 
• Limitations: retrospective design, limited biological data, and reliance on real-world endpoints

Why this study matters 
This real-world study shows that elranatamab and teclistamab provide similar overall effectiveness in patients with relapsed/refractory multiple myeloma. While outcomes such as survival and time to next treatment were comparable, each drug has a distinct side effect profile that may influence treatment choice. Teclistamab may offer additional benefits in certain high-risk patients, but this requires further confirmation. Careful monitoring for infections and immune-related side effects is essential for both therapies. Future prospective, head-to-head trials and biomarker-driven studies are needed to guide personalized treatment decisions.

Reference: 
Wang, YC., Li, PH., Lin, CH. et al. Elranatamab Versus Teclistamab in Relapsed and Refractory Multiple Myeloma: A Real-World Propensity Score-Matched Study. Targ Oncol (2026). https://doi.org/10.1007/s11523-026-01209-0

 
Next Generation Flow and Next Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma Patients: A Real-Life Italian Multicenter Harmonization Experience — Cancer Medicine (March 2026)

What is the purpose of the study? 
To report preliminary results from the Italian MM-MRD network, aiming to harmonize measurable residual disease (MRD) assessment across laboratories in multiple myeloma using next-generation flow cytometry (NGF) and next-generation sequencing (NGS). It evaluates reproducibility, concordance, and methodological challenges to improve standardization and clinical applicability of MRD testing.

Summary  
MRD is a key predictor of treatment response and survival in multiple myeloma, but variability across laboratories limits its widespread clinical use. This pilot study assessed MRD measurement using NGF and NGS across multiple centers, showing high inter-operator concordance for NGF (ICC 0.90) but moderate inter-laboratory agreement (ICC 0.63), with sensitivity reaching approximately 10⁻⁵. NGS demonstrated strong reproducibility, with 100% concordance in clonotype identification and 81–91% agreement in MRD quantification across quality-control rounds. Variability was mainly due to differences in sample handling, processing, and technical factors such as DNA input and software use. Overall, both NGF and NGS proved reliable and complementary, supporting their use in clinical practice if standardized protocols are implemented.

Key points

• Importance of MRD: 
 - Strongly correlates with progression-free survival (PFS) and overall survival (OS) 
 - Increasingly used for treatment monitoring and clinical decision-making

• Study objective: Harmonize MRD assessment across Italian laboratories using NGF and NGS

• NGF findings: 
 - High inter-operator concordance (ICC 0.90) 
 - Moderate inter-laboratory concordance (ICC 0.63) 
 - Sensitivity achieved: ~10⁻⁵ 
 - Variability linked to sample transport, processing, and data analysis

• NGS findings: 
 - 100% concordance in clonotype identification (QC1) 
 - MRD quantification concordance: 81% (QC2), 91% (QC3) 
 - Sensitivity of 10⁻⁵ achieved in most samples 
 - Challenges include clonotype selection and DNA input variability

• Technical considerations: 
 - Standardized protocols (e.g., EuroFlow) improve reproducibility 
 - Sample quality, timing, and logistics are critical 
 - Software harmonization and quality-control programs are essential

• Clinical implications: 
 - NGF: rapid, widely applicable for routine use 
 - NGS: higher sensitivity, useful for deep response assessment 
 - Both methods have similar prognostic value

• Limitations: 
 - Small sample size and number of laboratories 
 - Lack of real-world variability and direct NGF vs NGS comparison

Why this study matters 
This pilot study demonstrates that MRD assessment using both NGF and NGS is feasible and reproducible across multiple centers, though variability remains a significant challenge. Standardization of protocols, sample handling, and data analysis is essential to ensure consistent and comparable results. Both techniques offer complementary advantages, with NGF suited for rapid clinical decisions and NGS providing higher sensitivity for deeper disease monitoring. Despite limitations, this initiative lays the groundwork for a national MRD network and broader implementation in routine clinical practice. Continued collaboration, quality-control programs, and larger studies will be crucial to optimize MRD use and improve outcomes for patients with multiple myeloma.

Reference: 
S.Oliva, M.Martello, E.Saraci, et al., “Next Generation Flow and Next Generation Sequencing for Measurable Residual Disease Assessment in Multiple Myeloma Patients: A Real-Life Italian Multicenter Harmonization Experience,” Cancer Medicine15, no. 3 (2026): e71678, https://doi.org/10.1002/cam4.71678.

Real-world healthcare resource utilization and clinical outcomes among patients with relapsed/refractory multiple myeloma receiving ciltacabtagene autoleucel after four or more prior lines of therapy in inpatient versus outpatient settings — Journal of Medical Economics (March 2026)

What is the purpose of the study? 
To evaluate whether outpatient (OP) administration of ciltacabtagene autoleucel (cilta-cel, Carvykti) is as safe and effective as inpatient (IP) administration in patients with relapsed or refractory multiple myeloma (RRMM); and to compare healthcare resource utilization (HCRU), including hospital stays and clinical outcomes, between these two settings.

Summary  
In this real-world analysis of 242 RRMM patients treated with cilta-cel after ≥4 prior lines of therapy, outcomes were compared between inpatient (61.2%) and outpatient (38.8%) administration. Within the first 3 months, OP patients had significantly fewer hospital days but more outpatient visits, with nearly one-third avoiding hospitalization entirely. After 4 months, healthcare utilization between groups became similar. Importantly, rates of adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), as well as treatment-free interval (TFI) and overall survival (OS), were comparable between settings. These findings suggest that OP administration reduces hospital burden without compromising safety or effectiveness.

Key points 
• OP administration of cilta-cel reduced inpatient hospital days significantly in the first 3 months post-infusion. 
• About 32% of OP patients avoided hospitalization entirely during this period. 
• No significant differences in CRS, ICANS, TFI, or OS between OP and IP groups. 
• Healthcare resource use became similar after the initial 3-month period. 
• OP care may reduce costs and improve healthcare system efficiency while maintaining outcomes.

Why this study matters 
Outpatient administration of cilta-cel appears to be a safe and effective alternative to inpatient treatment for heavily pretreated RRMM patients. It significantly reduces early hospitalization needs, which may lower healthcare costs and resource burden. Clinical outcomes, including survival and adverse event rates, remain comparable between outpatient and inpatient settings. These findings support expanding outpatient CAR-T therapy programs with appropriate monitoring and infrastructure. Future research should focus on identifying which patients are best suited for outpatient treatment to further optimize care.

Reference: 
Janakiram, M., Fan, L., Ghosh, S., Alegria, V., Perciavalle, M., Emond, B., … Dima, D. (2026). Real-world healthcare resource utilization and clinical outcomes among patients with relapsed/refractory multiple myeloma receiving ciltacabtagene autoleucel after four or more prior lines of therapy in inpatient versus outpatient settings. Journal of Medical Economics, 29(1), 871–884. https://doi.org/10.1080/13696998.2026.2640811

 
Predictors of 30-day readmissions post-CAR-T in patients with relapsed/refractory multiple myeloma using the United States nationwide readmission database — Annals of Hematology (March 2026)

What is the purpose of the study? 
To evaluate real-world hospital outcomes, costs, and 30-day readmission risks in patients with relapsed/refractory multiple myeloma (RRMM) treated with BCMA-directed CAR-T therapies, including ide-cel and cilta-cel; and to identify complications and predictors of readmission following treatment.

Summary  
BCMA-directed CAR-T therapies such as ide-cel and cilta-cel have significantly improved outcomes in RRMM, with high response rates reported in clinical trials. However, this large U.S. real-world study found that 17% of patients were readmitted within 30 days, most commonly due to immune-related complications and infections. Serious side effects during initial hospitalization included cytokine release syndrome (CRS) in 68.4% and immune effector cell-associated neurotoxicity syndrome (ICANS) in 7.6% of patients. Factors such as hemophagocytic lymphohistiocytosis (HLH), mechanical ventilation, and treatment at non-metropolitan hospitals increased the risk of readmission. Despite strong treatment effectiveness, these findings highlight the ongoing need for close monitoring and supportive care after discharge.

Key points

• BCMA CAR-T therapies (ide-cel, cilta-cel) show high response rates (73–98%) in RRMM.  
• 30-day hospital readmission rate was 17%.  
• Most common readmission causes:  
 - Immune-related complications (33%)  
 - Infections (17.3%)  
• Common toxicities during initial hospitalization:  
 - CRS: 68.4%  
 - ICANS: 7.6%  
• Key predictors of readmission:  
 - HLH (HR 3.42)  
 - Mechanical ventilation (HR 11.30)  
 - Non-metropolitan hospital care (HR 4.77)  
• No significant difference in readmission risk between ide-cel and cilta-cel.  
• Mean readmission cost: ~$105,390; mortality during readmission: 7%.  

Why this study matters 
BCMA-directed CAR-T therapy has transformed the treatment of RRMM but is associated with substantial early complications and healthcare utilization. Nearly one in six patients require readmission within 30 days, primarily due to immune-related toxicities and infections. Severe complications during initial hospitalization, such as HLH and the need for mechanical ventilation, significantly increase readmission risk. The findings emphasize the importance of structured post-discharge monitoring, early intervention strategies, and coordinated care, especially in non-specialized centers. Improving outpatient management and supportive care pathways will be essential to maximize the benefits of CAR-T therapy while reducing its clinical and economic burden.

Reference: 
Shah, R., Vojjala, N., Cheng, T. et al. Predictors of 30-day readmissions post-CAR-T in patients with relapsed/refractory multiple myeloma using the United States nationwide readmission database. Ann Hematol 105, 198 (2026). https://doi.org/10.1007/s00277-026-06927-z

Enhanced dynamic risk stratification of smoldering multiple myeloma — Nature Medicine (March 2026)

What is the purpose of the study? 
To develop and validate the PANGEA-SMM model to more accurately predict progression from smoldering multiple myeloma (SMM) to active multiple myeloma (MM) by incorporating dynamic (evolving) biomarker changes over time. The goal is to improve risk stratification and guide earlier, individualized treatment while minimizing overtreatment.

Summary  
Researchers analyzed data from 2,344 patients with SMM across seven international centers to create the PANGEA-SMM risk model using longitudinal clinical and biological data. Unlike traditional models such as 20/2/20 and IMWG, this model incorporates evolving biomarkers, including increases in M-protein (≥0.2 g/dL), serum free light chain (sFLC) ratio (≥20), creatinine (>25%), and decreases in hemoglobin (≥1.5 g/dL), which were all linked to faster progression to MM. PANGEA-SMM demonstrated better predictive accuracy (C-statistic ~0.79) than existing models, even when limited data (e.g., no bone marrow biopsy or biomarker history) were available. The model allows continuous, personalized risk assessment and can classify patients into low-, intermediate-, or high-risk groups. It is available as an open-access, easy-to-use tool for clinical practice and research.

Key points 
• Large cohort: 2,344 patients with smoldering multiple myeloma from international centers  
• Key innovation: Uses dynamic (evolving) biomarkers instead of static measurements  
• Four high-risk biomarker changes:  
 - M-protein increase ≥0.2 g/dL  
 - sFLC ratio increase ≥20  
 - Creatinine increase >25%  
 - Hemoglobin decrease ≥1.5 g/dL  

• Performance: Higher predictive accuracy (C-statistic ~0.79) vs. 20/2/20 and IMWG models  
• Flexible use: Works even without bone marrow biopsy or full biomarker history  
• Clinical value: Enables personalized, continuous risk monitoring and better identification of high-risk patients for early treatment  

Why this study matters 
The PANGEA-SMM model represents a significant advancement in predicting progression from smoldering to active multiple myeloma by incorporating dynamic biomarker trends. It outperforms existing models by providing more accurate, personalized, and flexible risk assessments, even when clinical data are incomplete. This approach helps better identify patients at truly high risk who may benefit from early intervention while reducing unnecessary treatment in lower-risk individuals. Its accessibility as an open-access tool supports widespread clinical adoption and consistency in patient care. Overall, PANGEA-SMM improves decision-making and has the potential to enhance outcomes in patients with SMM.

The PANGEA-SMM models are available as a free, open-access web application with a user-driven validation tool at https://pangeamodels.org

Reference: 
Chabrun, F., Schwartz, D.E., Gentile, S. et al. Enhanced dynamic risk stratification of smoldering multiple myeloma. Nat Med (2026). https://doi.org/10.1038/s41591-026-04304-x

FREEDOMM: Fifth-Line or Later Real-World Evaluation of Efficacy and Disease Outcomes in Multiple Myeloma with Ciltacabtagene Autoleucel: Treatment-Free Interval and Overall Survival in the USA — Advances in Therapy (March 2026)

What is the purpose of the study? 
To evaluate real-world outcomes of ciltacabtagene autoleucel (cilta-cel) in patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 prior lines of therapy, and examine the impact of bridging therapy (BT) on treatment outcomes. The goal is to assess effectiveness and survival in routine U.S. clinical practice.

Summary  
In this real-world study of 242 patients with RRMM, treatment with ciltacabtagene autoleucel (Carvykti) showed strong outcomes, with about 80.3% of patients remaining treatment-free and 93.4% alive at 18 months after infusion. Most patients (75.2%) received bridging therapy, typically due to higher disease burden and frailty. Patients who received BT had trends toward improved treatment-free interval (TFI) and overall survival (OS), although results were not statistically significant. These findings are consistent with results from clinical trials such as CARTITUDE-1 and CARTITUDE-4, which also demonstrated high survival rates. Overall, the study supports the effectiveness of cilta-cel in real-world settings and highlights the potential role of BT in improving outcomes.

Key points 
• Population: 242 patients with relapsed/refractory multiple myeloma after ≥4 prior lines of therapy 
• Treatment: CAR-T therapy with ciltacabtagene autoleucel (cilta-cel) 
• Outcomes at 18 months: 
 - Treatment-free interval (TFI): 80.3% 
 - Overall survival (OS): 93.4%

• Bridging therapy (BT): 
 - Used in 75.2% of patients 
 - Associated with numerically improved TFI and OS

• Consistency with trials: 
 - CARTITUDE-1 (~89% OS at 12 months) 
 - CARTITUDE-4 (~84% OS at 12 months)

• Clinical implication: Supports cilta-cel effectiveness in routine care and suggests BT may improve outcomes

Limitations  
This study has several limitations due to its real-world, claims-based design. Clinical details (disease progression, cytogenetic risk, and response to bridging therapy) were not available, so outcomes like treatment-free interval (TFI) were used as indirect measures. Differences between patients who did and did not receive bridging therapy (BT) (e.g., disease severity, frailty) may have introduced bias, and residual confounding could affect comparisons. The relatively short follow-up period (median 11 months) limits understanding of long-term outcomes, and results may not apply to all patient populations, especially uninsured individuals or those treated outside captured networks. Additionally, variability in BT regimens and lack of data on CAR-T product specifications may impact the interpretation of effectiveness.

Why this study matters 
This real-world study confirms that ciltacabtagene autoleucel is highly effective for patients with RRMM who have received multiple prior treatments. Survival outcomes were strong and consistent with pivotal trials, reinforcing its benefit in clinical practice. Bridging therapy may further improve outcomes, particularly in patients with more aggressive disease, although more research is needed to determine the best regimens. These findings highlight the importance of individualized treatment strategies in CAR-T therapy. Future studies should explore optimal use of cilta-cel earlier in treatment and refine the role of bridging therapy.

Reference: 
Ailawadhi, S., Hansen, D.K., Dhakal, B. et al. FREEDOMM: Fifth-Line or Later Real-World Evaluation of Efficacy and Disease Outcomes in Multiple Myeloma with Ciltacabtagene Autoleucel: Treatment-Free Interval and Overall Survival in the USA. Adv Ther (2026). https://doi.org/10.1007/s12325-026-03554-y

 
Diagnosis Disclosure and Related Illness Experience in Patients with Multiple Myeloma and Precursor Plasma Cell Disorders — Clinical Lymphoma Myeloma and Leukemia (March 2026)

What is the purpose of the study? 
To examine how patients with multiple myeloma and precursor plasma cell disorders share their diagnosis and how disclosure affects coping, relationships, and overall illness experience; and to identify differences in coping between patients with active cancer and those with precursor conditions.

Summary  
In a survey of 510 patients, 98% reported sharing their diagnosis, most often within a week and primarily with close contacts such as partners and friends. The majority of patients who shared experienced improved coping (84%) and stronger relationships (55%), while those who did not share often reported increased isolation. Most participants (87%) did not regret disclosing their diagnosis, despite some challenges like unwanted advice or feeling pitied. Patients with precursor conditions (e.g., MGUS or smoldering myeloma) were significantly less likely to report coping well compared to those with multiple myeloma (56% vs. 78%, p<0.001). Overall, direct and personal communication was preferred over social media, and patients emphasized thoughtful timing, privacy, and education when sharing their diagnosis.

Key points 
• High disclosure rate: 98% of patients shared their diagnosis 
• Timing & method: 
 - 88% shared within days to a week 
 - 86% shared in person

• Who patients told: 
 - Spouses/partners (81%) 
 - Friends (81%)

•Benefits of sharing: 
- Improved coping (84%) 
- Stronger relationships (55%)

• Non-disclosure impact: Increased isolation (56%) 
• Precursor vs. cancer patients: Precursor patients less likely to cope well (56% vs. 78%, p<0.001) 
• Social media: Less impact on coping compared to personal communication 
• Patient advice: Be intentional about timing, audience, privacy, and education

Strengths 
• Large sample size (510 patients): Provides a broad view of diagnosis disclosure patterns. 
• Inclusion of both multiple myeloma and precursor conditions: Allows comparison between cancer and earlier disease stages. 
• Patient-centered design: Direct patient-reported experiences, including open-ended responses, offer real-world insights. 
• Novel focus: First study to specifically examine diagnosis disclosure and its impact on coping in this population.

Limitations 
• Selection bias: Participants were recruited through an online patient platform, likely overrepresenting more engaged, informed, or socially active patients. 
• Recall and optimism bias: Patients may overestimate the benefits of disclosure or misremember past experiences. 
• Limited diversity: Overrepresentation of White patients and older individuals may reduce generalizability. 
• Incomplete representation of precursor patients: Those participating may be more anxious or engaged than the broader population. 
• Survey-based design: Lacks clinical verification and may miss important contextual or medical details.

Why this study matters 
This study shows that sharing a diagnosis is common and generally beneficial for patients with multiple myeloma and precursor plasma cell disorders. Disclosure is strongly associated with better coping and stronger social connections, while not sharing may increase feelings of isolation. Patients with precursor conditions appear to struggle more with coping, highlighting an unmet need for targeted emotional and educational support. Although disclosure can involve challenges, most patients do not regret sharing and recommend a thoughtful, personalized approach. These findings underscore the importance of social support and patient-centered communication in improving quality of life.

Reference: 
Maria A. Malik, Akshay A. Dalvi, Andriy Derkach, Jorge A. Martínez, Jay R. Hydren, Gia Merlo, Ana M. Aldana, Jennifer M. Ahlstrom, Saad Z. Usmani, Susan Chimonas, Robin Ortiz, Urvi A. Shah, Diagnosis Disclosure and Related Illness Experience in Patients with Multiple Myeloma and Precursor Plasma Cell Disorders, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.015.

Impact of clinical surveillance on myeloma-related complications in patients with precursor plasma cell disorders — Blood Cancer Journal (March 2026)

What is the purpose of the study? 
To evaluate whether patients with multiple myeloma (MM) who had a prior diagnosis of precursor plasma cell disorders (PCDs)—such as monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM)—experience differences in symptoms, complications, and healthcare use compared to those without prior PCD. It aims to determine whether early detection and structured follow-up improve patient-centered outcomes at MM diagnosis.

Summary  
In this retrospective study of 415 MM patients, 95 had a known prior PCD (MGUS, SMM, or plasmacytoma), while 320 did not. Patients with prior PCD were diagnosed with MM earlier, had a shorter duration of symptoms (4.5 vs 7.6 months), and experienced fewer complications such as anemia, kidney failure, bone lesions, and hypercalcemia. They also had reduced healthcare utilization, including fewer emergency visits, hospitalizations, dialysis needs, and blood transfusions. Importantly, prior PCD was associated with a 71% lower risk of severe myeloma-related complications at diagnosis. However, no significant differences in progression-free or overall survival were observed between groups

Key points 
• MGUS and SMM are common precursor conditions to MM, especially in individuals over age 50.  
• Patients with prior PCD had earlier-stage MM at diagnosis and shorter symptom duration.  

• Significant reductions in complications were observed in prior PCD patients:  
 - Lower rates of anemia (35% vs 65%)  
 - Reduced renal insufficiency (11% vs 23%)  
 - Fewer bone lesions and fractures  
 - Lower incidence of hypercalcemia  

• Healthcare utilization was lower in prior PCD patients:  
 - Fewer emergency department visits (37% vs 64%)  
 - Fewer hospitalizations (35% vs 57%)  
 - Less dialysis and transfusion use  

• Prior PCD reduced the odds of severe clinical complications at diagnosis by 71% (OR 0.29, p < 0.001)  
• No significant difference in overall survival (OS) or progression-free survival (PFS) was observed  

Why this study matters  
This study shows that patients with known precursor conditions like MGUS or SMM who undergo regular monitoring are diagnosed with multiple myeloma earlier and with fewer serious complications. These patients experience less organ damage, reduced symptom burden, and lower healthcare use at the time of diagnosis. Although a survival advantage was not observed, the substantial reduction in morbidity highlights the clinical value of early detection and follow-up. The findings support routine monitoring of precursor plasma cell disorders as a way to improve patient outcomes and reduce strain on healthcare systems. Ongoing prospective studies, such as iStopMM (Iceland Screens Treats or Prevents Multiple Myeloma), will further clarify the benefits of screening and long-term follow-up in these patients.

Reference: 
Koo, E., Albert, S., Patrick, B. et al. Impact of clinical surveillance on myeloma-related complications in patients with precursor plasma cell disorders. Blood Cancer J. 16, 40 (2026). https://doi.org/10.1038/s41408-026-01463-5

Non-ICANS Neurologic Toxicity after BCMA CAR T: A systematic review and meta-analysis of 4630 multiple myeloma patients — Blood Advances (March 2026)

What is the purpose of the study? 
To evaluate the incidence and characteristics of non-ICANS neurologic toxicities (NINTs) in patients with multiple myeloma treated with BCMA-directed CAR-T therapies. It also compares risks across different CAR-T products, including ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel).

Summary  
Analyzing 55 cohorts with 4,630 patients, this study found that NINTs are rare, with a pooled incidence of 0.81%. However, the risk was significantly higher with cilta-cel (4.6%) compared to ide-cel (0.5%) and other experimental BCMA CAR-T therapies. The most common neurologic toxicities included cranial nerve palsies, followed by movement/neurocognitive events and peripheral neuropathies.

Key points 
• Meta-analysis included 55 cohorts and 4,630 patients treated with BCMA CAR-T therapy. 
• Overall pooled incidence of NINTs: 0.81% (95% CI, 0.37–1.77%). 
• Higher risk observed with: 
 - Cilta-cel: 4.6% 
 - Ide-cel: 0.5% 
 - Experimental constructs: 0.3%

• Cilta-cel independently associated with increased NINT risk (meta-regression). 
• Most common NINTs: 
 - Cranial nerve palsies (32.3%) 
 - Movement/neurocognitive events (12%) 
 - Peripheral neuropathies (7.5%)

• NINTs are distinct from ICANS and remain underreported. 
• Highlights need for standardized definitions and better monitoring.

Why this study matters 
Non-ICANS neurologic toxicities are uncommon but clinically important complications of BCMA-directed CAR-T therapy. The risk is significantly higher with cilta-cel compared to other products, emphasizing the need for careful monitoring. Improved reporting and standardized definitions are essential to better understand and manage these toxicities.

Reference: 
Herman J van Besien, Gwynne Ozkan, Neela Easton, Tobias Tix, Mohammad Alhomoud, Roni Shouval, Kai Rejeski, Samuel Yamshon; Non-ICANS Neurologic Toxicity after BCMA CAR T: A systematic review and meta-analysis of 4630 multiple myeloma patients. Blood Adv 2026; bloodadvances.2026019617. doi: https://doi.org/10.1182/bloodadvances.2026019617

Real-World Patient Characteristics, Treatment Patterns, and Clinical Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Receiving Teclistamab: A Panel Chart Review Study — Oncology and Therapy (March 2026)

What is the purpose of the study? 
To evaluate the real-world effectiveness and safety of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM) treated primarily in U.S. community oncology settings. It also compares outcomes between patients who met U.S. Prescribing Information (USPI)-aligned criteria and those treated outside these criteria.

Summary  
In this retrospective study of 101 RRMM patients, teclistamab demonstrated high overall response rates (ORR 80.2%; 90.0% in USPI-aligned and 76.1% in unaligned groups) with a median follow-up of 13.8 months, exceeding the 63.0% ORR reported in the MajesTEC-1 trial. Adverse events included cytokine release syndrome (32.7%), immune effector cell-associated neurotoxicity syndrome (8.9%), and infections (26.7%), generally at lower or comparable rates to clinical trials. These findings suggest strong real-world effectiveness despite patients having higher disease burden and worse baseline status than clinical trial populations.

Key points 
• Population: 101 RRMM patients; median age 65.4 years; 93.1% triple-class exposed, 65.3% refractory  
• Study Design: Retrospective, real-world cohort from a U.S. community oncology network  
• Efficacy:  
 - Overall response rate (ORR): 80.2%  
 - USPI-aligned: 90.0%  
 - USPI-unaligned: 76.1%  
 - Higher ORR than MajesTEC-1 trial (63.0%)  

• Safety:  
 - Cytokine release syndrome (CRS): 32.7% (mostly low grade)  
 - ICANS: 8.9%  
 - Infections: 26.7% (lower than prior studies)  

• Response Dynamics: Responses deepened over time (3–12 months)  
• Real-World Insight: Community-treated patients showed strong outcomes despite worse baseline characteristics  
• Limitations: Retrospective design, possible underreporting of adverse events, and limited subgroup sample sizes  

Why this study matters 
Teclistamab demonstrated high response rates and a manageable safety profile in real-world RRMM patients, including those with more advanced disease than typical clinical trial populations. Outcomes were consistent with or better than those observed in the MajesTEC-1 trial, supporting its effectiveness outside controlled settings. These findings reinforce teclistamab as a viable and practical treatment option in community oncology practice.

Reference: 
Dhakal, B., Levy, M.Y., Ko, G. et al. Real-World Patient Characteristics, Treatment Patterns, and Clinical Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Receiving Teclistamab: A Panel Chart Review Study. Oncol Ther (2026). https://doi.org/10.1007/s40487-026-00429-8

Dietary patterns among individuals with plasma cell disorders– opportunities for targeted interventions — Blood Cancer Journal (March 2026)

What is the purpose of the study? 
To examine dietary patterns and overall diet quality in individuals with plasma cell disorders (PCDs), including monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM). It aims to identify differences across patient subgroups and assess potential targets for dietary interventions using Healthy Eating Index (HEI-2020) scores.

Summary  
Using data from a large cohort of patients who completed the Block Food Frequency Questionnaire through the HealthTree Foundation (May 2023–January 2024), researchers analyzed diet quality and nutrient intake across demographic and clinical subgroups. Higher body mass index (BMI) and lower education levels were associated with poorer diet quality, including lower fiber intake and lower HEI-2020 scores, while sex and disease stage also influenced dietary patterns. Although overall diet quality appeared higher than the general U.S. population, likely due to selection bias, findings highlight disparities and opportunities for targeted nutritional interventions in patients with PCDs.

Key points 
• Plasma cell disorders (PCDs) include MGUS, SMM, and multiple myeloma (MM)  
• Study used the Block Food Frequency Questionnaire and HEI-2020 scoring system (range 0–100)  
• Higher BMI (obesity) associated with:  
 - Lower HEI scores (poorer diet quality)  
 - Lower fiber intake  
 - Higher added sugar intake (trend)  

• Lower education level linked to:  
 - Lower fiber intake  
 - Lower fruit consumption (trend)  
 - Higher added sugar intake (trend)  

• Males reported:  
 - Higher calorie intake  
 - Lower fiber and vegetable consumption  

• Dietary differences observed by sex, race/ethnicity, and disease stage (MGUS, SMM, MM)  
• Patients with MM showed higher fruit intake, possibly influenced by glucocorticoid therapy  
• Overall HEI scores were higher than the general U.S. population, likely due to selection bias  
• 57% of patients reported diet/nutrition was not discussed during oncology visits  
• Fiber intake was the most consistent dietary factor distinguishing subgroups  
• Study supports ongoing research such as the NUTRIVENTION trials on diet and MM outcomes  

Why this study matters 
Diet quality varies significantly among individuals with plasma cell disorders, with lower fiber intake and poorer HEI scores concentrated in higher-risk groups such as those with obesity and lower education levels. These findings highlight the importance of integrating dietary counseling and targeted interventions into routine care. Further prospective studies, including the NUTRIVENTION trials, are needed to clarify how diet influences disease progression, survival, and quality of life.

Reference: 
Traore, K., Castro, F., Derkach, A. et al. Dietary patterns among individuals with plasma cell disorders– opportunities for targeted interventions. Blood Cancer J. 16, 42 (2026). https://doi.org/10.1038/s41408-026-01468-0

Dexamethasone prophylaxis for excessive lymphocyte expansion after cilta-cel in multiple myeloma — Blood Advances (March 2026)

What is the purpose of the study?  
To evaluate whether high absolute lymphocyte count (ALC) after treatment with ciltacabtagene autoleucel (cilta-cel) predicts poor outcomes in patients with relapsed/refractory multiple myeloma, and whether dexamethasone prophylaxis can reduce these risks; and to assess associations with mortality and atypical neurologic events.

Summary  
Researchers analyzed outcomes in multiple myeloma patients treated with cilta-cel, comparing those treated before and after introducing dexamethasone prophylaxis for patients with ALC >5000/μL. High ALC was strongly associated with increased risk of atypical neurologic events (odds ratio 6.8) and lower overall survival (hazard ratio 6.2). Patients who received early dexamethasone prophylaxis showed fewer neurologic events, reduced mortality, and rapid lowering of ALC.

Key points 
• High absolute lymphocyte count (ALC >5000/μL) after cilta-cel is linked to increased mortality and atypical neurologic events.  
• ALC >5000/μL significantly predicted worse outcomes, including lower overall survival and higher neurologic risk.  
• Dexamethasone prophylaxis (3 days) in patients with elevated ALC reduced neurologic events and mortality.  
• Prophylaxis also led to rapid reduction in ALC levels.  
• Patients without intervention had notably higher rates of neurologic complications and death.  

Why this study matters 
An elevated ALC after cilta-cel therapy is a strong predictor of serious neurologic complications and increased mortality in patients with relapsed/refractory multiple myeloma. Early intervention with dexamethasone prophylaxis may significantly reduce these risks and improve survival outcomes. These findings support monitoring ALC closely and considering preventive treatment strategies in high-risk patients.

Reference: 
Peter A Forsberg, Jacqueline A. Turner, Marita Meyer, Diana Abbott, Sara Nicholson, Henning Schade, Jeffrey V. Matous, Tara Gregory; Dexamethasone prophylaxis for excessive lymphocyte expansion after cilta-cel in multiple myeloma. Blood Adv 2026; bloodadvances.2025018639. doi: https://doi.org/10.1182/bloodadvances.2025018639

Revised criteria for light chain MGUS enhance diagnostic accuracy and risk stratification — Blood Cancer Journal (March 2026)

What is the purpose of the study? 
To evaluate the performance of revised free light chain (FLC) reference intervals proposed by the International Myeloma Foundation’s (IMF) iStopMM (Iceland Screens, Treats, Or Prevents Multiple Myeloma) group for diagnosing light chain monoclonal gammopathy of undetermined significance (LC-MGUS); and to determine whether the revised criteria more accurately identify individuals at risk of progressing to multiple myeloma (MM) or related disorders.

Summary 
Using data from the Danish Lymphoid Cancer Research (DALY-CARE) cohort, researchers compared original and revised LC-MGUS diagnostic criteria in 360 individuals with abnormal FLC measurements. The revised criteria reduced LC-MGUS diagnoses by 40%, reclassifying 150 individuals as normal, while still capturing all cases that progressed to multiple myeloma or AL amyloidosis. Progression risk remained clinically meaningful in the revised group, with a 5-year cumulative incidence of 8.9% and an annual progression rate of 3%.

Key points 
• LC-MGUS is a precursor condition to multiple myeloma identified through abnormal free light chain (FLC) testing.  
• Revised iStopMM criteria significantly reduced LC-MGUS diagnoses (by 40%).  
• 150 individuals previously classified as LC-MGUS were reclassified as normal under revised criteria.  
• Only 1.3% of reclassified individuals progressed, with no cases progressing to multiple myeloma or AL amyloidosis.  
• In the revised LC-MGUS group:  
 - 9.8% experienced disease progression  
 - 5.1% progressed to multiple myeloma  
 - 3.3% progressed to AL amyloidosis  
• 2-year progression risk: 5.8%; 5-year progression risk: 8.9%  
• Annual progression rate: ~3%  

Why this study matters 
The revised iStopMM LC-MGUS criteria accurately identify individuals at risk for progression to multiple myeloma and related disorders while reducing overdiagnosis. Importantly, no high-risk cases were missed among those reclassified as normal. These findings support adopting the revised criteria to improve diagnostic precision and focus on monitoring patients who are most likely to benefit.

Reference: 
Andersen, L.S., Mæng, C.V., Rögnvaldsson, S. et al. Revised criteria for light chain MGUS enhance diagnostic accuracy and risk stratification. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01478-y

Management of hematological toxicities after BCMA-directed CAR-T cell therapy — Blood Cancer Journal (March 2026)

What is the purpose of the study? 
To evaluate whether the CAR-HEMATOTOX (CAR-HT) score can predict hematologic toxicity and guide supportive care in patients with multiple myeloma receiving BCMA-directed CAR-T therapy; and to determine its usefulness in anticipating complications such as cytopenias, transfusion needs, infections, and survival outcomes.

Summary  
In a cohort of 224 multiple myeloma patients treated with BCMA-directed CAR-T therapy (2016–2024), those with high CAR-HT scores (≥2) had significantly higher rates of severe immune effector cell-associated hematotoxicity (ICAHT), anemia, and thrombocytopenia compared to low-score patients. High-risk patients were seven times more likely to require blood and platelet transfusions and experienced more infections, while interventions like G-CSF, TPO agonists, and stem cell boosts showed variable effectiveness. Despite increased toxicity, progression-free survival and overall survival were similar across CAR-HT risk groups.

Key points

• CAR-HT score stratifies hematotoxicity risk in multiple myeloma patients receiving BCMA CAR-T therapy  
• High CAR-HT score (≥2) observed in 58% of patients  
• Higher rates of severe toxicities in high-risk group:  
 - Grade 3 ICAHT: 45.4% vs 23.3%  
 - Grade 4 ICAHT: 5.4% vs 1.2% (p = 0.0069)  

•Increased incidence of:  
- Grade ≥3 anemia: 43.1% vs 24.4%  
- Thrombocytopenia: 50.8% vs 27.9% (both p < 0.0001)  

• High-risk patients required 7× more red cell and platelet transfusions  
• Stem cell boosts (4% of patients) enabled rapid recovery of blood counts  
• Higher infection rates in high CAR-HT patients and those receiving intensive supportive care  
• No significant difference in progression-free survival or overall survival between groups  
• Cytopenia-directed interventions did not improve survival outcomes  

Why this study matters 
The CAR-HT score is an effective tool for predicting hematologic toxicity and transfusion needs in patients undergoing BCMA-directed CAR-T therapy. While high-risk patients experience more complications and infections, survival outcomes remain similar regardless of CAR-HT score or supportive interventions. These findings support using the CAR-HT score to guide clinical decision-making and optimize supportive care strategies.

Reference: 
Cook, J., Gupta, S., Abdallah, N. et al. Management of hematological toxicities after BCMA-directed CAR-T cell therapy. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01455-5  

The Evolving Role of Genomic Technologies in Multiple Myeloma: Implications for Diagnosis, Risk Stratification and Resistance — Molecular Diagnosis and Therapy (March 2026)

What is the purpose of the study?  
To review the current and emerging role of genomic diagnostics in multiple myeloma (MM), focusing on how genomic tools improve risk stratification, disease monitoring, and treatment selection; and to evaluate the challenges of integrating genomic advances into routine clinical practice.

Summary  
Multiple myeloma is driven by a complex and evolving genomic landscape, including mutations (e.g., KRAS, NRAS, TP53, BRAF), structural variants, and copy number changes. This review compares conventional methods like fluorescence in situ hybridization (FISH) with advanced technologies such as next-generation sequencing (NGS), whole-exome sequencing (WES), whole-genome sequencing (WGS), optical genome mapping, and circulating tumor DNA (ctDNA) analysis, highlighting their complementary roles in diagnosis and monitoring. While genomic profiling enhances risk stratification and detection of treatment resistance, barriers such as cost, lack of standardization, and complexity of interpretation limit widespread clinical implementation.

Key points

• Multiple myeloma is characterized by:  
 - Complex genomic heterogeneity  
 - Mutations (e.g., KRAS, NRAS, TP53, BRAF)  
 - Structural variants and copy number alterations  
• Next-generation sequencing (NGS) has significantly improved detection of genomic abnormalities  
• Genomic data increasingly informs:  
 - Risk stratification  
 - Treatment selection  
 - Understanding of therapy resistance  

• FISH remains the clinical gold standard but has limitations:  
 - Detects key abnormalities (e.g., t(4;14), t(11;14), del(17p), gain(1q))  
 - Limited depth and scope  

• Advanced genomic tools:  
 - Targeted gene panels: cost-efficient but limited flexibility  
 - WES/WGS: comprehensive genomic profiling  
 - Optical genome mapping: detects complex rearrangements  
 - ctDNA analysis: enables non-invasive monitoring  

• NGS recommended:  
 - At diagnosis (especially for fit patients)  
 - At relapse to detect resistance mutations  

• Key barriers to implementation:  
 - High cost  
 - Lack of standardized guidelines  
 - Complexity of genomic data interpretation  

• Emerging need for:  
 - Integration of genomic data into clinical workflows  
 - Repeated genomic testing over disease course  

Why this study matters 
Comprehensive genomic profiling is becoming essential in multiple myeloma, enabling more precise risk assessment, earlier detection of relapse, and better-informed treatment decisions. However, despite major technological advances, challenges such as cost, standardization, and data interpretation continue to limit routine clinical use. Overcoming these barriers and integrating genomic tools into practice will be critical to achieving personalized, genomics-driven care in MM.

Reference: 
Baďurová, K., Kapustová, V., Kotulová, J. et al. The Evolving Role of Genomic Technologies in Multiple Myeloma: Implications for Diagnosis, Risk Stratification and Resistance. Mol Diagn Ther (2026). https://doi.org/10.1007/s40291-026-00836-7

Bridging therapy before CAR-T for multiple myeloma: a survey from the CMWP and CTIWP of the EBMT — Bone Marrow Transplantation (March 2026)

What is the purpose of the survey? 
To evaluate real-world practices of bridging therapy in patients with multiple myeloma (MM) undergoing anti-BCMA CAR-T therapy; and to identify current treatment patterns, decision-making factors, and perceived risks and benefits through a multinational survey and narrative review.

Summary  
In a survey of 48 centers across 11 countries, bridging therapy was used in over 85% of MM patients awaiting CAR-T, typically initiated within one week after apheresis and continued for 1–2 months. Common regimens included proteasome inhibitors (90%), immunomodulatory drugs (85%), chemotherapy, bispecific antibodies (75%), and monoclonal antibodies (69%), with treatment selection driven mainly by prior therapy and disease burden. Despite widespread use, practices were highly variable with limited standardization, and most centers proceeded to CAR-T infusion even after disease progression during bridging.

Key points 
• Bridging therapy is used in >85% of MM patients prior to CAR-T infusion  
• Most centers report low standardization of bridging practices (40% not standardized at all)  
• Common therapies:  
 - Proteasome inhibitors (90%)  
 - Immunomodulatory drugs (85%)  
 - Chemotherapy & bispecific antibodies (75%)  
 - Monoclonal antibodies (69%)  

• Bridging typically lasts 1–2 months and starts within 1-week post-apheresis  
• Treatment choice driven by:  
 - Prior therapies/refractory status (92%)  
 - Disease burden (77%)  
 - Extramedullary disease (69%)  

• Monitoring mainly uses free light chains (96%) and serum M-protein (94%)  
• 95% of patients proceed to CAR-T despite progression during bridging 
• Increasing use of bispecific antibodies, often with short (2–4 week) washout periods  
• Limited access to CAR-T products and lack of prospective data remain key challenges  

Why this survey matters 
Bridging therapy is a critical and widely used component of the CAR-T treatment pathway in multiple myeloma, but current practices are highly heterogeneous and lack standardization. Treatment decisions are primarily guided by prior therapy and disease burden, with growing use of bispecific antibodies despite concerns about toxicity and optimal timing. These findings highlight the urgent need for prospective studies and consensus guidelines to optimize bridging strategies and improve patient outcomes.

Reference: 
Gagelmann, N., Merz, M., Baaij, L.G.A. et al. Bridging therapy before CAR-T for multiple myeloma: a survey from the CMWP and CTIWP of the EBMT. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02816-1  

Temporal trends in second primary malignancies among long-term survivors of multiple myeloma across treatment eras: a population-based analysis of the SEER database — Hematology (April 2026)

What is the purpose of the study? 
To evaluate how the risk of secondary primary malignancies (SPM) has evolved over time among long-term survivors of multiple myeloma, across treatment eras. Using SEER database (1975-2022), the study assesses whether modern therapies are associated with reduced long-term cancer risk.

Summary 
In this large retrospective cohort of 52,497 MM patients, 15,402 survived at least 5 years, and 9.14% developed SPMs over long-term follow-up. SPM rates significantly declined across treatment eras, from 11.43% (pre-2000) to 2.45% in the daratumumab era (2016+), suggesting improved long-term safety with newer therapies. The most common SPMs were prostate, lung, and breast cancers, while acute myeloid leukemia (AML) remained an important hematologic risk.

Key points 
• Data source: SEER 17 registries (1975–2022) 
• Population: 52,497 MM patients; 15,402 (29.34%) survived ≥5 years 
• Overall SPM incidence: 9.14% (1,408 patients) 
• Significant decline in SPM rates across treatment eras: 
 - Era 1 (≤2000): 11.43% 
 - Era 2 (2001–2010): 10.45% 
 - Era 3 (2011–2015): 7.78% 
 - Era 4 (2016+): 2.45%

• Common SPMs: 
 - Prostate cancer (13.81%) 
 - Lung cancer (10.17%) 
 - Breast cancer (7.42%)

• Key hematologic SPM: Acute myeloid leukemia (AML) (6.78%) 
• Decline likely linked to shift from alkylating chemotherapy to targeted therapies (e.g., proteasome inhibitors, IMiDs, monoclonal antibodies like daratumumab) 
• Results confirmed in 10-year survivors 
• Era 4 findings are preliminary due to shorter follow-up

Why this study matters 
The risk of second primary cancers in long-term multiple myeloma survivors has decreased substantially over time, with nearly a five-fold reduction from older chemotherapy eras to modern treatment approaches. This improvement likely reflects reduced use of genotoxic therapies and increased reliance on targeted treatments. While results from the daratumumab era are promising, longer follow-up is needed, and continued monitoring is important, especially for persistent risks like acute myeloid leukemia.

Reference: 
Lu, L., Lin, S., Chen, Y., & Huang, Y. (2026). Temporal trends in second primary malignancies among long-term survivors of multiple myeloma across treatment eras: a population-based analysis of the SEER database. Hematology, 31(1). https://doi.org/10.1080/16078454.2026.2653404

Teclistamab interference with anti-BCMA chimeric antigen receptor T-cell detection by flow cytometry: duration and clinical implications — Leukemia (April 2026)

What is the purpose of the study? 
To investigate whether prior treatment with teclistamab affects the detection of BCMA-directed CAR T-cells in patients with multiple myeloma (MM); and to evaluate the reliability of flow cytometry–based assays used before anti-BCMA CAR T-cell therapy.

Summary  
Researchers analyzed peripheral blood samples from MM patients who had received teclistamab within 14 days to 1 year before planned anti-BCMA CAR T-cell therapy, using multiparameter flow cytometry (MFC). They found that teclistamab can interfere with BCMA-CAR T-cell detection assays, causing false-positive anti-BCMA T-cell signals for up to 74 days (2.5 months) after treatment. The study highlights variability in drug clearance and emphasizes the need for alternative detection strategies, such as PCR-based methods, in recently treated patients.

Key points 
• Teclistamab can impair accurate detection of BCMA-CAR T-cells using standard flow cytometry assays. 
• False-positive anti-BCMA T-cell signals may persist for at least 74 days (2.5 months) after treatment. 
• Drug clearance varies widely between patients, influenced by body weight and disease characteristics. 
• Standard assay controls (FMO-based flow cytometry) may not fully eliminate detection errors. 
• Alternative detection methods include: 
 - PCR-based CAR T-cell monitoring 
 - Targeting alternative CAR structures (e.g., linker regions)

• Routine pre-CAR T-cell testing for anti-BCMA T-cells is recommended in patients previously treated with teclistamab. 
• Similar interference may occur with other bispecific antibodies (e.g., elranatamab, blinatumomab).

Why this study matters 
Teclistamab significantly interferes with flow cytometry–based detection of BCMA-CAR T-cells, leading to potential false-positive results for several weeks after treatment. Clinicians should perform pre-treatment screening and consider alternative monitoring approaches, especially PCR-based assays, in recently treated patients. Awareness of this limitation is essential to ensure accurate CAR T-cell monitoring and clinical decision-making.

Reference: 
Schadt, J., von Bonin, M., Oelschlägel, U. et al. Teclistamab interference with anti-BCMA chimeric antigen receptor T-cell detection by flow cytometry: duration and clinical implications. Leukemia (2026). https://doi.org/10.1038/s41375-026-02961-y  
 

Dietary intake and the risk of monoclonal gammopathy of undetermined significance: results from the population-based iStopMM screening study — Blood Cancer Journal (April 2026)

What is the purpose of the study? 
To evaluate whether dietary habits and patterns are associated with the risk of monoclonal gammopathy of undetermined significance (MGUS). Using data from the large iStopMM screening study, it aims to clarify diet’s potential role in the development of MGUS and related malignancies such as multiple myeloma.

Summary  
In the iStopMM study of 75,422 individuals in Iceland, 27,217 participants completed a food-frequency questionnaire, including 1,020 with MGUS. Overall, no significant associations were found between dietary patterns or specific food components and MGUS risk after adjusting for confounders. However, high dairy consumption was linked to increased odds of IgA MGUS (OR 2.01, 95% CI 1.16–3.65).

Key points 
• MGUS is an asymptomatic precursor to multiple myeloma (MM).  
• Study population: 75,422 screened; 27,217 completed dietary survey; 1,020 had MGUS.  
• No overall association between dietary patterns or specific foods and MGUS risk.  
• High dairy intake was associated with increased odds of IgA MGUS (OR 2.01, 95% CI 1.16–3.65).  
• Analyses adjusted for age, sex, physical activity, and education.  

Why this study matters 
Dietary habits do not appear to play a significant role in the overall risk of developing MGUS, suggesting they are unlikely to be major contributors to multiple myeloma development. The observed association between high dairy intake and IgA MGUS may warrant further investigation but does not alter the overall conclusion. Future research should explore other environmental or biological factors underlying MGUS and MM.

Reference: 
Hallsson, S., Gunnarsdottir, I., Thordardottir, M. et al. Dietary intake and the risk of monoclonal gammopathy of undetermined significance: results from the population-based iStopMM screening study. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01480-4 

The genetic landscape of extramedullary plasmacytoma: a comparative analysis with extramedullary disease of multiple myeloma — Haematologica (April 2026)

What is the purpose of the study? 
To characterize the genetic landscape of extramedullary plasmacytoma (EMP) and compare it with extramedullary disease of multiple myeloma (EMD); and to identify molecular differences that can aid diagnosis and risk stratification.

Summary  
EMP is a localized plasma cell neoplasm with generally favorable prognosis and low progression to multiple myeloma (MM), but it must be distinguished from the more aggressive EMD. Using fluorescence in situ hybridization (FISH), copy number profiling, and targeted next-generation sequencing in 24 EMP and 24 EMD cases, EMP showed significantly lower genomic complexity, with fewer copy number changes (4.3 vs. 19.3) and fewer mutations (median 2.0 vs. 3.0). EMP was enriched for TRAF3 mutations, while EMD more frequently harbored high-risk mutations such as NRAS/KRAS, TP53, TENT5C, ARID1A, and ATM, highlighting distinct molecular profiles.

Key points 
• EMP is a localized plasma cell neoplasm with favorable prognosis and low risk of progression to MM. 
• Differentiation between EMP and EMD is clinically critical due to differing aggressiveness. 
• EMP demonstrates significantly lower genomic complexity than EMD: 
 - Copy number changes: 4.3 (EMP) vs. 19.3 (EMD), p<0.001 
 - Mutations: median 2.0 (EMP) vs. 3.0 (EMD), p<0.01

• Shared features include IGH rearrangements and hyperdiploidy, though less frequent in EMP. 
• TRAF3 mutations are enriched in EMP and absent in EMD (p=0.022). 
• EMD is associated with high-risk mutations (NRAS/KRAS, TP53, TENT5C, ARID1A, ATM) linked to advanced MM. 
• Genetic profiling may help distinguish EMP from EMD and identify higher-risk EMP cases.

Why this study matters 
EMP exhibits a significantly less complex and partially distinct genetic profile compared to EMD, supporting its more favorable clinical behavior. The presence of unique mutations such as TRAF3 and fewer high-risk alterations may help differentiate EMP from EMD in challenging diagnostic scenarios. These findings also suggest a potential role for molecular profiling in identifying EMP patients at increased risk of progression.

Reference: 
Vogelsberg A, Salmerón-Villalobos J, Wilhelmi A-L, Otto F, Schneider A, Mankel B, Bag E, Colmenero A, Dettmer MS, Narbaitz M, Tzankov A, Salaverria I, Bonzheim I, Fend F. The genetic landscape of extramedullary plasmacytoma: a comparative analysis with extramedullary disease of multiple myeloma. Haematologica; https://doi.org/10.3324/haematol.2025.300201 [Early view].

Prognostic Factors Influencing the Efficacy and Safety of Teclistamab and Elranatamab in Multiple Myeloma: A Multicenter Propensity-Weighted Analysis — JCO Oncology Advances (April 2026)

What is the purpose of the study? 
To assess the real-world effectiveness and safety of BCMA-targeting bispecific antibodies (BsAbs), teclistamab and elranatamab, in patients with relapsed/refractory multiple myeloma (RRMM). Outcomes were compared with a propensity score-matched historical control group, focusing on survival, infection risk, and treatment-related adverse events.

Summary  
In this multicenter, retrospective study, 201 patients were treated with BsAbs and 162 matched controls. BsAb therapy was associated with a median progression-free survival (PFS) of 17.9 months overall, with variability between agents that likely reflected differences in patient characteristics rather than treatment effects alone. Compared with controls, BsAb-treated patients experienced significantly higher rates of severe infections (98.2 vs 27.1 per 100 patient-years), along with increased ICU admissions, while also showing signals of clinical benefit in patients who responded to therapy. Teclistamab-treated patients had higher observed 12-month overall survival (73.4% vs 53.9%), but this difference should be interpreted cautiously due to baseline imbalances between treatment groups.

Key points 
• Study design: Multicenter, retrospective real-world study of BsAbs vs matched historical controls in RRMM 
• Treatments studied: Teclistamab and elranatamab (BCMA-targeting bispecific antibodies) 
• Efficacy: Median PFS 17.9 months overall; outcomes influenced by patient risk factors and disease severity 
• Survival observation: Higher 12-month OS seen with teclistamab, likely affected by baseline patient differences 
• Major safety finding: Significantly increased severe infections in BsAb-treated patients (98.2 vs 27.1 per 100 patient-years; P < .001) 
• Common infections: Mainly bacterial and respiratory viral infections 
• Other adverse events: Cytokine release syndrome (50.2%, mostly low grade) and neurotoxicity (8.5%, including 5.9% grade ≥3) 
• Risk factors for worse outcomes: Poor performance status, low albumin, renal impairment, and advanced disease burden 
• Clinical context: BsAb patients were often heavily pretreated or high-risk, which likely influenced early outcomes 
• Supportive care note: Immunoglobulin use was associated with improved survival but did not fully eliminate infection risk

Why this study matters 
In real-world patients with RRMM, BCMA-targeting bispecific antibodies (teclistamab and elranatamab) are associated with meaningful clinical activity, particularly in responders, but also a substantially increased risk of serious infections. Differences observed between the two agents should be interpreted cautiously, as they are likely influenced by differences in patient characteristics rather than direct drug comparison. These findings emphasize the importance of careful patient selection, close monitoring, and proactive infection prevention strategies to improve the safety of BsAb therapy.

Reference: 
Jeremie Zerbit et al. Prognostic Factors Influencing the Efficacy and Safety of Teclistamab and Elranatamab in Multiple Myeloma: A Multicenter Propensity-Weighted Analysis. JCO Oncol Adv 3, e2500077(2026). DOI:10.1200/OA-25-00077

Breakthroughs of bispecific antibodies therapy in multiple myeloma: latest updates from 2025 ASH — Biomarker Research (April 2026)

What is the purpose of the study? 
To summarize updated clinical trial data presented at the 2025 ASH Annual Meeting on bispecific antibodies (BsAbs) for multiple myeloma (MM), including agents targeting BCMA, GPRC5D, and FcRH5; and to evaluate their efficacy and safety as monotherapy, combination therapy, and earlier-line interventions in both relapsed/refractory (RRMM) and newly diagnosed MM (NDMM).

Summary  
Bispecific antibodies demonstrate high overall response rates (ORR) and deep clinical responses in multiple myeloma, with several studies reporting substantial MRD negativity, particularly in select trials such as cevostamab consolidation post–CAR-T and frontline regimens like IFM2021-01. Combination approaches, including teclistamab plus daratumumab (MajesTEC-3) and dual BsAb therapy in RedirecTT-1, show enhanced efficacy with ORRs up to 89–92% and improved progression-free survival, although some outcomes remain immature or limited to early follow-up. Despite these promising results, infection-related toxicity (frequently severe and exceeding 90% in certain combination studies) remains a major safety concern, alongside high rates of grade ≥3 adverse events in combination regimens.

Key points 
• Strong efficacy in RRMM: 
 - LBL-034 (GPRC5D×CD3): ORR up to 78.1% in heavily pretreated patients 
 - Cevostamab (FcRH5×CD3): up to 93% MRD negativity post–CAR-T, with 12-month PFS/OS ~95% in consolidation setting 
 - Subcutaneous cevostamab: ORR 38.8%, reflecting inclusion of low-dose cohorts

• Enhanced efficacy with combination BsAb strategies: 
 - MajesTEC-3: PFS 83.4% vs 29.7%, ORR 89.0% vs 75.3%, CR ≥81.8% (vs 32.1%) 
 - RedirecTT-1: ORR up to 92.3% (non-EMD); durable survival benefits, though outcomes vary by EMD status 
 - Elranatamab + iberdomide: ORR 77.3%, CR ≥45.5% 
 - Etentamig + Pd: ORR 81%, VGPR or better 72%

• Frontline / early-line potential (NDMM): 
 - LINKER-MM4 (linvoseltamab): ORR 79%, CR ≥26%, MRD negativity (10⁻⁵) in 92% of evaluable patients, with limitations due to suboptimal dosing and short follow-up 
 - IFM2021-01 (teclistamab + daratumumab): ORR 100%, VGPR ≥97%, MRD negativity (10⁻⁶) 100% in evaluable patients (short follow-up; transplant-ineligible cohort) 
 - IMMUNOPLANT: 100% conversion from MRD-positive to MRD-negative after consolidation

• Safety and limitations: 
 - Infection risk is high across studies, exceeding 90% in some combination regimens (e.g., MajesTEC-3, RedirecTT-1) 
 - Grade ≥3 adverse events common, including neutropenia and infections (up to ~78%) 
 - Many frontline and combination studies have early follow-up, small sample sizes, or non-uniform dosing, limiting definitive efficacy conclusions

Why this study matters 
Bispecific antibodies represent a highly active and rapidly evolving therapeutic class in multiple myeloma, demonstrating deep and durable responses across both relapsed/refractory and newly diagnosed settings. Combination strategies and earlier-line use appear to further enhance efficacy, though many results remain preliminary with limited follow-up and heterogeneous dosing. The major unresolved challenge is managing substantial infectious toxicity while optimizing sequencing, durability, and long-term safety in larger confirmatory trials.

Reference: 
Zhao, B., Bu, Q., Chen, AL. et al. Breakthroughs of bispecific antibodies therapy in multiple myeloma: latest updates from 2025 ASH. Biomark Res 14, 41 (2026). https://doi.org/10.1186/s40364-026-00912-4

Exposure-response analyses for belantamab mafodotin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma from DREAMM-6 Arm B and DREAMM-7 — British Journal of Cancer ( April 2026)

What is the purpose of the study? 
To evaluate the exposure–response (E–R) relationship of belantamab mafodotin in combination with bortezomib and dexamethasone (BVd) using data from the DREAMM-6 and DREAMM-7 trials in patients with relapsed/refractory multiple myeloma (RRMM); and to determine the optimal dosing strategy by balancing efficacy and safety outcomes.

Summary  
Higher Cycle 1 exposure to belantamab mafodotin was associated with improved clinical responses, including higher rates of very good partial response or better (≥VGPR), without meaningful increases in clinically significant ocular toxicity such as visual acuity loss or grade ≥3 ocular adverse events. While increased exposure raised the incidence of ophthalmic exam findings, these were less clinically relevant and manageable with dose modifications. A starting dose of 2.5 mg/kg provided superior efficacy compared to 1.9 mg/kg, without reducing key safety risks.

Key points 
• Data derived from DREAMM-6 (phase I/II) and DREAMM-7 (phase III) trials in RRMM patients. 
• Higher belantamab mafodotin exposure improves response rates (≥VGPR, ≥CR). 
• No significant increase in clinically meaningful ocular toxicity (e.g., BCVA worsening to ≤20/50 in both eyes). 
• Ophthalmic exam findings increased with exposure but were manageable and less clinically impactful. 
• Lower dose (1.9 mg/kg) reduced efficacy without improving key safety outcomes. 
• Prognostic factors (e.g., extramedullary disease, prior anti-CD38 therapy, high IgG) influenced treatment response. 
• BVd regimen shows strong efficacy with manageable safety and convenient dosing (every 3 weeks).

Why this study matters 
The analysis supports a starting dose of 2.5 mg/kg belantamab mafodotin in the BVd regimen as it achieves deeper and faster clinical responses without significantly increasing meaningful safety risks. Lower dosing reduces efficacy without clear safety advantages. Overall, BVd represents an effective and tolerable treatment option for patients with RRMM in second-line and later settings.

Reference: 
Papathanasiou, T., Chen, X., Carreno, F. et al. Exposure-response analyses for belantamab mafodotin in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma from DREAMM-6 Arm B and DREAMM-7. Br J Cancer (2026). https://doi.org/10.1038/s41416-026-03437-7

Association of genetic ancestry with outcomes and toxicity of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma — Blood Cancer Journal (April 2026)

What is the purpose of the study? 
To determine whether efficacy and safety of idecabtagene vicleucel (ide-cel) CAR-T therapy vary by genetic ancestry in patients with relapsed/refractory multiple myeloma (RRMM).

Summary  
In this retrospective analysis of patients treated in the KarMMa-2 and KarMMa-3 trials or standard care, ide-cel demonstrated similar efficacy outcomes (overall response rate, progression-free survival, and overall survival) across genetic ancestry groups, despite worse baseline disease characteristics in patients with higher African (AFR) and Admixed American (AMR) ancestry. However, safety profiles differed, with higher rates of infections (mainly viral) and prolonged neutropenia observed in patients with higher AFR ancestry. These findings suggest that while CAR-T therapy may overcome traditional outcome disparities, tailored monitoring and supportive care are needed to address toxicity risks.

Key points 
• Single-center retrospective study at MD Anderson Cancer Center (2018–2023). 
• Included RRMM patients receiving ide-cel via KarMMa-2, KarMMa-3, or standard care. 
• Genetic ancestry (AFR, EUR, AMR) determined using genomic analysis (ADMIXTURE). 
• Efficacy outcomes (ORR, PFS, OS): similar across ancestry groups despite baseline disparities. 
• Patients with higher AFR/AMR ancestry had worse baseline health and more prior treatments.

• Safety differences: 
 - Higher infection rates (predominantly viral) in AFR ancestry 
 - Increased and prolonged neutropenia

• Possible biological mechanisms: differences in immune response, inflammation, and drug metabolism. 
• CAR-T therapy may mitigate traditional prognostic disparities in MM. 
• Highlights need for improved supportive care and increased diversity in clinical trials.

Why this study matters 
Anti-BCMA CAR-T therapy with ide-cel provides comparable efficacy across genetic ancestry groups in RRMM, even among patients with more advanced disease at baseline. However, differences in toxicity (particularly infections and hematologic complications) highlight the importance of personalized monitoring and supportive care. Expanding equitable access and improving representation in clinical trials will be essential to optimize outcomes for all patients.

Reference: 
Dillard, C.M., Lee, H., Kalariya, N. et al. Association of genetic ancestry with outcomes and toxicity of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. Blood Cancer J. 16, 59 (2026). https://doi.org/10.1038/s41408-026-01489-9

CAR-T therapy moving to first-line in multiple myeloma: latest updates from the 2025 ASH annual meeting — Journal of Hematology and Oncology (April 2026)

What is the purpose of the report? 
To summarize clinical trial results presented at the ASH Annual Meeting 2025 on CAR-T therapies in multiple myeloma (MM); and to describe efficacy outcomes in both relapsed/refractory and newly diagnosed settings.

Summary  
In the KarMMa-3 subgroup of patients aged ≥70 years, idecabtagene vicleucel showed higher overall response rates (81.6% vs. 48.1%) and longer median progression-free survival (18.9 vs. 5.7 months) compared with standard care; median overall survival was not reached in either group. In patients <70 years, overall response rates were 68.8% vs. 41.0%, with median overall survival of 39.5 vs. 27.9 months. These results indicate improved response and progression-free survival outcomes with CAR-T therapy in both age groups.

Key points 
• In relapsed/refractory MM: 
 - CARTITUDE-4: 30-month progression-free survival 71.0% vs. 43.2% (standard risk); 52.3% vs. 17.5% (high risk). 
 - iMMagine-1: overall response rate 97%; MRD negativity 93% (10⁻⁵ sensitivity).

• Early-phase studies of dual-target, allogeneic, and in vivo CAR-T therapies report high response rates, including up to 100% in small cohorts. 
• In newly diagnosed MM: 
 - Overall response rates up to 100% and stringent complete response rates up to ~94–97%. 
 - Reported progression-free and overall survival rates at ~30 months range from 74.5% to 92% across studies.

• Strengths 
 - Consistent reporting of high response rates across multiple trials and patient subgroups. 
 - Inclusion of older and high-risk patient populations.

• Limitations 
 - Small sample sizes in several studies. 
 - Limited follow-up duration in early-phase trials.

Why this report matters 
CAR-T therapies demonstrate high response rates and prolonged progression-free survival across multiple clinical trials in multiple myeloma. These findings are reported in both relapsed/refractory and newly diagnosed settings, including older and high-risk populations. Longer follow-up and larger studies are needed to determine durability of response and overall survival outcomes.

Reference: 
Geng, C., Chen, W. & Zhu, HH. CAR-T therapy moving to first-line in multiple myeloma: latest updates from the 2025 ASH annual meeting. J Hematol Oncol 19, 25 (2026). https://doi.org/10.1186/s13045-026-01793-8 

Clinical Trials

Carfilzomib, lenalidomide, and dexamethasone compared with lenalidomide treatment after autologous haematopoietic stem-cell transplantation in patients with multiple myeloma (ATLAS): primary analysis of a randomised, open-label, phase 3 trial — The Lancet Haematology (March 2026)

What is the purpose of the study? 
To compare the effectiveness and safety of carfilzomib–lenalidomide–dexamethasone versus lenalidomide alone as maintenance therapy after autologous hematopoietic stem-cell transplantation (HSCT) in patients with newly diagnosed multiple myeloma; and to determine whether a multidrug regimen improves progression-free survival (PFS) and outcomes.

Summary  
In the ATLAS phase 3 randomized trial (NCT02659293), 180 patients with newly diagnosed multiple myeloma post-HSCT were assigned to either carfilzomib–lenalidomide–dexamethasone or lenalidomide alone. After a median follow-up of 69 months, the 4-year progression-free survival was significantly higher with the combination therapy (67.5%) compared to lenalidomide alone (38.0%), with a hazard ratio of 0.46. Median PFS was nearly doubled (72.8 vs 37.3 months), demonstrating superior disease control. Rates of serious adverse events were slightly higher in the combination group, though common toxicities such as neutropenia occurred in both groups. The study also incorporated measurable residual disease (MRD)-guided treatment adjustments, allowing some patients to transition to less intensive therapy.

Key points

• ATLAS phase 3 trial compared carfilzomib–lenalidomide–dexamethasone vs lenalidomide alone after HSCT. 
• 4-year PFS: 67.5% (combination) vs 38.0% (lenalidomide); hazard ratio 0.46. 
• Median PFS: 72.8 months vs 37.3 months, favoring combination therapy. 
• MRD-guided de-escalation allowed some patients to switch to lenalidomide alone. 
• Grade 3–4 neutropenia was common in both groups; serious adverse events slightly higher with combination therapy. 
• Treatment-related deaths were rare but occurred in both groups.

Why this study matters 
The ATLAS trial demonstrates that carfilzomib–lenalidomide–dexamethasone significantly improves progression-free survival compared with lenalidomide alone in patients with multiple myeloma after HSCT. While the combination therapy is associated with slightly higher toxicity, the safety profile remains manageable. The use of MRD-guided treatment strategies allows for personalized therapy and potential de-escalation in lower-risk patients. These findings support intensifying maintenance therapy to improve long-term disease control. Overall, this approach represents an important advancement in post-transplant management of multiple myeloma.

Reference: 
Dytfeld D, Wróbel T, Jamroziak K, Kubicki T, Robak P, Puła A, Walter-Croneck A, Czyż J, Tyczyńska A, Druzd-Sitek A, Giannopoulos K, Nowicki A, Szczepaniak T, Łojko-Dankowska A, Matuszak M, Gil L, Puła B, Rybka J, Majcherek M, Usnarska-Zubkiewicz L, Szukalski Ł, Końska A, Zaucha JM, Walewski J, Mikulski D, Czabak O, Robak T, Lahoud OB, Zonder JA, Cooperrider JH, Derman BA, Karrison T, Jakubowiak AJ. Carfilzomib, lenalidomide, and dexamethasone compared with lenalidomide treatment after autologous haematopoietic stem-cell transplantation in patients with multiple myeloma (ATLAS): primary analysis of a randomised, open-label, phase 3 trial. Lancet Haematol. 2026 Mar 11:S2352-3026(26)00011-6. doi: 10.1016/S2352-3026(26)00011-6.

MajesTEC-3: Redefining what’s possible in multiple myeloma — Clinical Hematology International (March 2026)

What is the purpose of the study?  
To evaluate the effectiveness and safety of teclistamab-based therapies in treating relapsed or refractory multiple myeloma, particularly their ability to improve survival outcomes and achieve durable responses; and to explore strategies such as MRD-guided, time-limited treatment to optimize long-term efficacy while reducing toxicity and infection risk.

Summary 
Treatment for multiple myeloma (MM) has advanced significantly, with some patients now achieving survival of 15–20 years, suggesting the possibility of cure. The MajesTEC-3 trial showed that teclistamab (a BCMA-directed bispecific antibody) plus daratumumab reduced disease progression or death by 83% and mortality by 54% compared to standard therapies, with durable responses and a 3-year overall survival of 83%. However, serious infections (grade 3–4) occurred in over half of patients, particularly early in treatment, though improved prevention strategies reduced this risk. The MajesTEC-9 trial confirmed that teclistamab is also effective as monotherapy in heavily pretreated, refractory patients. Future strategies focus on minimal residual disease (MRD)-guided, time-limited therapy to balance efficacy, safety, and quality of life.

Key points

• MM outcomes have improved dramatically; long-term survival (15–20 years) is achievable in some patients. 
• MajesTEC-3 trial: 
 - 83% reduction in disease progression/death (HR 0.17) 
 - 54% reduction in mortality (HR 0.46) 
 - Median PFS not reached vs 18.1 months (control) 
 - 36-month overall survival: 83% vs 65%

• Durable responses observed, with >90% progression-free after 6 months and sustained up to 3 years. 
• Safety concerns: 
 - 54% had grade 3–4 infections; 13 infection-related deaths 
 - Risk highest in first 6 months, improved with prophylaxis and immunoglobulin replacement 
 - Cytokine release syndrome (CRS) mild (grade 1–2); ICANS rare (1%)

• MajesTEC-9 trial: 
 - Teclistamab monotherapy reduced progression/death risk by 71% (HR 0.29) 
 - Reduced mortality by 40% (HR 0.60) in refractory patients

• MRD-guided and fixed-duration therapy (12–24 months) may reduce toxicity and preserve immune function. 
• Bispecific antibodies (BsAbs) offer easier access than CAR T-cell therapy but require infrastructure, training, and cost considerations. 
• Ongoing research focuses on biomarkers, sequencing strategies, infection prevention, and earlier-line use.

Why this study matters  
The MajesTEC-3 and MajesTEC-9 trials establish teclistamab-based therapies as highly effective options across relapsed multiple myeloma, offering deep and durable responses comparable to advanced cellular therapies. While infection risk remains a key challenge, it appears manageable with appropriate preventive strategies and evolving clinical protocols. A major shift toward MRD-guided, time-limited treatment could reduce long-term toxicity while maintaining strong outcomes. Ensuring equitable access and proper implementation in community settings will be essential to maximize patient benefits. Overall, these advances bring the field closer to achieving long-term remission—and potentially cure—for a broader group of patients with MM.

Reference: 
Al Hadidi S, Gaballa M. MajesTEC-3: Redefining what’s possible in multiple myeloma. Clinical Hematology International. 2026;8(1):56-59. doi:10.46989/001c.158751

Descriptive study of current routine clinical practice in the management of patients with multiple myeloma in Spain: CROMMAS study — Clinical Lymphoma Myeloma and Leukemia (March 2026)

What is the purpose of the study? 
To characterize real-world treatment patterns for multiple myeloma in Spain, including therapies used across different patient groups and disease stages; and to highlight how clinical practice aligns with or diverges from evolving treatment guidelines in routine care.

Summary  
The CROMMAS study evaluated real-world treatment practices for multiple myeloma (MM) in Spain based on a survey of 23 hematologists. For patients eligible for autologous stem cell transplant (ASCT), the most common induction regimen was daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) (49.6%), followed by D-VTd (23.5%) and VRd (20.0%). Nearly all patients (97.8%) received maintenance therapy after ASCT, most commonly lenalidomide alone (77.0%). In transplant-ineligible patients, daratumumab + lenalidomide + dexamethasone (DRd) was the leading first-line treatment (66.1%). For relapsed/refractory (R/R) patients resistant to lenalidomide, isatuximab + carfilzomib + dexamethasone (58.3%) was the most frequently used second-line regimen.

Key points

• CROMMAS study: Survey of 23 hematologists describing real-world MM management in Spain 
• ASCT-eligible patients (induction therapy): 
 - D-VRd: 49.6% (most common) 
 - D-VTd: 23.5% 
 - VRd: 20.0%

• Post-ASCT maintenance: 
 - 97.8% received maintenance therapy 
 - Lenalidomide alone: 77.0% 
 - Lenalidomide + bortezomib: 12.8%

• ASCT-ineligible patients (first-line): 
 - DRd: 66.1% (most common) 
 - D-VMP: 16.5%

• Relapsed/Refractory MM (lenalidomide-refractory): 
 - Isatuximab + carfilzomib + dexamethasone: 58.3% 
 - DVd: 13.9% 
 - Pomalidomide-based regimens: 12.2%

• Highlights variability in real-world practice and evolving treatment landscape

Limitations

• Small sample size: Only 23 hematologists participated, which may not fully represent all clinical practices across Spain. 
• Survey-based design: Results relied on physicians’ self-reported answers to a a 57-question survey rather than actual patient-level data. 
• Aggregated data: The study did not include detailed individual patient outcomes, limiting insights into treatment effectiveness and safety. 
• Limited generalizability: Findings may not apply to other countries or healthcare systems with different resources and treatment access.

Overall, while useful for understanding real-world trends, the study does not provide definitive evidence on treatment efficacy or outcomes.

Why this study matters  
The CROMMAS study provides a snapshot of how multiple myeloma is currently treated in Spain in everyday clinical practice, including both newly diagnosed and relapsed or refractory patients. It highlights how doctors are adapting to rapidly evolving treatment options, even as existing guidelines may not fully reflect these changes. Because real-world data are still limited, these findings help fill important gaps in understanding current care. Overall, the study underscores the need for updated guidelines and more research to support treatment decisions.

Reference: 
Enrique M. Ocio, María-Victoria Mateos, Descriptive study of current routine clinical practice in the management of patients with multiple myeloma in Spain: CROMMAS study, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.004.

Comparison of Patient-Reported Outcomes for Elranatamab in MagnetisMM-3 Versus Real-World Physician Choice of Therapy for Triple-Class Refractory Multiple Myeloma — Clinical Lymphoma Myeloma and Leukemia (March 2026)

What is the purpose of the study? 
To compare patient-reported outcomes (PROs) in patients with triple-class refractory multiple myeloma (TCR MM) treated with elranatamab versus real-world physician’s choice of therapy; and to determine whether elranatamab improves quality of life and symptom burden.

Summary  
This analysis compared patients from the MagnetisMM-3 clinical trial receiving elranatamab with patients from real-world studies (MagnetisMM-13 and MagnetisMM-14) receiving standard therapies. Over 6 months, patients treated with elranatamab showed greater improvements in quality-of-life measures, including EQ-5D-5L scores and patient-reported symptom scales. Improvements were also seen in patient global impressions of severity (PGIS) and change (PGIC), as well as disease-related symptoms. These benefits were consistent even after adjusting differences between groups and across multiple sensitivity analyses. Overall, elranatamab provided similar or better patient-reported outcomes compared to real-world treatment options.

Key points

• Study population: Triple-class refractory multiple myeloma (TCR MM).  
• Treatments compared:  
 - Elranatamab (MagnetisMM-3)  
 - Physician’s choice therapy (MagnetisMM-13/14)  

• Sample size: 184 (elranatamab) vs 68 (PCT).  
• Elranatamab showed greater improvements in:  
 - Quality of life (EQ-5D-5L index, V6)  
 - Patient-reported symptom burden  
 - PGIS and PGIC scores  

• Results remained consistent after statistical adjustments and sensitivity analyses.  

Why this study matters  
Elranatamab improved or maintained patient-reported quality of life and symptoms compared with standard real-world treatments in TCR MM. These findings support its benefit not only in disease control but also in patient well-being.

Reference: 
Benjamin Hebraud, Charis Charalampous, Ricardo Parrondo, Saurabh Chhabra, Madhu Nagaraj, Marco DiBonaventura, Mei Sheng Duh, Priyanka J. Bobbili, Aolin Wang, Stephanie Frey-Koba, Joseph Milce, Maude Levy, Lily Chafetz, Ariane Faucher, Sarasa MA Johnson, Patrick Hlavacek, Paul Cislo, David Hughes, Guido Nador, Shaji K. Kumar, Comparison of Patient-Reported Outcomes for Elranatamab in MagnetisMM-3 Versus Real-World Physician Choice of Therapy for Triple-Class Refractory Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.03.014.

 
Efficacy and safety of selinexor combined with VRD in newly diagnosed multiple myeloma with EMD: a phase 2 trial — Blood Advances (March 2026)

What is the purpose of the study? 
To evaluate the efficacy and safety of the SVRd regimen (selinexor, bortezomib, lenalidomide, and dexamethasone) in patients with newly diagnosed multiple myeloma (NDMM) with extramedullary disease (EMD); and to determine response rates, survival outcomes, and tolerability in this high-risk population.

Summary  
This phase 2, multicenter, single-arm trial enrolled 30 patients (29 treated) with NDMM and EMD to assess SVRd induction therapy. The regimen achieved a high overall response rate (ORR) of 89.7%, including stringent complete response (sCR) in 58.6%, along with EMD regression in 89.7% of patients and complete resolution in 79.3%. At a median follow-up of 18 months, 12-month progression-free survival (PFS) and overall survival (OS) rates were 87.9% and 96.3%, respectively, with particularly favorable outcomes in paraskeletal EMD compared to extraosseous disease. Grade ≥3 adverse events occurred in 37.3% of patients, most commonly thrombocytopenia, neutropenia, and pneumonia, with no treatment-related deaths reported. The regimen enabled 51.7% of patients to proceed to autologous stem cell transplantation (ASCT), supporting its role as an effective induction strategy.

Key points

• SVRd induction achieved a high ORR (89.7%) with deep responses, including 58.6% stringent complete response (sCR). 
• High rates of EMD regression (89.7%) and complete resolution (79.3%) were observed. 
• Favorable survival outcomes: 12-month PFS 87.9% and OS 96.3% (medians not reached). 
• Efficacy was stronger in paraskeletal EMD compared to extraosseous disease. 
• Manageable toxicity profile, with grade ≥3 adverse events in 37.3% and no treatment-related deaths. 
• Enabled ASCT in 51.7% of patients, supporting its use as an induction regimen.

Why this study matters  
The SVRd regimen demonstrates strong clinical activity in NDMM patients with EMD, achieving deep hematologic responses and high rates of extramedullary disease clearance. Survival outcomes at 12 months are promising, particularly in patients with paraskeletal involvement, although extraosseous disease remains more challenging. The safety profile is manageable, with expected hematologic toxicities and no treatment-related mortality. Importantly, SVRD facilitates transition to ASCT in a substantial proportion of patients, reinforcing its role as an effective frontline induction therapy. Larger randomized trials with longer follow-up are needed to confirm durability and compare SVRd with other modern regimens, especially in high-risk and extraosseous subgroups.

Reference: 
Yuanyuan Jin, Xin Cheng, Xuezhong Zhang, Qinglin Shi, Yu Zhu, Jianyong Li, Lei Fan, Lijuan Chen; Efficacy and safety of selinexor combined with VRD in newly diagnosed multiple myeloma with EMD: a phase 2 trial. Blood Adv 2026; 10 (6): 2016–2022. doi: https://doi.org/10.1182/bloodadvances.2025018945

Final clinical data of a phase 1 dose-escalation study of WVT078, a BCMA×CD3 bispecific antibody, alone and in combination with γ-secretase inhibitor WHG626 in patients with relapsed and/or refractory multiple myeloma — Cancer (March 2026)

What is the purpose of the study? 
To evaluate the safety, tolerability, and early effectiveness of the BCMA×CD3 bispecific antibody WVT078, used alone and in combination with the γ-secretase inhibitor WHG626, in patients with relapsed/refractory multiple myeloma (RRMM); and to identify appropriate dosing and assess how the drugs behave in the body.

Summary  
In this first-in-human phase 1 study, 56 patients with RRMM received WVT078 either alone or with WHG626. The most common side effect across all doses was cytokine release syndrome, and seven patients experienced dose-limiting toxicities. WVT078 alone produced an overall response rate (ORR) of 27.3% and a complete response rate (CRR) of 12.1%. When combined with WHG626, responses improved to an ORR of 47.8% and a CRR of 21.7%. Although recommended doses were not established, and expansion did not proceed, the combination showed encouraging early activity.

Key points

• Phase 1 trial of WVT078 (BCMA×CD3 bispecific antibody) ± WHG626 in RRMM 
• 56 patients treated; 7 experienced dose-limiting toxicities 
• Most common side effect: cytokine release syndrome 
• WVT078 alone: ORR 27.3%, CRR 12.1% 
• WVT078 + WHG626: ORR 47.8%, CRR 21.7% 
• No recommended doses determined; no expansion phase initiated 
• Combination therapy showed improved response rates over monotherapy

Why this study matters 
WVT078, both alone and in combination with WHG626, demonstrated a manageable safety profile in patients with RRMM. While side effects such as cytokine release syndrome were common, they were consistent with similar therapies. The addition of WHG626 appeared to improve response rates compared to WVT078 alone, suggesting potential benefits from combination therapy. Although the study did not establish recommended doses or proceed to expansion, the early efficacy signals are encouraging. These findings support further research into WHG626 as a partner with BCMA-targeting treatments in RRMM.

Reference: 
Schjesvold F, Spencer A, Cohen YC, et al. Final clinical data of a phase 1 dose-escalation study of WVT078, a BCMA×CD3 bispecific antibody, alone and in combination with γ-secretase inhibitor WHG626 in patients with relapsed and/or refractory multiple myeloma. Cancer. 2026;e70341. doi:10.1002/cncr.70341

Linvoseltamab versus real-world International Myeloma Working Group standard-of-care in triple-class exposed relapsed/refractory multiple myeloma — Blood Cancer Journal (March 2026)

What is the purpose of the study? 
To evaluate the effectiveness of linvoseltamab, a BCMA×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM) from the LINKER-MM1 (NCT03761108) trial; and to compare outcomes from the trial with real-world standard-of-care data to better understand its clinical benefit.

Summary  
In the Phase 1/2 LINKER-MM1 trial, linvoseltamab 200 mg was assessed in heavily pretreated RRMM patients and compared with an external control arm representing real-world standard-of-care. Linvoseltamab demonstrated significantly higher objective response rates (odds ratio 3.0) and improved outcomes, including longer progression-free survival (hazard ratio 0.33), time to next treatment (0.34), and overall survival (0.72). These results suggest linvoseltamab provides meaningful clinical benefits over existing treatments in triple-class exposed or refractory patients.

Key points

• LINKER-MM1 (NCT03761108) is a Phase 1/2 trial of linvoseltamab in RRMM.  
• Included patients had ≥3 prior lines of therapy and were triple-class exposed or refractory.  
• Compared 105 trial patients with 203 real-world patients (external control arm).  
• Linvoseltamab significantly improved outcomes vs standard care:  
 - Objective response rate: OR 3.0 (95% CI: 1.9–4.1)  
 - Progression-free survival: HR 0.33  
 - Time to next treatment: HR 0.34  
 - Overall survival: HR 0.72  

• Statistical adjustment (inverse probability weighting) ensured balanced comparison.  

Why this study matters  
Linvoseltamab showed superior efficacy compared with real-world standard treatments in heavily pretreated RRMM patients. The improvements in response rates and survival outcomes highlight its potential as an important new therapeutic option. These findings support further use and study of linvoseltamab in this difficult-to-treat population.

Reference: 
Kumar, S., Jagannath, S., Weisel, K.C. et al. Linvoseltamab versus real-world International Myeloma Working Group standard-of-care in triple-class exposed relapsed/refractory multiple myeloma. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01466-2  

Health-related quality of life with linvoseltamab treatment for relapsed/refractory multiple myeloma in LINKER-MM1 — Blood Neoplasia (March 2026)

What is the purpose of the study? 
To evaluate the impact of linvoseltamab on health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma enrolled in the LINKER-MM1 trial; and to determine whether clinical responses to treatment were associated with meaningful improvements in patient-reported symptoms, functioning, and overall well-being.

Summary 
Linvoseltamab, a BCMA×CD3 bispecific antibody, demonstrated sustained improvements in patient-reported quality of life over a median follow-up of 21.3 months in 117 patients with heavily pretreated multiple myeloma. Significant improvements were observed across validated instruments (EORTC QLQ-C30, QLQ-MY20, and EQ-5D-3L), particularly in global health status, pain, and fatigue, with benefits emerging as early as week 16 and maintained through week 104. Patients who achieved at least a partial response experienced improvements across all domains, while nonresponders generally showed worsening trends.

Key points

• Patients receiving linvoseltamab showed improved function, symptoms, and overall quality of life over 2 years.  
• Clinically meaningful improvements in pain, fatigue, and global health status were observed and sustained through week 104.  
• Treatment responders improved across all quality-of-life scales.  
• Nonresponders generally experienced stable or worsening symptoms and functioning.  
• Patient-reported outcomes aligned with clinical response, supporting treatment benefit.  

Why this study matters  
Linvoseltamab treatment was associated with durable and clinically meaningful improvements in quality of life for patients with relapsed/refractory multiple myeloma. These benefits were most pronounced in patients who responded to therapy and were sustained over two years. Overall, the findings support a favorable benefit-risk profile, with patient-reported outcomes reinforcing the clinical efficacy of linvoseltamab.

Reference: 
James E. Hoffman, Naresh Bumma, Joshua Richter, Madhav V. Dhodapkar, Hans C. Lee, Attaya Suvannasankha, Jeffrey A. Zonder, Joseph J. Maly, Mansi R. Shah, Rachid Baz, Timothy J. Inocencio, Michelle DeVeaux, Cristina Ivanescu, Karen Rodriguez Lorenc, Glenn S. Kroog, Katherine Knorr, Lei Chi, James Harnett, Qiufei Ma, Sundar Jagannath, Health-related quality of life with linvoseltamab treatment for relapsed/refractory multiple myeloma in LINKER-MM1, Blood Neoplasia, 2026, 100225, ISSN 2950-3280, https://doi.org/10.1016/j.bneo.2026.100225

MRD-negative conversion with daratumumab monotherapy in newly diagnosed multiple myeloma patients in ≥VGPR/MRD-positive after first-line therapy: Final analysis of the open-label, single-arm multicentric phase 2 trial DART4MM — British Journal of Haematology (March 2026)

What is the purpose of the study? 
To evaluate whether daratumumab monotherapy could eliminate minimal residual disease (MRD) in patients with newly diagnosed multiple myeloma who had already achieved ≥very good partial response (VGPR) but remained MRD-positive after first-line therapy. The goal is to determine if MRD eradication could improve long-term outcomes such as progression-free survival (PFS).

Summary  
In this prospective single-arm trial, 50 MRD-positive multiple myeloma patients received daratumumab for up to 24 months. At 6 months, 30% of patients achieved MRD negativity, and 22% remained MRD-negative at 24 months. Achieving at least one MRD-negative result was associated with significantly improved progression-free survival (61 vs. 26 months), although 58% of patients eventually relapsed at a median follow-up of 50 months.

Key points

• Phase 2 DART4MM study in newly diagnosed multiple myeloma patients with ≥VGPR but MRD-positive disease (10⁻⁶ sensitivity)  
• Treatment: daratumumab monotherapy for 6–24 months  
• MRD negativity achieved in 30% at 6 months  
• 22% remained MRD-negative at 24 months  
• MRD negativity strongly correlated with longer PFS (61 vs. 26 months, p=0.0009)  
• Median progression-free survival: 45 months; overall survival not reached  
• 58% relapsed, but some patients maintained long-term disease control  
• Safety profile consistent with known daratumumab data  
• Study supports MRD-driven treatment strategies in multiple myeloma  

Why this study matters 
Daratumumab monotherapy demonstrated the ability to convert a subset of MRD-positive multiple myeloma patients to MRD-negative status, which was strongly associated with improved progression-free survival. Although relapse remained common, a proportion of patients achieved durable responses. These findings support the role of MRD-guided consolidation or maintenance strategies, though modern combination therapies may offer greater benefit in current clinical practice.

Reference: 
Gozzetti A, Pacelli P, Caroni F, Raspadori D, Bestoso E, Antonioli E, et al. MRD-negative conversion with daratumumab monotherapy in newly diagnosed multiple myeloma patients in ≥VGPR/MRD-positive after first-line therapy: Final analysis of the open-label, single-arm multicentric phase 2 trial DART4MM. Br J Haematol. 2026;00:1–10. https://doi.org/10.1111/bjh.70448

FDG-PET Medullary Total Tumor Volume Highlights High-Risk Newly Diagnosed Multiple Myeloma Patients in CASSIOPEIA Trial — Blood Advances (March 2026)

What is the purpose of the study? 
To evaluate whether medullary total metabolic tumor volume (mTMTV) measured by [18F]FDG-PET/CT can predict outcomes in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab-based therapy; and to compare mTMTV with established prognostic tools like the Revised International Staging System (R-ISS).

Summary  
In the CASSIOPET study (companion to CASSIOPEIA, NCT02541383), 195 NDMM patients underwent baseline [18F]FDG-PET/CT, with 81% showing PET-positive disease. Higher mTMTV was strongly associated with worse progression-free survival (PFS) and overall survival (OS), remaining independently predictive even when accounting for R-ISS. Machine learning models confirmed mTMTV as the most important prognostic factor, and combining mTMTV with R-ISS improved risk stratification by identifying new patient subgroups.

Key points

• mTMTV (PET-derived tumor burden) is a strong independent predictor of:  
 - Progression-free survival (PFS) (p < 0.001)  
 - Overall survival (OS) (p < 0.001)  

• Study population:  
 - 195 NDMM patients  
 - 81% PET-positive at baseline  

• Imaging method:[18F]FDG-PET/CT with automated segmentation  
• mTMTV adds prognostic value beyond R-ISS  
• Machine learning results:  
 - C-index: 0.609 (PFS), 0.659 (OS)  
 - mTMTV identified as most informative feature  

• Additional important predictors:  
 - R-ISS  
 - Bone marrow SUVmax  
 - Number of focal lesions  
 - Anemia  

• Combining mTMTV + R-ISS: Created improved risk stratification groups  
• Supports PET imaging in initial evaluation of NDMM in the era of anti-CD38 therapy (daratumumab)  

Why this study matters 
This study shows that mTMTV measured by [18F]FDG-PET/CT is a powerful and independent predictor of survival outcomes in newly diagnosed multiple myeloma. When combined with R-ISS, it improves risk stratification and helps identify distinct patient subgroups. These findings support incorporating advanced PET-based imaging markers into routine clinical assessment to guide more personalized treatment decisions.

Reference: 
Jamet Bastien, Shamimeh Ahrari, Sonja Zweegman, Aurore Perrot, Cyrille Hulin, Denis Caillot, Thierry Facon, Xavier Leleu, Karim Belhadj, Emmanuel Itti, Lionel Karlin, Clement Bailly, Mark-David Levin, Monique C. Minnema, Caroline Bodet-Milin, Bart de Keizer, Jill Corre, Pieter Sonneveld, Diana Mateus, Philippe Moreau, Cyrille Touzeau, Françoise Kraeber-Bodere, Thomas Carlier; FDG-PET Medullary Total Tumor Volume Highlights High-Risk Newly Diagnosed Multiple Myeloma Patients in CASSIOPEIA Trial. Blood Adv 2026; bloodadvances.2025019465. doi: https://doi.org/10.1182/bloodadvances.2025019465

Belantamab mafodotin, lenalidomide, and dexamethasone for intermediate-fit and frail patients with newly diagnosed myeloma – Blood (April 2026)

What is the purpose of the study? 
To evaluate the safety, tolerability, and effectiveness of the BelaRd regimen (belantamab mafodotin, lenalidomide, and dexamethasone) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM); and to assess whether a patient-reported vision-related anamnestic (VRA) tool could guide dosing and reduce reliance on ophthalmologist assessments for ocular adverse events (OAEs).

Summary  
In this phase 1/2 study, 42 patients treated at the recommended dose (belantamab mafodotin 1.9 mg/kg every 8 weeks) achieved a high overall response rate of 97.6%, with 18-month progression-free survival of 83.0% and durable disease control. Ocular side effects were manageable and similar whether assessed by ophthalmologists or guided by the VRA tool, with minimal impact on daily activities such as reading or driving. The findings suggest that the BelaRd regimen is highly effective, and that VRA-guided dosing may simplify monitoring while maintaining safety.

Key points

• BelaRd (belantamab mafodotin + lenalidomide + dexamethasone) showed high efficacy (overall response rate 97.6%) in transplant-ineligible NDMM patients.  
• Durable outcomes: 18-month progression-free survival was 83.0%; survival medians not yet reached.  
• Ocular adverse events (OAEs) were manageable and had minimal impact on quality of life (<1% stopped reading/driving).  
• VRA tool (patient-reported vision assessment) was effective for guiding treatment and aligned with ophthalmologist findings.  
• Potential to reduce need for frequent ophthalmology visits with VRA-guided monitoring.  
• Supports advancement to a phase 3 clinical trial.  

Why this study matters 
The BelaRd regimen demonstrates strong efficacy and tolerability in transplant-ineligible patients with newly diagnosed multiple myeloma, with high response rates and sustained disease control. Ocular side effects were manageable and had limited impact on daily life, and the VRA tool showed promise as a practical alternative to routine ophthalmologic monitoring. These results support further evaluation of BelaRd in larger phase 3 trials.

Reference: 
Evangelos Terpos, Maria Gavriatopoulou, Ioannis Ntanasis-Stathopoulos, Panagiotis Malandrakis, Despina Fotiou, Nikolaos Kanellias, Magdalini Migkou, Foteini Theodorakakou, Vasiliki Spiliopoulou, Eirini Solia, Evangelos Eleutherakis-Papaiakovou, Giorgos Psarros, Efstathios Kastritis, Meletios A. Dimopoulos; Belantamab mafodotin, lenalidomide, and dexamethasone for intermediate-fit and frail patients with newly diagnosed myeloma. Blood 2026; 147 (14): 1574–1583. doi: https://doi.org/10.1182/blood.2025031629

Genomic mechanisms of resistance to venetoclax in multiple myeloma with t(11;14)(CCND1;IGH) — Blood (April 2026)

What is the purpose of the study?  
To investigate why some patients with t(11;14) multiple myeloma (MM) do not respond to or develop resistance to the BCL2 inhibitor venetoclax; and to identify genomic factors, particularly mutations and clonal evolution patterns, associated with treatment response and resistance.

Summary  
Researchers analyzed genomic data from 34 patients with t(11;14) MM treated with venetoclax and found that RAS pathway mutations were strongly associated with shorter progression-free survival and poor treatment response. Additional genetic changes, including 1q gain and alterations in BCL2/MCL1 pathways, contributed to resistance, especially at relapse. Over time, venetoclax treatment promoted clonal evolution, selecting more genetically complex and resistant tumor cells, including those with TP53 and CDKN2C loss.

Key points

• RAS pathway mutations are a major predictor of poor response and shorter progression-free survival with venetoclax.  
• Venetoclax resistance occurs through multiple genomic mechanisms, including BCL2/MCL1 pathway alterations.  
• 1q gain is linked to worse outcomes in patients without RAS mutations.  
• Clonal evolution under treatment pressure leads to the selection of more aggressive, genomically complex tumor cells.  
• Loss of tumor suppressor genes such as TP53 and CDKN2C contributes to resistance and disease progression.  
• Comprehensive genomic profiling can help predict response and guide treatment decisions.  

Why this study matters 
This study shows that venetoclax resistance in t(11;14) multiple myeloma is driven by complex genomic changes, particularly RAS pathway mutations and alterations in apoptosis-related pathways. Clonal evolution during treatment further promotes the emergence of resistant disease. These findings highlight the importance of genomic profiling to better select patients and develop combination therapies to overcome resistance.

Reference: 
Marcella Kaddoura, J. Erin Wiedmeier-Nutor, Vikas A. Gupta, Tomas Jelinek, Bachisio Ziccheddu, Suganti Shivaram, Hongwei Tang, Rebecca W. Owens, Tereza Sevcikova, Rodrigo Fonseca, Michael Durante, Benjamin Diamond, Logan Zhao, Yuan X. Zhu, Chang-Xin Shi, Shannon M. Matulis, Constantine S. Mitsiades, Ola Landgren, Saad Usmani, Roman Hajek, Marta Chesi, P. Leif Bergsagel, Esteban Braggio, Lawrence H. Boise, Rafael Fonseca, Shaji Kumar, Francesco Maura, Linda B. Baughn; Genomic mechanisms of resistance to venetoclax in multiple myeloma with t(11;14)(CCND1;IGH). Blood 2026; 147 (14): 1598–1610. doi: https://doi.org/10.1182/blood.2025029996

BCMA/CD19 dual-targeting CAR T cell therapy in older patients with newly diagnosed multiple myeloma: a phase I study — Blood Advances (April 2026)

What is the purpose of the study?  
To evaluate the safety and preliminary effectiveness of AZD0120 (formerly GC012F), a dual-targeting BCMA/CD19 CAR T-cell therapy, as a frontline treatment in older patients (≥70 years) with newly diagnosed multiple myeloma (NDMM); and to assess the feasibility of using the FasTCAR® manufacturing platform in this population.

Summary  
In this single-arm trial, 8 older NDMM patients received induction therapy with VRD (bortezomib/lenalidomide/dexamethasone) followed by AZD0120 infusion. All patients achieved stringent complete response (sCR) and 100% minimal residual disease (MRD) negativity at 1 month, with sustained MRD negativity in evaluable patients at 6 and 12 months. The treatment showed a manageable safety profile, with mainly hematologic toxicities and only mild (grade 1) cytokine release syndrome, and no cases of neurotoxicity (ICANS).

Key points

• AZD0120 is a dual-targeting CAR T-cell therapy (BCMA and CD19) produced using the FasTCAR® platform.  
• Studied as a frontline treatment in older (≥70 years) NDMM patients, including frail individuals.  
• High efficacy: 100% of patients achieved stringent complete response (sCR) and MRD negativity at 1 month.  
• Durable responses: MRD negativity maintained in all evaluable patients at 6 and 12 months.  
• Manageable safety profile: mainly hematologic toxicities; 50% had cytokine release syndrome (all grade 1).  
• No neurotoxicity (ICANS) was observed.  
• Functional improvement noted in some frail patients (ECOG performance status improved).  

Why this study matters 
AZD0120 demonstrates promising early efficacy as a frontline CAR T-cell therapy in older patients with newly diagnosed multiple myeloma, achieving deep and durable responses. The treatment was generally well tolerated, with manageable side effects and no severe neurotoxicity. These findings support further investigation of AZD0120 in larger studies, particularly for older and frail patient populations.

Reference: 
Jin Liu, Xiaoqiang Fan, Liying Peng, Jia Liu, Haiyan He, Wanting Qiang, Lina Jin, Lang Shi, Jing Lu, Pei Guo, Nina Shah, Qi Zhang, Lianjun Shen, Juan Du; BCMA/CD19 dual-targeting CAR T cell therapy in older patients with newly diagnosed multiple myeloma: a phase I study. Blood Adv 2026; bloodadvances.2025019036. doi: https://doi.org/10.1182/bloodadvances.2025019036

Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial — Nature Medicine (April 2026)

What is the purpose of the study? 
To evaluate whether adding isatuximab to the standard carfilzomib–lenalidomide–dexamethasone (KRd) regimen improves treatment outcomes in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), with the main goal of comparing rates of measurable residual disease (MRD) negativity after induction, transplantation, and consolidation therapy.

Summary  
In the randomized phase 3 EMN24 Iskia trial of 302 patients aged ≤70 years, isatuximab–KRd (Isa-KRd) was compared with KRd alone as induction and post-transplant consolidation therapy. Isa-KRd significantly increased MRD negativity rates after consolidation at both 10⁻⁵ sensitivity (77% vs 67%) and 10⁻⁶ sensitivity (68% vs 48%), with faster, deeper, and more sustained responses. Safety profiles were similar between groups, and progression-free survival (PFS) data are still maturing.

Key points

• Trial: Phase 3 EMN24 IsKia  
• Population: 302 transplant-eligible patients with newly diagnosed multiple myeloma (≤70 years)  
• Intervention: Isa-KRd vs KRd  
• Primary endpoint: MRD negativity by next-generation sequencing (10⁻⁵ sensitivity or better)  

Efficacy results

• Post-consolidation MRD negativity:  
 - 10⁻⁵: 77% (Isa-KRd) vs 67% (KRd), P = 0.049  
 - 10⁻⁶: 68% vs 48%, P = 0.0004  

• Post-induction MRD negativity:  
 - 10⁻⁵: 46% vs 27%  
 - 10⁻⁶: 28% vs 14%  

• Sustained MRD negativity (1 year, 10⁻⁶): 52% vs 38%  
• Responses were rapid, deeper, and more durable with Isa-KRd  
• Benefit observed across subgroups, including high-risk patients  

Safety

• Similar rates of grade 3–4 adverse events  
• Comparable treatment discontinuations and deaths  
• No increase in cardiovascular or infection risk with isatuximab  

Why this study matters 
The addition of isatuximab to the KRd regimen significantly improves the depth, speed, and durability of response in transplant-eligible patients with newly diagnosed multiple myeloma, as shown by higher MRD negativity rates. The treatment demonstrates a manageable safety profile comparable to standard therapy. These findings support Isa-KRd as a promising frontline quadruplet option, particularly for achieving deep remission, although longer follow-up is needed to confirm survival benefits.

Reference:  
Gay, F., Roeloffzen, W., Dimopoulos, M.A. et al. Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04282-0

Daratumumab in high-risk MGUS and low-risk smoldering myeloma: results of the Phase II D-PRISM study — Nature Communications (April 2026)

What is the purpose of the study? 
To evaluate whether early treatment with single-agent daratumumab in patients with high-risk monoclonal gammopathy of undetermined significance (MGUS) and low-risk smoldering multiple myeloma (SMM) could induce deep responses and prevent progression to multiple myeloma (MM); and to assess safety and identify genomic and immune factors linked to disease progression.

Summary  
In this Phase II study of 41 patients, daratumumab achieved a Very Good Partial Response or better in 17% of patients, failing to meet the primary endpoint, though the overall response rate was 54%. Despite some deep responses, 51% of patients experienced biochemical progression and two developed multiple myeloma. Treatment was generally safe, with limited grade ≥3 toxicities, and exploratory analyses identified genomic and immune features associated with progression.

Key points

• Phase II D-PRISM trial (NCT03236428) evaluated daratumumab in early-stage disease (high-risk MGUS and low-risk SMM). 
• Primary endpoint not met: ≥Very Good Partial Response rate was 17% (95% CI: 7–32). 
• Overall response rate: 54%. 
• Disease progression: 51% biochemical progression; 2 patients progressed to multiple myeloma. 
• Safety: Grade ≥3 adverse events included hypertension (7%), diarrhea (2%), flu-like symptoms (2%), and headache (2%). 
• Exploratory analyses identified genomic and immune markers linked to progression. 
• Suggests the need for better patient selection using genomic and immune profiling.

Why this study matters 
Single-agent daratumumab showed limited efficacy in early-stage plasma cell disorders, as it did not meet the primary response endpoint despite inducing responses in some patients. The treatment was generally well tolerated, supporting its safety in this population. These findings highlight the importance of genomic and immune profiling to better identify patients who may benefit from early intervention.

Reference: 
Nadeem, O., Aranha, M.P., Redd, R.A. et al. Daratumumab in high-risk MGUS and low-risk smoldering myeloma: results of the Phase II D-PRISM study. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71483-z

Phase 1/1b study of BCMA-targeting bispecific T-cell engager pavurutamab in relapsed/refractory multiple myeloma — Blood (April 2026)

What is the purpose of the study? 
To evaluate the safety, tolerability, pharmacokinetics, and efficacy of pavurutamab (AMG 701), a BCMA-targeting bispecific T-cell engager, in patients with triple-class relapsed/refractory multiple myeloma (RRMM). The goal is to determine an appropriate dose and assess preliminary clinical benefit in heavily pretreated patients.

Summary  
Pavurutamab, administered intravenously with step-up dosing, showed an acceptable safety profile, with cytokine release syndrome (CRS) being common but manageable and no dose-limiting toxicities at the recommended phase 2 dose (RP2D). Among 73 patients treated at the RP2D, the overall response rate was 65.8%, with 60.3% achieving at least a very good partial response (VGPR), and median progression-free survival reached 16.8 months. These results indicate promising efficacy and durable responses in a heavily pretreated RRMM population.

Key points

• Pavurutamab (AMG 701) is a BCMA-targeting bispecific T-cell engager designed to redirect T cells to attack multiple myeloma cells 
• Acceptable safety profile with manageable adverse events; CRS was common (74.4%) but no dose-limiting toxicities occurred at RP2D 
• In heavily pretreated RRMM patients at RP2D (n=73): 
 - Overall response rate (ORR): 65.8% 
 - ≥VGPR: 60.3% 
 - Median progression-free survival (mPFS): 16.8 months 
 - Median duration of response (mDOR): 36.6 months

• Grade ≥3 infections occurred in 34.9% of patients 
• Pharmacokinetics showed dose-proportional exposure; higher soluble BCMA levels were associated with lower drug exposure

Why this study matters 
Pavurutamab demonstrates a favorable balance of safety and efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma, particularly at the RP2D. The high response rates and durable outcomes support further development of BCMA-targeting bispecific T-cell engager therapies. These findings suggest pavurutamab may become an important treatment option for patients with limited alternatives.

Reference: 
Hans C Lee, Wouter J. Plattel, Simon J. Harrison, Douglas W Sborov, Suzanne Lentzsch, Andrew Spencer, Ruben Niesvizky, Suzanne Trudel, Peter Mollee, Ravi Vij, Monique C Minnema, Leo Rasche, Vijay V Upreti, Di Zhou, Qing Xia, Mihaela Talpes, Tobias Eggert, Prashant Kapoor, Sikander Ailawadhi; Phase 1/1b study of BCMA-targeting bispecific T-cell engager pavurutamab in relapsed/refractory multiple myeloma. Blood 2026; blood.2025032044. doi: https://doi.org/10.1182/blood.2025032044

Benefit of selinexor dose reduction on outcomes with selinexor, bortezomib and dexamethasone in patients with lenalidomide-refractory multiple myeloma: Subgroup analysis of the BOSTON trial — British Journal of Haematology (April 2026)

What is the purpose of the analysis? 
To explore whether selinexor dose reductions are associated with differences in efficacy, safety, and quality of life in patients with lenalidomide-refractory multiple myeloma treated with the SVd regimen in the phase 3 BOSTON trial. The analysis focuses on a difficult-to-treat subgroup with prior resistance to lenalidomide.

Summary 
In this post hoc analysis of 53 patients, those who underwent selinexor dose reductions had improved clinical outcomes compared with those who remained on the full dose, including higher response rates (74.3% vs. 55.6%) and longer progression-free survival (13.9 vs. 5.1 months). These patients also experienced longer duration of response and improved quality of life, with fewer side effects such as nausea and fatigue, allowing longer treatment exposure. However, as this was a non-randomized, exploratory analysis with baseline differences between groups, the findings show association rather than definitive causation.

Key points

• Efficacy (association with dose reduction) 
 - Higher overall response rate: 74.3% vs. 55.6% 
 - Higher ≥VGPR rates: 48.6% vs. 11.1% 
 - Longer progression-free survival: 13.9 vs. 5.1 months 
 - Longer duration of response: 15.3 vs. 4.2 months 
 - Longer time to next treatment

• Response timing: Time to best response was longer with dose reduction (2.7 vs. 1.4 months) 
• Overall survival: Similar between groups (26.7 vs. 24.6 months; not statistically significant) 
• Quality of life (QOL): Greater and clinically meaningful improvements with dose reduction 
• Safety and tolerability 
 - Lower rates of gastrointestinal adverse events and fatigue after dose reduction 
 - Improved tolerability likely enabled longer treatment duration

• Treatment duration: Patients with dose reductions remained on therapy substantially longer 
• Baseline considerations: Dose-reduction group had somewhat worse prognostic features (e.g., performance status, cytogenetics)

Strengths 
• Derived from a phase 3 clinical trial (BOSTON) 
• Clinically relevant lenalidomide-refractory population 
• Consistent with prior analyses of selinexor dose adjustment

Limitations 
• Post hoc, exploratory subgroup analysis 
• Small sample size (n=53) 
• Non-randomized comparison → potential confounding

Why this analysis matters 
In patients with lenalidomide-refractory multiple myeloma, selinexor dose reductions within the SVd regimen were associated with improved response rates, longer progression-free survival, and better tolerability and quality of life. These benefits may be partly related to longer treatment exposure enabled by improved tolerability. However, given the exploratory and non-randomized nature of the analysis, prospective studies are needed to confirm these findings.

Reference:  
Delimpasi, S., Špička, I., Butler, J.P., Stevens, D.A., Mesa, M.G., Bygrave, C., Merlo, G.M., la Porte, C. and Dimopoulos, M.A. (2026), Benefit of selinexor dose reduction on outcomes with selinexor, bortezomib and dexamethasone in patients with lenalidomide-refractory multiple myeloma: Subgroup analysis of the BOSTON trial. Br J Haematol. https://doi.org/10.1111/bjh.70479 

Committee for Medicinal Products for Human Use (CHMP)/European Medicines Agency (EMA)

CHMP approves Darzalex (daratumumab) as first self-administered oncology injectable for patients or caregivers  

On Friday, March 27, Johnson & Johnson announced via press release that "the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted approval for a Type II variation to the labelling for DARZALEX®(daratumumab) subcutaneous (SC) formulation."

"The label update enables patients living with multiple myeloma or their caregivers to administer daratumumab from the fifth dose, if determined to be appropriate by their healthcare professional and following proper training. This landmark decision makes daratumumab the first oncology injectable approved for self-administration in Europe," Johnson & Johnson further stated.

“The possibility for self-administration of daratumumab subcutaneous represents meaningful progress for those who would prefer the opportunity for greater flexibility in how or where they receive their care. For the medical community, it reduces pressure on healthcare systems and provides healthcare professionals with more choice in how they tailor treatment to individual needs and preferences, while maintaining the well-established safety profile and efficacy of daratumumab," said Thomas Lund, M.D., Ph.D., Head of Hematological Section, Department of Medicine, Vejle Hospital, Department of Regional Health Research, University of Southern Denmark.

This label update helps patients and their healthcare providers choose the most appropriate way to receive treatment. It applies to all ten approved uses of subcutaneous daratumumab for multiple myeloma, smoldering multiple myeloma, and light chain (AL) amyloidosis.

For further information on daratumumab, view or download the EMA’s Summary of Product Characteristics. 
 

References:

Johnson & Johnson’s DARZALEX® (daratumumab) becomes the first oncology injectable approved for administration by patients or caregivers. Johnson & Johnson press release. March 27, 2026.

Darzalex (daratumumab):Summary of Product Characteristics. European Medicines Agency.  

CHMP-EMA recommends approval of Sarclisa (isatuximab) as subcutaneous formulation administered via on-body injector for multiple myeloma

On Friday, March 27, Sanofi announced via press release that "the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Sarclisa (isatuximab) subcutaneous (SC) in combination with approved standard-of-care regimens for the treatment of patients with multiple myeloma (MM) across all currently approved indications for Sarclisa intravenous (IV) formulation in the EU."

According to Sanofi, "[the] recommendation [was] based on positive results demonstrating comparable efficacy, pharmacokinetics, and safety of Sarclisa regimens administered subcutaneously compared to intravenous infusion."  

"If approved, Sarclisa would be the first available anticancer treatment to be administered through both an on-body injector (OBI) and manual injection, and the only anti-CD38 monoclonal antibody available in MM to offer the flexibility of both an OBI and manual injection. A final decision is expected in the coming months," Sanofi further stated.

The CHMP’s positive opinion is based mainly on the phase 3 IRAKLIA study (NCT05405166) in patients with relapsed or refractory multiple myeloma (RRMM). This study showed that the subcutaneous form of Sarclisa (isatuximab) worked just as well as the traditional intravenous (IV) form (non-inferior), with a similar safety profile. 
 

Other studies that supported the recommendation include: 
• Phase 3 GMMG-HD8 (NCT05804032) in newly diagnosed (NDMM), transplant-eligible  
• Phase 2 IZALCO (NCT05704049) in RRMM 
• Phase 2 ISASOCUT (NCT05889221) in transplant-ineligible NDMM  
• A phase 1b study (NCT04045795) in heavily pretreated RRMM patients

Across these studies, patients using SC Sarclisa with an on-body injector (OBI) reported higher satisfaction and preference compared to IV infusions and manual injections, based on questionnaire results from both patients and healthcare providers.

Overall, these results suggest that SC Sarclisa with OBI could offer a more convenient and patient-friendly option while maintaining its proven effectiveness and safety in both newly diagnosed and relapsed multiple myeloma.

Sarclisa (isatuximab) IV is currently approved in the European Union (EU) for four uses in multiple myeloma, including transplant-ineligible NDMM; transplant-eligible NDMM; and for patients at first relapse (RRMM).

A regulatory application is also under review with the U.S. Food and Drug Administration (FDA).

The subcutaneous (SC) version of Sarclisa, given either with an on-body injector (OBI) or manual injection, is still being studied in clinical trials. Its safety and effectiveness have not yet been confirmed or approved by any regulatory authority.

References:

Sanofi’s Sarclisa subcutaneous formulation administered via on-body injector recommended for EU approval by the CHMP to treat multiple myeloma. Sanofi press release. March 27, 2026.

Sarclisa (isatuximab). European Medicines Agency.

U.S. Food and Drug Administration 
 

FDA grants Regenerative Medicine Advanced Therapy (RMAT) designation to allogeneic anti-BCMA CAR T, CB-011 for treatment of RRMM

On Tuesday, March 31, Caribou Biosciences announced via press release that the U.S. Food and Drug Administration (FDA) has granted CB-011 (an allogeneic anti-BCMA CAR T-cell therapy) Regenerative Medicine Advanced Therapy (RMAT) designation for relapsed/refractory multiple myeloma (RRMM), adding that CB-011 “is being evaluated in the company’s ongoing open-label, multicenter CaMMouflage phase 1 clinical trial evaluating patients with RRMM.”

According to Caribou Biosciences, the RMAT designation was “based on promising initial clinical data, including previously disclosed recommended dose for expansion data of 92% ORR, 75% ≥CR rate, 91% MRD negativity in the 12-patient, BCMA-naïve RRMM patient cohort,”and that “ongoing dose expansion enrollment in CaMMouflage phase 1 clinical trial includes BCMA-naïve and BCMA-exposed cohorts; initial dose expansion and longer follow up on dose escalation data expected in 2026.”

The RMAT designation is a special program that speeds up the development and review of promising treatments for serious conditions with unmet medical needs. It allows faster regulatory processes (such as priority and rolling reviews and possible accelerated approval) if certain criteria are met.

According to the FDA, a drug may receive RMAT designation if it is a regenerative medicine therapy (such as cell or gene therapy); is intended to treat or cure a serious or life-threatening condition; and shows early clinical evidence that it could meet an unmet medical need. Some gene therapies and animal-derived cell therapies may also qualify under this designation.

The FDA provides definitions and more information on its Guidance for Industry, Expedited Programs for Regenerative Medicine Therapies for Serious Conditions.

References:

Caribou Biosciences Announces the FDA Granted Regenerative Medicine Advanced Therapy (RMAT) Designation to CB-011, an Allogeneic Anti-BCMA CAR-T Cell Therapy. Caribou Biosciences Inc. Press release. March 31, 2026.

Regenerative Medicine Advanced Therapy Designation. U.S. Food and Drug Administration.

Guidance Document: Expedited Programs for Regenerative Medicine Therapies for Serious Conditions (Guidance for Industry). U.S. Food and Drug Administration.

FDA grants Fast Track designation to dual EP300/CBP inhibitor OPN-6602 for treatment of RRMM  

 
On Wednesday, April 15, Opna Bio announced via press release that the U.S. Food and Drug Administration “has granted Fast Track designation to OPN-6602, a dual EP300/CBP inhibitor, for the treatment of multiple myeloma. The Fast Track designation applies to patients with relapsed/refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy.”  

According to Opna Bio, OPN-6602 is currently being evaluated in a phase 1 clinical trial (NCT06433947) for “safety, tolerability, pharmacokinetics and preliminary clinical activity in patients with RRMM.”

On February 12, 2025, OPN-6602 was granted Orphan Drug designation by the FDA.

The FDA’s Fast Track designation is “a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions,” states the FDA on its website.

“Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy. Any drug being developed to treat or prevent a condition with no current therapy obviously is directed at an unmet need,” the FDA stated further.

According to the FDA, if other therapies already exist, a drug seeking Fast Track designation must demonstrate a meaningful advantage. This can include being more effective (especially for serious outcomes) causing fewer or less severe side effects, improving early diagnosis of serious conditions, reducing common toxicities that often lead to stopping treatment, or addressing an emerging or anticipated public health need.

Drugs granted Fast Track designation receive several benefits to speed development and review. These include more frequent meetings and written communication with the FDA to guide the development process, as well as potential eligibility for Accelerated Approval and Priority Review if criteria are met. Additionally, companies may use Rolling Review, allowing them to submit sections of their application (BLA or NDA) as they are completed rather than waiting to submit the entire application at once.

References:

Opna Bio Announces Fast Track Designation Granted to OPN-6602 for the Treatment of Multiple Myeloma. Opna Bio press release. April 15, 2026.

Opna Bio Receives Orphan Drug Designation for OPN-6602, an Oral EP300/CBP Bromodomain Inhibitor, for Multiple Myeloma. Opna Bio press release. February 12, 2025.

Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. U.S. Food and Drug Administration. Current as of August 13, 2024. 
 

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.