February and March 2026: What's New in Myeloma? (https://www.myeloma.org/blog/february-march-2026-whats-new-myeloma)
A summary of some notable key multiple myeloma research from February-March 2026
Scope and Methodology
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals February-March 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 March 25, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.
Patient Education
Patient-Centered Education Through A Massive Open Online Course (MOOC) for Patients With Multiple Myeloma and Caregivers: Descriptive Study of Knowledge Gains by French Association of Patients With Multiple Myeloma (AF3M) and French-Speaking Myeloma Intergroup (IFM) — JMIR Formative Research (February 2026)
Background
As myeloma care increasingly relies on oral therapies and outpatient management, patients and caregivers are expected to take a more active role in daily disease management. Therapeutic patient education (TPE) aims to improve patients’ understanding, self-management skills, and empowerment. Massive open online courses (MOOCs) offer a scalable digital approach to deliver structured education, but few have been specifically developed and formally evaluated for patients with cancer or blood disorders.
What is the purpose of the online course?
To address this gap, the MOOC “Understanding and Living with Myeloma” was co-developed by the French Association of Patients with Multiple Myeloma (AF3M) and the French-Speaking Myeloma Intergroup (IFM).
Designed with input from patients, caregivers, and healthcare professionals, the 8-week program includes 5 modules covering disease biology, diagnosis, treatments, side effect management, and daily-life adaptation. Learning tools include educational videos, self-assessment quizzes, online discussion forums with peer support, and live expert webinars.
How was the online course conducted?
Participants rated their knowledge using a 52-item questionnaire (scale 1–5) before and after the course. Results were analyzed using the Wilcoxon signed-rank test (two-sided α=.05).
Key findings
Participant satisfaction was very high: 98% were satisfied or very satisfied, and 99% would recommend the course. Since 2018, the MOOC has been offered 6 times, enrolling a total of 2,400 participants, demonstrating its sustainability and national scalability.
Why this MOOC matters
This patient-centered, co-designed MOOC significantly improved knowledge and was highly valued by patients with MM and their caregivers. As a free, repeatable, peer-supported digital education tool, it complements medical consultations and traditional TPE programs and may serve as a model for digital education initiatives in other chronic diseases.
Reference:
Talbot A, Delcour B, Gillot L, Arnulf B, Avet Loiseau H, Boccaccio C, Frenzel L, Karlin L, Kraeuter K, Macro M, Mohty M, Perrot A, Touzeau C, Sonntag C, Hulin C, Moreau P, Decaux O Patient-Centered Education Through A Massive Open Online Course (MOOC) for Patients With Multiple Myeloma and Caregivers: Descriptive Study of Knowledge Gains by French Association of Patients With Multiple Myeloma (AF3M) and French-Speaking Myeloma Intergroup (IFM) JMIR Form Res 2026;10:e81225 doi: 10.2196/81225 (https://formative.jmir.org/2026/1/e81225) PMID: 41740161
Review
What’s New in Imaging for Multiple Myeloma — British Journal of Hospital Medicine (February 2026)
Background
Advanced imaging plays a central role in the diagnosis, staging, and monitoring of multiple myeloma, particularly for detecting lytic bone disease and assessing treatment response.
Whole-body magnetic resonance imaging (WB-MRI) with diffusion weighting and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) are widely recommended in national and international guidelines as gold-standard modalities. Evidence, including cost-effectiveness analyses from the UK National Institute for Health and Care Excellence, supports WB-MRI as a first-line strategy to avoid sequential low-sensitivity tests and delayed diagnosis.
Despite strong recommendations from organizations such as the International Myeloma Working Group (IMWG) and the British Society for Haematology, real-world implementation remains inconsistent due to scanner availability, workforce limitations, and financial constraints. Emerging approaches, including standardized reporting systems and artificial intelligence applications, aim to improve access, efficiency, and diagnostic accuracy.
Key points
• Bone disease burden: Lytic bone disease is common at diagnosis and relapse, requiring accurate cross-sectional imaging.
• Gold-standard modalities: Whole-body MRI and FDG-PET/CT are strongly recommended for suspected myeloma and symptom reassessment.
• Guideline support: Recommendations from the International Myeloma Working Group, British Society for Haematology, and National Institute for Health and Care Excellence advocate advanced imaging.
• Cost-effectiveness: UK economic analyses demonstrate that first-line WB-MRI is more efficient than sequential low-sensitivity imaging.
• Implementation gap: Persistent reliance on skeletal surveys and multiple inappropriate tests delays diagnosis and increases inefficiency.
• Future directions: Standardization initiatives such as MY-RADS and integration of artificial intelligence aim to improve reporting consistency and capacity.
Why this review matters
Advanced cross-sectional imaging is essential across the entire disease course of multiple myeloma, from diagnosis to relapse monitoring. Whole-body MRI, favored in UK guidance, offers high sensitivity without ionizing radiation and improves diagnostic efficiency when used as the first-line test.
Although international and national guidelines consistently recommend WB-MRI or FDG-PET/CT, implementation remains limited by resource, workforce, and infrastructure challenges. Standardized protocols and artificial intelligence–assisted reporting represent promising strategies to overcome these barriers.
Expanding equitable access to advanced imaging is critical to improving timely diagnosis, optimizing patient outcomes, and ensuring efficient healthcare resource utilization.
Reference:
Graham McIlroy, Olwen Westerland, Guy Pratt. What’s New in Imaging for Multiple Myeloma. Br. J. Hosp. Med. (Lond) 2026, 87(2), 50847. https://doi.org/10.31083/BJHM50847 (https://www.imrpress.com/journal/BJHM/87/2/10.31083/BJHM50847)
Next-Generation Biomarkers in Multiple Myeloma: Advancing Diagnosis, Risk Stratification, and Precision Therapy Beyond Current Guidelines — Pharmaceuticals (February 2026)
Summary
Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow. These abnormal cells multiply uncontrollably and usually produce large amounts of a single abnormal antibody (called a monoclonal protein). About 3–5% of patients have a rare form called non-secretory MM, in which this abnormal protein is not detectable in the blood.
MM is biologically complex and genetically diverse. It develops gradually, starting with premalignant conditions before becoming a symptomatic disease. Traditionally, treatment begins only when patients meet the SLiM-CRAB criteria (which include organ damage or very high disease burden). However, high-risk smoldering multiple myeloma (HR-SMM) is now sometimes treated earlier to delay or prevent progression.
Despite medical advances, MM remains incurable. Diagnosis is often delayed, and some patients are only identified after serious complications such as bone fractures. Earlier detection could be improved with routine laboratory tests such as serum protein electrophoresis and calcium levels.
Current guidelines from the National Comprehensive Cancer Network (NCCN) and the International Myeloma Working Group (IMWG) rely mainly on:
• Cytogenetic abnormalities (chromosome changes in myeloma cells)
• Free light chain (FLC) ratio
• Imaging tests
However, newer research (2018–2025) highlights emerging biomarker technologies that may significantly improve care. These include:
• Circulating tumor DNA (ctDNA) methylation testing from blood (“liquid biopsy”)
• Single-cell multiomics (analyzing tumor cells individually at multiple biological levels)
• Surface antigen proteomics
• Functional ex vivo drug testing
• Advanced PET/CT radiomics
These tools may help:
• Detect disease earlier
• Identify patients at higher risk of progression
• Monitor disease more precisely over time
• Guide personalized treatment selection
• Discover new therapeutic targets
Although these technologies are not yet fully incorporated into standard guidelines, they represent the next step toward precision medicine in MM. Integrating advanced biomarkers with current clinical practice may improve early diagnosis, refine risk assessment, and allow more individualized and potentially more effective treatment strategies.
Why this review matters
While MM remains a challenging and incurable cancer, combining established diagnostic methods with next-generation biomarker platforms offers hope for earlier detection, better monitoring, and more personalized care in the future.
Reference:
Lopes, M. M. d. C., Xavier, L. d. A., Nolasco, S. C. V. M., Ribeiro, S. R., Coutinho, D. F., & Sabino, A. d. P. (2026). Next-Generation Biomarkers in Multiple Myeloma: Advancing Diagnosis, Risk Stratification, and Precision Therapy Beyond Current Guidelines. Pharmaceuticals, 19(2), 320. https://doi.org/10.3390/ph19020320 (https://www.mdpi.com/1424-8247/19/2/320)
Increasing Trends of Minimal Residual Disease Measurement in Trials Focusing on Multiple Myeloma Treatment: A Systematic Analysis of Clinical Research Design From 2014 to 2025 — European Journal of Haematology (February 2026)
Background
Minimal residual disease (MRD) refers to very small numbers of multiple myeloma (MM) cells that remain in the body after treatment. New laboratory techniques can detect MRD at extremely low levels (as sensitive as 1 cancer cell among 100,000 normal cells, written as 10⁻⁵). Because of this high sensitivity, MRD is increasingly used in clinical trials to measure how deeply a treatment works and whether it may predict long-term outcomes such as progression-free survival (PFS) and overall survival (OS).
What is the purpose of the study? How was it conducted?
This study reviewed 1,336 multiple myeloma clinical trials registered between 2014 and 2025. It found that while most trials (86.4%) measured general treatment response, about one-third (30.9%) included MRD as a study outcome. The use of MRD has increased dramatically over time, from 6.7% of trials in 2014 to 56.8% in 2025. Nearly half of currently recruiting or upcoming trials now include MRD testing, meaning much more information about MRD will become available in the coming years.
Among studies that measured MRD:
• 28.4% used MRD as a primary endpoint
• 7.5% used MRD results to guide treatment decisions (MRD-adapted therapy)
• Most used next-generation flow (NGF) or next-generation sequencing (NGS) with a sensitivity of 10⁻⁵
Although MRD testing is becoming common, methods and reporting are not yet fully standardized.
Achieving a deep response in multiple myeloma is strongly linked to longer survival. Patients who reach complete remission generally live longer without disease progression, and MRD negativity builds on this by detecting even smaller amounts of remaining cancer. Sustained MRD negativity appears to be an even stronger predictor of long-term benefits.
In November 2024, the European Medicines Agency (EMA) recognized that MRD negativity has important prognostic value and may help support certain drug approvals. However, the agency also emphasized the need for standardized testing methods and stronger evidence showing that MRD improvements consistently translate into long-term survival benefits.
In addition, health technology assessment (HTA) bodies, which decide on reimbursement, usually require mature survival data, quality-of-life outcomes, and cost-effectiveness of information before approving payment for new treatments. This means MRD alone may not yet be enough for reimbursement decisions.
The study also highlights the importance of including patient experience data (such as quality of life, treatment burden, and daily functioning) when evaluating MRD. Linking biological improvements (like MRD negativity) with outcomes that matter directly to patients will strengthen its clinical relevance.
Future research priorities include:
• Determining the best timing for MRD testing.
• Understanding how MRD-guided treatment decisions affect long-term outcomes better.
• Improving consistency and transparency in how MRD is reported.
• Studying how MRD relates to patient-reported outcomes.
• Designing trials that meet both regulatory and reimbursement requirements.
New technologies may soon allow less invasive MRD monitoring using blood tests (such as circulating tumor DNA) instead of bone marrow samples. Advanced imaging and artificial intelligence tools are also being explored.
Early detection strategies are improving as well, as shown in the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) study, which demonstrated the value of screening for precursor conditions like MGUS and smoldering multiple myeloma.
In summary
MRD has rapidly evolved from a research biomarker to a potential regulatory endpoint in multiple myeloma. Its use in clinical trials is growing quickly, but standardization, stronger survival evidence, and better integration of patient-centered outcomes are still needed before MRD can be fully accepted for both drug approval and reimbursement decisions.
Reference:
M. Choon-Quinones, G. D. Obeng, B. Asiedu-Ayeh, et al., “Increasing Trends of Minimal Residual Disease Measurement in Trials Focusing on Multiple Myeloma Treatment: A Systematic Analysis of Clinical Research Design From 2014 to 2025,” European Journal of Haematology (2026): 1–9, https://doi.org/10.1111/ejh.70133 (https://onlinelibrary.wiley.com/doi/10.1111/ejh.70133).
Circulating tumour cells (CTCs) in haematological malignancies: Advances in biology and clinical relevance with a focus on multiple myeloma — British Journal of Haematology (February 2026)
What is the purpose of this review?
Circulating tumor cells (CTCs) are cancer cells that detach from a primary tumor and enter the bloodstream. The U.S. Food and Drug Administration (FDA) has approved CTC detection for monitoring certain solid tumors (such as breast, colorectal and prostate cancers), but its role in blood cancers (hematological malignancies) is still under active investigation. Because CTC testing uses a simple blood sample (a “liquid biopsy”), it offers a non-invasive way to:
• Detect disease earlier
• Monitor treatment response in real time
• Assess minimal residual disease (MRD)
• Predict progression-free survival (PFS) and overall survival (OS)
This review focused on the biological features and clinical value of CTCs in hematological malignancies, especially multiple myeloma (MM), and discussed current challenges and future directions.
How was the search strategy conducted?
A PubMed search (1980–February 2023) identified clinical studies on CTCs in hematological malignancies. After screening, 37 studies focused on multiple myeloma (MM); 14 studies examined CTCs in leukemia and lymphoma. Only human, English-language clinical studies were included.
CTCs in plasma cell malignancies (Multiple myeloma)
Multiple myeloma (MM) is the second most common hematological malignancy after lymphoma. Diagnosis and monitoring traditionally rely on bone marrow (BM) aspiration or biopsy. However, CTC detection in peripheral blood (PB) is emerging as a promising, less invasive alternative.
How CTCs are detected in myeloma
Unlike solid tumors, early CTC detection in MM often uses allele-specific oligonucleotide (ASO) PCR targeting immunoglobulin heavy-chain genes.
Currently, detection methods include:
• Antibody-based identification of cell surface markers
• Flow cytometry
• Magnetic bead capture
• Standardized next-generation flow (NGF) platforms such as the EuroFlow system
The EuroFlow platform provides standardized instrument settings, antibody panels and analysis protocols, improving sensitivity and reproducibility for diagnosis and MRD detection.
Clinical significance in myeloma
Research shows strong clinical correlations:
• Higher CTC counts are associated with shorter PFS and OS
• CTC levels correlate with clinical stage and tumor burden
• CTCs may reflect total disease burden better than marrow-infiltrating plasma cells
• Treatments such as autologous stem cell transplantation (ASCT) reduce CTC numbers
CTCs have been detected in 100% of MM and SMM patients, and in over 50% of MGUS patients. Higher CTC levels in MGUS are linked to faster progression to MM and shorter survival.
Genetic and molecular insights
CTCs show very high genetic similarity to bone marrow tumor cells:
• 95–99% overlap in somatic mutations
• 81–95% similarity in copy number alterations
• Shared mutations in KRAS, NRAS and BRAF
These findings support the use of CTCs as a non-invasive substitute for bone marrow in molecular profiling.
Other key findings:
• P-glycoprotein (P-gp) expression in CTCs correlates with drug resistance
• CD138-negative CTCs show stem cell–like features and chemotherapy resistance
• EMT-related transcription factors such as TWIST1 and ZEB1 are associated with aggressive disease, extramedullary spread and poor prognosis
• Markers of inflammation, hypoxia and stemness are enriched in CTCs
Single-cell RNA sequencing has identified rare circulating tumor plasma cells even in early asymptomatic patients and in MRD-positive cases after treatment, supporting their role in precision medicine.
Limitations
Despite promising findings, several challenges remain:
1. Technical limitations
• Detection relies on surface antigens.
• Low antigen expression can reduce sensitivity.
• CD138-only approaches may miss aggressive subclones.
2. Biological complexity
• CTC characteristics vary with disease stage, bone marrow microenvironment, and treatment.
• Distinguishing malignant from normal circulating plasma cells is difficult.
• Clonal plasma cells in MGUS complicate threshold settings.
3. Lack of standardized guidelines
• No unified clinical recommendations define how CTCs should guide diagnosis or treatment decisions.
• Large-scale validation studies are still needed.
How to improve clinical use
Research should focus on:
• Multiplex biomarker panels (including stemness and EMT markers such as CD138−/low, TWIST1, ZEB1)
• Single-cell sequencing for better characterization of tumor heterogeneity
• Integration with other liquid biopsy tools
• Combining CTC genomic profiling with standard MRD techniques (NGF and sequencing)
• Establishing standardized detection and reporting guidelines
Because MM bone marrow involvement is often patchy, CTC-based liquid biopsy may better capture the full genomic landscape and monitor clonal evolution over time.
Conclusion
CTC detection is FDA-approved for monitoring certain solid tumors but remains investigational in hematological malignancies.
In multiple myeloma, CTCs:
• Closely mirror bone marrow tumor genetics
• Correlate with disease stage and survival
• Provide a non-invasive tool for monitoring and molecular profiling
However, widespread clinical adoption requires:
• Standardized, highly sensitive detection protocols
• Broader validation in large clinical trials
• Deeper understanding of CTC biology and molecular mechanisms
Why this review matters
With continued technological advances, especially standardized platforms such as EuroFlow and integration with genomic profiling, CTC analysis has strong potential to become a key tool in personalized precision medicine for hematological malignancies.
Reference:
Hsu C-M, Hsu J-F, Huang J-F, Liu Y-C. Circulating tumour cells (CTCs) in haematological malignancies: Advances in biology and clinical relevance with a focus on multiple myeloma. Br J Haematol. 2026; 00: 1–16. https://doi.org/10.1111/bjh.70374 (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70374)
Extramedullary Multiple Myeloma — European Journal of Haematology (February 2026)
Background
Extramedullary disease (EMD) is a serious and advanced form of multiple myeloma (MM) in which myeloma cells spread outside the bone marrow (BM) into soft tissues or organs. It is associated with aggressive disease, drug resistance, and poorer survival.
What causes EMD?
EMD develops when myeloma cells acquire genetic and biological changes that allow them to escape the bone marrow and survive elsewhere.
1. Tumor microenvironment changes
• The bone marrow normally acts as a protective “home” for myeloma cells.
• Disruption of this environment (e.g., hypoxia, inflammation, treatment pressure) weakens cell anchoring and allows cells to spread.
2. Loss of adhesion and chemokine signaling
• Myeloma cells detach due to reduced adhesion molecules.
• Disruption of the SDF-1/CXCR4 axis, which normally keeps plasma cells in the BM, promotes escape into the bloodstream.
• Cells can later re-express chemokine receptors to colonize distant tissues.
3. Genetic abnormalities (more common in EMD)
EMD shows greater genomic instability than standard MM, including:
• 1q21 amplification – promotes proliferation and survival
• TP53 deletion – loss of tumor suppression, linked to aggressive behavior
• del(1p32) – more common in secondary EMD (sEMD)
4. Abnormal signaling pathways
• MAPK pathway activation (KRAS, NRAS, BRAF mutations) supports independent growth.
• MYC rearrangement/overexpression drives rapid proliferation and invasion.
These factors interact in a reinforcing network. EMD often arises from late-stage subclones with high-risk mutations. Different EMD lesions in the same patient may have distinct genetic profiles, explaining variable treatment responses.
Diagnosis
Diagnosis requires imaging plus biopsy confirmation of clonal plasma cells.
1. Imaging (per IMWG criteria)
• CT, whole-body low-dose CT
• PET-CT (commonly using 18F-FDG)
• Whole-body MRI with diffusion-weighted imaging (DWI)
2. PET-CT detects metabolically active disease and is useful for soft tissue lesions.
3. MRI with DWI is optimal for bone marrow and central nervous system (CNS) involvement.
The same imaging method should be used before and after treatment for consistency.
Pathology findings
Extramedullary plasma cells may show:
• Reduced CD38, CD56
• Increased CD44
• High proliferation index
• CCND1 positivity
• High BCL2 expression
Treatment
EMD is considered high-risk MM. There is no single standard treatment. Therapy is individualized based on subtype (e.g., secondary EMD [sEMD] vs bone-related EMD [bEMD]), location, prior therapy, and patient condition.
Key takeaways
• EMD represents aggressive, biologically complex MM with high-risk genetics.
• sEMD carries a particularly poor prognosis.
• Modern therapies (CAR-T, BiTEs, monoclonal antibodies) improve responses, but survival remains shorter than non-EMD MM.
• Tumor burden, lesion site, and genetic profile strongly influence outcomes.
• Future priorities include:
- EMD-specific clinical trials
- Integrated PET-CT and whole-body MRI-DWI monitoring
- Molecular profiling and ctDNA monitoring
- Therapies with better tissue and CNS penetration
Currently, EMD remains a major unmet need in multiple myeloma care.
Reference:
Z. Jingliang and Q. Xiaoqi, “Extramedullary Multiple Myeloma,” European Journal of Haematology (2026): 1–11, https://doi.org/10.1111/ejh.70145 (https://onlinelibrary.wiley.com/doi/10.1111/ejh.70145).
Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape — ESMO Open (March 2026)
Background
Multiple myeloma (MM) treatment has improved greatly over the past two decades, leading to longer survival and better quality of life for many patients. However, MM remains incurable, and patients with high-risk cytogenetics, renal impairment, or early drug resistance often have limited treatment options and poorer outcomes.
What is the purpose of the review?
This review focuses on selinexor, the first-in-class oral selective inhibitor of Exportin 1 (XPO1), which has shown promising results in relapsed or refractory multiple myeloma. Approved combinations such as selinexor–bortezomib–dexamethasone (SVd) and selinexor–dexamethasone (Sd) have demonstrated effectiveness even in difficult-to-treat patient groups.
The purpose of this review is to summarize the mechanism of action, clinical evidence, emerging drug combinations, and optimal treatment sequencing of selinexor in MM. It also discusses strategies to reduce treatment-related side effects and improve adherence, which are important for maintaining therapy effectiveness.
Key points
• Exportin 1 (XPO1) regulates the nuclear export of tumor-suppressor proteins; its overexpression is linked to poor prognosis in MM.
• Selinexor is the first-in-class selective inhibitor of XPO1 and has shown encouraging results in relapsed/refractory multiple myeloma (RRMM).
• Approved treatment combinations include:
- Selinexor + Bortezomib + Dexamethasone for patients with ≥1 prior therapy
- Selinexor + Dexamethasone for later relapse settings.
• Selinexor-based regimens show consistent efficacy across difficult-to-treat subgroups, including patients with:
- Triple-class refractory disease
- High-risk cytogenetics
- Renal dysfunction
- Prior anti-CD38 therapy.
• Preventive strategies for selinexor-related toxicities may improve treatment tolerance, adherence, and outcomes.
• Selinexor is particularly useful for patients ineligible for T-cell-redirecting therapies, such as CAR‑T cell therapy, Bispecific antibodies, or Antibody–drug conjugates targeting B‑cell maturation antigen (BCMA).
• Ongoing clinical trials are evaluating optimal dosing, new drug combinations, and sequencing strategies, including use before or after CAR-T or bispecific antibodies.
Conclusion
Over the past 20 years, treatment advances have significantly improved outcomes for patients with MM, although the disease remains incurable. Selinexor has demonstrated meaningful clinical activity in RRMM, particularly when combined with agents such as bortezomib and dexamethasone. These combinations have shown effectiveness even in difficult-to-treat patients, including those with high-risk cytogenetics, renal impairment, or triple-class refractory disease. Strategies to prevent or manage selinexor-related toxicities are important for maintaining treatment adherence and maximizing benefits. Ongoing research will further clarify the role of selinexor in treatment sequencing alongside newer therapies such as CAR-T cells and bispecific antibodies.
Why this review matters
Understanding the role of selinexor is important because it may provide a valuable treatment option for patients with limited alternatives, including those who cannot receive newer T-cell–redirecting therapies. Continued research is needed to clarify how selinexor can be best integrated into modern MM treatment to address ongoing unmet clinical needs.
Reference:
Gay F, Buda G, Petrucci MT, Bolli N, Cea M, Derudas D, Mangiacavalli S, Montefusco V, Antonioli E, Barilà G, Basso M, Bertazzoni P, Bertuglia G, Bianco R, Carlisi M, Giudice MLD, Pepa RD, Fazio F, Franceschini L, Furlan A, Gozzetti A, Liberatore C, Mancuso K, Martino EA, Mele G, Monaco F, Morè S, Paris L, Pavan L, Pezzatti S, Rago A, Ribolla R, Roncato R, Rossini B, Sgherza N, Vassallo F, Vincelli DI, Za T, Musto P, Zamagni E. Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape. ESMO Open. 2026 Mar 11;11(3):106054. doi: 10.1016/j.esmoop.2025.106054 (https://www.esmoopen.com/article/S2059-7029(25)01924-6/fulltext). Epub ahead of print.
Research
IMS-IMWG 2025 consensus genomic staging predicts outcomes with daratumumab-based quadruplet regimens for NDMM — Blood Advances (February 2026)
Background
The International Myeloma Society (IMS) and the International Myeloma Working Group (IMWG) recently introduced a new Consensus Genomic Staging (CGS) system to better identify people with high-risk newly diagnosed multiple myeloma (NDMM). This system aims to standardize how risk is defined in clinical trials and to help design studies specifically for high-risk patients.
What is new about this high-risk definition?
• It is the first to include TP53 gene mutations.
• It considers combined genetic changes, such as IgH translocations together with chromosome 1 abnormalities.
• Using this system, 31% of patients were classified as high-risk.
How was the study conducted?
Researchers studied 503 newly diagnosed myeloma patients treated at Memorial Sloan Kettering Cancer Center with daratumumab-based quadruplet induction therapy (a four-drug combination including daratumumab). Median follow-up is at 2.2 years (up to 7.9 years).
Key findings
• The CGS system identified 31% of patients as high-risk, helping better distinguish risk levels compared with older scoring systems.
• High-risk and standard-risk patients achieved minimal residual disease (MRD) negativity at similar rates after treatment.
• However, survival outcomes differed significantly:
- Progression-free survival (PFS) was 2.6 years in high-risk patients.
- In standard-risk patients, median PFS has not been reached.
- This difference was highly significant (p < 0.0001).
• Even among patients who became MRD-negative after autologous stem cell transplant, high-risk genetic status still predicted shorter PFS.
Why this study matters
Although daratumumab-based quadruplet therapy is effective, and many patients achieve deep responses (MRD-negativity), patients classified as high-risk by the IMS–IMWG genomic criteria still have poorer outcomes.
Conclusion
The IMS–IMWG CGS system is useful for standardizing clinical trial design in newly diagnosed multiple myeloma. However, clinical trials that guide treatment decisions based on MRD status should also consider a patient’s genomic (genetic) risk profile.
Reference:
Kylee H. Maclachlan, Carlyn Rose Tan, Tala Shekarkhand, Colin J. Rueda, Andriy Derkach, Hamza Hashmi, Hani Hassoun, Urvi A. Shah, Malin L Hultcrantz, Alexander M. Lesokhin, Sham Mailankody, Francesco Maura, Maximillian Merz, Ross S. Firestone, Eric M. Jurgens, Kevin C. Miller, Sridevi Rajeeve, Sergio A. Giralt, Gunjan L. Shah, Michael Scordo, Heather J. Landau, Yanming Zhang, Robert Cimera, Maria E. Arcila, Neha Korde, Saad Z. Usmani; IMS-IMWG 2025 consensus genomic staging predicts outcomes with daratumumab-based quadruplet regimens for NDMM. Blood Adv 2026; bloodadvances.2025018537. doi: https://doi.org/10.1182/bloodadvances.2025018537 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025018537/566636/IMS-IMWG-2025-consensus-genomic-staging-predicts)
The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D — Leukemia (February 2026)
Summary
Researchers describe a new, very advanced stage of multiple myeloma (MM) called hepta-refractory MM. This term refers to disease that no longer responds to:
• CD38 antibodies
• Two immunomodulatory drugs (IMiDs)
• Two proteasome inhibitors (PIs)
• BCMA-directed immunotherapy
• GPRC5D-directed immunotherapy
In a multi-center study of 37 patients, outcomes were poor:
• Median overall survival (OS): 12.8 months
• Progression-free survival (PFS) with additional (“salvage”) treatments: only 2.7–3.7 months
Key genetic findings
Using whole genome sequencing (WGS), researchers found that hepta-refractory MM is biologically aggressive and genetically complex:
• Frequent “double-hit” (biallelic) damage to tumor suppressor genes, especially TP53, linked to fast-growing, treatment-resistant disease
• Genetic changes associated with drug resistance were common:
- IMiD resistance: 71%
- BCMA resistance: 41%
- GPRC5D resistance: 35%
- CD38 resistance: 12%
• Nearly one-third of patients lost both BCMA (TNFRSF17) and GPRC5D, limiting future immunotherapy options
In about half of patients, at least one immunotherapy target (such as BCMA or GPRC5D) was lost. Importantly, loss of BCMA predicted lack of benefit from BCMA re-treatment, while patients who still expressed BCMA could respond again to BCMA-targeted CAR T-cell therapy.
How resistance develops
The study showed that myeloma cells evolve over time, even after deep remissions. Different cancer cell “subclones” developed separate mutations in TNFRSF17 (BCMA) and GPRC5D, suggesting that hidden resistant cells survive treatment and later cause relapse.
Most antigen loss was caused by biallelic gene damage, but immunohistochemistry (IHC) testing showed that BCMA protein expression could also be lost through other mechanisms.
Clinical implications
• Hepta-refractory MM represents an emerging “end-stage” category, especially in regions where modern therapies are widely available.
• Prognosis remains poor, with median survival of about 1 year.
• Integrated testing using whole genome sequencing (WGS) and immunohistochemistry (IHC) can help determine whether retreatment with BCMA- or other targeted therapies is likely to work.
• Some patients achieved longer survival with individualized treatment approaches, highlighting the need for personalized therapy.
Conclusion
Hepta-refractory MM is marked by:
• Severe drug resistance
• Loss of key immunotherapy targets
• High genetic complexity
• Poor survival outcomes
The findings highlight an urgent need for new therapies and broader use of genomic and protein testing to guide treatment decisions in this ultra-refractory population.
Reference:
Riedhammer, C., Truger, M., Lee, H. et al. The evolution to hepta-refractory myeloma involves sequential loss of CD38, BCMA and GPRC5D. Leukemia (2026). https://doi.org/10.1038/s41375-026-02889-3 (https://www.nature.com/articles/s41375-026-02889-3)
Impact of frailty on infection risk in non-transplant eligible multiple myeloma patients: a systematic review and meta-analysis — Leukemia (February 2026)
Background
Multiple myeloma (MM) mainly affects older adults (median age 66–70 years) and can lead to weakened immunity, bone damage, and organ problems. Many older patients are not eligible for high-dose chemotherapy with autologous stem cell transplantation (ASCT) because of age, other illnesses, or frailty. For this reason, assessing frailty is an important part of treatment planning.
Frailty in MM is commonly measured using the International Myeloma Working Group Frailty Index (IMWG-FI) and the Simplified Frailty Score. These tools classify patients as fit, intermediate, or frail based on age, comorbidities, and functional status. Frail patients are known to have a higher risk of treatment-related side effects.
Severe infections (grade 3–4) are a major complication in MM and can lead to longer hospital stays and increased risk of death. Risk prediction models such as FIRST, GEM-PETHEMA, and IRMM estimate infection risk, but they do not include frailty classification.
What is the purpose of the study?
To better understand the relationship between frailty and infection risk, researchers conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO: CRD420250654904). They analyzed studies of newly diagnosed MM (NDMM) patients who were not eligible for ASCT, comparing infection rates among fit, intermediate, and frail patients.
How was the analysis conducted?
Five studies (1,663 patients; mean age 73.6 years; 48.5% women) were included. The average treatment duration was 27.2 months, and 26.1% of patients developed severe infections. Treatment regimens included:
• Daratumumab, bortezomib, melphalan, and prednisone (DVMP) vs bortezomib, melphalan, and prednisone (VMP)
• Daratumumab, lenalidomide, and dexamethasone (DRd) vs lenalidomide and dexamethasone (Rd)
• Data from the HOVON-143 trial
Frailty was assessed using the Simplified Frailty Score, IMWG-FI, or DynaFiT across studies.
Main findings
• Non-frail patients (fit + intermediate) had a 23% lower risk of severe infection compared to frail patients, with consistent results across studies.
• Fit patients had a lower infection risk than frail patients, although this did not always reach statistical significance. After excluding one outlier study, the risk reduction increased to 42%.
• Intermediate patients had a slightly lower infection risk than frail patients, but this was borderline significant.
• No clear difference was seen between fit and intermediate patients.
In two studies, fit patients unexpectedly had more infections than intermediate patients. This paradox highlights limitations in current frailty scoring systems. A meta-regression analysis explored whether disease stage (ISS stage III) explained differences in infection risk, but results were inconsistent. ISS stage was not a reliable predictor of infection risk, which is not surprising because it was designed to predict survival, not infections.
Why this study matters
Overall, this meta-analysis confirms that frailty significantly increases the risk of severe infections in non-transplant-eligible patients with newly diagnosed MM. However, current frailty scores do not consistently predict which patients will develop infections.
Clinical implications
• Frail patients should be identified early to allow preventive strategies such as antimicrobial prophylaxis, vaccination, and immunoglobulin replacement in selected cases.
• Intermediate patients also require close monitoring, as their infection risk may approach that of frail patients.
• Because frailty can change over time, regular reassessment is important.
Limitations
Limitations of this analysis include the use of different frailty tools across studies and limited data on preventive measures such as antibiotics or immunoglobulin supplementation.
Conclusion
Frailty is a key factor driving infection risk in older MM patients who are not eligible for transplant. While frailty assessment should remain central to treatment decisions, current tools need refinement to better predict infectious complications. Future research should focus on improving risk stratification and developing targeted supportive care strategies to reduce infections and improve outcomes.
Reference:
Spataro, F., Armentaro, G., Di Gioia, G. et al. Impact of frailty on infection risk in non-transplant eligible multiple myeloma patients: a systematic review and meta-analysis. Leukemia (2026). https://doi.org/10.1038/s41375-026-02880-y (https://www.nature.com/articles/s41375-026-02880-y)
Prognosis and patterns of progression in smoldering multiple myeloma — Blood Advances (February 2026)
Summary
In a landmark 2007 study, Robert A. Kyle and colleagues reported that smoldering multiple myeloma (SMM) carried a progression risk of about 10% per year during the first 5 years, decreasing thereafter. Since then, diagnostic criteria have changed substantially. In 2014, the International Myeloma Working Group updated its criteria to include the SLiM biomarkers (≥60% bone marrow plasma cells, free light chain ratio ≥100, or >1 MRI focal lesion) as myeloma-defining events, in addition to CRAB features (hypercalcemia, renal dysfunction, anemia, bone lesions). Routine use of advanced imaging (PET-CT and whole-body MRI) has also improved detection of occult bone disease. As a result, many patients previously labeled high-risk SMM are now reclassified as having active multiple myeloma (MM) requiring treatment.
A recent study by Efstathios Kastritis and colleagues analyzed 427 patients diagnosed with SMM between 2014 and 2023 using modern criteria and systematic advanced imaging. They found that contemporary SMM appears more indolent than historically reported. Low-risk patients (about half the cohort) had very low progression rates, similar to monoclonal gammopathy of undetermined significance (MGUS). Even high-risk patients did not meet traditional thresholds for aggressive disease (median time to progression [TTP] of 24 months and ~50% progression at 2 years).
To validate these findings, investigators at Memorial Sloan Kettering Cancer Center studied 308 patients with SMM diagnosed between 2002 and 2019, all evaluated with advanced imaging and defined according to 2014 IMWG criteria. Risk was assessed using the 2/20/20 model (based on M-protein >2 g/dL, bone marrow plasma cells >20%, and free light chain ratio >20). Median follow-up was 79 months.
Key findings
• 108 patients progressed to MM or AL amyloidosis.
• At progression, 41% developed bone lesions, 27% anemia, 7.4% renal insufficiency, and 1 patient hypercalcemia.
• 27% progressed based only on biomarker criteria (free light chain ratio and/or ≥60% marrow plasma cells).
• 3.7% developed AL amyloidosis.
Overall progression risk:
• 1 year: 6.3%
• 2 years: 13.2%
• 3 years: 21.6%
• 5 years: 29.8%
• 10 years: 43.6%
• Median TTP: 142 months
The annual progression risk was approximately 6.8% during the first 5 years, lower than the historically reported 10%. When considering progression defined strictly by CRAB features, the risk was even lower (4.8% per year in the first 5 years).
Progression by 2/20/20 risk group:
• Low risk (49%): 2-year progression 4.8%; 5-year 12.2%; median TTP 213 months.
• Intermediate risk (30.5%): 2-year 12.1%; 5-year 34.1%; median TTP 128 months.
• High risk (20.5%): 2-year 34.8%; 5-year 66.7%; median TTP 34 months.
Notably, high-risk patients had lower progression rates than previously reported (~35% at 2 years rather than ~50%). Overall survival was favorable, with 5- and 10-year survival rates of 89.9% and 71.8%, respectively, and no significant survival difference between risk groups.
These results are consistent with findings from the population-based iStopMM study, which showed that more intensive diagnostic evaluation (including advanced imaging and bone marrow biopsy) identifies a larger proportion of low-risk SMM. This suggests that earlier studies may have overestimated progression risk due to undetected active MM.
Why this study matters
Contemporary SMM appears more indolent than previously thought. As early-treatment strategies expand for high-risk SMM, more precise tools are needed to identify patients who truly benefit from intervention. Current models such as 2/20/20 do not incorporate detailed disease biology (e.g., genomic abnormalities). Future approaches integrating dynamic biomarkers and genomic profiling may better distinguish patients at genuinely high risk and guide early therapy decisions.
Reference:
Theresia Akhlaghi, Kylee H. Maclachlan, Adriana Wiggins, Saad Z. Usmani, Andriy Derkach, Malin Hultcrantz; Prognosis and patterns of progression in smoldering multiple myeloma. Blood Adv 2026; 10 (4): 1344–1347. doi: https://doi.org/10.1182/bloodadvances.2025018021 (https://ashpublications.org/bloodadvances/article/10/4/1344/557280/Prognosis-and-patterns-of-progression-in)
Real-world comparison of progression-free survival and time to next therapy in 761 patients with newly diagnosed multiple myeloma — Blood Advances (February 2026)
Background
In clinical trials for newly diagnosed multiple myeloma (NDMM), progression-free survival (PFS) is a key measure of how long treatment keeps the disease from worsening or causing death, based on strict International Myeloma Working Group (IMWG) criteria. However, in everyday clinical practice, the detailed tests required to confirm IMWG-defined progression are not always consistently available.
Because of this, researchers often use time to next treatment (TTNT)—the time from starting first therapy to starting the next therapy or death—as a more practical measure in real-world data. TTNT is easier to track, but it can be affected by factors other than disease progression, such as side effects, patient or doctor preference, or access to medications. It has not been clear how closely TTNT reflects PFS in routine care.
What is the purpose of the study?
Researchers performed a retrospective chart review of 761 patients with NDMM treated outside clinical trials at centers in Canada and the United States (2015–2024). All patients received at least one “novel agent” (such as a proteasome inhibitor or immunomodulatory drug) as first-line therapy.
• 54% underwent autologous stem cell transplant (ASCT).
• Median follow-up was 5.1 years.
• Overall response rate was 92%.
PFS was defined as time from starting treatment to IMWG-defined progression or death.
TTNT was defined as time from starting treatment to second-line therapy or death.
Key findings
• Median PFS: 3.1 years
• Median TTNT: 3.0 years
• The two measures were very strongly correlated (Pearson r = 0.82).
• Survival curves for PFS and TTNT were not significantly different.
• At 5 years:
- 33.3% remained progression-free (PFS)
- 30.4% had not required next treatment (TTNT)
In most patients, disease progression occurred shortly before starting the next treatment (median difference: 26 days). Large differences between PFS and TTNT were uncommon.
When discrepancies occurred:
• TTNT was shorter than PFS mainly due to side effects or suboptimal response.
• TTNT was longer than PFS in some cases due to slow progression, patient choice, or unclear reasons.
Importantly, PFS and TTNT were closely aligned across different patient subgroups, including transplant eligibility, cytogenetic risk, treatment regimen, and maintenance therapy.
Why this study matters
Previous studies have shown mixed results regarding whether TTNT accurately reflects PFS, especially in older treatment eras or non-myeloma cancers. This study, conducted in the modern treatment era with novel agents, provides strong patient-level evidence that in real-world NDMM, TTNT closely mirrors PFS at both the individual and population levels.
Limitations
• Data came from only three centers.
• Only first-line treatment was studied.
• Results may differ in relapsed disease or with newer monitoring tools (e.g., minimal residual disease testing).
Conclusion
For patients with newly diagnosed multiple myeloma treated outside clinical trials, TTNT appears to be a reliable and practical substitute for PFS when strict IMWG progression assessment is not feasible. This supports using TTNT in real-world research and comparative effectiveness studies, especially as treatments continue to evolve.
Reference:
Hira Mian, Mariano Arribas, Rafael Fonseca, Erin Mutterback, Omar Shahid, Rohan Gouda, Gregory R. Pond, Alissa Visram; Real-world comparison of progression-free survival and time to next therapy in 761 patients with newly diagnosed multiple myeloma. Blood Adv 2026; 10 (4): 1405–1408. doi: https://doi.org/10.1182/bloodadvances.2025018655 (https://ashpublications.org/bloodadvances/article/10/4/1405/557393/Real-world-comparison-of-progression-free-survival)
A critical analysis of the IMWG multiple myeloma complete response criterion in the era of mass spectrometry — HemaSphere (February 2026)
Background
In multiple myeloma (MM), achieving a Complete Response (CR) means the disease has responded very well to treatment.
According to the International Myeloma Working Group (IMWG), CR requires:
• Negative immunofixation (IFE) in blood and urine
• Disappearance of any soft tissue plasmacytomas
• Fewer than 5% plasma cells (PCs) in the bone marrow (BM)
However, the need for bone marrow plasma cell counting and urine IFE in defining CR has been questioned.
How was the study conducted?
This study analyzed 716 paired blood and bone marrow samples from 290 newly diagnosed, transplant-eligible MM patients enrolled in the GEM12MENOS65 and GEM14MAIN clinical trials. Samples were collected at four key time points:
• After induction therapy
• After autologous stem cell transplant (ASCT)
• After consolidation
• After two years of maintenance
Researchers compared three main assessments:
• Serum immunofixation (sIFE)
• Bone marrow plasma cell percentage (<5% vs ≥5%)
• Mass spectrometry (MS), using Quantitative Immunoprecipitation Mass Spectrometry (EXENT Analyzer)
Key findings
1. Bone marrow plasma cell count and sIFE were limited in predicting outcomes. Neither plasma cell percentage nor sIFE status reliably distinguished patients with different median progression-free survival (mPFS). Even among patients who were sIFE-negative (often considered close to CR), plasma cell counting did not predict who would do better or worse.
2. Mass spectrometry (MS) was more predictive. MS clearly separated patients into two groups with significantly different mPFS. Among sIFE-negative samples:
• 117 patients were MS-positive and had significantly shorter mPFS.
• MS negativity strongly correlated with better outcomes.
Importantly, among 414 samples classified as CR by conventional criteria, MS still detected residual disease in 91 cases (22%). In contrast, 323 cases (78%) were MS-negative and could be considered in a deeper response (“MS-CR”).
3. MS added prognostic value beyond conventional CR. When patients were grouped by traditional CR status (≥CR vs <CR) and MS results:
• MS consistently identified two prognostic groups regardless of CR status.
• Conventional CR did not predict outcomes within either the MS-positive or MS-negative groups.
4. Bone marrow plasma cell counting provided little added value once sIFE was negative. Among sIFE-negative cases, very few patients were MS-negative but had ≥5% plasma cells, and most of these represented normal (polyclonal) plasma cells rather than active disease. The negative predictive value of MS compared with plasma cell counting was 90%.
Clinical implications
These findings suggest that:
• Performing bone marrow aspiration solely to confirm <5% plasma cells may not be necessary in patients who are already sIFE-negative.
• Bone marrow evaluation remains important for measurable residual disease (MRD) testing using next-generation sequencing (NGS) or next-generation flow (NGF), as recommended by IMWG.
• Mass spectrometry offers a highly sensitive, non-invasive blood test that may better reflect overall disease burden and more accurately predict outcomes than traditional CR criteria.
The study also highlights that imaging requirements for confirming disappearance of plasmacytomas are not clearly defined in CR criteria. Current IMWG guidelines recommend low-dose CT or PET-CT mainly when CR and bone marrow MRD negativity are achieved, suggesting that CR definitions may need refinement.
Limitations and future directions
This study involved transplant-eligible patients treated with intensive regimens but did not include anti-CD38 monoclonal antibodies, CAR-T therapy, or bispecific antibodies, which are now common in MM treatment. Therefore, further research is needed in:
• Transplant-ineligible patients
• Relapsed/refractory MM
• Patients receiving modern immunotherapies
Summary
In newly diagnosed transplant-eligible MM patients:
• Traditional CR criteria (especially bone marrow plasma cell percentage) have limited prognostic value once sIFE is negative.
• Mass spectrometry more accurately identifies patients with deeper responses and better progression-free survival.
• MS negativity could represent a more stringent, patient-friendly definition of complete response.
• Bone marrow procedures may be best reserved for MRD testing rather than routine plasma cell counting.
Overall, integrating sensitive, non-invasive tools like MS into response assessment may improve patient care and reduce unnecessary invasive procedures in multiple myeloma.
Reference:
Puig, N., Agulló, C., Paiva, B., Cedena, M.-T., Rosiñol, L., Contreras, T., Martínez-López, J., Oriol, A., Blanchard, M.-J., Ríos-Tamayo, R., Sureda, A., Lakhwani, S., de la Rubia, J., Cabañas, V., de Arriba, F., Paricio, M., Iñigo, M.-B., González-Calle, V., Ocio, E.M., Castro, S., Bargay, J., Bladé, J., San Miguel, J.F., Lahuerta, J.-J. and Mateos, M.V. (2026), A critical analysis of the IMWG multiple myeloma complete response criterion in the era of mass spectrometry. HemaSphere, 10: e70301. https://doi.org/10.1002/hem3.70301 (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70301)
Experiences with real-world teclistamab administration in community and outpatient settings: a mixed-methods study of hematology providers — Current Medical Research and Opinion (February 2026)
Background and clinical context
Before teclistamab, patients with triple-class exposed (TCE) RRMM had poor outcomes, with median progression-free survival (PFS) of about 4 months and overall survival (OS) of 12 months. In the MajesTEC-1 trial (median follow-up 30.4 months), teclistamab significantly improved outcomes:
• Median duration of response: 24 months
• Median PFS: 11.4 months
• Median OS: 22 months
These results support its growing use in both academic and community settings.
What is the purpose of the study?
This mixed-methods study examined how teclistamab step-up dosing (SUD) is being delivered in real-world U.S. practice, especially in community settings and outpatient models. Teclistamab is the first FDA-approved bispecific antibody (BsAb) for relapsed/refractory multiple myeloma (RRMM) and has been used in more than 15,900 patients worldwide.
How was the study conducted?
• A survey of 38 U.S. clinicians (March–August 2024)
- 76% worked in community-based practices
- 66% had treated ≥5 patients with teclistamab
• 8 follow-up interviews
• 1 roundtable discussion (7 participants)
The goal was to understand how practices manage step-up dosing (SUD), adverse events, and care transitions.
Real-world step-up dosing models
Among 38 practices:
• 53% used outpatient SUD
• 26% used inpatient SUD
• 21% referred patients elsewhere for SUD
Many inpatient or referral practices planned to transition to outpatient SUD.
Patient selection for outpatient SUD (n=20 practices)
Common requirements:
• Caregiver support (90%)
• Close proximity to treatment center (70%)
• Good performance status (65%)
• Low disease burden (30%)
Patients with social, logistical, or clinical risk factors were more likely to receive inpatient SUD.
Reasons for hospital admission
• Any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) (85%)
• Grade ≥2 cytokine release syndrome (CRS) (70%)
• Abnormal vital signs (60%)
Monitoring and safety in outpatient SUD
Outpatient SUD increases access and reduces hospitalization but requires close monitoring for adverse events such as CRS and ICANS.
Monitoring approaches varied:
• Home health visits
• Telehealth monitoring
• Wearable devices transmitting real-time vital signs
• Manual caregiver monitoring (e.g., checking vitals every 8 hours)
Successful implementation required:
• Multidisciplinary coordination (oncologists, pharmacists, nurses, advanced practice providers, administrators)
• Education of local emergency departments to recognize and treat CRS and ICANS
• Partnerships with nearby hospitals, especially in community practices
Some centers adjusted dosing schedules (e.g., days 1-3-8 instead of 1-3-5) to avoid weekend monitoring challenges.
Prophylaxis and supportive care
All practices using SUD provided medications to prevent adverse events.
Tocilizumab for CRS prevention
• 29% of practices used prophylactic tocilizumab.
• At the time of the study, it was not FDA-approved for CRS prevention, creating reimbursement challenges.
• In July 2025, the National Comprehensive Cancer Network (NCCN Guidelines®) supported prophylactic tocilizumab use for CRS prevention with BsAbs.
• The International Myeloma Working Group (IMWG) described it as investigational but noted growing evidence.
In the OPTec trial:
• 11 patients completed SUD
• No patient required hospitalization
• No grade ≥3 CRS or ICANS occurred
Real-world data have shown low CRS rates (11%, all grade 1) with prophylactic tocilizumab, suggesting prevention may reduce severity and incidence.
Infection prevention
Despite existing guidelines, 13% of practices reported not using infection prophylaxis (e.g., IVIG), indicating a need for improved education and adherence to infection prevention strategies.
Long-term dosing considerations
Many practices reduced teclistamab dosing frequency over time due to:
• Sustained response
• Concerns about infections or cytopenias
Modeling based on MajesTEC-1 suggests that in patients with ≥6 months of response:
• 3 mg/kg monthly dosing may provide similar drug exposure as 1.5 mg/kg every two weeks
Monthly dosing is not yet FDA-approved but is being studied in ongoing trials for earlier lines of therapy.
Key takeaways
• Outpatient teclistamab SUD has been successfully implemented, including in community practices.
• Careful patient selection, education, multidisciplinary coordination, and strong monitoring systems are critical.
• Prophylactic tocilizumab may reduce CRS, with increasing guideline support.
• Infection prevention strategies require greater uptake.
• Long-term dosing strategies are evolving to balance efficacy, safety, and quality of life.
Why this study matters
Overall, outpatient SUD can improve patient access, reduce hospitalization, and lower healthcare resource use when applied to appropriately selected patients.
Reference:
Derman, B., Jijun Liu, J., Bouchard, N., Figg, L., LaPorte, J., Goorha, S., … Baljevic, M. (2026). Experiences with real-world teclistamab administration in community and outpatient settings: a mixed-methods study of hematology providers. Current Medical Research and Opinion, 1–10. https://doi.org/10.1080/03007995.2026.2626367 (https://www.tandfonline.com/doi/full/10.1080/03007995.2026.2626367#abstract)
Early Mortality with Bispecific Antibody Therapy in RRMM: An IMWG Immunotherapy Database Real-World Analysis — Blood Advances (February 2026)
What is the purpose of the study?
In this large, real-world, multicenter study from the IMWG Immunotherapy Database, 441 adults with relapsed/refractory multiple myeloma (RRMM) received commercial bispecific antibodies (bsAbs)—teclistamab (n=234), talquetamab (n=140), or elranatamab (n=67)—between May 2022 and June 2025. Patients treated in clinical trials were excluded. Early mortality (EM), defined as death within 12 months of starting bsAb therapy, occurred in 148 patients (34%). The median time from bsAb initiation to death was 2.87 months, and most deaths (71% of EM cases) occurred within the first 6 months, particularly within the first 3 months.
Key results
The leading cause of early death was progressive myeloma (72%), followed by infection (13%). Importantly, 82% of patients who died early had active disease at the time of death, underscoring that uncontrolled myeloma was the main driver. Among those who died within 3 months, 74% died from disease progression. Documented fatal infections included bacterial, viral (including COVID-19), and opportunistic infections. Although infections were less common than progression, they remained a significant contributor to mortality.
Patients who died early had more advanced and aggressive disease features. They were heavily pretreated (median 6 prior lines; 88% triple-class refractory; 56% penta-drug refractory), and 84% would not have met eligibility criteria for pivotal trials such as MajesTEC-1, MagnetisMM-3, or MonumenTAL-1. High-risk cytogenetic abnormalities (1q+, t(4;14), t(14;16), t(14;20), del(17p)) were common, and many had extramedullary disease (EMD), poor performance status (ECOG ≥2), or renal impairment. Compared with patients who did not experience EM, the EM group had worse functional status, more EMD, and lower use of intravenous immunoglobulin (IVIG).
The overall response rate (ORR) in the full cohort was 66% (teclistamab 68%, talquetamab 69%, elranatamab 55%). However, in the EM group, the ORR was only 27%, compared with 84% in those who did not die early. Primary refractory disease was common among early deaths, with rapid progression (median 28 days). Achieving at least a partial response markedly reduced the risk of early mortality (HR 0.22, p<0.001).
On multivariable analysis, key predictors of early mortality were:
• Baseline thrombocytopenia (platelets <50 × 10⁹/L) before bsAb start (HR 1.93, p=0.02).
• Lack of response to bsAb (strongest risk factor).
• Extramedullary disease (suggestive risk factor).
• IVIG use showed a trend toward reduced risk (HR 0.58), though not statistically significant.
Progression-free survival (PFS) at 6 and 12 months for the overall cohort was 57.7% and 44.9%, respectively. Despite encouraging overall response rates, the 12-month early mortality rate remained substantial.
In summary
In real-world RRMM patients treated with bsAbs, approximately one-third died within 12 months, usually within the first 3 months, and most deaths were due to uncontrolled myeloma rather than treatment toxicity alone. Baseline severe thrombocytopenia and failure to respond to therapy were strongly associated with early death, while IVIG may help reduce risk, likely by lowering infection rates. These findings highlight the urgent need for better early disease control, careful patient selection, proactive infection prevention (including consideration of IVIG in hypogammaglobulinemia), and strategies to overcome primary resistance to bispecific antibodies.
Reference:
Carlyn Rose Tan, Saad Z. Usmani, Andriy Derkach, Andre De Menezes Silva Corraes, Ricardo D Parrondo, Sikander Ailawadhi, Sireesha Asoori, Mrugakshi Dave, Rakesh Popat, Oliver Morjaria, Roman Hajek, Jana Mihalyova, Myo Htut, Murali Janakiram, Alissa Visram, Efstathios Kastritis, Meletios A. Dimopoulos, Joaquín Martínez-López, Chandramouli Nagarajan, Susan Bal, Luciano J. Costa, Hermann Einsele, Torsten Steinbrunn, Johannes M. Waldschmidt, Christine Riedhammer, Rahul Banerjee, Wee Joo Chng, Allison CY Tso, Yi Lin, Tom G Martin, Hira Mian; Early Mortality with Bispecific Antibody Therapy in RRMM: An IMWG Immunotherapy Database Real-World Analysis. Blood Adv 2026; bloodadvances.2025019231. doi: https://doi.org/10.1182/bloodadvances.2025019231 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025019231/566834/Early-Mortality-with-Bispecific-Antibody-Therapy)
Real-World Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated With Front-Line Daratumumab Lenalidomide and Dexamethasone — American Journal of Hematology (February 2026)
Background
The phase III MAIA trial evaluated daratumumab, lenalidomide, and dexamethasone (DRd) versus lenalidomide and dexamethasone (Rd) in newly diagnosed, transplant-ineligible multiple myeloma (MM). MAIA showed unprecedented survival outcomes with DRd, including a median progression-free survival (PFS) of about 62 months and a 4-year overall survival (OS) rate of ~70%. In MAIA, daratumumab was given until disease progression, lenalidomide for up to 2 years, and dexamethasone weekly. A post hoc analysis suggested that staying on DRd for ≥18 months without modification led to better outcomes.
What is the purpose of the study?
This retrospective real-world (RW) study evaluated 202 newly diagnosed MM patients treated with DRd at the Mayo Clinic (2016–2023) to assess effectiveness and treatment patterns outside of a clinical trial.
Key findings
• The overall response rate (ORR) was 91%, with 64% achieving at least a very good partial response (VGPR). Among evaluable patients, 51% achieved minimal residual disease (MRD) negativity (10⁻⁵ sensitivity).
• Twenty-eight patients underwent autologous stem cell transplant (ASCT). In non-transplant patients, median PFS was 48 months and the 4-year OS rate was 52%. In transplant patients, median PFS was not reached; at 37 months, PFS was 65% and OS was 75%.
• Among non-transplant patients:
- Standard-risk patients had median PFS of 58 months, high-risk 42 months, and ultra–high-risk 37 months.
- Patients with extramedullary disease had shorter PFS (14 vs. 48 months).
- Patients with renal insufficiency or age ≥75 or ≥80 years had numerically shorter PFS, though differences were not statistically significant.
Treatment modifications were common and important:
• 67% of patients had dose modifications (most often reducing or stopping lenalidomide and/or dexamethasone), typically around 7 months after starting DRd.
• Patients with DRd modifications had significantly longer PFS (58 vs. 14 months) and remained on therapy three times longer (16 vs. 6.3 months).
• Even in a 6-month landmark analysis (to reduce bias), patients with dose modifications had superior PFS (51 vs. 8 months).
• Patients who required modification due to toxicity had somewhat shorter PFS than those modified for other reasons.
Notably, these findings contrast with MAIA’s post hoc analysis suggesting early modification (<18 months) reduced benefit. In this RW study, dose adjustments appeared to help patients remain on therapy longer, which may have improved outcomes.
This aligns with other data suggesting reduced dose intensity in MM does not necessarily worsen survival.
Compared with MAIA, RW patients were older (median 75 vs. 73 years) and had more high-risk cytogenetics (32% vs. 15%), likely contributing to somewhat inferior outcomes (median PFS 48 vs. 62 months; 4-year OS 52% vs. 70%).
After relapse on first-line DRd (45 patients), subsequent therapies—often proteasome inhibitor–based regimens such as bortezomib- or carfilzomib-based combinations—remained effective, with an ORR of 52%, 12-month PFS of 74%, and 12-month OS of 91%. Most deaths occurred in very elderly patients (median age 82), and many were not directly due to myeloma.
Why this study matters
In real-world practice, DRd remains an effective frontline therapy for transplant-ineligible newly diagnosed MM, though outcomes were modestly inferior to the MAIA trial, likely due to older and higher-risk patients. Importantly, dose modifications were common and associated with longer treatment duration and improved PFS, suggesting that individualized dose adjustments may help patients stay on therapy and maintain benefit. Even after progression on DRd, effective salvage options are available.
Reference:
R. D. Parrondo, R. C. B. de Menezes, H. Sledge, et al., “Real-World Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated With Front-Line Daratumumab Lenalidomide and Dexamethasone,” American Journal of Hematology (2026): 1–5, https://doi.org/10.1002/ajh.70258 (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70258).
Circulating tumor cells in myeloma are a compound biomarker for bone marrow high-risk genomic alterations and tumor load — Blood (February 2026)
Background
Circulating tumor cells (CTCs) are myeloma cells that can be detected in the blood. In newly diagnosed multiple myeloma (NDMM), high CTC levels are strongly linked to worse outcomes.
How was the study conducted?
Researchers analyzed paired bone marrow and blood samples from patients in the phase III PERSEUS and CASSIOPEIA trials using single-cell RNA sequencing and whole-genome sequencing. They also validated findings in the Multiple Myeloma Research Foundation CoMMpass study dataset.
Key findings
• CTCs closely resemble bone marrow tumor cells. At the genetic and transcriptional level, CTCs were nearly identical to bone marrow plasma cells. There was no distinct “circulating” subtype with unique biology.
• High CTC levels reflect higher tumor burden and faster tumor growth. Patients with high CTC levels had bone marrow tumor cells with strong gene signatures of increased proliferation.
• CTC levels are strongly linked to high-risk genetic abnormalities.
High CTC levels were associated with:
• Primary translocations involving MAF and CCND1
• Secondary high-risk genomic events, including:
- Amplification of 1q (amp1q)
- Deletion of 1p (del1p)
- Deletion of 13q (del13q)
- Biallelic TP53 mutations (loss of both TP53 copies)
- Increased APOBEC-related mutational activity
Some of these abnormalities (such as APOBEC-driven mutations) are known to increase myeloma cell growth and are linked to poorer survival.
• CTCs are not driven by enhanced migration ability. The study found no consistent gene expression pattern suggesting that certain myeloma cells are specially programmed to leave the bone marrow. Instead, higher CTC levels likely reflect more tumor cells overall, and more aggressive genetic features
Overall conclusion
CTC levels are not caused by a special circulating cell type. Instead, they represent the combined effect of:
• Tumor burden (how much myeloma is present)
• Increased tumor cell proliferation
• High-risk genetic abnormalities
As myeloma progresses and tumor load increases, more tumor cells enter the bloodstream. Therefore, CTC levels act as a practical and minimally invasive biomarker that reflects the genetic risk profile and biological aggressiveness of the disease.
In short, high CTC levels signal genomics-driven high-risk multiple myeloma, making CTC measurement a powerful tool for risk assessment at diagnosis.
Reference:
Cathelijne Fokkema, Luca Bertamini, Madelon M. E. de Jong, Sabrin Tahri, Davine Hofste op Bruinink, Zoltan Kellermayer, Natalie Papazian, Chelsea den Hollander, Michael P. W. Vermeulen, Elodie C. G. Stoetman, Gregory van Beek, Remco Hoogenboezem, Vincent H. J. van der Velden, Cyrille Hulin, Aurore Perrot, Philippe Moreau, Melissa Rowe, Diego Vieyra, Robin Carson, Mark van Duin, Mathijs A. Sanders, Annemiek Broijl, Pieter Sonneveld, Tom Cupedo; Circulating tumor cells in myeloma are a compound biomarker for bone marrow high-risk genomic alterations and tumor load. Blood 2026; 147 (9): 932–945. doi: https://doi.org/10.1182/blood.2025030083 (https://ashpublications.org/blood/article/147/9/932/557385/Circulating-tumor-cells-in-myeloma-are-a-compound)
Patients', clinicians' and research's priorities on important outcomes in multiple myeloma: A mixed-methods study — British Journal of Haematology (February 2026)
What is the purpose of the study?
This mixed-methods study examined which treatment outcomes matter most to people with multiple myeloma and their clinicians and compared these priorities with endpoints commonly used in randomized controlled trials (RCTs).
Researchers interviewed 10 patients and 6 clinicians, then surveyed 117 patients and 105 clinicians. Both groups ranked quality of life (QoL) as the most important outcome. However, differences emerged:
• Clinicians were more likely to prioritize:
- Overall survival (OS)
- Progression-free survival (PFS)
• Patients were more likely to prioritize:
- Pain reduction
- Daily functioning and symptom relief
When compared with RCT endpoints, important differences were seen:
• Patients strongly emphasized QoL and pain elimination.
• Trials more often focused on:
- PFS (OR 6.33; 95% CI 2.53–15.83)
- Response rates (OR 17.75; 95% CI 5.56–56.61)
Although clinicians valued QoL, they aligned more closely with trials in prioritizing PFS.
Key insights
• QoL was the shared top priority between patients and clinicians.
• Patients viewed QoL and symptom control as overarching goals.
• Clinicians focused more on extending survival (OS) and delaying progression (PFS), while recognizing treatment burden and side effects.
• Pain control was ranked lower by clinicians, likely because it is often managed with supportive treatments (e.g., corticosteroids, radiotherapy, vertebroplasty) rather than anti-myeloma therapy itself.
Surrogate endpoints: PFS and MRD
Patients find PFS difficult to understand because it includes several events (relapse, progression, or death). While many patients included PFS among their top five outcomes, few chose it as the single most important.
Minimal residual disease (MRD) negativity was not a top clinician priority but received some patient support. This may reflect how it was described in the survey (“elimination of cancer cells”), which could have led patients to interpret it as a cure, without fully understanding its technical meaning. These findings highlight the need for clear communication when using surrogate endpoints like PFS and MRD.
Broader context
Prior research similarly shows that patients with chronic diseases, including myeloma, often prioritize QoL and symptom relief over longer survival, especially when treatments mainly improve PFS without extending OS. Many patients are unwilling to accept added toxicity for PFS benefit alone if OS does not improve.
Despite being valued by both groups, QoL is:
• Inconsistently measured in trials
• Rarely used as a primary endpoint
• Often limited to short-term assessments
• Infrequently incorporated into regulatory decisions
Initiatives such as the Core Outcome Set (COS) for myeloma, the COMET Initiative, and PCORI promote patient involvement in selecting meaningful outcomes, including emotional well-being, fatigue, and treatment burden.
Limitations
• All participants were recruited in Greece, limiting generalizability.
• The sample size was modest.
• Patient understanding of complex surrogate endpoints (PFS, MRD) varies.
• The study did not assess treatment trade-offs (e.g., efficacy vs toxicity).
• Cultural norms may have influenced patient deference to clinicians.
Clinical implications
Shared decision-making in oncology can be challenging, especially at diagnosis when patients may feel overwhelmed. Clear explanations of treatment trade-offs and surrogate end-points—using plain language and balanced discussion of benefits and risks—are essential.
Why this study matters
Patients and clinicians agree that quality of life is central in multiple myeloma care, but they differ in how they prioritize survival measures such as OS and PFS. Current clinical trials emphasize surrogate endpoints (especially PFS and response rates) more than patients do. Greater integration of QoL and patient-reported outcomes into trial design and clinical decisions is needed to ensure that new therapies deliver outcomes that truly matter to patients.
Reference:
Mainou M, Karagiannis T, Pagkalidou E, Liakos A, Malandrakis P, Hatjiharissi E, et al. Patients', clinicians' and research's priorities on important outcomes in multiple myeloma: A mixed-methods study. Br J Haematol. 2026; 00: 1–10. https://doi.org/10.1111/bjh.70396 (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70396)
Summary of Research: Elranatamab Fixed Dosing—A Safe, Effective, and Convenient Dosing Approach — Oncology and Therapy (March 2026)
Background
This summary is based on the research article “Elranatamab Fixed Dosing: A Safe, Effective, and Convenient Dosing Approach.”
How was the summary created?
Researchers analyzed data from the MagnetisMM-3 trial, which evaluated the safety and effectiveness of elranatamab in people with multiple myeloma. Because body weight can sometimes affect how a drug works or how safe it is, the investigators examined whether weight influenced treatment outcomes.
In this analysis, participants from MagnetisMM-3 were divided into four groups (quartiles) based on body weight. All participants received the same fixed dose of elranatamab (76 mg).
Key results
• No clinically meaningful differences in pharmacokinetics (how the drug is absorbed, distributed, and processed in the body) across the different body weight groups.
• Similar types and severity of side effects across all weight groups.
• Clinically meaningful response rates in all four groups, with comparable effectiveness regardless of body weight.
Conclusion
Overall, the findings suggest that a fixed 76 mg dose of elranatamab is effective and has a manageable safety profile across a wide range of body weights, supporting the use of fixed dosing rather than weight-based dosing in patients with multiple myeloma.
Reference:
Elmeliegy, M., Soltantabar, P., Hibma, J. et al. Summary of Research: Elranatamab Fixed Dosing—A Safe, Effective, and Convenient Dosing Approach. Oncol Ther (2026). https://doi.org/10.1007/s40487-026-00415-0 (https://link.springer.com/article/10.1007/s40487-026-00415-0)
CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models — Blood Cancer Discovery (March 2026)
Summary
CD70 was investigated as a therapeutic target in high-risk multiple myeloma, particularly in patients relapsing after BCMA-directed therapy. Analyses of two patient cohorts, including the CoMMpass dataset and an independent MD Anderson cohort, used single-cell RNA sequencing, flow cytometry, and immunohistochemistry to evaluate CD70 expression and its association with cytogenetic risk and survival. CD70 expression was enriched in high-risk subgroups, including t(4;14), 1q21 amplification, del17p, ISS stage 2/3, and relapsed disease, and correlated with inferior survival. Preclinical evaluation of CAR27/IL-15–engineered NK cells targeting CD70 demonstrated potent in vitro and in vivo cytotoxicity comparable to CAR T cells, including activity in BCMA knockout models. These findings support CD70 as a promising therapeutic target and provide rationale for the ongoing phase I/II trial (NCT05092451) of CD70-targeting CAR NK cells.
Key points
• CD70 expression is elevated in high-risk multiple myeloma, including t(4;14), 1q21 amplification, del17p, ISS stage 2/3, and relapsed disease.
• High CD70 expression correlates with significantly poorer overall survival.
• Validation was performed using single-cell RNA sequencing, flow cytometry, and immunohistochemistry across independent patient cohorts.
• CAR27/IL-15 NK cells exhibit strong cytotoxicity against CD70+ myeloma cells in vitro and in xenograft models.
• CD70-targeting CAR NK cells remain effective in BCMA knockout models, supporting use after BCMA therapy relapse.
• Findings provide preclinical rationale for the ongoing phase I/II clinical trial (NCT05092451).
Conclusion
CD70 is highly expressed in biologically high-risk multiple myeloma and is strongly associated with inferior survival outcomes. Comprehensive transcriptomic and protein-level validation confirms its enrichment in aggressive cytogenetic subgroups and relapsed disease. CAR27/IL-15–engineered NK cells demonstrate potent and durable antitumor activity in preclinical models, including in BCMA-deficient settings that mimic resistance to BCMA-directed therapy. CD70 therefore represents a compelling therapeutic target, particularly for patients who relapse after BCMA-based treatments. Ongoing clinical evaluation of CD70-targeting CAR NK cells will determine their safety and efficacy in this high-risk population.
Reference:
Paul Lin, Sunil Acharya, Francia Reyes-Silva, Rafet Basar, Nadima Uprety, Luz Yurany Moreno Rueda, Pei Lin, April L. Gilbert, Pinaki P. Banerjee, Dexing Fang, Chenyu Zhang, Ana Karen Nunez Cortes, Luciana Melo Garcia, May Daher, Luis Muniz-Feliciano, Gary M. Deyter, Vernikka Woods, Seema Rawal, Ping Li, Corry M. Jones, Rejeena Shrestha, Muzaffar H. Qazilbash, Krina K. Patel, Hans C. Lee, Richard E. Champlin, David Marin, Elizabeth J. Shpall, Robert Z. Orlowski, Katayoun Rezvani; CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models. Blood Cancer Discov 1 March 2026; 7 (2): 234–249. https://doi.org/10.1158/2643-3230.BCD-25-0130 (https://aacrjournals.org/bloodcancerdiscov/article/7/2/234/774793/CD70-Targeting-CAR-NK-Cells-Overcome-BCMA)
Selective B-cell subset depletion underlies increased infection risk in patients with MM treated with anti-BCMA vs anti-GPRC5D bsAbs — Blood (March 2026)
Summary
Research on B‑cell maturation antigen (BCMA)–targeting bispecific antibodies (bsAbs) versus G protein–coupled receptor class C group 5 member D (GPRC5D)–targeting bsAbs in multiple myeloma (MM) investigated why infection rates differ between these therapies.
Single-cell RNA sequencing of bone marrow samples from patients and healthy donors, combined with next-generation flow cytometry immune profiling, was used to analyze antigen expression and immune-cell depletion patterns. BCMA expression was detected not only on plasma cells but also on early B-cell precursors, including small pre-B cells, whereas GPRC5D expression was largely restricted to malignant plasma cells.
Treatment with anti-BCMA bsAbs caused profound and persistent depletion of B-cell precursors, mature B cells, and normal plasma cells. In contrast, anti-GPRC5D bsAbs mainly targeted plasma cells and spared most normal B-cell populations, explaining the lower infection risk observed with GPRC5D-directed therapy.
Key points
• BCMA expression occurs earlier in B-cell development than previously recognized, including on small pre-B cells.
• Anti-BCMA bispecific antibodies deplete multiple stages of the B-cell lineage, from pre-B cells to mature B cells and plasma cells.
• GPRC5D expression is largely restricted to malignant plasma cells, with lower expression on normal plasma cells.
• Anti-GPRC5D bispecific antibodies selectively target plasma cells and largely spare B-cell precursors and mature B cells.
• Higher infection risk during anti-BCMA therapy is likely due to widespread depletion of the B-cell compartment and sustained suppression of humoral immunity.
Conclusion
Targeting B‑cell maturation antigen with bispecific antibodies results in broad depletion of the B-cell lineage because BCMA is expressed from the small pre-B-cell stage onward. This contrasts with therapies directed at G protein–coupled receptor class C group 5 member D, which primarily affect malignant plasma cells and spare most normal B-cell populations. The broader immune depletion caused by anti-BCMA therapies explains the increased susceptibility to infections observed in treated patients with multiple myeloma.
These mechanistic insights support tailoring infection-prevention strategies, such as individualized immunoglobulin replacement therapy, based on the targeted antigen. The ability of BCMA-targeted therapies to eliminate both B cells and plasma cells may also have therapeutic implications for other B-cell malignancies and autoimmune diseases.
Reference:
Tomas Jelinek, David Zihala, Aintzane Zabaleta, Ioannis V. Kostopoulos, Ondrej Soucek, Ondrej Venglar, Cristina Moreno, Despina Fotiou, Eva Radova, Luis Esteban Tamariz-Amador, Foteini Theodorakakou, Ludmila Muronova, Andrea Manubens, Ourania Tsitsilonis, Tereza Popkova, Carmen Gonzalez, Anjana Anilkumar Sithara, Francesco Corrado, Nayda Bidikian, Camila Guerrero, Veronika Kapustova, Daniel Bilek, Patrick R. Hagner, Marta Larrayoz, Jose A. Martinez Climent, Lucie Broskevicova, Jana Mihalyova, Maximilian Merz, Tereza Sevcikova, Irene M. Ghobrial, Jesus San Miguel, Meletios A. Dimopoulos, Paula Rodriguez-Otero, Jakub Radocha, Efstathios Kastritis, Bruno Paiva, Roman Hajek; Selective B-cell subset depletion underlies increased infection risk in patients with MM treated with anti-BCMA vs anti-GPRC5D bsAbs. Blood 2026; 147 (10): 1070–1082. doi: https://doi.org/10.1182/blood.2025029572 (https://ashpublications.org/blood/article/147/10/1070/557373/Selective-B-cell-subset-depletion-underlies)
REALiTEC: a multi-country observational retrospective study of teclistamab in patients with relapsed/refractory multiple myeloma outside of clinical trials — Haematologica (March 2026)
Summary
Teclistamab, an anti-BCMA bispecific antibody, was evaluated in the REALiTEC retrospective observational study involving patients with triple-class exposed relapsed/refractory multiple myeloma treated outside clinical trials in Europe and Israel.
Data from 113 patients across 23 centers were analyzed to assess real-world effectiveness and safety. Patients were heavily pretreated, with a median of six prior therapy lines and high rates of triple- and penta-class refractory disease.
Teclistamab produced a 60.2% overall response rate, with over half of patients achieving very good partial response or better, and responses lasting a median of 20.3 months.
Safety findings were consistent with earlier clinical trial data, with infections and cytokine release syndrome being the most common adverse events and no new safety concerns observed.
Key points
• REALiTEC analyzed real-world outcomes of teclistamab in 113 heavily pretreated RRMM patients across 23 centers in 8 countries.
• Median patient age was 66 years, with 6 prior therapy lines on average.
• Disease characteristics were high-risk:
- 78.8% triple-class refractory
- 44.2% penta-class refractory
- 35.4% previously treated with anti-BCMA therapy
• Efficacy outcomes:
- Overall response rate (ORR): 60.2%
- ≥VGPR achieved in 52.2% of patients
- Median duration of response: 20.3 months
- Median progression-free survival: 9.7 months
- Median overall survival: 26.3 months
• Patients achieving ≥VGPR showed improved outcomes, including 26.1-month median response duration and strong 12-month survival rates.
• Safety profile:
- Infections: 70.8%
- Cytokine release syndrome: 55.8%
- Neutropenia: 35.4%
- Anemia: 25.7%
• Infection rates declined over time, and immunoglobulin replacement therapy was used in up to 60% of patients.
• Findings align with results from the MajesTEC-1 clinical trial, confirming effectiveness in real-world settings.
Conclusion
REALiTEC demonstrates that teclistamab maintains strong clinical activity in heavily pretreated relapsed/refractory multiple myeloma patients treated outside clinical trials. High response rates and durable responses were observed despite the population having extensive prior therapies and significant refractory disease.
Outcomes were consistent across patient subgroups, including individuals with historically poorer prognoses. The safety profile matched prior clinical trial findings, with manageable adverse events and no new safety signals. These results reinforce teclistamab as an effective treatment option for advanced multiple myeloma in real-world clinical practice.
Reference:
Uttervall K, Kortum MK, Perrot A, Farmer SL, Cavo M, Kishore B, Jacquet C, Casanova M, Hansson M, Weisel K, Magen H, Liberatore C, Hansen CT, Gatt ME, Shragai T, Da Via MC, Alvarez TDS, Streetly M, Raab MS, Manier S, Aegesen J, Albrecht C, Hu P, Smirnov P, Santra D, Rubio-Azpeitia E, Popat R. REALiTEC: a multi-country observational retrospective study of teclistamab in patients with relapsed/refractory multiple myeloma outside of clinical trials. Haematologica; https://doi.org/10.3324/haematol.2025.289281 (https://haematologica.org/article/view/13372) [Early view].
Real-world outcomes of newly diagnosed multiple myeloma patients treated with front-line daratumumab bortezomib lenalidomide and dexamethasone — Haematologica (March 2026)
Summary
Daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) were evaluated in a real-world cohort of newly diagnosed multiple myeloma patients treated at the Mayo Clinic Comprehensive Cancer Center between 2018 and 2024.
A retrospective analysis of 464 patients assessed treatment patterns, response rates, minimal residual disease negativity (MRD-), and survival outcomes using IMWG criteria and Kaplan–Meier survival estimates.
Overall response rates were high, reaching 98% in patients undergoing autologous stem cell transplant (ASCT), with substantial MRD- rates and a 3-year progression-free survival of 85% and overall survival of 96%. Once-weekly versus twice-weekly bortezomib dosing produced similar response and MRD- rates, and outcomes were generally consistent with results from the PERSEUS phase III trial.
The findings support DVRd as an effective frontline regimen in real-world practice for transplant-eligible and non-transplant patients.
Key points
• Real-world cohort: 464 newly diagnosed multiple myeloma patients treated with DVRd across three Mayo Clinic sites (2018–2024).
• High response rates:
- ASCT patients: 98% overall response, 79% ≥VGPR, 36% MRD- after induction.
- Non-ASCT patients: 87% overall response, 35% MRD- at any time.
• Survival outcomes:
- ASCT group: 3-year PFS 85%, 3-year OS 96%.
- Non-ASCT group: median PFS 57 months, 3-year PFS 60%, 3-year OS 85%.
• Bortezomib dosing: Once-weekly dosing (used in 86% of patients) showed no difference in ORR or MRD- rates compared with twice-weekly dosing.
• MRD- prognostic value: Achieving MRD negativity significantly improved progression-free survival compared with MRD-positive disease.
• Second-line therapy outcomes: Among patients relapsing after DVRd, second-line therapy achieved 76% ORR with median PFS of 18 months.
• High-risk disease: Patients with high-risk cytogenetics had slightly lower but still favorable progression-free survival compared with standard-risk patients.
Conclusion
Real-world use of daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) in newly diagnosed multiple myeloma demonstrates strong effectiveness consistent with outcomes reported in the PERSEUS trial. High response rates, substantial MRD negativity, and durable survival were observed, particularly among patients who underwent autologous stem cell transplant. Weekly bortezomib dosing produced similar efficacy to twice-weekly schedules, supporting common U.S. clinical practice patterns. Achieving MRD negativity remained a key predictor of prolonged progression-free survival. Overall, the results reinforce DVRd as a highly effective frontline treatment strategy in real-world multiple myeloma management.
Reference:
Parrondo RD, de Menezes R, Sledge H, Nayyar M, Yadav K, Bergsagel L, Fonseca R, Kapoor P, Buadi F, Gertz MA, Dispenzieri A, Roy V, Sher T, Binder M, Abdallah N, Chhabra S, Rajkumar VS, Gonsalves WI, Cook J, Dingli D, Lin Y, Fernandez A, Flott C, Yadav U, Warsame RM, Wiedmeier-Nutor EE, Kourelis T, Leung N, Siddiqui MA, Kumar S, Chanan-Khan AA, Ailawadhi S. Real-world outcomes of newly diagnosed multiple myeloma patients treated with front-line daratumumab bortezomib lenalidomide and dexamethasone. Haematologica; https://doi.org/10.3324/haematol.2025.300401 (https://haematologica.org/article/view/13378) [Early view].
Clinical Trials
Belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone for relapsed or refractory multiple myeloma — Blood Advances (February 2026)
What is the purpose of the study?
This phase 1/2 clinical trial studied belantamab mafodotin (belamaf) given every 8 weeks in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with relapsed/refractory multiple myeloma (RRMM). Belamaf is an antibody–drug conjugate that targets B-cell maturation antigen (BCMA) and has shown activity as a single agent, but it can cause eye-related side effects (ocular toxicity).
How was the study conducted?
Patients had received at least one prior treatment and had not progressed while taking full-dose lenalidomide. In the dose-escalation phase (3+3 design), belamaf was tested at 1.4 mg/kg and 1.9 mg/kg every 8 weeks. The maximum tolerated dose and recommended phase 2 dose was 1.9 mg/kg, with no dose-limiting toxicities at that level.
Efficacy (19 patients treated)
• Overall response rate: 89.5%
• Very good partial response or better: 78.9%
• All patients who achieved complete response were minimal residual disease (MRD) negative, meaning no detectable cancer with sensitive testing.
• After a median follow-up of 19.3 months:
- 24-month progression-free survival: 74.3%
- 24-month overall survival: 85.1%
• Responses were deep and durable, including in patients with high-risk disease and those whose disease was resistant to lenalidomide maintenance doses.
Safety
• Keratopathy occurred in 94.7% of patients, but most cases were mild to moderate (grade 1–2), reversible, and manageable without stopping treatment permanently.
• Grade 3 or higher keratopathy: 31.6%, similar to previously reported rates despite less frequent dosing.
• Other side effects (blood count changes and gastrointestinal symptoms) were manageable and consistent with the known safety profiles of KRd or belamaf.
Conclusion
Belamaf given every 8 weeks in combination with KRd showed strong and lasting responses with manageable side effects in patients with relapsed/refractory multiple myeloma. These results support further evaluation in phase 2 trials to confirm clinical benefit.
Reference:
Shebli Atrash, James Symanowski, Myra Robinson, Cecilia Flynn, Sarah Norek, Robin Cox, Monica Plott, Kelly Bumgarner, Darynne Rhinehardt, Xhevahire Begic, Ami Pauline Ndiaye, Jordan D Robinson, Reed Friend, Barry A Paul, Cindy Varga, Christopher J Ferreri, Mauricio Pineda-Roman, David M Foureau, Manisha Bhutani, Peter M Voorhees; Belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone for relapsed or refractory multiple myeloma. Blood Adv 2026; bloodadvances.2025019050. doi: https://doi.org/10.1182/bloodadvances.2025019050 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025019050/566678/Belantamab-mafodotin-carfilzomib-lenalidomide-and)
Phase II Study of BCMA Chimeric Antigen Receptor T-Cell Therapy in Patients With Newly Diagnosed Multiple Myeloma Ineligible for or Not Proceeding to Autologous Stem-Cell Transplantation (CAREMM-001) — Journal of Clinical Oncology (February 2026)
What is the purpose of the study?
Frontline B-cell maturation antigen (BCMA) CAR-T therapy was evaluated in patients with newly diagnosed multiple myeloma (NDMM) who were ineligible for or not proceeding to autologous stem-cell transplantation.
How was the study conducted?
In the phase II, open-label, single-arm trial (NCT05860036), participants received induction therapy followed by BCMA CAR-T infusion, consolidation, and lenalidomide maintenance, with minimal residual disease (MRD) negativity at 10⁻⁵ at Month 3 post-infusion as the primary endpoint.
Among 36 infused patients, MRD negativity at Month 3 reached 100%, with no MRD recurrence observed at a median follow-up of 15.8 months.
Complete response rates deepened over time, rising from 33.3% pre-infusion to 94.4% at last follow-up.
Adverse events were primarily transient cytopenias, with low-grade cytokine release syndrome and neurotoxicity, and no deaths or disease progression reported.
Key points
• Population: Newly diagnosed multiple myeloma patients ineligible for or not proceeding to autologous stem-cell transplantation
• Design: Phase II, open-label, single-arm trial (NCT05860036)
• Primary endpoint: MRD negativity (10⁻⁵) at Month 3 postinfusion
• MRD negativity: 100% (36/36) at Month 3; no MRD recurrence at 15.8 months median follow-up
• Complete response rate: Increased from 33.3% preinfusion to 94.4% at last follow-up
• Safety: Mainly transient grade 3–4 cytopenias; cytokine release syndrome (52.8%, all grade 1–2); no deaths or disease progression
Conclusion
Frontline BCMA CAR-T therapy demonstrated rapid, deep, and durable responses in transplant-ineligible newly diagnosed multiple myeloma. Universal MRD negativity at three months and sustained remission without recurrence highlight the potent antimyeloma activity of this strategy.
Response rates improved over time, suggesting continued disease control with consolidation and maintenance. The safety profile was manageable, characterized mainly by transient cytopenias and low-grade immune-related events.
These findings support further investigation of BCMA CAR-T therapy as a potentially practice-changing frontline option for this population.
Reference:
Wenqiang Yan et al. Phase II Study of BCMA Chimeric Antigen Receptor T-Cell Therapy in Patients With Newly Diagnosed Multiple Myeloma Ineligible for or Not Proceeding to Autologous Stem-Cell Transplantation (CAREMM-001). J Clin Oncol 0, JCO-25-01969 DOI:10.1200/JCO-25-01969 (https://ascopubs.org/doi/10.1200/JCO-25-01969)
Isatuximab, bortezomib, lenalidomide, dexamethasone for multiple myeloma: dynamics of MRD-negativity in the IMROZ study — Blood (March 2026)
What is the purpose of the study?
The Phase 3 IMROZ clinical trial studied treatment for people with newly diagnosed multiple myeloma (NDMM) who were not eligible for stem cell transplant.
How was the study conducted?
In this study, patients received either:
• Isa-VRd (isatuximab + bortezomib + lenalidomide + dexamethasone) followed by Isa-Rd (isatuximab + lenalidomide + dexamethasone), or
• VRd (bortezomib + lenalidomide + dexamethasone) followed by Rd (lenalidomide + dexamethasone).
Key findings
• Deeper responses with Isa-VRd/Isa-Rd: More patients receiving Isa-VRd/Isa-Rd achieved MRD-negativity, and MRD-negative complete response (CR) compared with those receiving VRd/Rd.
• Benefits seen early and long term: Higher MRD-negativity rates were observed:
- At the end of the initial treatment phase
- During maintenance treatment
- Maintained for up to 60 months of follow-up
• Improved progression-free survival (PFS): Isa-VRd/Isa-Rd significantly prolonged progression-free survival, meaning patients lived longer without their disease worsening.
• Better time-to-progression (TTP): Patients who changed from MRD-positive to MRD-negative had significantly longer TTP with Isa-VRd/Isa-Rd. Even patients whose MRD status later changed from negative to positive had better outcomes with Isa-VRd compared with VRd.
• Benefit across patient groups: Improvements were seen in important subgroups, including patients older than 70 years as well as frail patients
Why this study matters
Achieving and maintaining MRD-negativity was linked to better long-term outcomes. Checking MRD at multiple timepoints may help guide decisions about continuing or adjusting treatment.
Overall, these results strengthen earlier findings from IMROZ and support Isa-VRd followed by Isa-Rd as a standard-of-care first-line treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma.
Reference:
Robert Z. Orlowski, Meletios A. Dimopoulos, Xavier Leleu, Thierry Facon, Tadao Ishida, Roman Hajek, Ivan Spicka, Joanna Romejko-Jarosinska, Vladimir I. Vorobyev, Britta Besemer, Sevgi Kalayoglu Besisik, Pawel Robak, Tomas Jelínek, Hartmut Goldschmidt, Thomas Martin, Mohamed Mohty, Sandrine Macé, Ercem Kodas, Christina Tekle, Andrea T Shafer, Philippe Moreau; Isatuximab, bortezomib, lenalidomide, dexamethasone for multiple myeloma: dynamics of MRD-negativity in the IMROZ study. Blood 2026; blood.2025030120. doi: https://doi.org/10.1182/blood.2025030120 (https://ashpublications.org/blood/article/doi/10.1182/blood.2025030120/566876/Isatuximab-bortezomib-lenalidomide-dexamethasone)
Efficacy and Safety of Belantamab Mafodotin with Bortezomib Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: the DREAMM-6 Arm B Trial — Clinical Cancer Research (March 2026)
What is the purpose of the study?
The Phase 1/2 DREAMM-6 Arm B clinical trial evaluated belantamab mafodotin combined with bortezomib and dexamethasone (BVd) in adults with relapsed/refractory multiple myeloma (RRMM)—patients whose cancer had returned or stopped responding after prior treatments.
How was the study conducted?
107 patients participated; they had received a median of 4 prior lines of therapy, meaning they were heavily pretreated. Different doses and schedules of belantamab mafodotin (intravenous) were tested, including:
• 1.9, 2.5, or 3.4 mg/kg every 3 weeks (Q3W)
• Split dosing (Days 1 and 8)
• Every 6 weeks (Q6W)
• A stepped-down dosing schedule
All patients also received bortezomib twice weekly, and dexamethasone four times weekly. Patients were followed for about 15 to 25 months.
The study evaluated:
• Dose-limiting toxicities (DLTs)
• Adverse events (AEs) and serious adverse events (SAEs)
• Overall response rate (ORR) (percentage of patients whose cancer shrank or improved)
• Drug levels in the body (pharmacokinetics)
Key results
• No dose-limiting toxicities were observed during dose escalation.
• The overall response rate (ORR) was 70% (95% confidence interval: 60.5–78.6%), meaning 7 out of 10 patients responded to treatment.
Side effects
• The most common serious (Grade 3/4) side effect was keratopathy, occurring in 53% of patients.
• Overall, 93% of patients experienced some type of eye-related event (such as changes in vision or corneal findings); 77% were Grade 3/4.
• 26% of patients had serious treatment-related side effects.
• There were 7 deaths due to serious adverse events; 3 were considered treatment-related.
Higher drug exposure was associated with greater likelihood of response, and higher rates of eye-related side effects.
Lower exposure reduced deep responses, with only small differences in eye-related events.
Conclusion
The combination of belantamab mafodotin, bortezomib, and dexamethasone (BVd) showed meaningful anti-myeloma activity in heavily pretreated RRMM patients. Although eye-related side effects were common, the safety profile was considered manageable.
Based on the balance of benefit and risk, 2.5 mg/kg every 3 weeks (Q3W) was supported as the recommended dose.
Reference:
Rakesh Popat, Bradley Augustson, Paul Cannell, Keith Stockerl-Goldstein, Andrew Spencer, Amit Khot, Ajay Nooka, Nashita Patel, Ravi S. Kasinathan, Astrid McKeown, Amy Curry, Rachel Rogers, Mehreen Shaikh, Fernando Carreno, Sumita Roy-Ghanta, Joanna Opalinska, Hang Quach; Efficacy and Safety of Belantamab Mafodotin with Bortezomib Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: the DREAMM-6 Arm B Trial. Clin Cancer Res 2026; https://doi.org/10.1158/1078-0432.CCR-25-3216 (https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-3216/774934/Efficacy-and-Safety-of-Belantamab-Mafodotin-with)
Phase 3 SUCCESSOR-2 study reveals positive interim results for mezigdomide in combination with carfilzomib and dexamethasone in RRMM; Signals potential use of next-generation CELMoDs as treatment for myeloma
On Monday, March 9, Bristol Myers Squibb announced via press release that “oral mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus carfilzomib and dexamethasone alone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM). Safety findings were consistent with the known profile of mezigdomide and the combination regimen. Patients will continue to be followed for survival and safety.”
The SUCCESSOR-2 trial (https://www.sciencedirect.com/science/article/pii/S253113792300977X?via%3Dihub) is a seamless Phase 2/3, multicenter, randomized, open-label study evaluating the oral CELMoD agent mezigdomide in combination with carfilzomib and dexamethasone (MeziKd) for patients with RRMM. The study compares this three-drug regimen with the standard combination of carfilzomib and dexamethasone (Kd).
The primary endpoint of the Phase 3 portion is progression-free survival (PFS). Key secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DoR), time to progression (TTP), time to next treatment (TTNT), minimal residual disease (MRD) negativity, and health-related quality of life (HR-QoL).
“These data underscore the potential of MeziKd as an oral regimen that could address a key unmet need for patients previously exposed to anti-CD38 and lenalidomide,” stated Paul Richardson, MD, Director of Clinical Research and Clinical Program Leader at the Jerome Lipper Multiple Myeloma Center, the Dana-Farber Cancer Institute and RJ Corman Professor of Medicine, Harvard Medical School.
According to Meletios-A. (Thanos) Dimopoulos, MD, Professor and Chairman, Department of Clinical Therapeutics at Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, “these positive interim data show that adding mezigdomide, a CELMoD specifically optimized for enhanced myeloma cell killing and immune activation compared with IMiD agents, to carfilzomib and dexamethasone may provide clinical benefit in earlier relapse.”
References:
Bristol Myers Squibb Announces Positive Phase 3 Results from the SUCCESSOR-2 Study of Oral Mezigdomide in Relapsed or Refractory Multiple Myeloma (https://news.bms.com/news/corporate-financial/2026/Bristol-Myers-Squibb-Announces-Positive-Phase-3-Results-from-the-SUCCESSOR-2-Study-of-Oral-Mezigdomide-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx). Bristol Myers Squibb press release. March 9, 2026.
PGR Md, MA Phd, JRB Md, CCM Phd, MAD Md, CTH Md, JKM Phd, AOM Phd, RZOM Phd, Md HQ, MSR Md, ARM Phd, DW Md, ZZ Phd, VHM Phd, JKM Phd, A Phase 3, Two-stage, Randomized Study of Mezigdomide, Carfilzomib, and Dexamethasone (MeziKd) versus Carfilzomib and Dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM); SUCCESSOR-2, Hematology, Transfusion and Cell Therapy, Volume 45, Supplement 4, 2023, Pages S426-S427, ISSN 2531-1379, https://doi.org/10.1016/j.htct.2023.09.801 (https://www.sciencedirect.com/science/article/pii/S253113792300977X?via%3Dihub).
Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy bb21217 for Relapsed and Refractory Multiple Myeloma: Results from the Phase I CRB-402 Study — Cancer Immunology Research (March 2026)
Background
bb21217 is a B-cell maturation antigen (BCMA)–targeted CAR T-cell therapy designed to improve durability of response in patients with relapsed or refractory multiple myeloma (RRMM).
What is the purpose of the study?
The phase I trial CRB-402 trial (NCT03274219) evaluated the safety, dosing, and effectiveness of bb21217, which is manufactured with the PI3K inhibitor bb007 to enrich CAR T cells with a memory-like phenotype that may persist longer in the body.
How was the study conducted?
72 heavily pretreated patients received escalating doses of the therapy and were monitored for side effects and treatment responses. The therapy produced an objective response rate of about 69%, with a median duration of response of 23.8 months. Results also showed that CAR T cells with stronger early memory characteristics expanded more effectively and were associated with deeper and longer responses.
Key points
• Therapy studied: bb21217, a BCMA-targeted CAR T-cell therapy manufactured with the PI3K inhibitor bb007 to create memory-like T cells.
• Patient population: 72 patients with RRMM who had received multiple prior treatments.
• Trial design: Phase I, open-label, dose-escalation and expansion study (CRB-402 trial).
• Efficacy: Objective response rate of 69.4% and median duration of response of 23.8 months.
• Safety: Low incidence of severe toxicity, including three cases each of grade ≥3 cytokine release syndrome and neurotoxicity.
• Biologic insight: CAR T cells with an early memory-like phenotype showed stronger expansion and deeper responses.
• Clinical implication: Lower tumor burden and earlier disease stage at cell collection may improve outcomes.
Conclusion
Treatment with bb21217 demonstrated promising activity and manageable safety in patients with relapsed or refractory Multiple Myeloma. The therapy achieved high response rates and a relatively long median duration of response, suggesting that enriching CAR T cells with a memory-like phenotype using bb007 may improve persistence and effectiveness. Findings also highlight that patient factors such as tumor burden and prior treatments can influence outcomes. These results support continued development of bb21217 and emphasize the potential benefit of using CAR T-cell therapies earlier in the disease course.
Why this study matters
For patients, strategies that enhance CAR T-cell durability may translate into longer-lasting remissions and improved treatment options.
Reference:
Melissa Alsina, Nina Shah, Sundar Jagannath, Jonathan L. Kaufman, David Siegel, Nikhil C. Munshi, Jacalyn Rosenblatt, Yi Lin, Andrzej J. Jakubowiak, Benjamin A. Derman, Aojun Li, Pingping Mao, Maeva Fincker, Ashish Yeri, Nathan Martin, Timothy B. Campbell, Olivia Finney, Anna Truppel-Hartmann, Fabio Petrocca, Jesus G. Berdeja, Noopur Raje; Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy bb21217 for Relapsed and Refractory Multiple Myeloma: Results from the Phase I CRB-402 Study. Cancer Immunol Res 2026; https://doi.org/10.1158/2326-6066.CIR-24-0527 (https://aacrjournals.org/cancerimmunolres/article-abstract/doi/10.1158/2326-6066.CIR-24-0527/775250/Anti-B-cell-Maturation-Antigen-Chimeric-Antigen?redirectedFrom=fulltext)
U.S. Food and Drug Administration (FDA)
FDA approves Tec-Dara for the treatment of RRMM; Third FDA approval under the Commissioner’s National Priority Voucher Pilot Program
On Thursday, March 5, the U.S. Food and Drug Administration (FDA) (https://www.fda.gov/news-events/press-announcements/fda-grants-third-approval-under-national-priority-voucher-program)approved teclistamab in combination with daratumumab hyaluronidase-fihj (Tec-Dara) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy.
The decision was issued 55 days after filing — the agency’s third approval under the new Commissioner’s National Priority Voucher (CNPV) pilot program. (https://www.fda.gov/industry/commissioners-national-priority-voucher-cnpv-pilot-program)
The voucher for Tec-Dara was awarded by the FDA on December 15, 2025 (https://www.myeloma.org/news-events/multiple-myeloma-news/tecvayli-darzalex-faspro-cnpv-pilot-program), based on the results of the MajesTEC-3 trial, where Tec-Dara “showed significant improvements over the standard of care in both progression-free survival and overall survival,” while “reducing the risk of disease progression or death by 83% relative to the standard of care control arm,” states the FDA news release.
Confirmatory evidence was provided by the Phase 3 trial for Tecvayli’s (teclistamab-cqyv) existing indication as monotherapy — to be converted from accelerated to traditional approval.
Prescribing information
A boxed warning is included in the prescribing information for Tecvayli for “life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). CRS is a severe inflammatory response, which causes high fever, low blood pressure, and in some cases death. Because of these risks, Tec-Dara is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli-Talvey REMS, (https://www.tec-talrems.com/#Main)” said the FDA.
The most common side effects of Tec-Dara include: hypogammaglobulinemia (low antibody levels), upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia (fever), headache, nausea, gastroenteritis, and decreased weight.
Risk Evaluation and Mitigation Strategies (REMS)
The Risk Evaluation and Mitigation Strategy (REMS) (https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems) is “a drug safety program that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks.” Learn more about REMS by visiting the FDA website on Drug Safety and Availability.
References:
FDA Grants Third Approval Under the National Priority Voucher Program. (https://www.fda.gov/news-events/press-announcements/fda-grants-third-approval-under-national-priority-voucher-program) U.S. Food and Drug Administration News Release. March 5, 2026.
Commissioner's National Priority Voucher (CNPV) Pilot Program (https://www.fda.gov/industry/commissioners-national-priority-voucher-cnpv-pilot-program), U.S. Food and Drug Administration. Current as of February 9, 2026.
Risk Evaluation and Mitigation Strategies (REMS) (https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems). U.S. Food and Drug Administration. Current as of May 20, 2025.
European Medicines Agency (EMA)
Submitted to the EMA: Teclistamab monotherapy application for RRMM after at least one line of therapy
On Tuesday, March 10, Johnson & Johnson announced via press release that it has submitted a Type II variation application to the European Medicines Agency (EMA). The application seeks approval “for an indication extension of Tecvayli (teclistamab) as monotherapy for the treatment of adult patients with relapsed/refractory multiple myeloma (RRMM), who have received at least one prior therapy.”
According to Johnson & Johnson, “the application is supported by data from the Phase 3 MajesTEC-9 trial evaluating the efficacy and safety of teclistamab versus the standard of care of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in 614 patients with RRMM.”
Results show that teclistamab significantly improved outcomes compared with standard-of-care treatments when used as early as second-line therapy for multiple myeloma. It reduced the risk of disease progression or death by 71% and lowered the risk of death by 40%, even in patients whose disease was resistant to anti-CD38 monoclonal antibodies and lenalidomide.
The safety profile of teclistamab monotherapy was consistent with previous studies and manageable, with infections addressed through monitoring, immunoglobulin therapy, and preventive antimicrobial treatment.
Because of these strong results, the Independent Data Monitoring Committee recommended unblinding the trial early, and global regulatory submissions are planned with full results to be presented at a future medical meeting.
Reference:
TECVAYLI®(teclistamab) monotherapy application submitted to the EMA for relapsed/refractory multiple myeloma after at least one prior therapy. (https://www.jnj.com/media-center/press-releases/tecvayli-teclistamab-monotherapy-application-submitted-to-the-ema-for-relapsed-refractory-multiple-myeloma-after-at-least-one-prior-therapy) Johnson & Johnson press release. March 10, 2026.
For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom. (https://www.myeloma.org/news-events/multiple-myeloma-news)
The International Myeloma Foundation medical and editorial content team
Comprised of leading medical researchers, hematologists, oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the multiple myeloma treatment and care landscape.
Additionally, the content on this page is medically reviewed by myeloma physicians and healthcare professionals.
Medically reviewed on March 25, 2026.
This blog reflects medical guidance available at the time of review and is not routinely updated.