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

Scope and Methodology  
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from April-May 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 May 27, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.

Guidelines and Recommendations

Integrating Recent Evidence and Expert Perspectives Into the Management of Multiple Myeloma: Consensus Recommendations From the 2025 Bridging the Gaps Conference — American Journal of Hematology (April 2026)
 

What is the purpose of the consensus review?
To address uncertainty in sequencing and clinical application of therapies for multiple myeloma (MM), this review summarizes consensus recommendations from the 2025 Bridging the Gaps Consensus Conference. It reflects expert evaluation of available evidence and areas of clinical debate.

Summary
A panel of 16 US MM experts used a modified Delphi approach to review data and vote on 51 clinical questions, resulting in 11 consensus recommendations. These recommendations address smoldering MM (SMM), frontline therapy, transplant, maintenance, and relapsed/refractory disease (RRMM). Key themes include integration of quadruplet induction, individualized maintenance, and early referral for CAR-T therapy, alongside recognition of ongoing evidence gaps.

 
Key points

Scope: Encompasses the MM care continuum, including SMM and RRMM
Methodology: Modified Delphi process with expert consensus on 51 questions
Major Recommendations/Themes:
• Integration of quadruplet induction
• Individualized maintenance approaches
• Early referral for CAR-T therapy

Strengths
• Structured expert consensus process
• Broad clinical scope across treatment settings
• Focus on practical clinical considerations

Limitations
• Based on expert consensus where evidence may be limited
• Reflects interpretation of available data rather than definitive evidence
• Identifies areas requiring further investigation
 
Why this review matters
This consensus review provides expert-derived recommendations addressing key aspects of multiple myeloma management. It highlights integration of quadruplet induction, individualized maintenance, and early referral for CAR-T therapy as emerging themes. Ongoing evidence gaps remain, underscoring the need for further research to inform clinical decision-making.
 
 
Reference:
A.Chari, C.Costello, A.Krishnan, et al., “Integrating Recent Evidence and Expert Perspectives Into the Management of Multiple Myeloma: Consensus Recommendations From the 2025 Bridging the Gaps Conference,” American Journal of Hematology (2026): 1–11, https://doi.org/10.1002/ajh.70339. (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70339)

Validation and refinement of the new Consensus Genomic Staging (CGS) of high-risk multiple myeloma (HRMM) in relapsed and refractory patients treated with BCMA CAR-T — Blood Cancer Journal (April 2026)

What is the purpose of the study?
To evaluate the updated Consensus Genomic Staging (CGS) criteria for high-risk multiple myeloma (HRMM) in patients with relapsed and refractory multiple myeloma treated with BCMA CAR-T therapy; and to explore whether adding clinical factors could improve risk stratification.

Summary  
In this retrospective study of 158 patients with relapsed and refractory multiple myeloma, 47% were classified as high-risk using CGS criteria. High-risk patients had significantly shorter progression-free survival (PFS; HR 1.89, p=0.003) and overall survival (OS; HR 3.06, p<0.001) compared with standard-risk patients after BCMA CAR-T therapy. Elevated lactate dehydrogenase (LDH >210 U/L) and extramedullary disease (EMD) were independent adverse prognostic factors, and a proposed four-tier risk model incorporating these variables showed distinct differences in survival outcomes.
 
Key points
• Retrospective analysis of 158 patients with relapsed/refractory multiple myeloma treated with BCMA CAR-T
• 47% met criteria for high-risk multiple myeloma (HRMM) based on updated CGS
• HRMM associated with worse outcomes:
 - PFS: HR 1.89 (p=0.003)
 - OS: HR 3.06 (p<0.001)

• Independent adverse prognostic factors:
 - LDH >210 U/L
 - Extramedullary disease (EMD)

• Proposed four-group risk stratification model:
 - Low risk: PFS 35.0 months; 24-month OS 90%
 - Intermediate-low risk: PFS 19.6 months; OS 69%
 - Intermediate-high risk: PFS 10.4 months; OS 66%
 - High risk: PFS 6.6 months; OS 26%

Strengths
• Evaluates CGS criteria in a real-world BCMA CAR-T–treated population
• Identifies additional clinically relevant prognostic factors (LDH, EMD)

Limitations
• Retrospective design
• Moderate sample size
• No external validation of the proposed staging model
• Potential selection bias
  
Why this study matters
The updated CGS criteria are associated with differences in survival outcomes among patients with relapsed and refractory multiple myeloma treated with BCMA CAR-T therapy, supporting their clinical relevance. Incorporating LDH levels and extramedullary disease may improve risk stratification by identifying subgroups with markedly different PFS and OS. Prospective and external validation studies are needed to confirm the utility of this proposed staging approach.

Reference:
Gustine, J.N., Attar, N., Puliafito, B.R. et al. Validation and refinement of the new Consensus Genomic Staging (CGS) of high-risk multiple myeloma (HRMM) in relapsed and refractory patients treated with BCMA CAR-T. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01510-1 (https://www.nature.com/articles/s41408-026-01510-1)

Guidelines and consensus for minimal residual disease-adapted therapy in multiple myeloma from the Pan-Pacific multiple myeloma working group — Clinical Hematology International (May 2026)

What is the purpose of the clinical consensus?
This expert consensus provides evidence-based guidance on how minimal residual disease (MRD) assessment may be incorporated into the treatment evaluation and monitoring of patients with multiple myeloma (MM), particularly in the era of CD38-based therapies. The document addresses MRD-guided clinical decision-making, standardization of MRD detection methods, and emerging approaches for disease surveillance.
 
Summary
The consensus panel recommends incorporating MRD assessment into treatment evaluation for most patients with multiple myeloma who achieve complete remission (CR), particularly those receiving CD38-based therapies. The panel states that achieving and sustaining MRD negativity is strongly associated with improved prognosis and long-term outcomes, although MRD negativity does not necessarily indicate cure, especially in patients with ultra-high-risk disease. The recommendations support combining bone marrow MRD assessment with imaging and peripheral blood–based assays to provide a more comprehensive evaluation of disease status.
 
The panel also recommends tailoring the timing and frequency of MRD testing according to treatment phase, including regular monitoring during maintenance therapy. Next-generation flow (NGF) and next-generation sequencing (NGS) were considered interchangeable specifically for prognostic assessment of MRD status. Peripheral residual disease (PRD) detection was identified as a promising future direction for less invasive disease monitoring, although current limitations include possible discordance with bone marrow–based MRD assessment. The consensus further notes that implementation in routine clinical practice may vary because of differences in treatment access, healthcare infrastructure, and MRD testing practices.
 
Key points
• MRD assessment is recommended as part of treatment evaluation for most patients with MM who achieve complete remission, particularly those receiving CD38-based therapy.
• Achieving and maintaining MRD negativity was strongly associated with improved prognosis and long-term outcomes in patients receiving CD38-based therapies.
• MRD negativity does not necessarily indicate cure, particularly in patients with ultra-high-risk disease (≥2 high-risk cytogenetic abnormalities).
• The panel recommends combining:
 - Bone marrow MRD assessment
 - Imaging studies
 - Peripheral blood–based assays to improve disease evaluation

• Suggested MRD monitoring during maintenance therapy:
 - Every 6 months for MRD-positive patients
 - Every 12 months for MRD-negative patients

• Dynamic MRD monitoring may support earlier therapeutic decisions, including:
 - Early intervention for MRD resurgence
 - Treatment intensification for persistent MRD

• NGF and NGS were considered interchangeable specifically for prognostic assessment of MRD status.
• Peripheral residual disease (PRD) testing is being explored as a less invasive future monitoring approach, although false-negative results compared with bone marrow testing remain a concern.
 
Strengths
• Provides practical, evidence-based guidance for integrating MRD assessment into MM management.
• Addresses treatment goals, maintenance strategies, standardized MRD testing, and emerging technologies.
• Emphasizes risk-adapted and personalized disease monitoring approaches.
 
Limitations
• Recommendations are based on expert consensus and available evidence, with some MRD-guided strategies not yet fully validated in prospective clinical trials.
• Real-world implementation may differ from clinical trial settings because of variability in patient populations, access to therapies, and consistency of MRD testing.
• MRD negativity may not fully overcome poor prognosis in patients with ultra-high-risk disease.
• Peripheral blood–based MRD approaches currently have limitations, including potential false-negative findings relative to bone marrow assessment.
• Recommendations may reflect regional clinical practices and healthcare infrastructure in the Pan-Pacific region and may require adaptation in other healthcare settings.
 
Why this consensus matters
This expert consensus supports incorporating MRD assessment into treatment evaluation and disease monitoring for patients with multiple myeloma, particularly in the context of CD38-based therapies. Sustained MRD negativity was associated with improved prognosis, and dynamic MRD monitoring may help support more individualized treatment decisions and risk stratification.
 
The document also highlights the importance of standardized MRD assessment methods and continued development of less invasive monitoring technologies such as peripheral blood–based detection. Further prospective validation and broader international collaboration will be important to clarify how MRD-guided strategies should be applied across diverse clinical settings.
 
Reference:
Chen W, Cai Z, Chim CS, et al. Guidelines and consensus for minimal residual disease-adapted therapy in multiple myeloma from the Pan-Pacific multiple myeloma working group. Clinical Hematology International. 2026;8(2):7-25. doi:10.46989/001c.160933 (https://chi.scholasticahq.com/article/160933-guidelines-and-consensus-for-minimal-residual-disease-adapted-therapy-in-multiple-myeloma-from-the-pan-pacific-multiple-myeloma-working-group)

Experiences and expert panel consensus on bridging therapy before anti-BCMA CAR-T cell therapy in multiple myeloma — Bone Marrow Transplantation (May 2026)

What is the purpose of the guidance?
To provide expert consensus guidance on the use of bridging therapy (BT) before anti-BCMA chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed/refractory multiple myeloma (RRMM), particularly heavily pretreated patients. The guidance focuses on optimizing BT selection, balancing efficacy and safety, and evaluating emerging options such as the GPRC5D×CD3 bispecific antibody talquetamab.
 
Summary
A panel of 10 European hematology experts with experience in CAR-T therapy and novel multiple myeloma treatments participated in qualitative interviews and a structured consensus workshop in 2025. The discussions addressed BT goals, patient eligibility, treatment duration, regimen selection, safety management, and strategies for difficult-to-treat populations including patients with extramedullary disease (EMD), renal impairment, and central nervous system involvement.
 
The experts agreed that BT should reduce tumor burden, maintain or improve performance status, and avoid toxicities that could delay CAR-T infusion. Talquetamab was discussed as a potential BT option based on expert clinical experience, clinical trial findings, and retrospective real-world evidence showing overall response rates (ORRs) of 62–100% in retrospective studies and 67–74% in the MonumenTAL-1 trial, with median time to first response of approximately 1.2–1.3 months. The publication also noted that talquetamab-associated adverse events, including cytokine-release syndrome (CRS), taste changes, skin reactions, and occasional immune effector cell-associated neurotoxicity syndrome (ICANS), require monitoring and supportive care.
 
Key points
• BT was defined as treatment administered after leukapheresis and before lymphodepleting chemotherapy preceding anti-BCMA CAR-T infusion.
• Experts recommended considering BT for most patients undergoing anti-BCMA CAR-T therapy, including those with slowly progressing disease.

• Main short-term goals of BT:
 - Reduce tumor burden
 - Maintain organ function and performance status
 - Avoid toxicities or cytopenias that could delay CAR-T therapy

• A ≥partial response was considered an appropriate practical target for most patients during BT.
• Typical BT duration was 6–8 weeks (1–2 cycles), with recommendations to keep therapy “as short as possible” but “as long as necessary.”
• Talquetamab, a GPRC5D×CD3 bispecific antibody, was highlighted by the expert panel as a potential BT option, particularly for heavily pretreated patients with limited remaining therapies.

• In the MonumenTAL-1 study:
 - ORR was 67–74%
 - Median duration of response reached 17.5 months with 0.8 mg/kg every-other-week dosing
 - Median time to first response was 1.2–1.3 months

• Retrospective real-world studies reported talquetamab BT ORRs ranging from 62–100%, with most reported patients successfully proceeding to CAR-T infusion.

• Reported talquetamab-associated adverse effects included:
 - Taste changes
 - Skin reactions
 - Cytokine-release syndrome (CRS)
 - Low rates of immune effector cell-associated neurotoxicity syndrome (ICANS)

• Anti-BCMA BT before anti-BCMA CAR-T therapy was discouraged because of concerns regarding resistance and uncertain effects on CAR-T efficacy.
• Additional BT options discussed included chemotherapy, immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, venetoclax for t(11;14) disease, and BRAF-targeted therapies for BRAF-mutated disease.
 
Strengths
• Included expert input from multiple European centers experienced in RRMM and CAR-T therapy.
• Addressed practical clinical management issues not fully covered by existing guidance documents.
• Included discussion of difficult-to-treat patient populations and emerging therapies.
 
Limitations
• Recommendations were primarily based on expert consensus, retrospective studies, and clinical experience rather than prospective randomized clinical trials.
• No standardized or universally approved BT regimen currently exists.
• Evidence supporting talquetamab as BT remains limited and requires further prospective evaluation.
 
Why this consensus guidance matters
This expert consensus emphasizes that bridging therapy is an important component of anti-BCMA CAR-T treatment for relapsed/refractory multiple myeloma and should balance disease control with preservation of eligibility for CAR-T infusion. The panel supported individualized BT selection based on disease characteristics, prior therapies, and patient condition, while minimizing treatment-related toxicities.
 
Talquetamab was identified by the expert panel as a promising bridging therapy option for heavily pretreated patients because of its rapid response rates and activity observed in clinical trials and retrospective real-world studies, although prospective studies are still needed to confirm its optimal role before anti-BCMA CAR-T therapy.
 
Reference:
Rasche, L., Krauth, M.T., Agis, H. et al. Experiences and expert panel consensus on bridging therapy before anti-BCMA CAR-T cell therapy in multiple myeloma. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02905-1 (https://www.nature.com/articles/s41409-026-02905-1)
 

Review

Circulating Tumor Cells in Multiple Myeloma: From Peripheral Clues to Central Insights — American Journal of Hematology (April 2026)
 

What is the purpose of the review?

To examine the biological and clinical relevance of circulating tumor cells (CTC) in multiple myeloma (MM), including their origin, detection, and role in disease monitoring; and to evaluate how CTC analysis may contribute to prognostication and personalized clinical decision-making.
 
Summary  
Circulating tumor cells (CTC) in MM arise from bone marrow (BM) plasma cells through transcriptional and functional adaptations that enable detachment, survival in circulation, and dissemination, while remaining largely genomically and transcriptionally similar to BM counterparts. Molecular profiling demonstrates that CTC can reflect the mutational landscape of MM and occasionally capture additional subclonal alterations, providing insight into spatial heterogeneity not fully represented by single-site BM biopsy. Advances in detection methods, particularly next-generation flow (NGF) cytometry and sequencing approaches, have improved sensitivity, although technical variability and lack of standardization persist. Clinically, CTC quantification at diagnosis is an independent prognostic marker, with increasing levels associated with inferior progression-free survival (PFS) and overall survival (OS), supported by correlative analyses from studies such as FORTE and PERSEUS. CTC also provide complementary information for monitoring disease dynamics and minimal residual disease (MRD), though their current sensitivity is lower than BM-based methods and they are not a substitute for marrow assessment.
 
Key points
 
Biological insights
• CTC originate from BM plasma cells via adaptive transcriptional changes enabling circulation and dissemination.
• They are highly similar to BM cells, with limited differences often reflecting patient-specific biology rather than a distinct circulating clone.
• CTC may reveal additional subclonal mutations (e.g., TP53 alterations), contributing to understanding spatial heterogeneity.
 
Technological advances
• NGF cytometry enables highly sensitive detection (up to ~10⁻⁶).
• Sequencing methods (ULP-WGS, single-cell RNA-seq) allow genomic and transcriptomic profiling but face limitations such as low input material, amplification bias, and technical artifacts.
 
Clinical relevance
• CTC levels at diagnosis are independently associated with prognosis (PFS, OS).
• Prognostic thresholds are not standardized and vary across studies (~0.01% to ≥0.1%), reflecting methodological and clinical differences.
• CTC burden is best interpreted as a continuous biomarker, with higher levels indicating progressively worse outcomes.
• Evidence from trials (e.g., FORTE, PERSEUS) is based on exploratory/correlative analyses, supporting but not definitively establishing clinical utility.

- Applications across disease spectrum
- Detectable in precursor conditions (MGUS, SMM) and associated with increased risk of progression, supporting a continuum of disease dissemination.
 
MRD monitoring
• CTC detection provides complementary, systemic information and may identify residual disease not captured by localized BM sampling.
• However, CTC assays currently have lower sensitivity than BM-based MRD methods and lack standardized thresholds.
• Persistent CTC after treatment is prognostically adverse, even in BM-MRD–negative patients, likely reflecting underlying disease biology rather than superior detection sensitivity.

Strengths
• Minimally invasive “liquid biopsy” enabling repeated, real-time monitoring.
• Captures spatial heterogeneity and systemic disease features.
 
Limitations
• Very low abundance, particularly during treatment.
• Lack of assay standardization and validated clinical thresholds.
• Technical challenges in molecular profiling (e.g., low DNA/RNA input, need for amplification).
• Not yet suitable to replace BM-based MRD assessment.
 
Why this study matters

CTC analysis in MM offers a minimally invasive approach that reflects disease burden, clonal heterogeneity, and prognostic risk, with consistent evidence supporting its role as an independent biomarker at diagnosis. However, variability in thresholds, reliance on exploratory clinical data, and lower sensitivity for MRD detection currently limit its standalone clinical application. Further prospective studies and methodological standardization are required to define its role in risk stratification and MRD-guided treatment strategies.
 
Reference:
B. Podvin, B. Paiva, I. M. Ghobrial, and S. Manier, “Circulating Tumor Cells in Multiple Myeloma: From Peripheral Clues to Central Insights,” American Journal of Hematology (2026): 1–14, https://doi.org/10.1002/ajh.70326 (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70326)

Review of the first on-body injector (obi) for the subcutaneous delivery of an oncology drug: isatuximab in multiple myeloma — Expert Opinion on Drug Delivery (April 2026)
 

What is the purpose of the review?
To summarize the development and available clinical evidence for subcutaneous isatuximab delivered via an on-body injector (OBI) in the treatment of multiple myeloma; and to evaluate data from clinical trials and literature regarding its safety, efficacy, and practical considerations compared with intravenous and manual subcutaneous administration methods.

Summary  
The review describes the investigational use of isatuximab administered subcutaneously via an on-body injector (OBI) in patients with multiple myeloma (MM) as an alternative to intravenous infusion and manual subcutaneous injection. Evidence from clinical studies, including the phase 3 IRAKLIA trial and phase 2 IZALCO trial and ISASOCUT trial, indicates that SC OBI administration demonstrated efficacy and safety comparable to established IV and SC manual push approaches. Across trials, injection success rates were reported as nearly 100%, though findings are primarily based on controlled clinical trial settings rather than routine clinical practice. The OBI approach may offer practical advantages such as reduced need for manual injection handling and the possibility of shorter or more flexible administration workflows, but these outcomes are largely based on trial experience and expert interpretation rather than fully validated real-world data. Overall, the evidence suggests feasibility and potential utility of this delivery method, with ongoing studies evaluating its broader clinical application.
 
Key points
 
Strengths
• Clinical trials show efficacy and safety comparable to IV and manual SC administration.
• High reported injection success rates (approximately near 100%) in trial settings.
• Potential to streamline administration processes by reducing manual injection requirements.
• May offer improved convenience features such as hands-free delivery and a small, hidden needle design.
 
Limitations / Considerations
• Evidence is primarily derived from clinical trials rather than real-world implementation.
• Operational and logistical considerations (training, workflow integration, storage, and disposal) remain important.
• Cost implications of device adoption and system integration are not fully defined.
• Broader outcomes such as long-term patient-reported benefits and system-wide efficiency gains require further validation.
 
Why this review matters
Current clinical evidence supports the feasibility of subcutaneous isatuximab delivery via an on-body injector with comparable efficacy and safety to established administration methods in trial settings. However, most advantages remain investigational and dependent on controlled study environments, with limited real-world validation to date. Further research is needed to confirm its practical benefits and long-term impact in routine clinical care.
 
 
Reference:
Ocio, E. M., Parmar, G., Mateos, M. V., Leleu, X., Buck, T. T., Tan, C. R., … Moreau, P. (2026). Review of the first on-body injector (obi) for the subcutaneous delivery of an oncology drug: isatuximab in multiple myeloma. Expert Opinion on Drug Delivery. https://doi.org/10.1080/17425247.2026.2659263 (https://www.tandfonline.com/doi/full/10.1080/17425247.2026.2659263#d1e497)

Environmental exposures and multiple myeloma risk: A contemporary review of epidemiologic associations and mechanistic plausibility — Blood Reviews (April 2026)
 

What is the purpose of the review?
To synthesize current epidemiologic and mechanistic evidence examining associations between environmental exposures and multiple myeloma (MM) risk; and to evaluate limitations in study design and exposure assessment and highlights future directions to improve causal understanding through more precise and biologically integrated research approaches.
 
Summary
The review summarizes epidemiologic studies that have reported associations between multiple myeloma risk and environmental or occupational exposures, including pesticides, dioxins, combustion byproducts, and disaster-related exposures. While some exposures show relatively consistent associations across cohorts, the evidence is heterogeneous and largely observational, limiting causal inference. Experimental studies suggest possible biological mechanisms such as oxidative stress, DNA damage, and immune-related signaling pathways, which may provide biological plausibility but do not confirm causation. The authors emphasize that current exposure data are often limited by misclassification, lack of dose and timing resolution, and inconsistent definitions, and that longitudinal, biospecimen-linked studies are needed to better clarify disease mechanisms and progression.
 
Key points
• Most consistently reported associations:
 - Pesticides and dioxins show the most reproducible epidemiologic associations with MM risk
 - Firefighting, disaster-related exposures, and combustion byproducts are also frequently reported

• Biological plausibility (not causality):
 - Proposed mechanisms include oxidative stress, DNA damage, and immune dysregulation
 - Aryl hydrocarbon receptor signaling is suggested as a potential pathway for some exposures

Major limitations in current evidence
• Predominantly observational studies limit causal inference
• Exposure misclassification due to self-reporting and static residential/occupational data
• Inability to precisely measure dose, timing, or life-course exposure windows
• Heterogeneous exposure definitions across studies
• Confounding from occupational, socioeconomic, and environmental factors
• Limited ability to link exposures to transitions between MGUS, smoldering myeloma, and MM

Strengths of the literature base
• Integration of epidemiologic and mechanistic evidence
• Identification of recurrent exposure signals across multiple independent cohorts
 • Emerging use of geospatial modeling and multi-omic approaches to improve exposure resolution
 
Why this review matters
The available evidence suggests that certain environmental exposures, particularly pesticides and dioxins, are repeatedly associated with multiple myeloma risk, but the overall evidence remains observational and not sufficient to establish causality. Mechanistic studies provide supportive biological plausibility, though they do not confirm direct causal pathways. Addressing key limitations in exposure measurement, study design, and longitudinal data integration will be necessary to clarify whether and how environmental factors contribute to multiple myeloma development and progression.
 
 
Reference:
Maria Victoria del Rosal, Mike Z. He, Sundar Jagannath, Samir Parekh, Itai Kloog, Manish Arora, Santiago Thibaud, Environmental exposures and multiple myeloma risk: A contemporary review of epidemiologic associations and mechanistic plausibility, Blood Reviews, 2026, 101392, ISSN 0268-960X, https://doi.org/10.1016/j.blre.2026.101392 (https://www.sciencedirect.com/science/article/pii/S0268960X26000317).

Bone-modifying therapy in multiple myeloma: a comprehensive review — Frontiers in Oncology (April 2026) 

What is the purpose of the review?
To examine the mechanisms underlying bone disease and skeletal-related events in multiple myeloma and summarize current evidence-based, guideline-recommended treatments. It also evaluates emerging therapies, biomarkers, and cost-effectiveness considerations to identify gaps in clinical management.

Summary
Multiple myeloma–related bone disease is driven by disrupted bone remodeling involving cytokines and signaling pathways, leading to osteolytic lesions and skeletal-related events. Standard treatments include bisphosphonates (e.g., zoledronic acid, pamidronate) and denosumab, with guideline recommendations emphasizing monitoring of renal function, calcium/vitamin D levels, and risk of osteonecrosis of the jaw. Emerging therapies (e.g., monoclonal antibodies, anabolic agents, and microRNA-based approaches) show potential but remain limited by small studies, safety concerns, and insufficient randomized clinical trial evidence.

Key points
• Disease mechanism: Bone disease in multiple myeloma results from increased osteoclast activity and suppressed osteoblast function mediated by cytokines and molecular pathways.

• Current treatments:
 - Bisphosphonates and denosumab are FDA-approved and guideline-recommended.
 - Denosumab is preferred in renal impairment but requires monitoring for hypocalcemia.

• Guideline recommendations:
 - Baseline dental evaluation and avoidance of invasive dental procedures.
 - Routine monitoring of calcium, vitamin D, and renal function.
 - Treatment duration typically ~2 years, with risk-adapted adjustments.

• Efficacy and safety:
 - Zoledronic acid may reduce mortality and is cost-effective.
 - Adverse events include osteonecrosis of the jaw and renal toxicity.

• Emerging therapies:
 - Agents such as narlumosbart, romosozumab, sotatercept, and BHQ880 are under investigation.
 - MicroRNAs show promise as biomarkers but lack clinical applicability due to safety and technical limitations.

• Cost-effectiveness:
 - Zoledronic acid is generally more affordable.
 - Denosumab may be cost-effective in some regions, but access varies widely.
 
Strengths
• Comprehensive overview of pathophysiology, guidelines, and treatment options.
• Inclusion of emerging therapies and economic considerations.
 
Limitations
• Limited high-quality randomized clinical trial data for newer therapies.
• Some guideline recommendations may be outdated.
• Evidence for novel biomarkers and treatments is based on small or early-phase studies.
 
Why this review matters
Bone disease in multiple myeloma remains a major contributor to morbidity and mortality, with bisphosphonates and denosumab forming the cornerstone of treatment. While denosumab may be advantageous in patients with renal impairment, both drug classes require careful monitoring due to adverse effects. Advances in biomarkers and novel therapies offer potential for personalized treatment, but robust clinical trial evidence is still needed to guide practice.
 
Reference:
Baljevic M (2026) Bone-modifying therapy in multiple myeloma: a comprehensive review. Front. Oncol. 16:1722230. doi: 10.3389/fonc.2026.1722230 (https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1722230/full)

How Laboratory Innovations Are Shaping the Future of Multiple Myeloma Care — Cancers (April 2026)
 

What is the purpose of the review?
To examine emerging laboratory technologies for improving the diagnosis and monitoring of Multiple Myeloma. It focuses on tools that enhance detection sensitivity, assess measurable residual disease (MRD), and support more personalized treatment strategies.

Summary  
The review describes advances beyond traditional biomarkers such as β2-microglobulin, albumin, and serum protein electrophoresis, highlighting high-throughput and minimally invasive approaches. These include liquid biopsy techniques (circulating tumor cells, cell-free DNA/RNA), mass spectrometry for detecting monoclonal proteins, and single-cell and multi-omics technologies for MRD assessment. The integration of artificial intelligence and machine learning is also discussed as a way to improve interpretation of complex clinical and biological data.
 
Key points
• Innovative diagnostics: Liquid biopsy and mass spectrometry enable more sensitive and less invasive detection of disease.
• MRD assessment: High-throughput and single-cell technologies improve detection of measurable residual disease beyond conventional bone marrow methods.
• Personalized care: Multi-omics approaches and AI-driven tools may enhance risk stratification and treatment decisions.

Strengths
• Comprehensive overview of emerging technologies
• Highlights integration of advanced diagnostics with clinical care

Limitations
• High cost and need for specialized equipment and expertise
• Limited validation in large prospective clinical trials
• Challenges in standardization, regulatory approval, and workflow integration
• Complex data analysis and logistical constraints

Why this review matters
Emerging laboratory technologies have the potential to significantly improve the diagnosis, monitoring, and risk assessment of Multiple Myeloma by providing more sensitive and comprehensive disease evaluation. However, broader clinical adoption requires further validation, standardization, and demonstration of clinical benefits in prospective studies. Addressing these challenges may enable more precise and personalized patient management in the future.
 
Reference:
Caetano, J., Pires, A. M., Costa, C., Bergantim, R., Roque, A., Ferraz, P., Cunha, M. R., Bolli, N., Puig, N., & João, C. (2026). How Laboratory Innovations Are Shaping the Future of Multiple Myeloma Care. Cancers, 18(8), 1275. https://doi.org/10.3390/cancers18081275 (https://www.mdpi.com/2072-6694/18/8/1275)

The Role of Genomics in the Development and Treatment of Multiple Myeloma: Understanding the Challenges and Opportunities — OncoTargets and Therapy (April 2026)
 

What is the purpose of the review?
To examine recent advances in the genomics of multiple myeloma and how these discoveries are shaping clinical practice. It aims to clarify how genetic abnormalities influence disease behavior, prognosis, and treatment strategies.

Summary
Multiple myeloma is a genetically heterogeneous hematologic cancer characterized by abnormal plasma cells, bone lesions, and monoclonal immunoglobulins. Advances in next-generation sequencing and single-cell technologies have identified key driver mutations (e.g., NRAS/KRAS, TP53, MYC), copy number variations such as 1q21 amplification, and epigenetic changes that influence disease progression and treatment response. These genomic insights are increasingly applied to risk stratification, treatment selection, and minimal residual disease (MRD) monitoring, while emerging approaches like liquid biopsy and targeted therapies show potential but require further validation.
 
Key points
• Genetic heterogeneity: Major contributor to differences in prognosis, treatment response, and drug resistance.
• Driver mutations: Includes NRAS/KRAS, TP53, and MYC, with ongoing discovery of additional genomic and epigenetic regulators.
• High-risk abnormalities: Examples include +1q amplification and del(17p), associated with poorer outcomes.
• Clinical applications: Genomics informs risk stratification, therapy selection, MRD monitoring, and relapse prediction.
• Emerging tools: Liquid biopsy (ctDNA, circulating tumor cells, miRNAs) offers a less invasive alternative to bone marrow MRD testing but currently has lower sensitivity.
• Therapeutic developments: Targeted therapies (e.g., for BRAF V600E), HDAC inhibitors, and CELMoDs show promise.
• Strengths: Comprehensive integration of genomic, epigenetic, and clinical data; highlights translational relevance.
• Limitations: Challenges include invasive MRD testing, limited sensitivity of blood-based assays, small sample sizes in studies, technical variability, and insufficient external validation of multi-omics models.
 

Why this review matters
Genomic research has substantially improved understanding of multiple myeloma biology, enabling more precise risk assessment and guiding targeted treatment strategies. While promising advances such as liquid biopsy and multi-omics integration are emerging, technical limitations and validation challenges remain barriers to routine clinical use. Continued research is needed to translate genomic data into reliable, widely applicable tools that improve patient outcomes.
 
Reference:
Ren L, Ru F, Zhang K. The Role of Genomics in the Development and Treatment of Multiple Myeloma: Understanding the Challenges and Opportunities. Onco Targets Ther. 2026;19:595435
https://doi.org/10.2147/OTT.S595435 (https://www.dovepress.com/the-role-of-genomics-in-the-development-and-treatment-of-multiple-myel-peer-reviewed-fulltext-article-OTT)

Access to Bispecific Therapies for Multiple Myeloma: An Overview of Barriers and Emerging Solutions — Clinical Lymphoma Myeloma and Leukemia (April 2026)
 

What is the purpose of the overview?
To examine barriers that limit patient access to bispecific T-cell engager therapies for relapsed/refractory multiple myeloma (RRMM) and evaluate strategies to improve equitable access. It aims to explain how disparities in healthcare delivery affect the real-world effectiveness of these treatments.

Summary  
Bispecific T-cell engagers and other immunotherapies have improved outcomes in RRMM, including response rates, progression-free survival, and overall survival, but their benefits depend on patient access. Barriers such as geographic distance from specialized centers, financial burden, limited provider experience, and systemic healthcare inequalities (particularly affecting underserved and racially diverse populations) restrict access to these therapies. This overview discusses potential solutions, including expanding provider education, improving healthcare infrastructure, and addressing socioeconomic disparities to enhance equitable treatment delivery.
 
Key points
• Bispecific antibodies (e.g., teclistamab, elranatamab, talquetamab, linvoseltamab) are effective treatments for RRMM and can often be administered in outpatient settings.
• Access to these therapies is limited by geographic, socioeconomic, patient-level, and health system–level barriers.
• Disparities disproportionately affect underserved and racially/ethnically diverse populations, contributing to poorer outcomes.
• Use of bispecific therapies is more common in academic centers than community settings due to differences in experience and infrastructure.
• Strategies to improve access include provider training, expanding treatment availability, and addressing financial and systemic inequities.
 
Strengths
• Comprehensive overview of multiple real-world barriers affecting access to novel therapies.
• Highlights disparities and proposes evidence-based strategies to improve equity.
 
Limitations
• Narrative review without new primary clinical data.
• Does not quantify the relative impact of each barrier or evaluate specific interventions prospectively.

Why this overview matters
Bispecific T-cell engager therapies offer significant clinical benefits for patients with RRMM, but access barriers limit their real-world impact. Addressing geographic, financial, and systemic inequities, along with improving provider familiarity and infrastructure, is essential to ensure broader and more equitable use. Efforts to reduce disparities may improve outcomes across diverse patient populations.
 
Reference:
Emmanuel Ekpenyong, Maryam Mohsin, Samer Al Hadidi, Sarvari V Yellapragada, Access to Bispecific Therapies for Multiple Myeloma: An Overview of Barriers and Emerging Solutions, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.04.010 (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(26)00109-6/abstract).
 

Implementation of a Model Program at an Independent Community Oncology Practice for the Outpatient Administration of B-Cell Maturation Antigen–Directed Bispecific Antibody Step-Up Doses — JCO Oncology Practice (April 2026)
 

What is the purpose of the review?
To describe the development and implementation of an outpatient (OP) program for administering B-cell maturation antigen (BCMA)-CD3 bispecific antibodies (BsAbs) in patients with relapsed or refractory multiple myeloma. It aims to share real-world clinical experience and outline the feasibility and operational considerations of delivering step-up dosing (SUD) regimens outside the hospital setting.

Summary
The program at New England Cancer Specialists (NECS) presents a structured outpatient care model that includes patient selection, caregiver involvement, education, and coordinated toxicity monitoring for therapies such as elranatamab. Patients undergoing SUD are monitored through scheduled follow-up and home-based vital sign tracking to identify adverse events such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). This descriptive, experience-based report suggests that outpatient administration is feasible with appropriate infrastructure, though it does not provide formal comparative safety or efficacy outcomes.
 
Key points
• Descriptive Design: This is an experience-based report outlining program structure and workflow, not a controlled clinical trial.
• Feasibility: Outpatient administration of BCMA-CD3 BsAbs (e.g., elranatamab) appears feasible with structured protocols and monitoring.
• Safety Approach: Risk mitigation relies on step-up dosing, premedications, caregiver support, and frequent toxicity assessments for CRS and ICANS.
• Access and Convenience: OP programs may reduce healthcare utilization and improve access, especially for rural or underserved populations.
• Operational Requirements: Successful implementation requires multidisciplinary coordination, standardized workflows, and collaboration with local hospitals.
• Ongoing Research: Prospective clinical trials are underway to more rigorously evaluate outpatient use of BsAbs.
 
Strengths
• Provides detailed real-world implementation framework in a community oncology setting
• Emphasizes practical considerations for safety monitoring and care coordination
• Addresses barriers to access in rural populations
 
Limitations
• Descriptive and non-comparative; lacks quantitative safety and efficacy data
• Based on a single institutional experience, which may limit generalizability
• Limited evidence for higher-risk patient groups
 
Why this review matters
This experience-based report indicates that outpatient administration of BCMA-directed bispecific antibodies for multiple myeloma is feasible when supported by careful patient selection, education, and structured monitoring systems. While the approach may improve access and reduce reliance on inpatient care, the findings are not derived from formal clinical evaluation. Further prospective studies are needed to establish safety, effectiveness, and best practices across broader patient populations.
 
Reference:
Yonatan Resnick et al. Implementation of a Model Program at an Independent Community Oncology Practice for the Outpatient Administration of B-Cell Maturation Antigen–Directed Bispecific Antibody Step-Up Doses. JCO Oncol Pract 0, OP-25-00585 DOI:10.1200/OP-25-00585 (https://ascopubs.org/doi/10.1200/OP-25-00585)

Defining High-Risk Disease Biology in Multiple Myeloma: A Narrative Review — Blood and Lymphatic Cancer: Targets and Therapy (April 2026)
 

What is the purpose of the review?
To evaluate the biological determinants of high-risk multiple myeloma (MM) and their role in improving risk stratification, prognosis, and treatment selection. It focuses on integrating genomic, proliferative, and disease dissemination factors with evolving clinical frameworks to guide precision-based management.

Summary
High-risk MM is defined by three major biological domains: molecular/genomic abnormalities (e.g., IgH translocations, del(17p), TP53 mutation, gain(1q)), increased proliferative capacity (elevated S-phase fraction), and extramedullary disease biology, including circulating tumor cells and soft-tissue involvement. The 2025 IMS/IMWG framework incorporates these features into a standardized risk model, while measurable residual disease (MRD) provides dynamic, real-time prognostic refinement during treatment. Emerging approaches, including comprehensive molecular profiling and AI-driven data integration, aim to further individualize risk assessment and therapy.

Key points
• Core determinants of high-risk MM:
 - Genomic abnormalities (e.g., del(17p), TP53 mutation, 1q gain, high-risk translocations) strongly predict poor outcomes.
 - Increased tumor proliferation (S-phase ≥2%) is independently associated with shorter progression-free survival (1.4 vs. 2.9 years) and overall survival (3.9 vs. 9.2 years).
 - Extramedullary disease and circulating tumor cells indicate aggressive, marrow-independent disease with inferior prognosis.

• Risk stratification advances:
 - The 2025 IMS/IMWG framework standardizes high-risk classification, including “double-hit” and “triple-hit” disease.
 - MRD negativity (sensitivity up to 10⁻⁶) is a strong predictor of improved outcomes, though relapse risk persists in ultra–high-risk subgroups.

• Clinical implications:
 - High-risk patients benefit from intensified treatment strategies (e.g., quadruplet regimens, transplant, prolonged maintenance).
 - Risk stratification informs clinical trial enrollment and use of novel therapies (e.g., CAR-T, T-cell engagers).

Strengths
• Comprehensive integration of genomic, functional, and clinical risk factors.
• Incorporation of both baseline and dynamic (MRD-based) risk assessment.
• Inclusion of emerging technologies and future directions.

Limitations
• Some biomarkers and technologies (e.g., advanced sequencing, AI models) are not yet widely standardized or accessible.
• Heterogeneity in outcomes persists despite improved classification systems.
• Limited prospective validation for certain novel risk markers and combined models.
 
Why this review matters
High-risk multiple myeloma is driven by complex interactions between genomic abnormalities, tumor proliferation, and extramedullary disease biology, all of which contribute to adverse clinical outcomes. The 2025 IMS/IMWG framework and MRD-based dynamic assessment improve risk stratification and guide treatment decisions, but challenges remain in implementation and standardization. Continued advances in molecular profiling and data integration are expected to enhance precision medicine approaches and improve patient outcomes.
 
Reference:
Aljumaa, M., Hamam Refai, H., Chawla, Y., & Gonsalves, W. I. (2026). Defining High-Risk Disease Biology in Multiple Myeloma: A Narrative Review. Blood and Lymphatic Cancer: Targets and Therapy, 16. https://doi.org/10.2147/BLCTT.S586948 (https://www.tandfonline.com/doi/full/10.2147/BLCTT.S586948)
 

BCMA-directed CAR-T cell therapy in relapsed/refractory multiple myeloma: efficacy, safety, survival, and future directions – A systematic review and meta-analysis — Current Problems in Cancer (May 2026)

What is the purpose of the review?
To systematically evaluate the efficacy and safety of BCMA-directed CAR-T cell therapy in adults with relapsed or refractory multiple myeloma (RRMM). It seeks to provide pooled estimates of response rates and treatment-related toxicities across prospective clinical trials.

Summary
This meta-analysis included 14 prospective trials with 1,278 heavily pretreated RRMM patients receiving BCMA-targeted CAR-T therapy. The pooled overall response rate (ORR) was 86% (95% CI: 80–90%), indicating strong antitumor activity, while severe neurotoxicity (grade ≥3 ICANS) was uncommon at 3%. However, treatment-related mortality was 5%, and high-grade hematologic toxicities were frequent, highlighting important safety concerns despite high efficacy.
 
Key points
 
• Efficacy
 - High pooled ORR: 86% (95% CI: 80–90%)
 - Effective in patients with 3–8 prior treatment lines

• Safety
 - Low incidence of severe neurotoxicity (ICANS): 3%
 - Treatment discontinuation due to toxicity: 4%
 - Treatment-related mortality (TRM): 5%
 - Frequent grade ≥3 hematologic toxicities (e.g., neutropenia, anemia, thrombocytopenia)

• Clinical Insights
 - Cytokine release syndrome (CRS) common but usually mild
 - Infections and prolonged cytopenias are key contributors to serious complications and mortality

Strengths
• Inclusion of prospective interventional trials
• Large pooled sample size (n=1,278)
• Robust statistical methods (heterogeneity, sensitivity analyses)

Limitations
• Predominance of single-arm, early-phase trials
• High heterogeneity (I² = 75.9% for ORR)
• Limited survival data (e.g., progression-free survival, overall survival)
• Potential publication bias and limited generalizability to real-world populations
 

Why this review/meta-analysis matters
BCMA-directed CAR-T cell therapy demonstrates substantial efficacy in heavily pretreated RRMM, with high response rates and low incidence of severe neurotoxicity. However, the risk of treatment-related mortality and frequent severe hematologic toxicities remains clinically significant. These findings support its role as an important treatment option while emphasizing the need for careful patient selection and improved toxicity management strategies.
 
 
Reference:
Muhammad Shaheer Mannan, Adeena Musheer, Muhammad Waqas Khan, Hur Abbas, Sheikh Abdul Qadir Jillani, Ali Shan Hafeez, BCMA-directed CAR-T cell therapy in relapsed/refractory multiple myeloma: efficacy, safety, survival, and future directions – A systematic review and meta-analysis, Current Problems in Cancer, 2026, 101301, ISSN 0147-0272, https://doi.org/10.1016/j.currproblcancer.2026.101301. (https://www.sciencedirect.com/science/article/pii/S0147027226000358?via%3Dihub)

Smoldering multiple myeloma in transition: redefining early myeloma in the modern era — Leukemia (May 2026)
 

What is the purpose of the review?
To review advances in the understanding and management of smoldering multiple myeloma (SMM), focusing on evolving diagnostic criteria, risk stratification, and early treatment strategies. It evaluates how new therapies (particularly daratumumab) and emerging technologies are reshaping the traditional “watch-and-wait” approach for selected patients.

Summary
Smoldering multiple myeloma (SMM) has traditionally been monitored without treatment until progression to active multiple myeloma (MM), but recent advances are challenging this approach. The phase II CENTAURUS and phase III AQUILA trials supported FDA approval of daratumumab for high-risk SMM, demonstrating a 51% reduction in progression risk compared with observation, although overall survival benefit remains unproven. Emerging tools such as next-generation sequencing, minimal residual disease (MRD) assessment, and advanced imaging may improve risk stratification and could eventually redefine SMM into biologically distinct groups, though this remains investigational.
 
Key points
• Daratumumab is FDA-approved specifically for high-risk SMM, based on the CENTAURUS and AQUILA trials.
• AQUILA demonstrated a 51% reduction in risk of progression, but no confirmed overall survival benefit yet.
• The traditional “watch-and-wait” strategy is being reconsidered, particularly for high-risk patients, but is still relevant for lower-risk disease.
• Current risk models (e.g., 20/2/20 model) are widely used but limited by lack of genomic, immune, and advanced imaging data.
• Emerging technologies (MRD assays, ctDNA, sequencing, imaging) may refine risk prediction and guide treatment decisions but are not yet fully integrated into standard care.

• Proposed reclassification of SMM into:
 - Early multiple myeloma (requiring treatment)
 - Benign monoclonal gammopathy (minimal monitoring) remains hypothetical and under investigation.

• Combination immunotherapy and CAR-T approaches show deep responses in early studies but are not proven curative and may carry significant toxicity risks, which are particularly important in a precursor condition.
 
Strengths
• Integrates recent pivotal trial data (CENTAURUS, AQUILA) with evolving clinical concepts
• Provides a comprehensive overview of biological, diagnostic, and therapeutic advances
• Highlights key unanswered questions and future research directions
 
Limitations
• Some evidence is based on early-phase or small studies with limited follow-up
• Long-term outcomes, including overall survival and optimal treatment duration, remain uncertain
• Risk of overtreatment persists, especially in patients with biologically indolent disease
 

Why this review matters
The management of smoldering multiple myeloma is shifting toward earlier intervention in high-risk patients, supported by evidence that daratumumab delays disease progression. Advances in diagnostics and disease biology may further refine patient selection and potentially redefine disease categories, although these approaches remain investigational. Ongoing challenges include determining long-term benefits, optimizing treatment strategies, and avoiding overtreatment in patients unlikely to progress.
 
Reference:
Landgren, O. Smoldering multiple myeloma in transition: redefining early myeloma in the modern era. Leukemia (2026). https://doi.org/10.1038/s41375-026-02979-2 (https://www.nature.com/articles/s41375-026-02979-2)
 

Bispecific Antibodies in Hematologic Malignancies in the Outpatient and Community Settings — Advances in Hematology (May 2026)
 

What is the purpose of the review?
To examine the feasibility and safety considerations for administering bispecific antibodies (BsAbs) in outpatient and community settings. It discusses immune-related toxicities associated with BsAbs, summarizes early outpatient experiences, and proposes a disease-agnostic framework for safe implementation and monitoring.
 
Summary
Bispecific antibodies are anticancer therapies that engage both tumor-associated antigens and CD3 on endogenous T cells to promote cancer cell death. The review notes that immune-mediated toxicity rates reported with BsAbs are generally lower than those observed with CAR T-cell therapy, supporting investigation of outpatient administration strategies. The article summarizes early outpatient experiences with agents including teclistamab and blinatumomab, as well as operational lessons from outpatient CAR T-cell therapy programs, to outline approaches for patient monitoring, toxicity management, and multidisciplinary care coordination.
 
In a Mayo Clinic analysis, 24 patients with relapsed/refractory multiple myeloma received 223 teclistamab infusions in the outpatient setting, with 93% of infusions not requiring inpatient admission. Cytokine release syndrome (CRS) occurred in 13 patients, and 93% of CRS events were Grade 1 and managed primarily with corticosteroids. The review also describes outpatient monitoring approaches such as wearable monitoring devices, scheduled toxicity assessments, standardized treatment protocols, and rapid escalation pathways for higher levels of care.
 
Key points
• Bispecific antibodies (BsAbs) activate endogenous T cells by targeting both tumor-associated antigens and CD3.
• Reported immune-mediated toxicity rates with BsAbs are generally lower than those observed with CAR T-cell therapy.
• The article is a narrative review and framework proposal, incorporating findings from small outpatient studies and experiences with CAR T-cell therapy programs.
• Early outpatient studies suggest that outpatient administration of selected BsAbs may be feasible in appropriately monitored patients.

• In the Mayo Clinic teclistamab analysis:
 - 24 patients received 223 outpatient infusions.
 - 93% of infusions did not require inpatient admission.
 - CRS occurred in 13 patients.
 - 93% of CRS events were Grade 1.

• Outpatient safety strategies discussed include:
 - Multidisciplinary care teams.
 - Staff and patient education.
 - Remote wearable monitoring systems.
 - Standardized toxicity management protocols.
 - Rapid hospital escalation pathways.

• Patient selection considerations include:
 - Tumor burden and comorbidities.
 - Transportation and social support.
 - Access to communication technology.
 - Prior therapy tolerance.

• Monitoring approaches may differ depending on the specific BsAb, expected timing of toxicities, and REMS requirements.
 
Strengths
• Summarizes practical outpatient experiences with BsAbs and CAR T-cell therapy programs.
• Provides a structured framework for outpatient and community implementation.
• Addresses operational, educational, and safety considerations for broader access to therapy.
 
Limitations
• Much of the evidence comes from small, single-center, retrospective experiences.
• Limited prospective and long-term outpatient safety data are currently available.
• Standardized consensus guidelines for outpatient BsAb administration remain under development.
 
Why this review matters
This review outlines a proposed framework for outpatient administration of bispecific antibodies and summarizes early clinical experiences supporting this approach. Reported toxicities, particularly CRS, were often low grade and manageable with monitoring and established treatment protocols. Early real-world experiences suggest that outpatient administration of selected BsAbs may be feasible in carefully monitored patients, although evidence remains limited, and additional prospective studies and standardized protocols are needed.
 
Reference:
Gonugunta, Amrit S., Haider, Asad, Mohlere, Virginia, Aljurf, Mahmoud, Hashmi, Shahrukh, Abid, Muhammad Bilal, Bispecific Antibodies in Hematologic Malignancies in the Outpatient and Community Settings, Advances in Hematology, 2026, 4529571, 11 pages, 2026. https://doi.org/10.1155/ah/4529571 (https://onlinelibrary.wiley.com/doi/10.1155/ah/4529571)
 

Research

Safety and efficacy of ciltacabtagene autoleucel for relapsed/refractory multiple myeloma: a CIBMTR study — Blood Cancer Journal (April 2026)
 

What is the purpose of the study?
To evaluate the safety and efficacy of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T therapy, in patients with relapsed/refractory multiple myeloma (RRMM) using registry data from standard clinical practice.

Summary
In 595 RRMM patients with a median of 7 prior lines of therapy, the overall response rate was 87%, with 75% achieving at least a very good partial response and 35% achieving complete response. At 12 months, progression-free survival was 73% (95% CI: 68–77%) and overall survival was 85% (95% CI: 81–88%). Cytokine release syndrome occurred in 80% (grade ≥3: 4%), ICANS in 22% (grade ≥3: 4%), infections in 47%, and treatment-related mortality was 5%.
 
Key points
• Population: 595 patients; median age 64; 57% male; 70% with ≥1 comorbidity
• Disease characteristics: Extramedullary disease (13%); marrow plasma cells ≥50% (14%)
• Prior treatment: Median 7 prior lines; 8% prior BCMA-directed therapy

• Efficacy outcomes:
 - Overall response rate: 87%
 - ≥ Very good partial response: 75%
 - ≥ Complete response: 35%
 - 12-month progression-free survival: 73% (95% CI: 68–77%)
 - 12-month overall survival: 85% (95% CI: 81–88%)

• Safety outcomes:
 - Cytokine release syndrome: 80% (grade ≥3: 4%)
 - ICANS: 22% (grade ≥3: 4%)
 - Non-ICANS neurotoxicity: 5% (Parkinsonism 2.7%; cranial nerve palsies 2.5%)
 - Infections: 47%
 - Treatment-related mortality: 5%

Strength: Large registry-based cohort reflecting standard-of-care use
Limitation: Observational design; median follow-up 12 months; no comparator group
 
Why this study matters
Cilta-cel demonstrated an overall response rate of 87% and 12-month progression-free and overall survival rates of 73% and 85%, respectively, in patients with RRMM. Adverse events included cytokine release syndrome, neurotoxicity, infections, and 5% treatment-related mortality. These findings describe outcomes observed in a large registry-based population treated in standard clinical practice.
 
Reference:
Hansen, D.K., Dima, D., Mian, H. et al. Safety and efficacy of ciltacabtagene autoleucel for relapsed/refractory multiple myeloma: a CIBMTR study. Blood Cancer J. (2026). https://doi.org/10.1038/s41408-026-01496-w (https://www.nature.com/articles/s41408-026-01496-w)
 

Monocyte-mediated metabolic rewiring via CD31-CD38 interactions promotes growth and drug-resistance in multiple myeloma — HemaSphere (April 2026)

What is the purpose of the study?
To investigate how monocytes in the bone marrow microenvironment influence multiple myeloma (MM) cell metabolism and treatment resistance, and whether the CD38-targeting antibody daratumumab can disrupt this process. It aims to define the mechanisms of extracellular vesicle (EV)-mediated mitochondrial transfer and their impact on tumor behavior.

Summary
Researchers found that monocytes transfer functional mitochondria to MM cells via EVs through CD38–CD31 interactions, increasing mitochondrial content and enhancing oxidative phosphorylation (OXPHOS), which promotes tumor growth, migration, and drug resistance. The monoclonal antibody daratumumab blocks this transfer and induces mitochondrial removal from MM cells via trogocytosis, reducing mitochondrial content and impairing tumor cell function. This metabolic disruption increased sensitivity to mitochondria-dependent therapies such as bortezomib and doxorubicin, highlighting a preclinical mechanism of treatment response.

Key points
• Monocytes support MM progression by transferring mitochondria to tumor cells via extracellular vesicles (EVs).
• This transfer depends on CD38 (MM cells) and CD31 (monocytes).
• Increased mitochondrial content shifts MM cells toward higher OXPHOS, enhancing growth, migration, and drug resistance.
• Daratumumab blocks mitochondrial transfer and promotes mitochondrial removal via trogocytosis.
• Disruption of mitochondrial transfer improves response to mitochondria-dependent drugs (bortezomib, doxorubicin), but not pomalidomide.
 
Strengths
• Identifies a novel EV-mediated metabolic interaction between immune cells and MM cells.
• Demonstrates an additional, non-classical mechanism of action for daratumumab.
• Links tumor metabolism directly to drug resistance mechanisms.
 
Limitations
• Findings are based on in vitro and ex vivo models and may not fully reflect the in vivo bone marrow environment.
• Lacks validation in animal models or clinical trial settings.
 

Why this study matters
This study shows that EV-mediated mitochondrial transfer from monocytes to MM cells drives metabolic reprogramming, tumor progression, and drug resistance. Daratumumab disrupts this process by blocking transfer and inducing mitochondrial removal via trogocytosis, reducing tumor cell fitness and enhancing sensitivity to certain therapies. These findings support targeting tumor metabolism and the microenvironment as a potential, but currently preclinical, strategy in multiple myeloma treatment.
 
Reference:
Raoof, R., Dal Collo, G., Simon-Molas, H., Tzortzi, P., Kulaj, K., Demirez, E.N., Massaro, C., Poels, R., Korst, C.L.B.M., O'Neill, C.A., Bruins, W.S.C., Broekmans, M.E.C., Behradkia, P., Krevvata, M., Zweegman, S., Kater, A.P., Baglio, S.R., Mutis, T. and van de Donk, N.W.C.J. (2026), Monocyte-mediated metabolic rewiring via CD31-CD38 interactions promotes growth and drug-resistance in multiple myeloma. HemaSphere, 10: e70358. https://doi.org/10.1002/hem3.70358 (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70358)
 

Comparison of adverse event profiles of carfilzomib-, elotuzumab-, and ixazomib-based therapies combined with lenalidomide and dexamethasone in patients with multiple myeloma using VigiBase — Leukemia Research (April 2026)
 

What is the purpose of the study?
To directly compare adverse event (AE) profiles of KRd (carfilzomib, lenalidomide, dexamethasone), EloRd (elotuzumab, lenalidomide, dexamethasone), and IxaRd (ixazomib, lenalidomide, dexamethasone) in patients with multiple myeloma using real-world pharmacovigilance data. It seeks to identify therapy-specific toxicities to inform treatment selection.

Summary
Using the World Health Organization VigiBase database (through December 2024), the study analyzed 3,950 KRd, 1,210 EloRd, and 3,948 IxaRd AE reports and performed disproportionality analyses with reporting odds ratios (RORs). KRd was associated with higher rates of hematologic and cardiac disorders (e.g., neutropenia, cardiac failure), while IxaRd showed the broadest AE profile, including gastrointestinal and nervous system disorders (e.g., nausea, peripheral neuropathy). EloRd demonstrated a comparatively narrower AE profile without strong disproportionality signals versus the other regimens.
 
Key points
• Distinct AE profiles identified
 - KRd: increased blood/lymphatic and cardiac toxicities (ROR up to 2.14).
 - IxaRd: broadest AE spectrum, especially gastrointestinal (ROR up to 3.05) and neurologic effects.
 - EloRd: narrower AE profile with fewer distinct signals.

• Clinical relevance
 - Findings highlight the importance of therapy-specific toxicity when selecting treatment for multiple myeloma.
 - Differences likely reflect the individual agents (carfilzomib, elotuzumab, ixazomib) within a shared lenalidomide–dexamethasone backbone.

Strengths
• Large, real-world dataset (VigiBase).
• First direct comparative analysis of KRd, EloRd, and IxaRd AE profiles.
• Use of standardized disproportionality (ROR) analysis.

Limitations
• Spontaneous reporting bias (underreporting, selective reporting).
• Lack of true incidence rates due to unknown denominators.
• Limited clinical detail (e.g., comorbidities, concomitant drugs).
• Differences in drug approval timing and reporting practices across regions.
• Cannot establish causality or fully adjust for confounders.
 

Why this study matters
KRd and IxaRd are associated with distinct and clinically relevant adverse event profiles, while EloRd shows a comparatively narrower range of reported toxicities. IxaRd demonstrated the broadest spectrum of AEs, whereas KRd was more strongly linked to hematologic and cardiac events. These findings support incorporating therapy-specific safety profiles, alongside efficacy, into individualized treatment decisions for patients with multiple myeloma.
 
Reference:
Jun Matsumoto, Tatsuaki Takeda, Shiho Sugimoto, Tomonori Sakai, Beatrix Bermudo Loyao, Tsukasa Higashionna, Hirofumi Hamano, Gerard Lee Lo See, Noritaka Ariyoshi, Yoshito Zamami, Comparison of adverse event profiles of carfilzomib-, elotuzumab-, and ixazomib-based therapies combined with lenalidomide and dexamethasone in patients with multiple myeloma using VigiBase, Leukemia Research, Volume 166, 2026, 108236, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2026.108236. (https://www.sciencedirect.com/science/article/abs/pii/S0145212626000809?via%3Dihub)

Whole-genome sequencing of cell-free DNA for assessment of minimal residual disease in high-risk smoldering multiple myeloma — HemaSphere (April 2026)

What is the purpose of the study?
To evaluate whether tumor-informed whole-genome sequencing (WGS) of plasma cell-free DNA (cfDNA) can detect minimal residual disease (MRD) in multiple myeloma (MM) and how it compares with standard bone marrow (BM) flow cytometry. The study also assesses the method’s ability to monitor disease over time and predict clinical outcomes.

Summary
In high-risk smoldering multiple myeloma (HR-SMM), tumor-informed cfDNA WGS was applied to 87 longitudinal plasma samples, achieving a median detection limit of ~1.2 × 10⁻⁴. The method showed 73.3% concordance with BM flow cytometry, capturing most BM-positive cases while also identifying additional MRD-positive cases not detected in BM, likely reflecting its ability to assess systemic disease rather than localized sampling. Tumor fraction (TF) levels and their changes over time were associated with disease progression, supporting their prognostic relevance.
 
Key points
• Noninvasive MRD detection: cfDNA WGS enables systemic assessment without repeated BM biopsies.
• Detection characteristics: While BM flow cytometry has a deeper limit of detection, cfDNA WGS can identify disease missed by BM due to spatial heterogeneity.
• Concordance with standard methods: 73.3% agreement with BM flow; most BM-positive cases were detected, with rare exceptions.
• Systemic disease insight: Detected MRD in some BM-negative cases, suggesting improved representation of whole-body disease burden.
• Prognostic value: Higher baseline TF and increasing TF over time were associated with disease progression (P < 0.001).
• Dynamic monitoring: Serial TF measurements may provide early indication of relapse or progression.
 
Strengths
• Tumor-informed, genome-wide approach improves individualized detection.
• Longitudinal design enables tracking of disease dynamics.
• Captures systemic disease beyond localized BM sampling.
 
Limitations
• BM-based assays achieve deeper detection limits in very low disease settings.
• Requires baseline tumor WGS, limiting use in some patients.
• Limited ability to detect specific resistance mutations due to low coverage.
• Findings derived from HR-SMM cohort may limit broader applicability.
 

Why this study matters
Tumor-informed cfDNA WGS provides a complementary, noninvasive approach to MRD detection in multiple myeloma, offering systemic disease assessment and prognostic information. Although BM-based methods remain more sensitive at very low disease levels, cfDNA WGS can detect residual disease missed by localized sampling and track disease dynamics over time. Further validation is needed to define its role alongside established MRD assessment techniques.
 
 
Reference:
Baker, C., Hill, E., Kazandjian, D., Papadimitriou, M., Durante, M., Pandey, A., Ziccheddu, B., Jelinek, T., Coffey, D., Walker, B., Young, R., Maclachlan, K., Korde, N., Parkinson, N., Goldstein, Z.R., Runnels, A., Hooper, W.F., Landau, D., Robine, N., Maura, F., Landgren, O. and Diamond, B. (2026), Whole-genome sequencing of cell-free DNA for assessment of minimal residual disease in high-risk smoldering multiple myeloma. HemaSphere, 10: e70367. https://doi.org/10.1002/hem3.70367 (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70367)
 

Real-World Description of Non-ICANS Neurologic Events Among Patients with Relapsed or Refractory Multiple Myeloma Treated with Ciltacabtagene Autoleucel Using Two Large US Databases — Oncology and Therapy (April 2026)

What is the purpose of the study?
To characterize new-onset nonimmune effector cell-associated neurotoxicity syndrome (non-ICANS) neurologic events (NEs) in patients with relapsed or refractory multiple myeloma (RRMM) treated with ciltacabtagene autoleucel (cilta-cel) in real-world settings. It also compares these event rates with those observed in the CARTITUDE-1 and CARTITUDE-4 clinical trials.

Summary
This retrospective analysis used two large real-world databases (Komodo Research Database and Loopback Analytics) to evaluate neurologic events after cilta-cel infusion in patients with 1–3 or ≥4 prior lines of therapy (LOT). Among patients with 1–3 prior LOT (n=124 and 79; median follow-up ~3.4–3.5 months), cranial nerve palsy occurred in ~5%, with no reported parkinsonism or Guillain–Barré syndrome. In patients with ≥4 prior LOT (n=524 and 191; median follow-up ~13.2–13.3 months), parkinsonism occurred in 1.0%, cranial nerve palsy in 1.0–4.6%, and Guillain–Barré syndrome in 0.2–0.5%; overall rates were comparable to or lower than those reported in CARTITUDE-1 and CARTITUDE-4.
 
Key points
• Neurologic safety profile of cilta-cel
 - Low rates of non-ICANS neurologic events across both early (1–3 LOT) and later (≥4 LOT) treatment settings.
 - Cranial nerve palsy was the most commonly observed event (~5% in earlier LOT; 1.0–4.6% in later LOT).
 - Parkinsonism (~1%) and Guillain–Barré syndrome (≤0.5%) were rare and mainly observed in later LOT.

• Comparison with clinical trials
 - Event rates were similar to or lower than those reported in CARTITUDE-1 and CARTITUDE-4.
 - Differences may reflect less intensive monitoring in real-world practice compared with trials.

• Timing and clinical relevance
 - Most neurologic events occurred within the first 1–3 months after infusion.
 - Findings support the need for continued monitoring beyond the acute post-infusion period.

Strengths
• Use of two large, complementary real-world datasets (claims and electronic medical records).
• Inclusion of patients across different treatment lines and care settings.
• Consistent findings across independent data sources.

Limitations
• Retrospective design with potential underreporting and coding inaccuracies.
• Lack of detailed clinical data (e.g., disease status, concomitant therapies).
• Shorter follow-up in earlier LOT group may miss delayed events.
• Cannot establish causality or precise incidence rates.
• Possible underestimation of milder neurologic events due to reliance on recorded diagnoses.
 

Why this study matters
In real-world clinical practice, ciltacabtagene autoleucel is associated with low rates of non-ICANS neurologic events, including parkinsonism, cranial nerve palsy, and Guillain–Barré syndrome. These rates are comparable to or lower than those observed in CARTITUDE-1 and CARTITUDE-4, although differences in monitoring may influence reporting. Ongoing surveillance and longer follow-up are needed to better understand risk factors, timing, and management of these neurologic events.
 
Reference:
Sidana, S., Nagar, S.P., Ghosh, S. et al. Real-World Description of Non-ICANS Neurologic Events Among Patients with Relapsed or Refractory Multiple Myeloma Treated with Ciltacabtagene Autoleucel Using Two Large US Databases. Oncol Ther (2026). https://doi.org/10.1007/s40487-026-00433-y (https://link.springer.com/article/10.1007/s40487-026-00433-y)
 

Real-World Treatment Patterns and Outcomes for Patients With Relapsed/Refractory Multiple Myeloma and Prior Exposure to Lenalidomide and Proteasome Inhibitors in the United States — Clinical Lymphoma Myeloma and Leukemia (April 2026)
 

What is the purpose of the study?
To evaluate real-world treatment patterns and clinical outcomes in patients with early relapsed/refractory multiple myeloma (RRMM) in the United States using the Flatiron Health Research Database. It aims to characterize variability in therapy use and assess real-world progression and survival outcomes in early lines of therapy.

Summary
The retrospective study analyzed 1,858 patients with RRMM treated between January 2021 and January 2025, most of whom had received 1–3 prior lines of therapy including proteasome inhibitors and lenalidomide. Treatment regimens showed high variability, and at a median follow-up of 24.5 months, median real-world progression-free survival (rwPFS) was 10.1 months, time to next line of therapy was 12.7 months, and median overall survival was not reached. Poorer outcomes were associated with higher ECOG performance status, high-risk cytogenetics, and lenalidomide-refractory disease.
 
Key points
• Study design: Retrospective real-world analysis using the Flatiron Health Research Database (US-based).
• Population: 1,858 patients with early RRMM (1–3 prior LOTs), ECOG PS <3, and prior exposure to proteasome inhibitors and lenalidomide.
• Treatment patterns: High variability in regimens with no clear standard of care.
• Outcomes: Median rwPFS 10.1 months; median time to next therapy 12.7 months; median OS not reached at 24.5-month follow-up.
• Risk factors: Worse outcomes associated with high ECOG PS, high-risk cytogenetics, and lenalidomide refractoriness.
• Strengths: Large real-world cohort reflecting current US clinical practice.
• Limitations: Retrospective design, potential for missing data, and variability in treatment documentation.
 
Why this study matters
This study demonstrates substantial heterogeneity in treatment approaches for early RRMM in real-world US practice. Despite modern therapies, outcomes remain limited, with relatively short progression-free intervals and early need for subsequent treatment. These findings highlight an ongoing unmet need for more effective and standardized therapeutic strategies earlier in the disease course.
 
Reference:
Luciano J. Costa, Sandhya Nair, Marguerite O’Hara, Mary Slavcev, Niodita Gupta-Werner, Margaret Doyle, Eric Ammann, Sunny Patel, Xiwu Lin, Maria-Victoria Mateos, Real-World Treatment Patterns and Outcomes for Patients With Relapsed/Refractory Multiple Myeloma and Prior Exposure to Lenalidomide and Proteasome Inhibitors in the United States, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.04.009. (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(26)00110-2/fulltext)

 

Prognostic Impact of Chromosome 1q Gain/Amplification in Multiple Myeloma Treated With Daratumumab-Based Regimens — European Journal of Haematology (April 2026)
 

What is the purpose of the study?
To evaluate whether gain/amplification of chromosome arm 1q (+1q) remains a poor prognostic factor in multiple myeloma patients treated with daratumumab-based therapies (DBTs). It specifically assesses the impact of +1q on survival outcomes, including progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS).

Summary
In this single-center retrospective study of 174 multiple myeloma patients treated with DBTs (mainly daratumumab-lenalidomide-dexamethasone [DaraRd]), +1q abnormalities were associated with worse clinical outcomes. Patients with isolated +1q had significantly shorter PFS and TTNT compared to standard-risk patients, while those with +1q plus additional high-risk cytogenetic abnormalities (HiRCAs) had the poorest outcomes across all endpoints, including OS. Multivariate analysis confirmed +1q as an independent predictor of inferior outcomes, and results were consistent in the DaraRd subgroup.
 
Key points
• Prognostic impact of +1q:
 - Isolated +1q significantly worsened PFS (HR ~4.6–4.8) and TTNT (HR ~3.6–3.8).
 - +1q with additional HiRCAs had the highest risk (PFS HR ~7.7–8.4; OS HR ~6.0–6.2).

• Treatment context:
 - Majority of patients received DaraRd.
 - Median follow-up: 30.7 months.

• Clinical implication:
 - +1q remains an adverse prognostic marker despite modern DBTs.
 - Co-existing high-risk cytogenetic abnormalities further worsen outcomes.

Strengths
• Real-world dataset reflecting routine clinical practice.
• One of the larger analyses focused on +1q in early lines of DBT treatment.

Limitations
• Retrospective, single-center design.
• Cytogenetic data missing in ~47% of patients.
• Limited representation of younger/transplant-eligible patients and quadruplet regimens.
• Follow-up insufficient for mature overall survival analysis.
 
Why this study matters
This study shows that +1q remains a significant adverse prognostic factor in multiple myeloma patients treated with daratumumab-based therapies, particularly when combined with other high-risk cytogenetic abnormalities. Even isolated +1q is associated with inferior survival outcomes, suggesting current treatments may not fully overcome its negative impact. These findings support the need for improved risk stratification and development of more effective treatment strategies for patients with +1q abnormalities.
 
Reference:
E. Barbieri, L. Arletti, M. Quaresima, et al., “Prognostic Impact of Chromosome 1q Gain/Amplification in Multiple Myeloma Treated With Daratumumab-Based Regimens,” European Journal of Haematology (2026): 1–13, https://doi.org/10.1111/ejh.70198 (https://onlinelibrary.wiley.com/doi/10.1111/ejh.70198).

 

Clinical Benefit of Multiple Myeloma Drugs at Regulatory Approval in Brazil, Europe, and the USA: A Retrospective Cohort Study (2003–2024) — Clinical Drug Investigation (April 2026)
 

What is the purpose of the study?
To evaluate the magnitude of clinical benefit of multiple myeloma (MM) drugs approved by the European Medicines Agency (EMA), Food and Drug Administration (FDA), and Brazilian Health Regulatory Agency (Anvisa) between 2003 and 2024 using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale for Haematological Malignancies (ESMO-MCBS:H v1.1).

Summary
Seventeen MM drugs were approved by both the EMA and FDA, and 12 by Anvisa, with most approvals based on single-arm studies and expedited regulatory pathways. Only 4 of 17 drugs (23.5%) demonstrated meaningful clinical benefit (ESMO-MCBS:H score ≥4) in the non-curative setting. Accelerated approvals in Brazil were significantly associated with biological therapies, monoclonal antibodies, and Breakthrough Therapy designation (p < .05).
 
Key points
• Majority of MM drug approvals relied on single-arm studies (EMA 64.7%, FDA 70.6%)
• High use of expedited or accelerated approval pathways across agencies
• Only 23.5% of drugs showed meaningful clinical benefit per ESMO-MCBS:H v1.1
• Accelerated timelines in Brazil linked to biologics, monoclonal antibodies, and Breakthrough Therapy status
• Strength: Standardized assessment using ESMO-MCBS:H v1.1 across multiple regulatory agencies
• Limitation: Reliance on publicly available data and pivotal trials, with many approvals based on limited or non-randomized evidence
 
Why this study matters
Most multiple myeloma therapies approved between 2003 and 2024 entered the market with limited evidence of meaningful clinical benefit based on ESMO-MCBS:H criteria. The frequent use of expedited pathways and single-arm studies highlights potential gaps in the robustness of supporting evidence at approval. Findings from this retrospective cohort study suggest that structured tools like ESMO-MCBS:H may help inform regulatory and reimbursement decisions, particularly in resource-constrained settings.
 
 
Reference:
Rodrigues, M.A., de Pádua, C.A.M., de Miranda Drummond, P.L. et al. Clinical Benefit of Multiple Myeloma Drugs at Regulatory Approval in Brazil, Europe, and the USA: A Retrospective Cohort Study (2003–2024). Clin Drug Investig (2026). https://doi.org/10.1007/s40261-026-01552-0 (https://link.springer.com/article/10.1007/s40261-026-01552-0)

Gene expression-based dissemination score predicts early spread and poor outcomes in multiple myeloma — Leukemia (April 2026)
 

What is the purpose of the study?
To develop and validate a gene expression–based Dissemination Score (DS) to quantify biological mechanisms underlying the spread of multiple myeloma beyond the bone marrow. It also evaluates whether DS adds prognostic value to established risk models.

Summary
Researchers analyzed RNA sequencing, microarray, and single-cell datasets to identify 1,357 dissemination-associated genes and derived a 30-gene Dissemination Score using Elastic Net Cox regression. In the MMRF CoMMpass cohort (n=754), DS stratified overall survival (54.5 vs 102.5 months; C-index 0.71) and improved prognostic performance when combined with established models (UAMS70, EMC92). Independent validation confirmed its ability to distinguish survival outcomes (52.1 vs 113.6 months) and predict earlier dissemination events (2.1 vs 6.8 years), with higher scores observed in circulating and extramedullary plasma cells.
 
Key points
• A 30-gene Dissemination Score (DS) was developed to quantify dissemination biology in multiple myeloma.
• DS stratified overall survival and predicted timing of dissemination events across cohorts.
• DS improved prognostic performance when added to existing risk models (UAMS70, EMC92), rather than replacing them.
• Higher DS was observed in circulating and extramedullary plasma cells, consistent with more advanced disease spread.
• DS was associated with adverse stromal interaction (ASI), supporting biological relevance.
 
Strengths
• Large, multi-cohort design with independent validation.
• Integration of multiple transcriptomic platforms (RNA-seq, microarray, single-cell).
• Consistent findings across disease stages and sample types.
 
Limitations
• Retrospective analysis of existing datasets.
• Moderate predictive performance (C-index 0.71).
• Requires prospective validation before clinical implementation.
• Does not directly assess treatment response or guide therapy decisions.
 
Why this study matters
The Dissemination Score provides a quantitative measure of disease spread biology in multiple myeloma and is associated with overall survival and earlier dissemination events. It adds prognostic value when combined with existing gene expression–based risk models and reflects underlying tumor–microenvironment interactions. Prospective studies are needed to confirm its clinical utility and role in patient management.
 
 
Reference:
Bohra, A., Dasari, S., Zanwar, S. et al. Gene expression-based dissemination score predicts early spread and poor outcomes in multiple myeloma. Leukemia (2026). https://doi.org/10.1038/s41375-026-02931-4 (https://www.nature.com/articles/s41375-026-02931-4)
 

A multi-center study of progression-risk and outcomes in solitary bone plasmacytoma with and without marrow involvement — Blood Advances (April 2026)
 

What is the purpose of the study?
To compare post-radiation therapy outcomes and patterns of disease progression in patients with solitary bone plasmacytoma (SBP) and solitary bone plasmacytoma with minimal marrow involvement (SBPmm). It also seeks to characterize differences in time to progression and risk factors for progression to multiple myeloma.

Summary
This multi-center study analyzed 141 patients with SBP and 102 patients with SBPmm treated with definitive radiation therapy between 2010 and 2024, followed by observation. Patients with SBPmm had a significantly higher rate of progression to multiple myeloma (92%) compared with SBP (76%) and a shorter median time to progression (15 months vs 43 months; p<0.0001). Multifocal lytic bone lesions were the most common myeloma-defining event in both groups, and cytogenetic abnormalities such as del(17p) and 1q gain were associated with faster progression in SBPmm.
 
Key points
• SBPmm is associated with higher and earlier progression risk: 92% progressed to multiple myeloma vs 76% in SBP, with most SBPmm patients progressing within 2 years.
• Progression pattern is predominantly skeletal: Multifocal lytic bone lesions were the most common myeloma-defining event (89% SBPmm, 81% SBP).
• Time to progression differs significantly: Median TTP was 15 months in SBPmm vs 43 months in SBP (p<0.0001).
• Cytogenetic risk factors identified: del(17p) and 1q gain were linked to shorter time to progression in SBPmm.
• Progression phenotype differences: SBP patients more often progressed as new solitary bone lesions compared with SBPmm (21% vs 4%).
 
Strengths
• Large multi-center cohort spanning 14 years
• Direct comparison between SBP and SBPmm under similar treatment approach
• Detailed analysis of progression patterns and cytogenetic risk factors
 
Limitations
• Retrospective observational design
• Potential selection bias and variability in clinical management across centers
• Lack of randomized treatment comparison or intervention beyond radiation therapy
 
Why this study matters
Patients with SBPmm demonstrate a substantially higher and earlier risk of progression to multiple myeloma compared with SBP, with most cases progressing within two years after diagnosis. Progression is most commonly characterized by multifocal lytic bone disease, and specific cytogenetic abnormalities further increase risk. These findings suggest that SBPmm represents a higher-risk subgroup that may warrant evaluation of earlier systemic therapy in prospective studies.
 
Reference:
Kenneth JC Lim, Maximilian Johannes Steinhardt, Matthew J. Rees, Patricia T. Greipp, Katalin Kelemen, Angela Dispenzieri, Dragan Jevremovic, Linda B Baughn, Francis K Buadi, David Dingli, Suzanne R Hayman, Prashant Kapoor, Eli Muchtar, Nelson Leung, Amie L Fonder, Miriam A Hobbs, Yi Lisa Hwa, Rahma Warsame, Taxiarchis V. Kourelis, Joselle Cook, Moritz Binder, Nadine Abdallah, Saurabh S. Zanwar, Yi Lin, Ronald S. Go, Mustaqeem Siddiqui, Ricardo D Parrondo, Sikander Ailawadhi, Vivek Roy, Rachel Elizabeth Cooke, Karen Dun, Adrian Carl Zordan, Slavisa Ninkovic, Sharene Best, Gabriela Alatorre, Julia Erin Wiedmeier-Nutor, K. Martin Kortüm, Hermann Einsele, Saurabh Chhabra, P. Leif Bergsagel, Robert A Kyle, Morie A Gertz, Shaji K Kumar, S. Vincent Rajkumar, Rafael Fonseca, Wilson I Gonsalves, Udit Yadav; A multi-center study of progression-risk and outcomes in solitary bone plasmacytoma with and without marrow involvement. Blood Adv 2026; bloodadvances.2025019136. doi: https://doi.org/10.1182/bloodadvances.2025019136 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025019136/567920/A-multi-center-study-of-progression-risk-and)

Functional high-risk phenotype predicts poor survival in multiple myeloma independent of front-line treatment: A secondary analysis of CIBMTR data — British Journal of Haematology (April 2026)
 

What is the purpose of the retrospective analysis?
To evaluate whether the type of front-line induction therapy affects overall survival (OS) in patients with functional high-risk multiple myeloma (FHRMM) who experience early disease progression after autologous hematopoietic stem cell transplantation (AHSCT). It also aims to clarify whether early relapse reflects aggressive disease biology independent of initial treatment.

Summary
This retrospective analysis combines data from three Center for International Blood and Marrow Transplant Research studies (MM18-02, MM19-01, MM20-03), including patients who relapsed within 12, 18, or 24 months after front-line AHSCT. Patients received either lenalidomide-based triplet regimens such as VRd (bortezomib, lenalidomide, dexamethasone) or KRd (carfilzomib, lenalidomide, dexamethasone), or other regimens (VTd, VCd, Vd, Rd). While lenalidomide-containing triplets were associated with a lower incidence of early relapse, post-relapse overall survival was similar across treatment groups (e.g., 21 vs. 17 months in FHR12; hazard ratio 0.94, p=0.69), indicating no significant survival advantage once FHRMM develops.
 
Key points
• Functional high-risk multiple myeloma (FHRMM) is defined by progression within 12–24 months after AHSCT.
• Lenalidomide-based triplet regimens (VRd/KRd) reduced the likelihood of early relapse compared to other regimens.
• After early relapse occurs, overall survival is poor and similar regardless of initial therapy.
• Median post-relapse OS ranged ~20–27 months depending on FHR definition.
• No significant interaction between type of induction therapy and timing of relapse in predicting survival.
• Findings support the use of newer therapies such as T-cell–redirecting treatments (e.g., CAR T-cell therapy, bispecific antibodies) at relapse.
 
Strengths
• Large, pooled dataset from multiple registry studies.
• Inclusion of real-world patients across different treatment regimens.
• Multivariable analysis adjusting for clinical and disease-related factors.
 
Limitations
• Retrospective design with potential selection bias.
• Lack of detailed data on maintenance and salvage therapies.
• Limited applicability to current treatment approaches (e.g., daratumumab-based quadruplet regimens).
• Possible residual confounding due to unavailable variables.
 
Why this analysis matters
Early relapse after AHSCT in multiple myeloma remains a strong predictor of poor survival, regardless of the type of front-line induction therapy used. Although lenalidomide-based triplet regimens reduce the risk of developing FHRMM, they do not improve survival once early relapse occurs. These findings highlight the need for improved risk stratification and support prioritizing advanced therapies, such as T-cell–redirecting approaches, at first relapse.
 
Reference:
Goel U, Dragomirescu C, Zanwar S, Cassano RC, Cicero KI, Cowan AJ, et al. Functional high-risk phenotype predicts poor survival in multiple myeloma independent of front-line treatment: A secondary analysis of CIBMTR data. Br J Haematol. 2026;00:1–9. https://doi.org/10.1111/bjh.70490 (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70490)

Identifying High-Risk Smoldering Multiple Myeloma for Early Intervention — JAMA Oncology (April 2026)
 

What is the purpose of the study?
To compare two risk stratification methods (the AQUILA trial criteria vs 2/20/20 model) to evaluate how they classify high-risk smoldering multiple myeloma (SMM) and estimate risk of progression to active disease.

Summary
In two cohorts (193 individuals from the iStopMM screening study and 1,147 from the DALY-CARE clinical registry), the AQUILA criteria classified a larger proportion of patients as high-risk compared with the 2/20/20 model (34% vs 8% in the screened cohort; 55% vs 19% in the clinical cohort). However, patients categorized as high-risk by AQUILA had lower observed progression risk (2-year risk 27.0%) than those classified as high-risk by the 2/20/20 model (2-year risk 44.1%). These findings suggest that the 2/20/20 model identifies a smaller subgroup with higher observed progression risk, although no definitive standard for “true” high risk was assessed.
 
Key points
• Question: How do the AQUILA trial criteria and the 2/20/20 model differ in identifying high-risk SMM and estimating progression risk?

• Main Findings
 - AQUILA criteria classified more patients as high-risk than the 2/20/20 model.
 - High-risk patients per AQUILA had lower observed progression rates than those identified by the 2/20/20 model.
 - The 2/20/20 model identified a smaller group with higher observed progression risk.

• Important Data
 - High-risk classification (clinical cohort): AQUILA 55% vs 2/20/20 19%
 - 2-year progression risk: AQUILA 27.0% vs 2/20/20 44.1%
 - Annual progression rate: AQUILA 14.5% vs 2/20/20 27.3%

Strengths
• Large combined sample size across two independent cohorts
• Inclusion of both screened and clinically diagnosed populations
• Direct comparison of two commonly used risk models

Limitations
• Retrospective analysis
• Differences between screened and clinical populations may affect generalizability
• No external gold standard to confirm which model best defines “true” high risk
• Study evaluates progression risk, not treatment outcomes
 
Why this study matters
The AQUILA criteria classify a larger proportion of patients with smoldering multiple myeloma as high-risk but identify a group with lower observed progression risk compared with the 2/20/20 model. In contrast, the 2/20/20 model identifies a smaller subset with higher observed likelihood of progression. These findings highlight differences in how risk models define high-risk disease and may inform clinical decision-making, although implications for treatment benefit were not directly evaluated.
 
Reference:
Maeng CV, Rögnvaldsson S, Brieghel C, et al. Identifying High-Risk Smoldering Multiple Myeloma for Early Intervention. JAMA Oncol. Published online April 23, 2026. doi:10.1001/jamaoncol.2026.0831 (https://jamanetwork.com/journals/jamaoncology/article-abstract/2847979)

Real-world treatment patterns and outcomes of patients with multiple myeloma initiating elranatamab: results from the ALTITUDE-1 and ALTITUDE-2 retrospective cohort studies — Future Oncology (April 2026)
 

What is the purpose of the study?
To assess real-world treatment patterns and effectiveness of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM) using two U.S. datasets (ALTITUDE-1 and ALTITUDE-2). It also contextualizes these findings in relation to the MagnetisMM-3 (NCT04649359) clinical trial.

Summary
This real-world analysis included 574 patients (183 in ALTITUDE-1; 391 in ALTITUDE-2) with a median age of 73–75 years who were heavily pre-treated; 33.0–43.2% had prior penta-drug exposure and 17.5–21.0% had prior BCMA-targeted therapy. Elranatamab was administered less frequently than the labeled schedule (approximately 27–28 vs 39 vials per year), with evidence of extended dosing intervals such as biweekly or monthly dosing occurring earlier than specified in prescribing information. Median overall survival and time-to-next-treatment or death were not reached; landmark analyses estimated 18-month survival rates of 70.0% (ALTITUDE-1) and 60.7% (ALTITUDE-2), with cross-study comparisons to MagnetisMM-3 limited by differences in patient populations and study design. 
 

Key points
 
• Patient population:
 - Relapsed/refractory multiple myeloma; 574 total patients
 - Median age: 73–75 years
 - Prior treatments: 33.0–43.2% penta-drug exposed; 17.5–21.0% prior BCMA-targeted therapy

• Treatment patterns:
 - Lower-than-label dosing (~27–28 vs 39 vials/year)
 - Extended dosing intervals (e.g., earlier transition to every-2-week or monthly dosing)

• Effectiveness outcomes:
 - Median overall survival (OS) and time-to-next-treatment/death (TTNT/D) not reached
 - 18-month overall survival: 70.0% (ALTITUDE-1), 60.7% (ALTITUDE-2)

• Comparison with clinical trial: Outcomes generally aligned with MagnetisMM-3, though interpretation is limited by differences in baseline characteristics (e.g., prior BCMA exposure, comorbidities)

Strengths
• Use of two independent, large real-world datasets
• Early evaluation of post-approval use in routine clinical practice
    
Limitations
• Median follow-up duration <12 months
• Potential overlap of patients between datasets
• Use of administrative/claims data, which may include coding inaccuracies
• Limited ability to assess supportive care use and reasons for dose modifications
 
Why this study matters
In U.S. real-world practice, elranatamab is used in heavily pre-treated patients with relapsed/refractory multiple myeloma, including those with prior BCMA-targeted therapy, and is often administered at lower frequency than specified in the prescribing label. Survival outcomes, including 18-month overall survival rates of approximately 60–70%, were observed, although median survival endpoints were not reached during the available follow-up period. Further research with longer follow-up is needed to clarify long-term outcomes and the clinical impact of modified dosing patterns.

 
Reference:
Banerjee, R., Mohan, M., Shah, B., Prince, P., Gautam, N., Beebe, E., … DiBonaventura, M. (2026). Real-world treatment patterns and outcomes of patients with multiple myeloma initiating elranatamab: results from the ALTITUDE-1 and ALTITUDE-2 retrospective cohort studies. Future Oncology, 1–10. https://doi.org/10.1080/14796694.2026.2662504 (https://www.tandfonline.com/doi/full/10.1080/14796694.2026.2662504#d1e2334)

A Survey Study of Patient-Physician Communication and Treatment Decision-Making Preference at Treatment Initiation and After Disease Stabilization in Newly Diagnosed Multiple Myeloma — eJHaem (April 2026)
 

What is the purpose of the study?
To evaluate patient–physician communication and decision-making preferences in patients with newly diagnosed multiple myeloma (NDMM) who had not undergone hematopoietic stem cell transplantation. It also examines how patients’ expectations, emotions, knowledge, and preferences change from treatment initiation to disease stabilization.
 
Summary
In a Japan-based observational survey study (UMIN000055606), which included 220 patients and 120 physicians, notable discrepancies were found between patient-reported and physician-reported communication about treatment options and preferences. While physicians reported frequently discussing options, fewer patients recalled such discussions, and only about one-fifth experienced shared decision-making despite nearly half preferring it. Over time, patients’ knowledge improved, emotions shifted toward more positive states, and expectations evolved, particularly regarding long-term disease management.
 
Key points
• Communication gap: Patients reported lower rates of receiving explanations (45.9–50.3%) compared to physicians’ reports (65.0–82.5%).
• Decision-making mismatch: ~44.5% of patients preferred shared decision-making, but only 21.8% experienced it at treatment initiation.
• Evolving patient perspective: Knowledge increased, emotions improved, and expectations (e.g., longer time to recurrence) changed from initiation to stabilization.
• Ongoing concerns: Despite improvement, ~50% of patients continued to feel worried even during disease stabilization.
• Missed discussions: 21.4% of patients reported no opportunity to discuss future treatment strategies at stabilization.
 
Strengths
• Real-world data capturing both patient and physician perspectives.
• Evaluation across two clinically relevant timepoints (treatment initiation and stabilization).
 
Limitations
• Conducted only in Japan, limiting generalizability.
• Survey not validated and subject to recall bias.
• Patient and physician responses were not paired.
• Potential selection bias (patients from advocacy groups, relatively stable disease).
 
Why this survey study matters
This study identified consistent discrepancies between patient and physician perceptions of communication and decision-making in NDMM care. Patients’ expectations, emotional states, and knowledge evolve over time, underscoring the need for ongoing, adaptive communication. Improving alignment between patient preferences and clinical practice, particularly regarding shared decision-making, may enhance patient satisfaction and overall care quality.
 
Reference:
H.Hanamoto, M.Iino, K.Joko, et al. “A Survey Study of Patient-Physician Communication and Treatment Decision-Making Preference at Treatment Initiation and After Disease Stabilization in Newly Diagnosed Multiple Myeloma.” eJHaem7, no. 2 (2026): e70247. https://doi.org/10.1002/jha2.70247 (https://onlinelibrary.wiley.com/doi/10.1002/jha2.70247)

Real-world incidence of severe infections in multiple myeloma patients receiving bispecific antibodies: a meta-analysis — Annals of Hematology (April 2026)
 

What is the purpose of the study?
To determine the real-world incidence of severe (grade 3–4) infections in patients with relapsed/refractory multiple myeloma (RRMM) treated with bispecific antibodies. It also explores factors associated with infection risk and compares outcomes between commonly used agents, such as teclistamab and talquetamab.

Summary
This systematic review and meta-analysis included 10 retrospective studies with 1,373 RRMM patients treated with bispecific antibodies,[JM8]  showing a pooled severe infection rate of 25% (95% CI, 0.22–0.30) over a median follow-up of 8.3 months. Infection rates were similar between teclistamab (26%) and talquetamab (23%), suggesting a class-related effect of T-cell–redirecting therapies. An inverse association was observed between infection risk and prior lines of therapy or prior BCMA exposure, likely reflecting selection of fitter patients in real-world settings.
 
Key points
• Approximately 1 in 4 patients (25%) receiving bispecific antibodies developed grade 3–4 infections.
• Comparable infection rates between teclistamab (26%) and talquetamab (23%), suggesting a class effect.
• Infection risk is linked to immunosuppression and hypogammaglobulinemia from T-cell–redirecting therapy.
• Inverse relationship between infection rates and prior therapies/BCMA exposure, likely due to selection bias.
• Findings are consistent with prior studies reporting ~30% severe infection rates.
 
Strengths
• Large pooled sample size (1,373 patients).
• Focus on real-world data, improving clinical applicability.
• Use of meta-analysis methods with subgroup and meta-regression analyses.
 
Limitations
• Predominantly retrospective studies, increasing risk of bias.
• Heterogeneity in patient populations, follow-up, and reporting.
• Limited data for talquetamab (fewer studies).
• Inconsistent reporting of infection prevention strategies.
 
Why this study matters
Severe infections occur in about 25% of RRMM patients treated with BiTEs, confirming infection risk as a significant clinical concern with these therapies. The similar rates between agents support the idea of a class-wide effect rather than drug-specific toxicity. These findings highlight the importance of proactive monitoring and preventive strategies, including immunoglobulin replacement, prophylaxis, and vaccination, in routine clinical care.

 
Reference:
Spataro, F., Desantis, V., Einsele, H. et al. Real-world incidence of severe infections in multiple myeloma patients receiving bispecific antibodies: a meta-analysis. Ann Hematol 105, 269 (2026). https://doi.org/10.1007/s00277-026-07026-9 (https://link.springer.com/article/10.1007/s00277-026-07026-9)

Performance and additional benefits of MALDI-TOF-MS in M-protein detection in plasma cell disorders — Annals of Medicine (April 2026)

What is the purpose of the study?
To evaluate the performance of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) for detecting monoclonal (M) proteins in patients with plasma cell disorders (PCDs), compared with standard methods such as immunofixation electrophoresis (IFE), serum protein electrophoresis (SPEP), and serum free light chains (sFLC). It also assesses whether MALDI-TOF-MS provides additional molecular information, including light chain (LC) glycosylation and post-translational modifications (PTMs).

Summary
In 137 newly diagnosed PCD patients, MALDI-TOF-MS showed a higher detection rate for M-proteins (98.5%) than SPEP (75.9%), IFE (86.9%), sFLC (71.5%), and urine IFE (76.0%). Sensitivity varied by subtype, with higher detection for IgG (93.5%) than IgA (65.5%), moderate performance for κ (75.8%) and λ (80.0%) light chains, and limitations in heavy chain discrimination. The method also detected LC glycosylation and PTMs, with preliminary findings from a very small subset suggesting that changes in glycosylation patterns may correlate with treatment response.
 
Key points
• Higher detection rate: MALDI-TOF-MS outperformed conventional methods for identifying M-proteins in serum samples.
• Subtype variability: Sensitivity differed by immunoglobulin type (higher for IgG, lower for IgA), light chains, and was less robust for heavy chains.
• Additional molecular insights: Capable of detecting LC glycosylation (17 patients) and PTMs (4 patients).
• Potential monitoring role: Changes in glycosylation peaks were associated with treatment response in a very small subset of patients.
• Sample considerations: Serum samples showed better performance than plasma samples.
 
Strengths
• Direct comparison with established diagnostic standards (SPEP, IFE, sFLC).
• Inclusion of multiple PCD subtypes (e.g., multiple myeloma, AL amyloidosis, MGUS).
• Ability to detect additional molecular features beyond standard assays.
 
Limitations
• No negative control group, limiting assessment of specificity.
• Small sample size, particularly for subgroup and treatment-response analyses.
• Limited evaluation of the quantitative clinical significance of MALDI-TOF-MS findings.
 
Why this study matters
MALDI-TOF-MS demonstrated a high detection rate for M-proteins and provided additional molecular information, such as LC glycosylation and PTMs, that are not captured by conventional methods. While preliminary findings in a very small number of patients suggest a possible association between glycosylation changes and treatment response, further validation in larger cohorts is needed. Overall, MALDI-TOF-MS may serve as a complementary or alternative tool for diagnosing and managing plasma cell disorders.
 
Reference:
Dong, M., Ye, H., Xiao, X., Li, F., Yan, H., Chen, J., … Cai, Z. (2026). Performance and additional benefits of MALDI-TOF-MS in M-protein detection in plasma cell disorders. Annals of Medicine, 58(1). https://doi.org/10.1080/07853890.2026.2654933 (https://www.tandfonline.com/doi/full/10.1080/07853890.2026.2654933#abstract)
 

Targeted therapeutics and U.S. population-level mortality trends in multiple myeloma: A SEER-based analysis from 1975 to 2023 — Oncotarget (April 2026)
 

What is the purpose of the study?
Using U.S. SEER data (1975–2023), this study evaluates trends in multiple myeloma (MM)–specific mortality and examine how these trends align with major treatment advances, including autologous stem cell transplantation (ASCT), immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), monoclonal antibodies, CAR T-cell therapies, and bispecific antibodies.

Summary
In this retrospective population-based analysis, MM mortality increased from 1975–1994 (APC +1.43%), followed by progressive declines associated with successive treatment eras, including ASCT (1994–2002, –0.70%) and IMiDs/PIs (2002–2009, –1.85%). After a plateau (2009–2014), mortality declined again (2014–2021, –1.73%) and showed the steepest reduction from 2021–2023 (–5.64%), coinciding with the introduction of CAR T-cell therapies (e.g., ide-cel, cilta-cel) and bispecific antibodies (e.g., teclistamab). These findings suggest improved survival at the population level, although causality cannot be confirmed.
 
Key points
• Long-term trends: MM mortality rose until the mid-1990s, then declined in phases corresponding to therapeutic innovations.
• Major treatment milestones:
 - ASCT associated with initial mortality decline (1994–2002).
 - IMiDs and PIs linked to further reductions (2002–2009).
 - Monoclonal antibodies and combination therapies supported continued improvement (2014–2021).
 - CAR T-cell therapies and bispecific antibodies aligned with the steepest recent decline (2021–2023).

• Clinical impact: Advances have transformed MM into a more chronic, treatable disease with improved survival outcomes.
• Ongoing challenges: Increased treatment complexity, long-term toxicities (e.g., cytopenias, neuropathy), and rising costs.
 
Strengths
• Large, nationally representative SEER dataset.
• Long follow-up period (1975–2023) covering multiple treatment eras.
• Use of age-adjusted mortality rates for consistent comparisons.
 
Limitations
• Observational, retrospective design with potential confounding and bias.
• Lack of detailed clinical data (e.g., cytogenetics, MRD status, specific treatments).
• Temporal associations do not establish causation.
• Variability in treatment access and reporting across populations.
 
Why this study matters
Multiple myeloma mortality in the United States has declined substantially over the past five decades, with the most pronounced improvement occurring after the introduction of advanced immunotherapies such as CAR T-cell therapies and bispecific antibodies. These population-level trends align with major therapeutic advances but do not prove direct causation. Continued efforts are needed to address treatment-related toxicity, cost, and disparities in access to ensure sustained and equitable improvements in outcomes.
 
Reference:
Kahlon N., Bansal N., Baddam S., Rajput J., Qureshi Z. Targeted therapeutics and U.S. population-level mortality trends in multiple myeloma: A SEER-based analysis from 1975 to 2023. Oncotarget. 2026; 17: 216-225. https://doi.org/10.18632/oncotarget.28877 (https://www.oncotarget.com/article/28877/text/) 

Efficacy and safety of talquetamab in relapsed/refractory multiple myeloma and renal impairment: a quaternary cancer center cohort — Blood Cancer Journal (April 2026)
 

What is the purpose of the study?
To evaluate the safety and effectiveness of talquetamab (Tal), a GPRC5D-targeting bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM) with and without renal impairment (RI), including those with severe RI and dialysis dependence. It aims to address the lack of clinical trial data in this high-risk population.

Summary
In this retrospective cohort study of 36 heavily pretreated RRMM patients, outcomes with talquetamab were compared between those with RI (n=12) and without RI (n=24). Safety profiles, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), were similar across groups, with mostly low-grade events. Efficacy outcomes showed comparable or improved overall response rates (ORR) and progression-free survival (PFS) in patients with RI, including those with severe RI and are on dialysis.

Key points
• Patient population: 36 RRMM patients; 33.3% had renal impairment, including severe RI and dialysis-dependent subgroups
• Treatment: Subcutaneous talquetamab with step-up dosing followed by maintenance

• Safety:
 - CRS occurred in 66.7% of both groups, mostly low-grade
 - ICANS was less frequent and similar between groups
 - Infection rates were low and comparable

• Efficacy:
 - Day-30 ORR: 50% (RI) vs 45.8% (no-RI)
 - Day-90 ORR: 66.7% (RI) vs 25% (no-RI)
 - PFS: 8.48 months (RI) vs 2.63 months (no-RI), statistically significant
 - Activity observed in severe RI and dialysis patients

Strengths
• Inclusion of underrepresented high-risk population (RI, dialysis)
• Real-world clinical data reflecting routine practice

Limitations
• Retrospective, single-center design
• Small sample size, especially in subgroups
• Short follow-up duration limiting long-term outcomes
 
Why this study matters
Talquetamab demonstrated manageable safety and meaningful clinical activity in RRMM patients regardless of renal function, including those with severe impairment and dialysis dependence. Outcomes suggest that renal impairment does not reduce treatment effectiveness and may be associated with longer progression-free survival. Larger, prospective studies are needed to confirm these findings and better define long-term outcomes in this population.
 
Reference:
Ali, H.M., Mazzoni, S., Goel, U. et al. Efficacy and safety of talquetamab in relapsed/refractory multiple myeloma and renal impairment: a quaternary cancer center cohort. Blood Cancer J. 16, 65 (2026). https://doi.org/10.1038/s41408-026-01512-z (https://www.nature.com/articles/s41408-026-01512-z)

When Timing Matters Most: Early Relapse Outweighs Baseline Risk in Myeloma — Cancer Medicine (April 2026)

What is the purpose of the study?
To examine whether traditional baseline risk factors (such as cytogenetics and ISS stage) continue to predict outcomes in patients with functionally high-risk multiple myeloma (FHRMM), defined by early relapse within 12 months of initial therapy or autologous stem cell transplant. It aims to determine if early relapse itself overrides baseline risk stratification in predicting overall survival.

Summary
Using data from the CoMMpass study, 181 patients with FHRMM were analyzed and categorized into standard-risk and high-risk groups based on baseline features. Despite more favorable initial profiles, standard-risk patients had similar overall survival compared to high-risk patients (20.7 vs. 18.1 months, p=0.059), with comparable treatments and response rates across groups. Within this cohort, only ISS stage I remained associated with improved survival, indicating that early relapse is a dominant predictor of poor outcomes regardless of baseline risk. 

Key points
• Early relapse within 12 months defines functionally high-risk multiple myeloma (FHRMM) and is associated with poor prognosis (median OS ~19 months).
• Baseline risk stratification (cytogenetics, gene expression such as SKY92) did not significantly differentiate survival outcomes in FHRMM.

• Standard-risk and high-risk groups had similar:
 - Overall survival (20.7 vs. 18.1 months)
 - Treatment regimens (e.g., PI–IMiD combinations)
 - Response rates (~44–45% achieving ≥VGPR)

• ISS stage retained prognostic value:
 - Stage I: median OS 57.7 months
 - Stage II/III: ~17–18 months

• Emerging therapies (e.g., anti-CD38 antibodies, BCMA-targeted CAR T-cell therapies) show promising response rates in early relapse settings.
 
Strengths
• Use of a large, prospective dataset (CoMMpass) with longitudinal follow-up
• Clear definition of FHRMM focusing on early relapse after initial response
• Comprehensive comparison of clinical, genomic, and treatment variables
 
Limitations
• Relatively small FHRMM sample size (n=181), limiting statistical power
• Use of ISS rather than more advanced staging systems (R-ISS, R2-ISS)
• Missing prognostic variables (e.g., extramedullary disease)
• Data predates widespread use of newer therapies (e.g., anti-CD38 in frontline setting)
 
Why this study matters
In patients with multiple myeloma who relapse early, prognosis is uniformly poor and largely independent of baseline risk features, suggesting that early relapse itself defines a high-risk disease state. ISS stage remains the only baseline factor with retained prognostic value in this setting. These findings support prioritizing effective salvage strategies and clinical trial enrollment, including consideration of newer immunotherapies such as CAR T-cell approaches.
 
 
Reference:
X.Shan and S. P.Susanibar-Adaniya, “When Timing Matters Most: Early Relapse Outweighs Baseline Risk in Myeloma,” Cancer Medicine15, no. 5 (2026): e71900, https://doi.org/10.1002/cam4.71900. (https://onlinelibrary.wiley.com/doi/10.1002/cam4.71900)
 
 

Peripheral blood cfDNA detection using clonoSEQ assay in multiple myeloma is concordant with bone marrow and clinical biomarkers — Blood Cancer Journal (April 2026)

What is the purpose of the study?
To evaluate whether peripheral blood (PB) cell-free DNA (cfDNA) testing using the clonoSEQ® next-generation sequencing assay can reliably detect minimal residual disease (MRD) and reflect disease burden in multiple myeloma compared with bone marrow (BM) assessments. It aims to determine the clinical utility of a less invasive, blood-based approach for MRD monitoring.

Summary
In a retrospective analysis of 149 PB samples from 100 patients with multiple myeloma, PB cfDNA results were compared with paired BM MRD status and conventional biomarkers (M-protein and free light chain ratio). PB cfDNA showed high specificity (90.1%) and positive predictive value (94.9%) for detecting MRD positivity but had low sensitivity (33.9%) and negative predictive value (21.7%), indicating limited ability to rule out disease when negative. PB cfDNA positivity correlated strongly with higher disease burden and clinical progression, while negativity was associated with deep treatment responses such as complete response. 

Key points
• Clinical relevance
 - PB cfDNA MRD testing using clonoSEQ® is feasible and less invasive than BM biopsy.
 - PB cfDNA status correlates with established disease markers (BM MRD, M-protein, free light chain ratio).

• Diagnostic performance
 - High specificity (90.1%) and PPV (94.9%) vs BM MRD → reliable when positive.
 - Low sensitivity (33.9%) and NPV (21.7%) → negative results do not exclude disease.

• Clinical associations
 - PB cfDNA positivity linked to active disease, relapse, and higher tumor burden.
 - PB cfDNA negativity associated with deep responses (CR/sCR, VGPR).

• Longitudinal findings: PB cfDNA trends mirrored treatment response and disease progression over time.

Strengths
• Use of paired PB and BM samples across disease stages.
• Integration with multiple clinical biomarkers and longitudinal data.
• Standardized NGS-based assay with defined detection thresholds.

Limitations
• Retrospective design and relatively small sample size.
• Limited sensitivity, especially in patients with low tumor burden.
• Non-standardized sampling timepoints.
• Approximately 10% of patients lack identifiable clonotypes for tracking.
 
Why this study matters
PB cfDNA MRD assessment using the clonoSEQ® assay demonstrates strong specificity and clinical correlation with disease burden in multiple myeloma, supporting its role as a complementary monitoring tool. However, limited sensitivity restricts its use as a standalone method to exclude residual disease, particularly in patients with deep responses. Prospective studies are needed to optimize detection strategies and define its role alongside bone marrow–based MRD testing.
 
Reference:
Wiedmeier-Nutor, J.E., Kosiorek, H.E., Arribas, M. et al. Peripheral blood cfDNA detection using clonoSEQ assay in multiple myeloma is concordant with bone marrow and clinical biomarkers. Blood Cancer J. 16, 66 (2026). https://doi.org/10.1038/s41408-026-01508-9 (https://www.nature.com/articles/s41408-026-01508-9)

Clinical outcomes with ciltacabtagene autoleucel among patients with relapsed/refractory multiple myeloma after four or more prior lines of therapy overall and among subgroups based on age, frailty, and CRAB symptoms — Current Medical Research and Opinion (April 2026)

What is the purpose of the study?
To describe and evaluate real-world outcomes of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)–directed CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 prior lines of therapy. It also explores outcomes across subgroups defined by age, frailty, and presence of CRAB symptoms.

Summary
In this retrospective analysis of 203 patients using electronic medical records (from February 2021-June 2025, Loopback Analytics), treatment-free interval (TFI) and overall survival (OS) were assessed after cilta-cel infusion, with a median follow-up of 17.6 months. Estimated rates of remaining treatment-free at 12 and 18 months were 85.5% and 76.5%, respectively, while OS rates were 95.1% and 93.0%. Outcomes appeared broadly similar across subgroups, although analyses were descriptive and older patients (≥75 years) had numerically lower estimates. 
 

Key points

• Clinical context
 - Evaluates real-world outcomes of cilta-cel in heavily pretreated RRMM (≥4 prior lines of therapy).
 - Includes subgroups often underrepresented in clinical trials (older, frail, symptomatic patients).

• Outcomes measured
 - Treatment-free interval (TFI) used as a proxy for progression-free survival (PFS).
 - TFI estimates: 85.5% at 12 months; 76.5% at 18 months.
 - Overall survival (OS): 95.1% at 12 months; 93.0% at 18 months.

• Subgroup findings
 - Outcomes appeared generally consistent across age, frailty, and CRAB symptom subgroups.
 - Older patients showed numerically lower TFI and OS estimates.
 - Analyses were descriptive, without statistical comparisons or adjustments.

Strengths
• Reflects routine clinical practice using real-world data.
• Includes clinically relevant subgroups (age, frailty, disease severity).
• Provides follow-up beyond 12 months in a real-world setting.

Limitations
• Retrospective, descriptive design without a control group.
• Use of TFI as a proxy for PFS may overestimate disease control.
• Limited clinical detail (e.g., cytogenetics, direct progression data).
• Potential missing or misclassified data in electronic medical records.
• Small subgroup sizes and lack of standardized data collection.
 
Why this study matters
In this real-world, descriptive study, cilta-cel was associated with high estimated overall survival and treatment-free rates at 12 and 18 months in patients with RRMM after multiple prior therapies. These outcomes appeared similar across examined subgroups, although interpretations are limited by the non-comparative design and use of surrogate endpoints. Further prospective and comparative studies are needed to better define outcomes and subgroup differences.
 
 
Reference:
Hansen, D. K., Castaneda Puglianini, O. A., Grajales-Cruz, A., Nagar, S. P., Ghosh, S., Fan, L., … Janakiram, M. (2026). Clinical outcomes with ciltacabtagene autoleucel among patients with relapsed/refractory multiple myeloma after four or more prior lines of therapy overall and among subgroups based on age, frailty, and CRAB symptoms. Current Medical Research and Opinion, 1–9. https://doi.org/10.1080/03007995.2026.2660494 (https://www.tandfonline.com/doi/full/10.1080/03007995.2026.2660494#d1e1019)

Immune biomarkers of increased infection risk in multiple myeloma — Blood (April 2026)
 

What is the purpose of the study?
To identify immune biomarkers associated with infection risk in patients with multiple myeloma, and to determine whether these markers could be measured in peripheral blood as a minimally invasive surrogate for bone marrow immune status.
 
Summary
Researchers performed immune profiling using next-generation flow cytometry on bone marrow and peripheral blood samples from 1,786 patients with multiple myeloma across different disease stages and treatment settings. They found that lower CD27+ B cells, lower CD27− natural killer (NK) cells, and an increased CD27−/CD27+ T-cell ratio were associated with a higher risk of infection. These findings were validated in three independent cohorts, and an immune score combining these factors was significantly associated with infection incidence (60% vs 35%, P < .001) and independently predicted infection risk alongside disease stage and therapies targeting CD38, B-cell maturation antigen (BCMA), or G protein-coupled receptor class C group 5 member D (GPRC5D). 
 

Key points
• Immune alterations in bone marrow associated with multiple myeloma progression and treatment can be reflected in peripheral blood measurements.
• Lower CD27+ B cells, lower CD27− NK cells, and an increased CD27−/CD27+ T-cell ratio are independent risk factors for infection.
• An immune score incorporating these markers stratifies patients by infection risk (60% vs 35% incidence; OR 2.31, P < .001).
• Findings were validated across three independent datasets, supporting reproducibility.
• Immune biomarkers were detectable using routine laboratory methods, supporting potential clinical applicability.
 
Strengths
• Large multicenter cohort (n=1,786)
• Validation in independent datasets
• Use of clinically accessible immune profiling techniques.  

Limitations
• Observational design limits causal inference
• Infection risk may be influenced by heterogeneous treatments and disease stages
 
Why this study matters
This study identifies specific immune cell alterations in multiple myeloma that are associated with increased infection risk and can be assessed using both bone marrow and peripheral blood samples. An immune-based risk score incorporating CD27-related B-cell, NK-cell, and T-cell markers provides stratification of infection risk and shows independent predictive value alongside disease stage and therapy type. These findings suggest that immune profiling may help identify patients at higher risk of infection, although further prospective studies are needed to confirm clinical utility.
 
 
Reference:
Aintzane Zabaleta, Luis-Esteban Tamariz-Amador, Ioannis V. Kostopoulos, Romanos Sklavenitis-Pistofidis, Febe Smits, Paula Rodriguez-Otero, Carmen Roncal, Michelle P. Aranha, David Zihala, Michaela Machu, Nikolaos Tsakirakis, Panagiotis Bakouros, Ourania Tsitsilonis, Irene Solia, Cristina Moreno, Catarina Maia, Esperanza Martin-Sanchez, José J. Perez, Cristina Encinas, Rafael Rios-Tamayo, Albert Oriol, María-Jesús Blanchard, Felipe de Arriba, María-Esther Gonzalez, Sunil Lakhwani, Anna Sureda, Valentin Cabañas, Fernando Escalante, Estrella Carrillo-Cruz, Albert Pérez-Montaña, Enrique M. Ocio, Joan Bargay, Alberto Orfao, Tomas Jelinek, Irene M. Ghobrial, Tuna Mutis, Sonja Zweegman, Evangelos Terpos, Efstathios Kastritis, Joaquin Martinez-Lopez, Juan-José Lahuerta, Carlos Fernandez de Larrea, Laura Rosiñol, Joan Bladé, Maria-Victoria Mateos, Jesús San-Miguel, Maria-Teresa Cedena, Noemi Puig, Bruno Paiva; Immune biomarkers of increased infection risk in multiple myeloma. Blood 2026; 147 (18): 2081–2088. doi: https://doi.org/10.1182/blood.2025031744 (https://ashpublications.org/blood/article-abstract/147/18/2081/566336/Immune-biomarkers-of-increased-infection-risk-in)

 

The Association of Age and Frailty With Adverse Events for Bortezomib and Carfilzomib: A Population-Based Analysis — American Journal of Hematology (April 2026)
 

What is the purpose of the study?
To evaluate how age and frailty influence the risk of new-onset adverse events in patients with multiple myeloma treated with proteasome inhibitors, bortezomib and carfilzomib. It also directly compares the safety profiles of these two drugs across a large, diverse patient population.

Summary
In this retrospective cohort study of 23,766 patients from the TriNetX database, increasing age and higher frailty were associated with greater risks of cardiovascular, infectious, and thromboembolic adverse events, including dyspnea and heart failure, for both bortezomib and carfilzomib. Carfilzomib showed higher adjusted odds of dyspnea (OR 1.49), heart failure (OR 1.27), lung infection (OR 1.17), and thromboembolic events (OR 1.68), but lower odds of peripheral neuropathy (OR 0.82) compared with bortezomib. Peripheral neuropathy with bortezomib showed only a small numerical increase with age, while frailty was a more consistent predictor of adverse events across multiple categories than age alone.
 
Key points
• Large retrospective real-world study including 23,766 patients with multiple myeloma treated between 2009 and 2025.
• Increasing age and frailty were associated with higher rates of cardiovascular (dyspnea, heart failure), infectious, and thromboembolic adverse events.
• Carfilzomib was associated with higher risks of cardiovascular and thromboembolic events but lower risk of peripheral neuropathy compared with bortezomib.
• Peripheral neuropathy with bortezomib did not meaningfully increase with age, showing only small numerical differences across age groups.
• Frailty (measured by mFI-10) was a stronger and more consistent predictor of adverse events across multiple outcomes than chronological age.
• Rates of neuropathy, heart failure, and lung infection with bortezomib decreased over time, while thromboembolic events increased; most adverse event rates with carfilzomib remained stable over time except for thromboembolism.
 
Strengths
• Large, diverse real-world dataset improving generalizability, especially to older adults.
• Direct comparison of two commonly used proteasome inhibitors within the same cohort.
• Multivariable adjustment for key confounders (age, frailty, sex, race, treatment line).
 
Limitations
• Retrospective observational design limits causal interpretation.
• Reliance on administrative coding may underestimate adverse events, especially milder cases.
• Lack of detailed data on dosing, treatment duration, and route of administration.
• Potential missing data from healthcare systems outside the TriNetX network.
• Exclusion of patients with prior adverse events may underestimate true incidence rates.
 
Why this study matters
Carfilzomib is associated with higher risks of cardiovascular and thromboembolic adverse events compared with bortezomib, while bortezomib carries a higher risk of peripheral neuropathy. Both age and frailty increase the likelihood of adverse events, but frailty is a more consistent predictor across multiple outcomes than age alone. These findings support incorporating frailty assessment and individualized risk evaluation into treatment decisions rather than relying solely on chronological age.
 
Reference:
M.Lemieux, F.Chunara, A.Szabo, et al., “The Association of Age and Frailty With Adverse Events for Bortezomib and Carfilzomib: A Population-Based Analysis,” American Journal of Hematology (2026): 1–5, https://doi.org/10.1002/ajh.70349. (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70349)
 

Use of CD38 antibodies in high-risk newly diagnosed Multiple Myeloma – A meta-analysis — Clinical Lymphoma Myeloma and Leukemia (April 2026) 

What is the purpose of the study?
To evaluate whether adding anti-CD38 monoclonal antibodies (daratumumab or isatuximab) to frontline treatment improves outcomes in patients with newly diagnosed multiple myeloma (NDMM), including those with high-risk disease. It specifically assesses progression-free survival (PFS) across transplant-eligible and transplant-ineligible settings.

Summary
In this meta-analysis, data from nine prospective clinical trials (MAIA, ALCYONE, CEPHEUS, IMROZ, OCTANS, CASSIOPEIA, GRIFFIN, PERSEUS, and GMMG-HD7) were analyzed to compare outcomes with and without anti-CD38 monoclonal antibodies. The addition of these agents improved progression-free survival in both standard-risk (HR 0.51; 95% CI 0.46–0.58) and high-risk patients (HR 0.64; 95% CI 0.49–0.84). While benefits were observed across all groups, the magnitude of improvement was smaller in high-risk patients, particularly in non-transplant settings.
 
Key points
• Anti-CD38 monoclonal antibodies (Daratumumab, Isatuximab) improved progression-free survival in NDMM.
• Benefit was seen in both standard-risk (HR 0.51) and high-risk patients (HR 0.64).
• Standard-risk patients had consistent benefit regardless of transplant status.
• High-risk patients showed greater benefit in transplant studies (HR 0.57) than non-transplant studies (HR 0.71).
• Strengths: Inclusion of 9 prospective clinical trials; large pooled dataset; analysis of both risk groups and treatment settings.
• Limitations: Variability across trials (heterogeneity in design and populations); less pronounced benefit in high-risk and non-transplant subgroups; meta-analysis design limits causal inference compared to a single randomized trial.
 
Why this study matters
Adding anti-CD38 monoclonal antibodies to frontline therapy improves progression-free survival in patients with newly diagnosed multiple myeloma, including those with high-risk disease. However, the magnitude of benefit is smaller in high-risk patients, particularly in non-transplant settings. These findings support the use of CD38-targeted therapies while highlighting the need for optimized strategies for high-risk populations.
 
Reference:
Divaya Bhutani, Yusha Liu, Rajshekhar Chakraborty, Michael Hughes, Suzanne Lentzsch, Samuel Rubinstein, Use of CD38 antibodies in high-risk newly diagnosed Multiple Myeloma – A meta-analysis, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.04.016. (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(26)00127-8/abstract)
 

Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma — Blood Neoplasia (May 2026)
 

What is the purpose of the study?
To understand the molecular and cellular mechanisms that influence the function and persistence of B-cell maturation antigen (BCMA)–targeted CAR T cells in patients with multiple myeloma. Using single-cell multiomics, researchers analyze how CAR T-cell behavior evolves over time in bone marrow and peripheral blood.

Summary
The study found that CAR T cells in the bone marrow were more activated and exhausted compared to those in peripheral blood, which retained more memory-like features associated with longer persistence. Impaired transition from effector to memory states led to increased terminally differentiated CAR T cells and reduced long-term survival of these cells. Additionally, a hyperexpanded IL-10–producing CAR T-cell clone, likely driven by combined CAR and T-cell receptor (TCR) activation, was identified in a patient with partial response and may contribute to reduced treatment effectiveness.
 
Key points
• Impaired effector-to-memory transition is associated with increased terminal differentiation and reduced CAR T-cell persistence.
• Bone marrow CAR T cells show higher activation and exhaustion, while peripheral blood CAR T cells display more memory-associated features.
• Early expansion is dominated by CD8+ CAR T cells, with minimal CD4+ representation post-infusion.
• A hyperexpanded IL-10–producing CD8+ CAR T-cell clone was observed in a partial responder, potentially linked to treatment resistance.
• Dual activation through CAR and endogenous TCR increases IL-10 production, which may impair CAR T-cell proliferation and persistence.
 
Strengths
• Use of single-cell multiomics provides detailed, high-resolution insight into CAR T-cell dynamics.
• Longitudinal sampling from both bone marrow and peripheral blood allows comparison across compartments and over time.
 
Limitations
• Exploratory study with limited patient sample size, which may reduce generalizability.
• Findings require further validation in larger cohorts and clinical trials.
 
Why this study matters
This study identifies key mechanisms affecting CAR T-cell persistence in multiple myeloma, including impaired memory formation, increased exhaustion in the bone marrow, and IL-10–associated clonal expansion. These findings suggest that targeting terminal differentiation, immune exhaustion pathways, and TCR-mediated signaling may improve CAR T-cell durability. Further research is needed to confirm these results and translate them into optimized therapeutic strategies.
 
 
Reference:
Lorea Jordana-Urriza, Guillermo Serrano, Sergio Camara-Peña, Maria E. Calleja-Cervantes, Patxi San Martin-Uriz, Aintzane Zabaleta, Aina Oliver-Caldes, Marta Español-Rego, Diego Alignani, Teresa Lozano, Saray Rodriguez-Diaz, Elena Iglesias, Valentin Cabañas, Juan L. Reguera, Veronica Gonzalez-Calle, Maria V. Mateos, Fermin Sanchez-Guijo, Bruno Paiva, Juan J. Lasarte, Susana Inoges, Ascension Lopez-Diaz de Cerio, Azucena Gonzalez-Navarro, Manel Juan, Carlos Fernandez de Larrea, Esteban Tamariz, Ana Alfonso-Pierola, Paula Rodriguez-Otero, Jesus F. San-Miguel, Mikel Hernaez, Juan R. Rodriguez-Madoz, Felipe Prosper; Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma. Blood Neoplasia 2026; 3 (2): 100203. doi: https://doi.org/10.1016/j.bneo.2026.100203 (https://www.sciencedirect.com/science/article/pii/S2950328026000142?via%3Dihub)
 

A differentiated effector T cell repertoire defines a functionally high-risk group of smoldering myeloma patients — Blood Cancer Journal (May 2026)

What is the purpose of the study?
To evaluate whether peripheral blood T-cell immune profiles are associated with early progression from smoldering multiple myeloma (SMM) to active multiple myeloma (MM), independent of tumor burden–based risk models. It aims to identify immune features that may help distinguish patients at higher risk of progression.

Summary
Researchers analyzed peripheral blood samples from 18 risk-matched SMM patients (9 with early progression and 9 without progression) using spectral cytometry, plasma proteomics, and a random forest model. Early progression was associated with increased terminally differentiated and exhausted T cells (including CD8+ and CD4+ TEMRA cells) and higher levels of inflammatory markers such as IL-18 and MMP-1. The model showed 75% accuracy in this small cohort and identified Granzyme B, Granzyme K, CD272 (BTLA), and CD45RA as markers associated with progression, though these findings are exploratory and not yet validated for clinical use. 

Key points
• Peripheral blood immune profiling identified T-cell features associated with early progression in SMM.
• Early progression correlated with increased exhausted and terminally differentiated T cells (TEMRA phenotype).
• Higher inflammatory markers were observed, including IL-18 (2-fold increase, p=0.0037) and MMP-1 (p=0.0065).
• A random forest model (75% accuracy in this dataset) identified key markers: Granzyme B, Granzyme K, CD272 (BTLA), and CD45RA.
• Findings suggest a potential “myeloma-like” immune phenotype, but this represents an association rather than a validated prognostic tool.
 
Strengths
• Use of high-dimensional immune profiling and machine learning.
• Risk-matched cohort design, reducing confounding from tumor burden–based risk models.
• Identification of measurable immune markers with potential translational relevance.
 
Limitations
• Very small sample size (n=18).
• Retrospective, single-center, exploratory study.
• No external or prospective validation, limiting generalizability and clinical applicability.
 
Why this study matters
Peripheral blood immune profiling identified T-cell characteristics associated with early progression in SMM, including increased differentiation, exhaustion, and inflammatory signaling. These findings suggest a possible link between immune dysfunction and progression risk, independent of traditional models. However, given the small, exploratory dataset, these results require validation in larger prospective studies before clinical use. 
 

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

Immunomodulatory Agent Adherence Trajectories and Survival Among Older Patients With Multiple Myeloma — JCO Oncology Practice (May 2026)

What is the purpose of the study?
To assess patterns of adherence to immunomodulatory agents (IMiDs) in Medicare beneficiaries with newly diagnosed multiple myeloma and identified patient characteristics associated with different adherence trajectories. It also evaluates the association between adherence patterns and overall survival.
 
Summary
Among 4,452 Medicare beneficiaries with newly diagnosed multiple myeloma (2007–2019), four IMiD adherence patterns were identified: persistently high (33.1%), quick decline then increase (17.5%), moderate decline (21.2%), and quick decline (28.2%). Poor adherence was associated with older age (≥85 years), higher comorbidity burden, presence of CRAB features (hypercalcemia, renal failure, anemia, bone disease), and low-income subsidy status; non-Hispanic Black patients were more likely to be in the lowest adherence group. Patients in poorer adherence groups had over a 20% higher risk of mortality compared with the persistently high adherence group, with descriptive analyses suggesting a median survival difference exceeding 12 months between the best and worst adherence groups.
 
Key points
• Adherence patterns: Four distinct longitudinal trajectories; only 33.1% maintained persistently high adherence.
• Risk factors for poor adherence: Advanced age (especially ≥85 years), higher comorbidity burden, CRAB features, and low-income subsidy status.
• Disparities: Non-Hispanic Black patients were more likely to fall into the lowest adherence (quick-decline) group.
• Survival association: Poor adherence was associated (not causal) with >20% increased mortality risk.

Strengths
• Large, population-based SEER-Medicare cohort.
• Use of group-based trajectory modeling to capture adherence changes over time.

Limitations
• Claims data measure prescription fills, not confirmed medication intake.
• Lack of key clinical variables (e.g., cytogenetics, performance status).
• Reasons for treatment interruption (e.g., toxicity) not captured.
• Inclusion required survival ≥1 year after IMiD initiation, which may underestimate poor adherence in patients with early mortality.
• Findings are primarily generalizable to older Medicare fee-for-service populations.
 
Why this study matters
iMiD adherence among Medicare beneficiaries with newly diagnosed multiple myeloma is frequently suboptimal and varies across distinct trajectories associated with clinical and socioeconomic factors, including CRAB features. Lower adherence is associated with significantly worse survival outcomes, although causality cannot be established from this observational study. These findings support the need for targeted, early interventions to improve adherence in higher-risk populations, particularly older adults, those with greater comorbidity burden, and individuals with socioeconomic disadvantage.
 
Reference:
Rong Wang et al. Immunomodulatory Agent Adherence Trajectories and Survival Among Older Patients With Multiple Myeloma. JCO Oncol Pract 0, OP-25-00615 DOI:10.1200/OP-25-00615 (https://ascopubs.org/doi/10.1200/OP-25-00615)
 

Ikaros degradation by mezigdomide reduces T-cell dysfunction and improves the efficacy of antimyeloma T-cell therapies — Blood (May 2026)
 

What is the purpose of the study?
To investigate whether mezigdomide can reduce T cell dysfunction and improve T cell activity in multiple myeloma (MM), with the aim of enhancing the effectiveness of anti-BCMA CAR-T cell therapy and bispecific T cell engager (TCE) therapies. It also examines the molecular mechanisms involved, particularly the role of the transcription factor Ikaros in regulating T cell exhaustion-related genes.
 
Summary
Using bone marrow samples from patients with multiple myeloma, the study found that mezigdomide reduced dysfunctional and exhausted-like T cell populations expressing markers such as TIGIT. In in vitro and preclinical in vivo models, mezigdomide improved T cell function, cytotoxicity, and the activity of bispecific TCE and anti-BCMA CAR-T therapies. Multi-omics analyses, including ATAC-seq, ChIP-seq, HiC, and RNA-seq, identified Ikaros as a regulator of exhaustion-associated genes, and mezigdomide-mediated degradation of Ikaros was associated with reduced expression of these genes and improved T cell activity.
 
Key points
• Mezigdomide reduced exhausted-like T cell populations in bone marrow samples from patients with multiple myeloma.
• Treatment decreased expression of T cell exhaustion markers, including TIGIT.
• Mezigdomide improved T cell function and cytotoxicity in in vitro models of T cell dysfunction and bispecific TCE therapy.
• The study identified a mechanistic role for Ikaros in regulating exhaustion-associated genes in T cells.
• In preclinical in vivo models, mezigdomide enhanced the activity of anti-BCMA CAR-T therapy and was associated with improved survival outcomes.
• Findings support further investigation of approaches targeting T cell dysfunction in multiple myeloma immunotherapy.
 
Strengths
• Included analyses of primary bone marrow samples from multiple myeloma patients.
• Combined functional experiments with multiple genomic and epigenomic techniques to investigate mechanisms.
• Evaluated effects in both in vitro and preclinical in vivo models.
 
Limitations
• Findings are primarily based on laboratory and preclinical models rather than clinical trials in patients.
• Clinical efficacy, durability of response, and long-term safety of combining mezigdomide with CAR-T or bispecific therapies remain unknown.
• The study focused mainly on mechanistic and translational findings rather than direct clinical outcomes in patients.
 
Why this study matters
The study found that mezigdomide reduced exhausted-like T cell populations and improved T cell function in preclinical models of multiple myeloma. Mechanistic analyses suggested that degradation of Ikaros reduced expression of exhaustion-associated genes such as TIGIT, and mezigdomide enhanced the activity of anti-BCMA CAR-T and bispecific T cell engager therapies in vitro and in vivo. Further clinical studies are required to determine whether these findings translate into patient benefit.
 
Reference:
Lucia Y Chen, Adolfo Aleman, Marta Larrayoz, Hsiling Chiu, Junfei Zhao, Oliver Van Oekelen, Geoffrey Kelly, Seunghee Kim-Schulze, Alessandro Lagana, Sundar Jagannath, Tracy T. Chow, Teresa Lozano, Juan J Lasarte, Joseph C. Hamley, Warren Baker, Benjamin L Ebert, Udo Oppermann, Michael D Amatangelo, Anita Krithivas Gandhi, Patrick Ryan Hagner, Jose A Martínez-Climent, Sarah Gooding, Thomas A Milne, Samir Parekh; Ikaros degradation by mezigdomide reduces T-cell dysfunction and improves the efficacy of antimyeloma T-cell therapies. Blood 2026; blood.2025030891. doi: https://doi.org/10.1182/blood.2025030891 (https://ashpublications.org/blood/article/doi/10.1182/blood.2025030891/568277/Ikaros-degradation-by-mezigdomide-reduces-T-cell)

Patient-reported outcomes after idecabtagene vicleucel vs. ciltacabtagene autoleucel CAR-T for multiple myeloma — Bone Marrow Transplantation (May 2026)

What is the purpose of the study?
To evaluate changes in patient-reported outcomes (PROs), including health-related quality of life (HRQoL), symptoms, emotional well-being, and cognitive function, among patients with relapsed/refractory multiple myeloma (RRMM) receiving standard-of-care CAR-T therapy. The study also compares PRO trajectories between two FDA-approved CAR-T therapies: idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel).
 
Summary
This prospective study included 99 patients with RRMM treated with ide-cel (n=49) or cilta-cel (n=50), with PRO assessments collected from before treatment through 90 days after CAR-T infusion. Many PRO measures, including overall HRQoL, physical well-being, functional well-being, fatigue, physical function, and social function, worsened before day 7 and improved after day 7, while anxiety, sleep disturbance, pain interference, and pain intensity remained stable before day 7 and improved afterward. By day 90, many PROs had returned to baseline levels or improved beyond baseline.
 
Overall, PRO trajectories were similar between ide-cel and cilta-cel recipients for most measures. Differences between treatment groups were observed in social well-being before day 7 and cognitive function after day 7, with cognitive function improving among cilta-cel recipients but not ide-cel recipients during the post-treatment period. The clinical significance and mechanisms underlying these differences remain uncertain and require further investigation. Findings were generally consistent with prior observations from the KarMMa and CARTITUDE-1 clinical trials.
 
Key points
• First study to compare longitudinal patient-reported outcomes between ide-cel and cilta-cel in standard clinical practice for RRMM.

• Included 99 patients:
 - ide-cel: 49 patients
 - cilta-cel: 50 patients

• ide-cel recipients were older than cilta-cel recipients (median age 73 vs. 64 years; p<0.001).
• PROs were assessed at baseline, infusion day, and days 7, 14, 21, 30, 60, and 90 after treatment.

• Many PROs worsened before day 7 and improved afterward, including:
 - Overall HRQOL
 - Physical well-being
 - Functional well-being
 - Fatigue
 - Physical function
 - Social function

• Several PROs remained stable before day 7 and improved afterward, including:
 - Anxiety
 - Sleep disturbance
 - Pain interference
 - Pain intensity

• Emotional well-being showed the largest improvement from baseline to day 90.
• Overall PRO trajectories were similar between ide-cel and cilta-cel for most measures.

• Differences between groups included:
 - Social well-being worsened before day 7 among cilta-cel recipients but not ide-cel recipients.
 - Cognitive function improved after day 7 among cilta-cel recipients but not ide-cel recipients.

• Cilta-cel recipients had higher rates of non-ICANS neurotoxicity than ide-cel recipients (14% vs. 0%).
• Findings were generally consistent with prior CAR-T studies, including the KarMMa and CARTITUDE-1 trials.
 
Strengths
• Prospective study design with serial longitudinal PRO assessments.
• Used validated and psychometrically robust PRO measures.
• High participant retention (>90% through day 90).
• Equal representation of ide-cel and cilta-cel recipients enabled direct comparison between therapies.
 
Limitations
• Single-center study design may limit generalizability.
• Participants were predominantly non-Hispanic White and highly educated.
• Treatment assignment was not randomized, introducing potential selection bias and confounding.
• Follow-up was limited to 90 days, preventing assessment of longer-term PRO trajectories and delayed toxicities.
• Racial and ethnic minority populations were underrepresented.
 
Why this prospective study matters
In patients with RRMM receiving standard-of-care CAR-T therapy, many patient-reported outcomes worsened or remained stable during the first week after treatment and improved afterward, with many measures returning to baseline levels or better by day 90. PRO trajectories were generally similar between ide-cel and cilta-cel recipients, although differences in social well-being and cognitive function were observed. Additional studies with larger and more diverse populations and longer follow-up are needed to clarify these findings and evaluate longer-term outcomes.
 
 
Reference:
Oswald, L.B., Li, X., Gudenkauf, L.M. et al. Patient-reported outcomes after idecabtagene vicleucel vs. ciltacabtagene autoleucel CAR-T for multiple myeloma. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02899-w (https://www.nature.com/articles/s41409-026-02899-w)

Clinical Tests

Clinical whole genome sequencing assay test consolidates multiple analyses and provides 72-hour molecular profile for myeloma patients — TGen and City of Hope (May 2026)
 

What is the purpose of the clinical test?
Translational Genomics Research Institute (part of City of Hope) launched JAYseq — a clinical whole-genome sequencing (WGS) test designed to identify genetic abnormalities in patients with multiple myeloma and related plasma cell disorders. The test aims to provide comprehensive genomic information within 72 hours to support treatment selection and risk assessment.
 
Summary
JAYseq is a WGS-based diagnostic test developed by the TGen Clinical Laboratory for patients with newly diagnosed, relapsed, or refractory multiple myeloma. Using proprietary ALTseq technology, the test analyzes the entire genome and detects mutations, insertions, deletions, copy number changes, translocations, and complex rearrangements from bone marrow samples.
 
According to a TGen media release, JAYseq provides results in approximately 72 hours and is intended to help clinicians identify high-risk disease features and evaluate eligibility for targeted therapies and immunotherapies, including CAR T-cell and bispecific antibody treatments. The launch builds on prior genomic research collaborations between TGen and the Multiple Myeloma Research Foundation through studies such as CoMMpass Study.
 
Key points
• JAYseq is a clinical WGS test for multiple myeloma and related plasma cell disorders.

• The test is intended for:
 - Newly diagnosed multiple myeloma
 - Related plasma cell disorders

• Results are reported within approximately 72 hours.
• The test analyzes all 3 billion base pairs of the genome rather than selected regions only.

• Detectable genomic alterations include:
 - Small mutations
 - Insertions and deletions
 - Copy number changes
 - Translocations
 - Complex genomic rearrangements

• The assay uses CD138+ magnetic cell sorting and high-throughput sequencing to improve tumor cell isolation from bone marrow samples.

• The test may help identify:
 - High-risk disease markers
 - Potential resistance-related mutations
 - Targets for immunotherapies such as CAR T-cell and bispecific antibody therapies

• Development of the test was supported by prior multiple myeloma genomic studies and philanthropic funding.
 
Strengths
• Comprehensive whole-genome analysis in a single test.
• Faster turnaround time compared with some conventional cytogenetic and FISH-based approaches.
• Potential to support personalized treatment planning and risk stratification.
 
Limitations
• The media release does not provide clinical validation data, sensitivity/specificity metrics, or patient outcome data.
• Comparative performance against existing standard-of-care testing was not quantitatively reported.
• Availability, cost, insurance coverage, and broader clinical implementation details were not discussed.
 
Why this clinical test matters
The launch of JAYseq introduces a rapid whole-genome sequencing approach for patients with multiple myeloma and related disorders. The test is designed to provide comprehensive genomic profiling that may assist clinicians in selecting targeted and immunotherapy-based treatments. However, the media release did not include detailed clinical performance or outcomes data, so the real-world impact on patient management and survival remains to be established through further study.
 
Reference:
New TGen Clinical Test For Multiple Myeloma Consolidates Multiple Analyses And Provides Detailed Information In 3 Days (https://www.tgen.org/news/new-tgen-clinical-test-for-multiple-myeloma-consolidates-multiple-analyses-and-provides-detailed-information-in-3-days/). TGen media release. May 7, 2026.

Clinical Trials

Ciltacabtagene autoleucel in high-risk smoldering multiple myeloma: the CAR-PRISM phase 2 trial — Nature Medicine (April 2026)
 

What is the purpose of the study?
To evaluate the safety and efficacy of the BCMA-directed CAR T cell therapy ciltacabtagene autoleucel (cilta-cel) in patients with high-risk smoldering multiple myeloma (HR-SMM), with the objective of assessing whether early, single-infusion CAR T therapy without induction or bridging treatment could induce deep minimal residual disease (MRD)-negative responses and delay or prevent progression to symptomatic multiple myeloma.

Summary
Twenty patients with HR-SMM, excluding those with >40% bone marrow involvement, received a single infusion of cilta-cel at two dose levels (0.3–0.5 × 10⁶ or >0.5 × 10⁶ CAR+ T cells/kg) without induction or bridging therapy. No dose-limiting toxicities occurred; cytokine release syndrome (CRS) occurred in all patients but was limited to grade 1–2 with proactive management, and transient grade 3/4 cytopenias were observed in 90%. All patients achieved MRD negativity (10⁻⁶) within 2 months and remained MRD negative at a median follow-up of 15.3 months, though long-term durability beyond this follow-up period remains unconfirmed; 16 patients with ≥6 months of follow-up achieved complete response, and no progression or deaths were reported.
 
Key points
• Intervention & design
 - Single-arm, phase 2 trial of cilta-cel in HR-SMM
 - No induction or bridging therapy (“one-and-done” approach)
 - Excluded patients with >40% bone marrow plasma cell involvement

• Efficacy outcomes
 - 100% of patients achieved MRD negativity (10⁻⁶) by 2 months
 - MRD negativity was sustained through a median 15.3-month follow-up, but long-term durability is not yet established
 - 16/20 patients with ≥6 months follow-up achieved complete response
 - No reported disease progression or deaths during follow-up

• Safety outcomes
 - No dose-limiting toxicities observed
 - CRS occurred in 100% of patients but was limited to grade 1–2 and managed proactively
 - Grade 3/4 cytopenias occurred in 90% and were transient
 - Neurologic toxicities (NINTs) occurred in 7 patients:4 cases of cranial nerve palsies (mostly reversible); 3 patients had persistent grade 1 symptoms

Strengths
• First prospective study of CAR T therapy in a precursor plasma cell disorder
• Uniform MRD-negative responses across all patients
• Demonstrates feasibility of early, single-infusion CAR T strategy without prior cytoreduction
• Consistent safety profile aligned with known cilta-cel toxicity patterns

Limitations
• Small sample size (n=20) and single-center, single-arm design
• Limited follow-up for a precursor disease setting; durability of response remains uncertain
• Exclusion of higher tumor burden (>40% marrow involvement) limits generalizability
• No comparator arm, preventing direct efficacy comparison to other early interventions
 
Why this study matters
In this phase 2 study, cilta-cel induced universal and rapid MRD-negative responses in patients with high-risk smoldering multiple myeloma, with a manageable safety profile consistent with known CAR T–related toxicities. Although responses have been sustained over a median follow-up of 15.3 months, the long-term durability and potential to prevent progression remain unproven. Further studies with larger cohorts and longer follow-up are needed to define the role of early CAR T therapy in altering disease trajectory in HR-SMM.
 
Reference:
Nadeem, O., Cordas dos Santos, D.M., Nikiforow, S. et al. Ciltacabtagene autoleucel in high-risk smoldering multiple myeloma: the CAR-PRISM phase 2 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04365-y (https://www.nature.com/articles/s41591-026-04365-y)
 

iPREFER: Patients’ Experiences and Preference of Treatment for Multiple Myeloma Following Multiple Lines of Treatment – A Qualitative Study — Patient Preference and Adherence (April 2026)
 

What is the purpose of the study?
To explore the experiences of patients with multiple myeloma (MM) receiving multiple lines of therapy, focusing on treatment decision-making, preferences, and factors influencing quality of life. The qualitative study aims to identify patient priorities and how these shape treatment choices in the context of long-term, multi-line cancer therapy. (ClinicalTrials.gov Identifier: NCT06322927)
 
Summary
Nine semi-structured interviews were conducted with patients who had received at least five lines of MM treatment, including oral, intravenous (IV), and subcutaneous therapies. Four themes were identified: the impact of MM on quality of life, factors influencing treatment decisions (including family involvement and information needs), treatment experience (including practical and self-management challenges), and treatment preferences shaped by individual circumstances. While experiences varied, patients often prioritized life extension or disease control and were generally willing to accept substantial treatment burdens in pursuit of these goals, though preferences were not uniform across participants or treatment modalities.
 
Key points
• Study design: Qualitative study using semi-structured interviews with 9 patients with MM (≥5 prior treatment lines).
• Analytical approach: Inductive thematic analysis, with interpretation supported by the Theoretical Framework of Acceptability (TFA).
• Key themes:
 - MM and its treatment significantly affect physical, emotional, and social aspects of quality of life.
 - Treatment decisions are influenced by shared decision-making, family involvement, and information needs.
 - Treatment experience varies by modality (oral vs IV/subcutaneous) and includes logistical and self-management challenges.
 - Preferences are individualized and shaped by personal circumstances, with a strong emphasis on treatment goals such as life extension.

Strengths
• In-depth qualitative exploration of long-term, multi-line treatment experiences in MM.
• Integration of findings with the TFA framework to contextualize decision-making processes.

Limitations
• Small sample size from a single center limits generalizability.
• Limited demographic diversity (all participants identified as British).
• Difficulty separating experiences across specific treatment lines due to overlapping long-term therapies.
 
Why this study matters
This qualitative study highlights that treatment experiences in MM are shaped by complex interactions between disease burden, treatment side effects, and individual life circumstances. While patients differ in preferences, many prioritize extending survival and may accept substantial treatment-related burden to achieve this. The findings support the need for individualized, patient-centered care that incorporates structured shared decision-making and clearer communication of treatment impacts, alongside further research in more diverse populations and with measurable patient-reported outcomes.
 
Reference:
Perry, M. B., Lochhead Devaraj, R., Law, K., Ashby, F., & Taylor, S. (2026). iPREFER: Patients’ Experiences and Preference of Treatment for Multiple Myeloma Following Multiple Lines of Treatment – A Qualitative Study. Patient Preference and Adherence, 20. https://doi.org/10.2147/PPA.S576524 (https://www.tandfonline.com/doi/full/10.2147/PPA.S576524)

Phase 3 MagnetisMM-5 trial: Elranatamab monotherapy significantly and clinically improves primary endpoint of PFS vs standard-of-care DPd in RRMM patients who had received at least one prior line of therapy — Pfizer (April 2026) 

What is the purpose of the study?
To evaluate the efficacy and safety of Elrexfio (elranatamab) monotherapy compared with daratumumab plus pomalidomide and dexamethasone (DPd) in adults with relapsed/refractory multiple myeloma (RRMM) who had received at least one prior line of therapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR).

Summary
This randomized, open-label Phase 3 study enrolled 497 patients with RRMM across 26 countries. Elranatamab demonstrated a statistically significant improvement in PFS compared with DPd at the time of interim analysis, as assessed by BICR. Safety findings were consistent with the known profile of elranatamab, with no new safety signals identified; overall survival data (as a secondary endpoint) were not yet available.
 
Key points
• Study design: Phase 3, open-label, randomized, multicenter trial (MagnetisMM-5)
• Population: 497 patients with RRMM who received ≥1 prior therapy (including lenalidomide and a proteasome inhibitor)
• Intervention vs comparator: Elranatamab monotherapy vs daratumumab + pomalidomide + dexamethasone (DPd)
• Primary endpoint: Progression-free survival (PFS) assessed by blinded independent central review (BICR)
• Efficacy results: Statistically significant improvement in PFS with elranatamab at interim analysis

Safety
• No new safety signals identified
• Safety consistent with known profile of elranatamab

Limitations
• Interim analysis; overall survival data not yet available
• Open-label design may introduce potential bias
• Long-term outcomes remain pending
 
Why this study matters
In the MagnetisMM-5 phase 3 trial, elranatamab improved progression-free survival compared with standard-of-care therapy in patients with relapsed/refractory multiple myeloma at interim analysis. The safety profile was consistent with prior experience, with no new safety signals reported. Ongoing follow-up is required to assess overall survival and long-term clinical outcomes.
 
Reference:
Pfizer’s ELREXFIO Significantly Improves Progression-Free Survival for Double-Class Exposed Patients with Relapsed or Refractory Multiple Myeloma (https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elrexfio-significantly-improves-progression-free). Pfizer press release. April 29, 2026.
 

Latest interim results from the ongoing REDEEM-1 Phase 1/2a trial evaluating TPST-2003 — Tempest Therapeutics (April 2026)

What is the purpose of the study?
To evaluate the safety, tolerability, and preliminary efficacy of TPST-2003, a dual-targeting CD19/BCMA CAR-T therapy, in patients with relapsed/refractory multiple myeloma (RRMM) in the ongoing Phase 1/2a REDEEM-1 clinical trial. It also aims to assess early clinical activity and support further development of the therapy.

Summary
REDEEM-1 is a multicenter, open-label Phase 1/2a trial conducted in China assessing TPST-2003 in patients with RRMM, including those with high-risk disease features and extramedullary involvement. Interim results reported earlier included a 100% complete response rate in six efficacy-evaluable patients based on International Myeloma Working Group (IMWG) criteria, along with a favorable safety profile. The trial continues toward a target enrollment of 29 patients to further evaluate durability of response and overall clinical outcomes.
 
Key points
• Study design: Phase 1/2a, open-label, multicenter REDEEM-1 trial (China)
• Therapy: TPST-2003, autologous dual-targeting CD19/BCMA CAR-T cell therapy
• Population: Patients with relapsed/refractory multiple myeloma, including high-risk and extramedullary disease
• Interim efficacy: 100% complete response in 6 evaluable patients (IMWG criteria)
• Safety: Reported as favorable in interim analysis

Strengths
• Novel dual-targeting CAR-T design addressing antigen escape and tumor heterogeneity
• Early evidence of strong clinical response
• Multicenter clinical evaluation

Limitations
• Very small interim sample size (n=6 evaluable patients)
• Early-phase (Phase 1/2a) data not yet indicative of long-term outcomes
• Data derived from a single geographic region (China)
• Ongoing trial with incomplete enrollment and limited durability data
 
Why this study matters


Early interim results from the REDEEM-1 trial suggest that TPST-2003 may demonstrate strong initial anti-myeloma activity with a manageable safety profile in patients with relapsed/refractory multiple myeloma. However, these findings are based on a small, early-stage dataset and require confirmation in a larger patient population with longer follow-up. Ongoing enrollment and further clinical evaluation are needed to determine the durability and broader applicability of these results.
 
Reference:
Tempest to Advance Dual-Targeting CAR-T Platform with Clinical Update at ISCT 2026 Annual Meeting. (https://www.globenewswire.com/news-release/2026/04/29/3283678/0/en/Tempest-to-Advance-Dual-Targeting-CAR-T-Platform-with-Clinical-Update-at-ISCT-2026-Annual-Meeting.html) Tempest Therapeutics press release. April 29, 2026.

BRIDGE (OP-107): A Phase 2 Pharmacokinetic Study of Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Impaired Renal Function — Clinical Lymphoma Myeloma and Leukemia (April 2026)

What is the purpose of the study?
To evaluate the pharmacokinetics (PK) and safety of melflufen (melphalan flufenamide) plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) and moderate to severe renal impairment. The study specifically assesses how renal function affects exposure to melphalan, the active metabolite of melflufen.

Summary
This open-label Phase 2 study enrolled 35 RRMM patients with moderate or severe renal impairment who received melflufen (20–40 mg IV every 28 days) plus weekly dexamethasone. Pharmacokinetic results showed lower melphalan exposure (Cmax and AUC) with worsening renal impairment and a modest increase in elimination half-life. Treatment-emergent adverse events occurred in most patients (34/35), and 6 patients died in the setting of a TEAE; no new safety signals were identified.
 
Key points
• Design: Phase 2, open-label study in RRMM patients with moderate or severe renal impairment
• Population: 35 patients total (moderate RI cohorts n=31; severe RI cohort n=4)
• Intervention: Melflufen 20–40 mg IV every 28 days plus dexamethasone 40 mg weekly
• Pharmacokinetics: Melphalan exposure (Cmax, AUC) decreased with worsening renal function; elimination half-life increased modestly
• Safety: TEAEs occurred in 34/35 patients; 6 deaths occurred in patients with TEAEs; no new safety signals reported
• Efficacy: Response rate reported as consistent with prior studies (no detailed comparative efficacy analysis provided)

Strengths
• Prospective evaluation of pharmacokinetics across defined renal impairment strata
• Inclusion of both moderate and severe renal impairment populations

Limitations
• Small overall sample size, especially in severe renal impairment cohort (n=4)
• Open-label, non-comparative design
• Limited ability to draw efficacy conclusions
 
Why this study matters
The BRIDGE study demonstrates that renal impairment is associated with reduced melphalan exposure following melflufen administration and a modest prolongation of elimination half-life. No new safety signals were identified in patients with moderate to severe renal impairment, although treatment-emergent adverse events and deaths were observed in this heavily pretreated population. Overall, the findings support the use of a reduced melflufen dose (30 mg) in patients with moderate renal impairment based on pharmacokinetic results.

 
Reference:
Ludek Pour, Sosana Delimpasi, Wojciech Legiec, Jiri Minarik, Ivan Spicka, Sebastian Grosicki, Marcin Rymko, Jacek Najda, Argiris Symeonidis, Birgitta Andersson, Gunilla Huledal, Stefan Norin, Meletios-Athanasios Dimopoulos, BRIDGE (OP-107): A Phase 2 Pharmacokinetic Study of Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Impaired Renal Function, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.04.022. (https://www.sciencedirect.com/science/article/pii/S2152265026001357)

Infections in Patients Receiving Daratumumab for Newly Diagnosed Multiple Myeloma: A Pooled Analysis of MAIA and ALCYONE — Blood Advances (May 2026)
 

What is the purpose of the study?
To evaluate the incidence, timing, and management of infections in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) receiving daratumumab-based regimens (D-Rd or D-VMP) versus standard therapies (Rd or VMP). The aim is to better characterize infection risk and inform prevention strategies during treatment.

Summary
In this pooled analysis of the phase 3 MAIA and ALCYONE trials, patients (median age 72 years) receiving daratumumab-containing regimens had higher crude rates of grade 3/4 (36.9% vs 22.4%) and grade 5 (3.0% vs 1.5%) infections compared with standard therapy, although exposure-adjusted incidence rates were broadly similar between groups. The risk of severe infections was highest within the first 6 months after treatment initiation. Infections led to treatment discontinuation in approximately 2% of patients across all groups, and reported time-to-event estimates for first severe infection should be interpreted cautiously due to potential limitations in follow-up or estimation. 
 

Key points
• Higher crude incidence of grade 3/4 and grade 5 infections with daratumumab-based regimens (D-Rd, D-VMP)
• Exposure-adjusted infection rates were generally comparable to Rd and VMP
• Greatest risk of severe infections occurs within the first 6 months of treatment
• Low treatment discontinuation due to infections (~2%) across all groups
• Strength: Large, pooled dataset from two phase 3 randomized trials (MAIA, ALCYONE)
• Limitation: Higher observed infection rates with daratumumab and uncertainty in time-to-event estimates may require careful interpretation
 
Why this pooled analysis matters
Daratumumab-based regimens in transplant-ineligible NDMM are associated with higher observed rates of severe infections, particularly early in treatment, although overall exposure-adjusted risks are similar to standard therapies. Infection-related treatment discontinuation is uncommon. Careful monitoring and adherence to infection prevention guidelines remain important to reduce risk and support continued therapy.
 
 
Reference:
Nizar J. Bahlis, Thierry Facon, Jesús F. San-Miguel, Saad Z. Usmani, Meletios-Athanasios A. Dimopoulos, Philippe Moreau, Sonja Zweegman, Aurore Perrot, Salomon Manier, Ajai Chari, Noopur S. Raje, Robert Z. Orlowski, Hartmut Goldschmidt, Supratik Basu, Cyrille Hulin, Katja C Weisel, Mohamad Mohty, Xavier Leleu, Torben Plesner, Andrzej J Jakubowiak, Gordon Cook, Hang Quach, Christopher P. Venner, Michele Cavo, Mai Ngo, Kasey Bolyard, Robin Carson, Fredrik Borgsten, Maria-Victoria Mateos, Shaji K Kumar; Infections in Patients Receiving Daratumumab for Newly Diagnosed Multiple Myeloma: A Pooled Analysis of MAIA and ALCYONE. Blood Adv 2026; bloodadvances.2025019323. doi: https://doi.org/10.1182/bloodadvances.2025019323 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2025019323/568183/Infections-in-Patients-Receiving-Daratumumab-for)

A dexamethasone-free daratumumab–ixazomib regimen in frail elderly patients with relapsed or refractory multiple myeloma: Results of the IFM 2018-02 phase II study — British Journal of Haematology (May 2026)

What is the purpose of the study?
To evaluate the efficacy and safety of a dexamethasone-free combination of daratumumab and ixazomib in elderly, frail patients with relapsed or refractory multiple myeloma (RRMM). The study aims to assess whether this regimen could achieve meaningful response rates while maintaining tolerability in a high-risk population.

Summary
This phase 2 IFM 2018-02 trial (NCT03757221)enrolled 55 patients (median age 82 years) across 14 centers of the Intergroupe Francophone du Myélome, all aged ≥65 with frailty and early relapsed or refractory disease. Patients received daratumumab plus ixazomib in 28-day cycles, with methylprednisolone support. After a median follow-up of 35.3 months, 32% achieved very good partial response or better, median progression-free survival was 19.5 months, and median overall survival was not reached (75% survival at 33.6 months). Grade ≥3 adverse events occurred in 67% of patients, most commonly cytopenias and infections.
 
Key points
• Design: Phase 2, prospective, multicenter study (14 IFM centers), NCT03757221
• Population: 55 elderly (median age 82), frail patients with relapsed/refractory multiple myeloma
• Intervention: Dexamethasone-free regimen of daratumumab + ixazomib with methylprednisolone

• Efficacy:
 - ≥VGPR rate: 32%
 - Median PFS: 19.5 months
 - OS: not reached (75% at 33.6 months)

• Safety:
 - Grade ≥3 adverse events in 67%
 - Most common: cytopenias (18 patients), infections (8 patients, including pneumonia)
 
Strengths
• Focus on a very elderly and frail population often underrepresented in clinical trials
• Multicenter prospective design
• Extended follow-up (~35 months) allowing survival assessment
 
Limitations
• Single-arm phase 2 study without a comparator group
• Small sample size (n=55), limiting statistical power
• Potential selection bias and limited generalizability beyond similar frail populations
 
Why this study matters
The IFM 2018-02 trial suggests that a dexamethasone-free combination of daratumumab and ixazomib can achieve clinically meaningful responses and survival outcomes in very elderly, frail patients with relapsed or refractory multiple myeloma. However, the high rate of grade ≥3 adverse events highlights the ongoing need to balance efficacy with tolerability in this population. Controlled studies would be needed to better define comparative benefit and safety.
 
 
Reference:
Bobin A, Macro M, Touzeau C, Mariette C, Manier S, Brechignac S, et al. A dexamethasone-free daratumumab–ixazomib regimen in frail elderly patients with relapsed or refractory multiple myeloma: Results of the IFM 2018-02 phase II study. Br J Haematol. 2026;00:1–9. https://doi.org/10.1111/bjh.70512 (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70512)
 
 
 

U.S. Food and Drug Administration

FDA extends review period for subcutaneous Sarclisa (isatuximab-irfc) Biologics License Application (BLA); Target action date set for July 2026
 

On Wednesday, April 22, Sanofi announced via press release that the U.S. Food and Drug Administration (FDA) has extended the review period of the biologics license application (BLA) for subcutaneous Sarclisa (isatuximab-irfc) “in combination with approved standard-of-care regimens for the treatment of multiple myeloma (MM) across all currently approved U.S. indications of Sarclisa intravenous (IV) formulation.” The revised target action date is on July 23, 2026.
 
According to the FDA, the Biologics License Application (BLA) Process (CBER) “is a request for permission to introduce, or deliver for introduction, a biologic product into interstate commerce (21 CFR 601.2). The BLA is regulated under 21 CFR 600 – 680. A BLA is submitted by any legal person or entity who is engaged in manufacture or an applicant for a license who takes responsibility for compliance with product and establishment standards.”
 
 
References:
 
Sanofi provides update on the regulatory submission for Sarclisa subcutaneous in the US (https://www.sanofi.com/en/media-room/press-releases/2026/2026-04-22-05-00-00-3278646). Sanofi press release. April 22, 2026.
 
Biologics License Applications (BLA) Process (CBER). (https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/biologics-license-applications-bla-process-cber) U.S. Food and Drug Administration. Current as of January 27, 2021.
 
 

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.  (https://www.myeloma.org/news-events/multiple-myeloma-news)