A summary of some notable key multiple myeloma research from July-August 2026   

Scope and Methodology    
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from July-August 2026. Content was developed by the International Myeloma Foundation medical editorial team using various medical abstracts on new guidelines, recommendations, clinical updates, 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 August  26, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.     
 

Guidelines & Recommendations 

International Myeloma Working Group Recommendations for the Diagnosis and Management of Solitary Plasmacytomas — Journal of Clinical Oncology (July 2026) 
 

What is the purpose of the updated recommmendations? 
To provide updated recommendations from the International Myeloma Working Group (IMWG) for the diagnosis, evaluation, treatment, response assessment, and follow-up of solitary plasmacytomas (SPs). The recommendations incorporate advances in imaging, bone marrow assessment, and disease monitoring to refine diagnostic definitions and management strategies. 
 
Summary  
Solitary plasmacytomas are localized clonal plasma cell tumors occurring in bone (solitary bone plasmacytoma [SBP]) or soft tissue (solitary extramedullary plasmacytoma [SEMP]) without myeloma-defining events and with either no bone marrow involvement or minimal involvement (<10% clonal plasma cells by immunohistochemistry). The updated IMWG recommendations emphasize comprehensive exclusion of multiple myeloma using advanced imaging, sensitive bone marrow evaluation, and blood and urine testing before confirming the diagnosis. Local radiotherapy remains the standard treatment, while functional whole-body imaging (WB-MRI with diffusion-weighted imaging or FDG-PET/CT) and serial biochemical monitoring are recommended for response assessment and long-term follow-up; the clinical benefit of systemic therapy in SP remains poorly defined. 
 
Key points 
• Solitary plasmacytoma is defined by: 
 - Histologic and immunohistochemical confirmation of a monoclonal plasma cell tumor
 - No additional skeletal or extramedullary lesions on advanced functional imaging
 - Less than 10% clonal plasma cells in bone marrow by immunohistochemistry 
 - Absence of myeloma-defining events. 

• Patients with minimal bone marrow involvement (<10%) should be classified separately because they have a different risk of progression to multiple myeloma. 
• Approximately 50% of patients with solitary bone plasmacytoma progress to symptomatic multiple myeloma within 3–5 years after definitive local radiotherapy, with 10-year progression rates of 65%–84%. 
• For solitary extramedullary plasmacytoma, local recurrence is approximately 10%, and progression to multiple myeloma ranges from 11% to 36%, lower than for solitary bone plasmacytoma. 

• Diagnosis requires comprehensive assessment using: 
 - Advanced whole-body imaging
 - Sensitive bone marrow evaluation
 - Blood and urine testing

• Local radiotherapy remains the mainstay of treatment. 
• The clinical benefit of adding systemic therapy for solitary plasmacytoma is currently not well defined. 

• Response assessment recommendations include: 
 - Functional imaging 6–9 months after radiotherapy using the same imaging modality as baseline. 
 - Preference for WB-MRI (DWI) or FDG-PET/CT using standardized interpretation criteria (MY-RADS or IMPETUS). 
 - Cautious interpretation of imaging performed at approximately 3 months because radiotherapy-related changes may produce false-positive findings. 

• Follow-up recommendations include: 
 - Annual functional imaging for the first 5 years after complete imaging remission. 
 - More frequent imaging (every 6 months) for residual or uncertain abnormalities until complete response or stable findings are documented. 
 - Regular clinical assessment with serum and urine testing for persistent M-protein (for example, 3 months after radiotherapy and every 6 months thereafter). 
 - Persistent M-protein alone should not prompt immediate systemic therapy but should be monitored carefully. 
    
• Patients who progress to overt multiple myeloma should receive standard multiple myeloma systemic therapy. 
 
Why these updated IMWG recommendations matter 
The updated IMWG recommendations refine the diagnosis and management of solitary plasmacytomas by emphasizing thorough exclusion of multiple myeloma with advanced imaging, sensitive bone marrow evaluation, and laboratory testing. Local radiotherapy remains the standard treatment, with structured imaging and biochemical follow-up recommended to monitor response and detect progression. Although improved diagnostic methods have refined disease assessment, the role of systemic therapy in solitary plasmacytoma remains uncertain based on current evidence. 
 
Reference: 
Efstathios Kastritis et al. International Myeloma Working Group Recommendations for the Diagnosis and Management of Solitary Plasmacytomas. J Clin Oncol 0, JCO-26-00410 DOI:10.1200/JCO-26-00410 (https://ascopubs.org/doi/10.1200/JCO-26-00410) 

American Society of Hematology 2026 guidelines on diagnosis of light chain amyloidosis — Blood Advances (July 2026) 
 

What is the purpose of the guidelines? 
These evidence-based American Society of Hematology (ASH) guidelines provide recommendations that support the timely and accurate diagnosis of light chain (AL) amyloidosis. The guidelines aim to improve early detection, diagnostic decision-making, and assessment of organ involvement using systematically reviewed evidence and the GRADE framework. 
 
Summary  
A multidisciplinary ASH guideline panel, including clinical specialists and a patient representative, conducted systematic evidence reviews (through March 6, 2023) and used the GRADE methodology to develop recommendations for the diagnosis of AL amyloidosis. The panel issued 12 recommendations addressing diagnostic evaluation, including methods to increase clinical suspicion, biopsy approaches, and assessment of organ involvement. The guidelines recommend using serum immunofixation (SIFE), urine immunofixation (UIFE), and serum free light chains (sFLC) to increase suspicion of AL amyloidosis and state that diagnosis can be established through surrogate biopsies using both bone marrow biopsy and abdominal fat-pad sampling, while recognizing that target organ biopsy may be preferred in selected clinical situations. 
 
Key points 
• Study type: Evidence-based clinical practice guidelines developed by the American Society of Hematology (ASH). 
• Development process: 
 - Multidisciplinary panel of 22 experts and 1 patient representative. 
 - Systematic evidence reviews updated through 6 March 2023. 
 - Recommendations developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and evidence-to-decision frameworks. 
    
• Main findings:
 - The panel developed 12 recommendations for the diagnosis of AL amyloidosis. 
 - SIFE, UIFE, and sFLC testing are recommended to enhance clinical suspicion of AL amyloidosis. 
 - Available evidence showed these combined tests had 99% sensitivity and 77% specificity in studies of patients with suspected cardiac amyloidosis. 
 - Diagnosis can be established through surrogate biopsies, requiring both bone marrow biopsy and abdominal fat-pad sampling. 
 - Target organ biopsy may be preferred in specific clinical circumstances. 
 - Assessment of major organ involvement and multidisciplinary care were identified as important good practice statements. 
    
• Implementation considerations: 
 - Urine free light chain testing is not recommended for detection of monoclonal protein. 
 - Interpretation of sFLC results should account for kidney function and assay-specific reference intervals. 
 - Monoclonal proteins may also occur in conditions other than AL amyloidosis, including monoclonal gammopathy of undetermined significance (MGUS), autoimmune diseases, chronic infections, and some neurologic disorders. 
 
Strengths 
• Recommendations were based on systematic evidence reviews and developed according to established guideline development standards using the GRADE framework. 
• The guideline development panel included multidisciplinary specialists and a patient representative, with measures to minimize conflicts of interest. 
• Public comment was incorporated into the guideline development process. 
 
Limitations 
• Evidence was limited because AL amyloidosis is a rare disease, resulting in relatively few studies. 
• Many recommendations were supported by low or very low certainty evidence, primarily due to risk of bias and imprecision in available studies. 
• Differences among studies in diagnostic reference standards and test cutoffs required reliance on the face validity of individual studies. 
• Availability of diagnostic tests and expertise varies across healthcare settings, which may affect implementation. 
• The single-comparison PICO framework may not fully capture the complexity of diagnostic decision-making in AL amyloidosis. 
 
Why these 2026 ASH guidelines matter 
These ASH guidelines provide evidence-based recommendations for the diagnosis of AL amyloidosis using systematic evidence review and the GRADE framework. The guidelines support the use of SIFE, UIFE, and sFLC testing to increase clinical suspicion and recommend diagnosis through surrogate biopsies with bone marrow biopsy and abdominal fat-pad sampling, while acknowledging that target organ biopsy may be appropriate in selected situations. The guideline also recognizes that evidence is limited for many recommendations because of the rarity of AL amyloidosis and identifies multiple priorities for future research to strengthen the diagnostic evidence base. 
 
 
Reference: 
Vishal Kukreti, Matthew Seftel, Maria Adela Aguirre, Muayad Azzam, Deborah D. Boedicker, Naresh Bumma, Antonia S. Carroll, Raymond Comenzo, Joselle Cook, Noel Dasgupta, Alfredo De La Torre, Angela Dispenzieri, Faizi Jamal, Hassan Kawtharany, Jack Khouri, Nelson Leung, Jamil Nazzal, Maria M. Picken, Shahzad Raza, Vaishali Sanchorawala, Nitasha Sarswat, Hira Shaikh, Daulath Singh, Reem A. Mustafa; American Society of Hematology 2026 guidelines on diagnosis of light chain amyloidosis. Blood Adv 2026; 10 (14): 5113–5152. doi: https://doi.org/10.1182/bloodadvances.2025017073  (https://ashpublications.org/bloodadvances/article/10/14/5113/566264/American-Society-of-Hematology-2026-guidelines-on)

Optimizing the Real-World Use of BCMA-Targeted T-Cell-Engaging Therapies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: An Italian Modified Delphi Consensus — Cancers (August 2026) 

 
What is the purpose of the consensus study? 
To develop expert consensus on the practical use of B-cell maturation antigen (BCMA)-targeting bispecific antibodies (BsAbs) in patients with triple-class-exposed (TCE) relapsed/refractory multiple myeloma (RRMM). It focuses on key challenges in applying these therapies in real-world clinical practice. 
 
Summary 
A modified Delphi expert consensus study was conducted from April–November 2025, involving 15 Italian hematologists with expertise in TCE RRMM who completed two Delphi rounds. Agreement (≥67% of panelists) was reached on most topics, including outpatient step-up dosing under specific circumstances, dosing de-escalation in responding patients, and the feasibility of anti-BCMA BsAbs in selected challenging subgroups, including frail patients (93%), high-risk cytogenetics (93%), extramedullary disease (93%), end-stage renal disease (86%), active plasma cell leukemia (79%), and central nervous system involvement (67%). 
 
Key points 
• Study design: Modified Delphi expert consensus study. 
• Participants: 15 Italian hematologists experienced in treating TCE RRMM. 
• Study period: April–November 2025; two Delphi rounds. 
• Consensus definition: Agreement by ≥67% of panelists. 
• Outpatient treatment: All panelists considered step-up dosing feasible in an outpatient setting under specific circumstances. 
• Dosing: Panelists agreed on dosing de-escalation in responding patients to reduce the risk of adverse events. 
• Challenging patient groups: Agreement supported the feasibility of anti-BCMA BsAbs in: 
 - Frail patients: 93% 
 - High-risk cytogenetics: 93% 
 - Extramedullary disease: 93% 
 - End-stage renal disease: 86% 
 - Active plasma cell leukemia: 79% 
 - Central nervous system involvement: 67% 

• Sequential BCMA-targeting therapy: 93% agreement on possible sequential use of BCMA-targeting therapies, with a preference for BsAbs following CAR-T therapy; however, switching to a different target antigen was stated to be the primary consideration. 
 
Why this study matters 
The modified Delphi process identified areas of expert agreement regarding the real-world use of anti-BCMA BsAbs in TCE RRMM, including outpatient step-up dosing, dosing de-escalation in responding patients, and treatment of selected challenging patient subgroups. The authors present these expert recommendations as a complement to existing guidelines and as a means of addressing practical questions for clinical practice. 
 
Reference: 
Cavo, M., Bersanelli, M., Corso, A., Galeone, C., Mangiacavalli, S., Mina, R., Zambello, R., Antonioli, E., Belotti, A., Botta, C., Buda, G., Di Raimondo, F., Galli, M., Gay, F., Offidani, M., Petrucci, M. T., Romano, A., Zamagni, E., Semeraro, A., ... Mariani, P. (2026). Optimizing the Real-World Use of BCMA-Targeted T-Cell-Engaging Therapies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: An Italian Modified Delphi Consensus. Cancers, 18(16), 2572. https://doi.org/10.3390/cancers18162572 (https://www.mdpi.com/2072-6694/18/16/2572) 
 
 

Review 

Bridging Randomized Trial Efficacy and Real-World Effectiveness in Multiple Myeloma: Integrating Clinical Trials and Real-World Evidence for Individualized Care — European Journal of Haematology (July 2026) 
 

What is the purpose of the review? 
To examine the differences between efficacy reported in randomized clinical trials (RCTs) and effectiveness observed in real-world data (RWD) for multiple myeloma (MM). It evaluates how differences in patient characteristics, frailty, treatment delivery, and study methodology influence the applicability of trial findings to routine clinical practice and discusses approaches to better integrate RCT and RWD evidence. 
 
Summary  
The review describes that pivotal MM RCTs primarily enroll younger, fitter patients with fewer comorbidities, whereas real-world populations are generally older, frailer, and have greater comorbidity. It summarizes evidence that RCT outcomes are most reproducible in patients who resemble trial populations, while real-world effectiveness is often reduced in older or frail patients because of increased toxicity, lower dose intensity, and earlier treatment discontinuation. The review also outlines methodological priorities, including standardized real-world data collection, routine frailty assessment, robust causal-inference methods, and closer alignment between RCTs and real-world populations. 
 
Key points 
• Multiple myeloma predominantly affects older adults, but pivotal RCTs largely include younger, fitter patients with fewer comorbidities. 
• Differences between RCT populations and routine clinical populations contribute to differences between trial efficacy and real-world effectiveness. 
• Real-world patients are more likely to be older, frail, have impaired performance status, renal impairment, cardiovascular disease, and other comorbidities. 
• Outcomes observed in RCTs are most reproducible in patients who closely resemble trial participants. 
• In older, frail, and comorbid patients, treatment effectiveness is frequently reduced because of: 
 - Increased toxicity
 - Reduced dose intensity
 - Earlier treatment discontinuation

• Frailty, rather than chronological age alone, is identified as the principal determinant of differences between RCT and real-world outcomes. 
• Frailty has prognostic and predictive value but is inconsistently measured in both RCTs and real-world datasets. 
• Real-world data complement RCTs by providing information on treatment effectiveness, tolerability, treatment patterns, dose intensity, and treatment persistence in broader patient populations. 
• The review proposes integrating trial-derived efficacy estimates with real-world information on toxicity, dose intensity, and treatment persistence to support patient-centered treatment decisions. 

• Methodological priorities include: 
 - Standardized data elements and clinical endpoints. 
 - Routine incorporation of validated frailty assessments (such as the IMWG frailty index). 
 - Use of robust causal inference methods for observational analyses. 
 - More pragmatic trial designs with broader eligibility criteria. 
 - Greater inclusion of patient-reported outcomes, functional status, and quality-of-life measures. 
 
Strengths  
• Reviews evidence from both RCTs and multiple real-world data sources, including registries and observational cohorts. 
• Presents a framework integrating RCT efficacy with real-world effectiveness for individualized treatment decisions. 
• Identifies methodological priorities to improve future evidence generation and interpretation. 
 
Limitations  
• Real-world data are limited by heterogeneous data sources, inconsistent endpoint definitions, variable data quality, incomplete frailty assessment, and inconsistent documentation of treatment delivery. 
• Observational studies are susceptible to confounding, selection bias, informative censoring, and residual bias despite advanced analytical methods. 
• Current RCTs have limited external validity because they underrepresent older, frail, and comorbid patients. 
 
Why this review matters 
This review concludes that RCTs and real-world data provide complementary evidence in multiple myeloma, with RCTs defining treatment efficacy under controlled conditions and real-world data describing treatment effectiveness in broader patient populations. Frailty is identified as a major factor influencing treatment tolerance, dose intensity, treatment persistence, and clinical outcomes, but it remains inconsistently assessed. The review highlights standardized real-world data collection, routine frailty assessment, robust analytical methods, and more pragmatic clinical trial designs as priorities for improving the integration of evidence into routine care. 
 
Reference: 
E. A. Martino, E. Vigna, A. Bruzzese, et al., “Bridging Randomized Trial Efficacy and Real-World Effectiveness in Multiple Myeloma: Integrating Clinical Trials and Real-World Evidence for Individualized Care,” European Journal of Haematology (2026): 1–17, https://doi.org/10.1111/ejh.70263 (https://onlinelibrary.wiley.com/doi/10.1111/ejh.70263). 

Exercise for myeloma patients with bone disease: a scoping review — Supportive Care in Cancer (July 2026) 
 

What is the purpose of the review? 
To evaluate published exercise interventions in patients with multiple myeloma that included individuals with multiple myeloma bone disease (MMBD); and to summarize evidence on safety, assessment methods, intervention characteristics, bone-related outcomes, and research gaps specific to MMBD. 
 
Summary  
A scoping review following the Joanna Briggs Institute framework searched PubMed, OVID-MEDLINE, and CINAHL (1946 to October 2025) and included 12 studies involving 346 participants, with MMBD prevalence ranging from 69% to 86%; no study focused exclusively on patients with MMBD. Seven exercise-related adverse events were reported, but studies did not specify whether these occurred in participants with MMBD; most studies used medical clearance, imaging, or standardized assessment tools before exercise and commonly excluded patients with spinal instability, spinal cord compression, or fracture risk. Exercise programs were implemented across all disease stages and typically consisted of tailored aerobic and resistance exercise supervised or prescribed by physiotherapists, but reporting of MMBD characteristics, exercise adaptations, practitioner experience, and bone-specific outcomes was inconsistent, with only two studies assessing bone-related outcomes as secondary endpoints and reporting no significant effects. 
 
Key points 
• Study design: Scoping review conducted using the Joanna Briggs Institute framework. 
• Search period: PubMed, OVID-MEDLINE, and CINAHL from 1946 to October 2025. 
• Included evidence: 12 studies involving 346 participants. 
• MMBD representation: MMBD prevalence ranged from 69% to 86%, but no study enrolled only patients with MMBD. 
• Safety findings: 
 - Seven exercise-related adverse events were reported. 
 - Studies did not report whether these adverse events occurred in participants with MMBD. 
 - Reported exercise-related adverse events were infrequent, generally mild, and resolved without long-term consequences. 

• Participant assessment: 
 - Most studies used medical clearance, imaging, or standardized assessment tools before exercise. 
 - Hematological parameters were considered in only one study. 
 - Common exclusion criteria included spinal instability, spinal cord compression, and increased fracture risk. 
    
• Exercise interventions: 
 - Conducted across all disease stages. 
 - Most programs included tailored aerobic and resistance exercise with supervised and/or home-based components. 
 - Physiotherapists most commonly prescribed or supervised exercise. 
 - Reporting exercise modifications for MMBD and practitioner qualifications was limited. 
    
• Bone-related outcomes: 
 - No study evaluated bone changes as a primary outcome. 
 - Two studies assessed bone outcomes as secondary measures using imaging or bone turnover markers and reported no significant effects. 
    
• Research gaps identified: 
 - Need for trials focused exclusively on MMBD. 
 - Need for standardized reporting of MMBD characteristics, assessment procedures, exercise adaptations, adverse events, and bone-specific outcomes. 
 - Need to determine optimal exercise type, intensity, and duration for MMBD. 
 
Strengths  
• First review specifically mapping safety, assessment, outcomes, and intervention characteristics of exercise studies focused on patients with myeloma bone disease. 
• Comprehensive search strategy. 
• Use of an established scoping review framework. 
 
Limitations  
• Methodological quality and risk of bias of included studies were not assessed. 
• Quality and risk of bias of included studies were not assessed. 
• Exclusion of grey literature may have resulted in omission of relevant data.  
 
Why this review matters 
This scoping review found that exercise interventions (including for patients with MMBD) were generally reported as feasible and associated with infrequent, mostly mild exercise-related adverse events, although studies usually did not specify whether these events occurred in participants with MMBD. Reporting of MMBD characteristics, assessment methods, exercise adaptations, and bone-specific outcomes was inconsistent, limiting clinical translation. The review identifies a need for dedicated MMBD-focused studies with standardized reporting and evaluation of bone-related and patient-reported outcomes. 
 
Reference: 
Land, J., McCourt, O., Kyriakou, C. et al. Exercise for myeloma patients with bone disease: a scoping review. Support Care Cancer 34, 759 (2026). https://doi.org/10.1007/s00520-026-10958-7  (https://link.springer.com/article/10.1007/s00520-026-10958-7)

Machine Learning for the Interpretation of Serum Protein and Immunofixation Electrophoresis in Multiple Myeloma: A Scoping Review — Diagnostics (July 2026) 
 

What is the purpose of the review? 
To evaluate published evidence on the use of machine learning (ML) for the diagnosis and classification of multiple myeloma (MM), with a particular focus on automated interpretation of serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). It also assesses methodological quality and risk of bias of the included studies using the PROBAST+AI framework. 
 
Summary  
Following PRISMA-ScR guidance, the authors searched PubMed, Web of Science, and Scopus for studies published between January 2015 and April 2025 and included 13 studies applying ML to MM diagnosis. The review identified two main application areas: ML-based analysis of IFE images and SPE patterns. Deep learning models, particularly convolutional neural networks, achieved reported IFE accuracies up to 99.82% with F1-scores frequently above 0.90, while ML models for SPE reported areas under the curve (AUC) of 0.90–0.99, accuracies of 82.8%–99.1%, and F1-scores up to 0.98; however, external validation, multimodal integration, explainability, and prospective real-world implementation were limited. 
 
Key points 
• The review included 13 studies published between January 2015 and April 2025. 
• Two primary ML application areas were identified: 
 - Automated interpretation of immunofixation electrophoresis (IFE). 
 - Automated interpretation of serum protein electrophoresis (SPE). 

• Deep learning models, especially convolutional neural networks (CNNs), reported: 
 - IFE accuracy up to 99.82%
 - F1-scores frequently >0.90. 
    
• ML models for SPE reported: 
 - AUC: 0.90–0.99
 - Accuracy: 82.8%–99.1%
 - F1-score: up to 0.98
    
• Some studies reported model precision comparable to or higher than human expert panels for specific tasks. 
• Explainable artificial intelligence (XAI) methods were increasingly incorporated, although multimodal explainability remained absent. 

• Risk of bias assessment using PROBAST+AI found: 
 - Generally appropriate data sources and well-defined predictors and outcomes. 
 - Universal uncertainty regarding blinding procedures during model development and evaluation. 
 - Frequent concerns regarding limited sample sizes, inadequate reporting of class imbalance handling, and limited dataset representativeness in some studies. 
 - Strong use of validation approaches such as cross-validation or bootstrapping in most studies. 
    
• The review noted publication bias as a potential limitation, with studies reporting favorable ML performance being more likely to be published. 
 
Strengths  
• Comprehensive literature search following PRISMA-ScR guidance. 
• Methodological quality and applicability were assessed using the PROBAST+AI risk-of-bias framework. 
• Most studies employed rigorous validation methods, including resampling techniques such as cross-validation or bootstrapping. 
 
Limitations  
• Many studies used small, single-center retrospective datasets. 
• Limited external and multicenter validation. 
• Universal lack of clearly reported blinding procedures. 
• Inconsistent reporting and management of class imbalance. 
• Variable comparison with human experts. 
• Predominance of black-box models and lack of multimodal explainable AI. 
• Limited prospective clinical workflow studies and real-world implementation. 
• Potential publication bias favoring studies with positive ML performance. 
 
Why this review matters 
This scoping review found that machine learning models have demonstrated high reported performance for automated interpretation of SPE and IFE in multiple myeloma, with several studies reporting expert-level diagnostic metrics. However, the available evidence is limited by methodological and implementation gaps, including limited external validation, predominantly retrospective single-center studies, insufficient reporting of blinding and class imbalance handling, and limited real-world evaluation. The authors conclude that future research should prioritize multicenter validation, explainable AI, multimodal data integration, standardized reporting, and prospective clinical implementation studies. 
 
Reference: 
Mohd Murshid, N., Ahmad Azman, A. H., & Nasuruddin, D. N. (2026). Machine Learning for the Interpretation of Serum Protein and Immunofixation Electrophoresis in Multiple Myeloma: A Scoping Review. Diagnostics, 16(14), 2201. https://doi.org/10.3390/diagnostics16142201  (https://www.mdpi.com/2075-4418/16/14/2201)

Circulating Tumor DNA in Multiple Myeloma: Current Insights and Future Perspectives — Biology (July 2026) 
 

What is the purpose of the review? 
To evaluate current evidence on the role of circulating tumor DNA (ctDNA) analysis in multiple myeloma (MM), including its applications in disease characterization, molecular profiling, tumor burden assessment, treatment monitoring, minimal residual disease (MRD) assessment, and emerging immunotherapeutic strategies. It also discusses current technical and biological limitations and future requirements for implementation of ctDNA in routine clinical practice. 
 
Summary  
This review summarizes evidence that ctDNA is a minimally invasive biomarker capable of providing information on tumor burden, clonal evolution, molecular heterogeneity, treatment response, molecular relapse, and MRD in MM. The review describes advances in ctDNA detection methods, including digital droplet polymerase chain reaction (ddPCR), next-generation sequencing (NGS), and Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq), and reports substantial concordance between ctDNA and bone marrow genomic profiles while noting its ability to capture spatially heterogeneous and extramedullary disease. Although ctDNA may complement existing monitoring approaches, routine clinical implementation remains limited by low ctDNA concentrations in patients with minimal disease burden, methodological variability, lack of standardized testing protocols, and the need for large prospective multicenter validation studies. 
 
Key points 
• Role of ctDNA in multiple myeloma: ctDNA is being investigated as a minimally invasive biomarker for: 
 - Disease characterization 
 - Tumor burden assessment 
 - Molecular profiling 
 - Clonal evolution monitoring 
 - Treatment response assessment 
 - Detection of molecular relapse 
 - Minimal residual disease (MRD) assessment 
 - Identification of treatment-resistant subclones 
    
• ctDNA detection methods: Molecular techniques discussed include: 
 - Digital droplet polymerase chain reaction (ddPCR), which enables highly sensitive quantification of predefined genomic alterations, including KRAS, NRAS, BRAF, and TP53 alterations. 
 - Next-generation sequencing (NGS)-based approaches, including targeted deep sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). 
 - Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq), which may improve sensitivity for MRD assessment and longitudinal monitoring by identifying multiple tumor-specific mutations. 
    
• Comparison with bone marrow-based assessment 
 - Studies have demonstrated substantial concordance between ctDNA and bone marrow genomic profiles for detection of mutations, copy number alterations, and clonal evolution. 
 - ctDNA may capture genomic information from multiple disease sites, including extramedullary disease, whereas single-site bone marrow biopsy may not fully represent spatial disease heterogeneity. 
 - ctDNA is currently considered complementary rather than a replacement for bone marrow-based molecular assessment. 
    
• Minimal residual disease (MRD) monitoring 
 - Current MRD assessment primarily relies on bone marrow-based next-generation flow cytometry (NGF) and next-generation sequencing (NGS), which have validated sensitivities of up to 10⁻⁵–10⁻⁶. 
 - ctDNA may allow non-invasive serial monitoring, but reported concordance between ctDNA-based and bone marrow-based MRD assessment remains variable. 
 - Low ctDNA levels during deep remission or MRD negativity may reduce detection sensitivity and increase false-negative results. 
    
• Precursor disease (MGUS and smoldering multiple myeloma) 
 - Monoclonal gammopathy of undetermined significance (MGUS) typically progresses to MM at an average rate of approximately 1% per year. 
 - ctDNA has been detected in some patients with MGUS and smoldering multiple myeloma (SMM), and detectable ctDNA has been associated with increased risk of progression in reported studies. 
 - Large prospective studies are required to validate the role of ctDNA in progression risk assessment and early intervention strategies. 
    
• Emerging applications in immunotherapy: ctDNA monitoring is being investigated in patients receiving: 
- Chimeric antigen receptor T-cell (CAR-T) therapy 
- Bispecific antibodies 
- Current evidence suggests ctDNA may provide information on treatment response, clonal evolution, and emerging resistance, but these applications remain investigational. 
 
Limitations 
• Low ctDNA concentrations, particularly in patients with low tumor burden, precursor disease, or deep remission, may reduce analytical sensitivity and increase false-negative results. 
• Lack of standardization in: 
 - Blood collection 
 - Plasma processing 
 - Sequencing platforms 
 - Bioinformatic analysis 
 - Reporting criteria limits reproducibility and comparison between studies. 

• Most available evidence comes from relatively small, heterogeneous cohorts, including predominantly single-center studies with limited follow-up. 
• The clinical role of ctDNA alongside established diagnostic and monitoring approaches remains to be defined. 
• Formal cost-effectiveness analyses are needed to evaluate implementation in routine care. 
• Large prospective multicenter studies are required to validate ctDNA-guided clinical decisions and establish clinically meaningful thresholds. 
 
Why this review matters 
Current evidence indicates that ctDNA is a developing minimally invasive approach for molecular characterization, disease monitoring, and MRD assessment in multiple myeloma. ctDNA may complement conventional bone marrow-based evaluation by providing information on tumor heterogeneity, clonal evolution, and treatment-related molecular changes, but it cannot currently replace established bone marrow MRD methods. Standardized methodologies and prospective multicenter studies are needed to determine its role in routine clinical management. 
 
Reference: 
Sretenovic, A., Mitrovic, M., Vukosavljevic, N., Kecman, N., Kraguljac Kurtović, N., Denčić Fekete, M., & Bila, J. (2026). Circulating Tumor DNA in Multiple Myeloma: Current Insights and Future Perspectives. Biology, 15(14), 1208. https://doi.org/10.3390/biology15141208  (https://www.mdpi.com/2079-7737/15/14/1208)

Mechanistic and Clinical Differences Between Daratumumab and Isatuximab in Multiple Myeloma: Emerging Roles of 1q Gain and Immune Remodeling — Cells (July 2026) 
 

What is the purpose of the review? 
To examine the biological and immunological differences between the anti-CD38 monoclonal antibodies daratumumab and isatuximab in multiple myeloma (MM). It summarizes evidence on their distinct mechanisms of action and discusses how these differences may relate to treatment selection, measurable residual disease, extramedullary disease, and sequencing with BCMA- and GPRC5D-directed immunotherapies. 
 
Summary 
Both daratumumab and isatuximab target CD38 but differ in epitope recognition, biological activity, and immunomodulatory effects. The review describes that isatuximab binds near the CD38 catalytic site, leading to enzymatic inhibition, enhanced antibody internalization, FOXM1 suppression, and reactive oxygen species-mediated cytotoxicity, with potential sensitivity in MM harboring 1q21 amplification. In contrast, daratumumab is reported to have stronger Fc-dependent immune effects, including trogocytosis-mediated downregulation of CD38 and VLA-4, reduced cell adhesion-mediated drug resistance, and remodeling of the immune microenvironment, with discussion of potential implications for measurable residual disease and sequencing with BCMA- and GPRC5D-directed immunotherapies. The review also presents a biology-guided treatment-selection framework that is explicitly described as hypothesis-generating and not a validated clinical treatment algorithm. 
 
Key points 
• Both daratumumab and isatuximab target CD38 but differ in epitope recognition, biological activity, and immunomodulatory properties. 
• Isatuximab: 
 - Binds near the CD38 catalytic site
 - Produces potent CD38 enzymatic inhibition
 - Enhances antibody internalization 
 - Suppresses FOXM1
 - Induces reactive oxygen species-mediated cytotoxicity
 - May preferentially target MM with 1q21 amplification based on mechanistic evidence

• Daratumumab: 
 - Produces prominent Fc-dependent immune effects
 - Induces trogocytosis-mediated downregulation of CD38 and VLA-4
 - Suppresses cell adhesion-mediated drug resistance
 - Modulates the immune microenvironment
 - May influence subsequent T-cell-redirecting therapies
    
• The review discusses the potential relevance of these mechanistic differences to: 
 - Measurable residual disease (MRD). 
 - Extramedullary disease. 
 - Sequencing with BCMA- and GPRC5D-directed immunotherapies. 
    
• A biology-guided treatment-selection model integrating genomic alterations, tumor biology, and immune remodeling is proposed as a hypothesis-generating framework for future biomarker-driven research. 
• The authors state that current clinical decisions should continue to rely on approved indications, randomized clinical trial evidence, and individual patient characteristics until prospective validation is available. 
 
Strengths  
• Integrates molecular, immunological, and genomic evidence to compare daratumumab and isatuximab. 
• Proposes a hypothesis-generating framework to support future biomarker-driven prospective studies. 
 
Limitations  
• The proposed treatment-selection model is hypothesis-generating and is not a clinical recommendation or validated treatment algorithm. 
• Mechanistic and indirect clinical evidence requires prospective biomarker-driven validation before informing treatment selection. 
• The review explicitly states that 1q gain alone should not be used to recommend isatuximab for all affected patients. 
 
Why this review matters 
This review describes biological differences between daratumumab and isatuximab despite their shared targeting of CD38, including differences in enzymatic inhibition, immune modulation, and potential associations with specific molecular features such as 1q gain and the PBX1–FOXM1 axis. The authors conclude that these findings support further prospective biomarker-driven studies to determine whether genomic and immune microenvironment characteristics can guide anti-CD38 antibody selection, while emphasizing that the proposed framework is investigational and should not be used as a current clinical treatment recommendation. 
 
Reference: 
Kikuchi, J., & Yasui, H. (2026). Mechanistic and Clinical Differences Between Daratumumab and Isatuximab in Multiple Myeloma: Emerging Roles of 1q Gain and Immune Remodeling. Cells, 15(15), 1331. https://doi.org/10.3390/cells15151331  (https://www.mdpi.com/2073-4409/15/15/1331)

 
Targeting BCMA in patients with relapsed/refractory multiple myeloma in 1 to 3 prior lines of therapy — Blood Advances (July 2026) 
 

What is the purpose of the review? 
To summarize evidence from randomized clinical trials, evaluating B-cell maturation antigen (BCMA)-directed therapies for patients with multiple myeloma who have received 1–3 prior lines of therapy. It also discusses factors that influence treatment selection, including patient characteristics, disease features, treatment access, and practical considerations in common clinical scenarios. 
 
Summary  
The review examines evidence for three BCMA-directed treatment approaches: antibody-drug conjugates (ADCs) such as belantamab mafodotin, chimeric antigen receptor T-cell (CAR-T) therapies including ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), and T-cell engager (TCE) antibodies such as teclistamab. Randomized phase 3 trials reported improved progression-free survival for multiple BCMA-directed therapies compared with standard treatments, with some studies also reporting overall survival benefits, while each treatment class had distinct toxicity profiles, treatment logistics, and eligibility considerations. The review emphasizes that treatment selection should integrate clinical trial evidence with patient fitness, disease biology, treatment urgency, access to therapy, and shared decision-making. 
 
Key points 
• Scope 
 - Reviews randomized phase 3 evidence for BCMA-directed therapies in patients with relapsed/refractory multiple myeloma after 1–3 prior lines of therapy. 
 - Discusses practical treatment selection in common early-relapse clinical scenarios. 
    
• Antibody-drug conjugates (ADCs) 
 - Belantamab mafodotin monotherapy was not superior to pomalidomide plus dexamethasone in DREAMM-3. 
 - In DREAMM-7, belantamab mafodotin + bortezomib + dexamethasone (BVd) improved progression-free survival and overall survival compared with daratumumab + bortezomib + dexamethasone (DVd). 
 - In DREAMM-8, belantamab mafodotin + pomalidomide + dexamethasone (BPd) achieved a median progression-free survival of 32.6 months and improved progression-free survival and response outcomes compared with pomalidomide + bortezomib + dexamethasone (PVd); overall survival data remain immature. 
 - Common adverse effects included keratopathy, blurred vision, and thrombocytopenia. Most ocular events resolved, and treatment discontinuation because of ocular toxicity occurred in 7% (BVd) and 9% (BPd). 

• CAR-T therapies 
 - In CARTITUDE-4, cilta-cel improved progression-free survival and overall survival compared with standard-of-care regimens in patients with lenalidomide-refractory disease. 
 - At a median follow-up of 33.6 months, the estimated 36-month progression-free survival was 57%. 
 - Reported toxicities included: 
   • Grade ≥3 cytokine release syndrome (CRS): 1% 
   • Immune effector cell-associated neurotoxicity syndrome (ICANS): 5% 
   • Parkinsonism: 1% 
   • Secondary hematologic malignancies: 3% 
   • Infections of any grade: 63.5% (grade ≥3: 28.4%) 
      
 - In KarMMa-3, ide-cel improved progression-free survival (13.8 vs 4.4 months) versus standard care but did not demonstrate an overall survival benefit, which the review notes was likely influenced by trial crossover. 
    
• T-cell engager (TCE) antibodies 
 - In MajesTEC-3, teclistamab + daratumumab (Tec-Dara) improved progression-free survival, complete response rate, measurable residual disease negativity, and overall survival compared with daratumumab-containing triplets. 
 - The study reported 3-year progression-free survival and overall survival of 83%. 
 - Reported safety findings included: 
   • No grade ≥3 CRS 
   • ICANS: 1.1% 
   • Treatment discontinuation due to adverse events: 4.6% 

• Infections of any grade: 96.5% (grade ≥3: 54.1%), particularly during the first 6 months. 
 - Preliminary results from MajesTEC-9 suggest improved progression-free survival and overall survival with teclistamab monotherapy compared with standard care. 
    
• Treatment selection considerations 
 - Choice among BCMA-directed therapies should consider: 
   • Age, physiologic reserve, frailty, and comorbidities
   • Disease biology, including relapse kinetics and tumor burden
   • Treatment urgency
   • Prior therapies and sequencing. 
   • Access to specialized treatment centers and caregiver support. 
   • Patient preferences through shared decision-making. 

 - The review describes differences among modalities: 
   • CAR-T: concentrated early treatment burden with potential treatment-free interval. 
   • TCEs: continuous therapy with ongoing infection risk and immunosuppression. 
   • ADCs: lower-intensity option that requires ophthalmologic monitoring. 
 
Strengths  
• Synthesizes evidence from multiple randomized phase 3 trials of BCMA-directed therapies. 
• Discusses clinical trial applicability, treatment access, logistical considerations, and common real-world clinical scenarios relevant to treatment selection. 
 
Limitations  
• Differences in patient populations, trial designs, and real-world applicability make comparisons and treatment selection more complex. 
• Some trial findings have limited applicability because treatment patterns in current clinical practice differ from trial populations (for example, prior use of bortezomib and daratumumab). 
• Formal frailty assessment is lacking in randomized trials supporting BCMA-directed therapy after 1–3 prior lines of therapy. 
• Prospective evidence for optimal sequencing of BCMA-directed therapies in early relapse is lacking. 
• Registrational trials primarily enrolled fit patients with limited comorbidities, limiting generalizability to frail populations. 
• Some recommendations for specific clinical scenarios rely on emerging or real-world evidence because prospective randomized data are limited. 
 
Why this review matters 
Randomized clinical trials reviewed in this article show that BCMA-directed therapies (including belantamab mafodotin-based ADCs, CAR-T therapies, and T-cell engager antibodies) provide effective treatment options for patients with multiple myeloma after 1–3 prior lines of therapy, although they differ in safety profiles, treatment logistics, and eligibility requirements. The review concludes that treatment selection should be individualized using clinical trial evidence together with patient fitness, disease characteristics, treatment urgency, access to therapy, and shared decision-making, while acknowledging current evidence gaps in treatment sequencing and frailty assessment. 
 
Reference: 
Doris K. Hansen, Maria Victoria Mateos, Luciano J. Costa; Targeting BCMA in patients with relapsed/refractory multiple myeloma in 1 to 3 prior lines of therapy. Blood Adv 2026; 10 (14): 4931–4940. doi: https://doi.org/10.1182/bloodadvances.2026019699 (https://ashpublications.org/bloodadvances/article/10/14/4931/568812/Targeting-BCMA-in-patients-with-relapsed?searchresult=1) 

Non-ICANS neurologic toxicity after BCMA CAR-T therapy: a systematic review and meta-analysis of 4630 patients with multiple myeloma — Blood Advances (August 2026) 
 

What is the purpose of the systematic review? 
To characterize the incidence, clinical phenotypes, and treatment-related risk factors of non-ICANS neurologic toxicities (NINTs) occurring after BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy. It uses a systematic review and meta-analysis of prospective clinical trials and real-world studies to better define these uncommon toxicities. 
 
Summary 
This systematic review and meta-analysis included 55 cohorts comprising 4,630 patients treated with BCMA-directed CAR-T therapy; the pooled point estimate for NINTs was 0.81% (95% CI, 0.37%-1.77%). NINTs occurred significantly more frequently with ciltacabtagene autoleucel (cilta-cel) than with idecabtagene vicleucel (ide-cel) (4.6% vs 0.5%; P = .001) and experimental BCMA-directed constructs (4.6% vs 0.3%; P = .02), with cilta-cel independently associated with increased NINT risk compared with ide-cel in meta-regression.   
The most frequently reported NINT phenotype was cranial nerve palsy (32.3%, 43 events), followed by movement and neurocognitive treatment-emergent adverse events (12%, 16 events) and peripheral neuropathies (7.5%, 10 events). 
 
Key points 
• Study design: Systematic review and meta-analysis conducted according to PRISMA guidelines, using random-effects meta-analysis and meta-regression. 
• Population: 4,630 treated patients across 55 cohorts from prospective clinical trials and real-world studies. 
• Overall NINT frequency: Pooled point estimate of 0.81% (95% CI, 0.37%-1.77%). 
• Product-specific frequency: 
 - Cilta-cel: 4.6% 
 - Ide-cel: 0.5% 
 - Experimental BCMA-directed constructs: 0.3% 
 - NINT frequency was significantly higher with cilta-cel than ide-cel (P = .001) and experimental constructs (P = .02). 
    
• Risk factors: Cilta-cel was independently associated with increased NINT risk compared with ide-cel. No additional significant associations were identified for previous autologous stem-cell transplantation (ASCT), median lines of therapy, treatment era, or bridging therapy. 
    
• Most frequently reported phenotypes: 
 - Cranial nerve palsies: 32.3% (43 events) 
 - Movement and neurocognitive treatment-emergent adverse events: 12% (16 events) 
 - Peripheral neuropathies: 7.5% (10 events) 
    
• Potentially relevant factors: The authors noted a trend toward increased NINTs after previous BCMA-targeted therapy but stated that this could be affected by reporting bias. Emerging evidence regarding rapid CAR-T expansion and nonresponse to bridging therapy could not be reliably evaluated from the included studies. 
    
• Management: The discussion states that effective, standardized management approaches are lacking, and that NINTs may be resistant to general immunosuppressive regimens. 
 
Strengths 
• The authors describe this as, to their knowledge, the first and largest systematic review and meta-analysis characterizing NINTs after BCMA-directed CAR-T therapy. 
• The similar occurrence of NINTs in clinical trials and real-world studies was also noted as supporting adequate capture of these rare events in clinical trials. 
 
Limitations  
• Reporting and publication bias may have underestimated the pooled point estimate. 
• Some overlap between real-world and clinical-trial patient populations could not be completely excluded. 
• NINTs were heterogeneous, with many events unspecified or not fitting the predefined categories. 
• Potential overlap between ICANS and NINTs may have introduced confounding. 
• Some studies of experimental, non-FDA-approved constructs may not have reported NINTs with sufficient rigor for reliable estimation. 
• Some NINTs can emerge weeks or months after infusion, and inadequate follow-up in some studies may have limited detection. 
 
Why this review matters 
NINTs after BCMA-directed CAR-T therapy were uncommon, with a pooled point estimate of 0.81%, but were reported more frequently after cilta-cel than after ide-cel or experimental BCMA-directed constructs. Cranial nerve palsies were the most frequently reported phenotype, while the authors identified limitations in event reporting, standardized definitions, grading, surveillance, and management that warrant further study. 
 
Reference: 
Herman van Besien, Gwynne Ozkan, Neela Easton, Tobias Tix, Mohammad Alhomoud, Roni Shouval, Kai Rejeski, Samuel Yamshon; Non-ICANS neurologic toxicity after BCMA CAR-T therapy: a systematic review and meta-analysis of 4630 patients with multiple myeloma. Blood Adv 2026; 10 (15): 5413–5425. doi: https://doi.org/10.1182/bloodadvances.2026019617 (https://ashpublications.org/bloodadvances/article/10/15/5413/567447/Non-ICANS-neurologic-toxicity-after-BCMA-CAR-T) 

T-Cell Engagers Targeting BCMA, GPRC5D, or FcRH5 in Relapsed/Refractory Multiple Myeloma: The Landscape Beyond CAR-T Cell Therapy-A Systematic Review and Network Meta-Analysis — International Journal of Molecular Sciences (August 2026) 
 

What is the purpose of the review? 
To evaluate and compare the efficacy and safety of bispecific T-cell engagers (BsAbs) targeting BCMA, GPRC5D, or FcRH5 in patients with relapsed/refractory multiple myeloma (RRMM). Because few head-to-head trials are available, the analysis uses both direct and indirect comparisons with standard of care (SOC). 
 
Summary 
The meta-analysis included 44 studies and found that talquetamab, teclistamab, elranatamab, and linvoseltamab had higher odds of objective response rate (ORR) than SOC, while progression-free survival (PFS) was also improved with these agents. In pooled single-arm data, ORR was 72% with talquetamab, 61% with teclistamab, 56% with elranatamab, 60% with linvoseltamab, and 49% with cevostamab; cytokine release syndrome (CRS) occurred in 68%, 61%, 52%, 51%, and 61%, respectively. Linvoseltamab and elranatamab showed numerically longer overall survival (OS) than SOC, whereas Teclistamab and talquetamab showed numerically shorter OS, but these findings were based on adjusted cross-trial comparisons and were subject to limitations including heterogeneous studies, follow-up duration, censoring, and residual confounding. 
 
Key points 

Efficacy
• Compared with SOC, ORR odds were higher with: 
- Talquetamab: 5.73 
- Teclistamab: 4.86 
- Elranatamab: 3.84 
- Linvoseltamab: 2.63 

• PFS was improved versus SOC with: 
- Teclistamab: HR 0.50 (95% CI 0.36–0.55) 
- Talquetamab: HR 0.50 (95% CI 0.36–0.55) 
- Elranatamab: HR 0.45 (95% CI 0.36–0.55) 
- Linvoseltamab: HR 0.23 (95% CI 0.17–0.31) 
    
• In pooled single-arm analyses, ORR was 72% for talquetamab, 61% for teclistamab, 60% for linvoseltamab, 56% for elranatamab, and 49% for cevostamab. 

Overall survival 
• Linvoseltamab and elranatamab had numerically longer OS than SOC: 
- Linvoseltamab: HR 0.41 (95% CI 0.24–0.70) 
- Elranatamab: HR 0.58 (95% CI 0.43–0.78) 
    
• Teclistamab and Talquetamab had numerically shorter OS than SOC: 
- Teclistamab: HR 1.82 (95% CI 1.37–2.42) 
- Talquetamab: HR 1.75 (95% CI 1.20–2.57) 
    
• The authors state that these OS findings are hypothesis-generating rather than definitive, given the lack of head-to-head randomized data, limited follow-up, censoring, residual confounding, and unavailable PFS2/subsequent-treatment information. 

Safety 
• CRS occurred in 68% with talquetamab, 66% with Teclistamab, and 74% with elranatamab in the analyses described in the Discussion. 
• ICANS occurred more frequently with talquetamab (25%) than with elranatamab (11%) or Teclistamab (7%). 
• Infections occurred in 58% with talquetamab, 66% with teclistamab, and 60% with elranatamab; ≥grade 3 infections occurred in 22%, 34%, and 27%, respectively. 
• Dysgeusia occurred in nearly 70% of patients receiving GPRC5D-targeting agents and was described as low grade and manageable. 

Treatment targeting 
• The analysis discussed antigen escape, T-cell fitness, antigen density, disease burden, and the tumor microenvironment as factors affecting T-cell engager activity and toxicity. 
• The authors reported ORR of 86% with combined talquetamab and teclistamab, compared with 68% with talquetamab alone and 61% with teclistamab alone; these findings were explicitly described as descriptive and hypothesis-generating. 
 
Strengths  
• Inclusion of heterogeneous populations from different geographical regions. 
• Integration of real-world physicians’ choice data with clinical-trial outcomes. 
• Use of IPTW and MAIC to adjust for baseline differences between clinical-trial and real-world populations. 
• Inclusion of both direct and indirect/network comparisons among BsAbs and SOC. 
 
Limitations  
• Most included BsAb studies were single-arm, with few head-to-head comparisons. 
• Real-world data were not uniformly adjusted for cytogenetic risk, extramedullary disease (EMD), or ECOG performance status, resulting in potential unmeasured confounding. 
• Exclusion of patients with insufficient electronic health-record information introduced potential selection bias. 
• Heterogeneity among studies and lack of randomized head-to-head comparisons limit definitive comparisons between individual BsAbs. 
• Limited follow-up and substantial censoring reduced the precision of some OS estimates. 
• PFS2 and subsequent-treatment details were not reported, preventing assessment of treatment sequencing and post-progression survival effects on OS. 
 
Why this meta-analysis matters 
The network meta-analysis found that BsAbs targeting BCMA, GPRC5D, or FcRH5 had higher ORR than SOC, with PFS benefits observed in the analyzed comparisons; however, the PFS effect in BCMA-exposed populations was heterogeneous and should be considered hypothesis-generating pending prospective, subgroup-specific analyses. The authors emphasize that OS and comparisons between specific BsAbs remain hypothesis-generating, and that prospective randomized or pragmatic head-to-head studies are needed to confirm comparative efficacy and survival findings. 
 
 
Reference: 
Shambhavi, S., Joy, A. A., Singh, H., Amonica, T., Grover, A., Singh, T., Paul, S. S., & Pompa, T. (2026). T-Cell Engagers Targeting BCMA, GPRC5D, or FcRH5 in Relapsed/Refractory Multiple Myeloma: The Landscape Beyond CAR-T Cell Therapy-A Systematic Review and Network Meta-Analysis. International Journal of Molecular Sciences, 27(16), 7179. https://doi.org/10.3390/ijms27167179  (https://www.mdpi.com/1422-0067/27/16/7179)

Translocation t(11;14) and BCL2-inhibition in multiple myeloma — Haematologica (August 2026) 

What is the purpose of the review? 
This review examines the biological and clinical significance of translocation t(11;14) in multiple myeloma, with a focus on its role as a biomarker for response to BCL2 inhibitors. It also summarizes evidence on the efficacy, safety, resistance mechanisms, and future clinical development of BCL2 inhibitor–based therapies, particularly venetoclax and second-generation BCL2 inhibitors. 
 
Summary  
Translocation t(11;14) is present in approximately 15–20% of patients with multiple myeloma at diagnosis and is associated with increased dependence on the anti-apoptotic BCL2 protein, making it a predictive biomarker for response to BCL2 inhibitors. Clinical studies reviewed reported higher response rates and longer progression-free survival with venetoclax-based treatment in patients with t(11;14) and/or high BCL2 expression, while increased rates of serious infections were observed, particularly in patients without these biomarkers. The review also discusses emerging second-generation BCL2 inhibitors, mechanisms of resistance, and ongoing research evaluating biomarker-guided treatment strategies and combination regimens. 
 
Key points 
• Translocation t(11;14) is a primary cytogenetic abnormality present in 15–20% of newly diagnosed multiple myeloma cases. 
• The presence of t(11;14) is associated with increased dependence on BCL2, providing a biological rationale for treatment with BCL2 inhibitors. 
• In a phase I study of venetoclax monotherapy: 
 - Overall response rate (ORR): 21% (14/66) overall
 - ORR in t(11;14) patients: 40% (12/30)

• In a phase I/II study of venetoclax plus dexamethasone in relapsed/refractory t(11;14) multiple myeloma: 
 - ORR: 48%. 
 - 36% achieved a very good partial response or better
 - Median time to progression: 10.8 months

• The phase III BELLINI trial reported: 
 - Median progression-free survival (PFS): 23.4 vs. 11.4 months with venetoclax versus placebo (HR 0.58) in the overall study population. 
 - In the t(11;14) subgroup, median PFS was 36.8 vs. 9.3 months (HR 0.17). 
 - Patients with high BCL2 expression also had longer PFS (30.1 vs. 9.9 months; HR 0.36). 
 - Increased rates of grade ≥3 infections and infection-related deaths were observed in the venetoclax group. 

• An updated phase I/II study of venetoclax, daratumumab, and dexamethasone reported: 
 - ORR: 96.4% vs. 65.4% compared with bortezomib, daratumumab, and dexamethasone. 
 - Minimal residual disease (MRD)-negative rates: 38% vs. 8%
 - Higher 33-month PFS rate: 73.4% vs. 38.8%
    
• In the phase III CANOVA trial: 
 - ORR: 63% vs. 35% for venetoclax plus dexamethasone versus pomalidomide plus dexamethasone. 
 - The primary PFS endpoint was not met, although a post hoc analysis reported longer PFS (9.4 vs. 4.0 months; HR 0.651, P=0.003). 
    
• Early studies of second-generation BCL2 inhibitors, including sonrotoclax, demonstrated: 
 - ORR: 80.6%
 - Very good partial response or better: 55.6% in heavily pretreated patients
    
• Common adverse events of BCL2 inhibitors include: 
 - Hematologic: neutropenia and thrombocytopenia. 
 - Non-hematologic: infections and gastrointestinal symptoms, particularly diarrhea. 
    
• The review discusses ongoing research on: 
 - Earlier use of BCL2 inhibitors in newly diagnosed disease. 
 - Combination with T-cell engager therapies. 
 - Improved biomarkers beyond t(11;14) alone. 
 - Mechanisms of resistance and optimized treatment sequencing. 
 
Limitations  
• Evidence remains limited for patients with concurrent t(11;14) and additional high-risk cytogenetic abnormalities such as del(17p) or 1q gain/amplification. 
• Data on outcomes with T-cell engager therapies in patients with t(11;14) are described as sparse. 
• The CANOVA study did not meet its primary progression-free survival endpoint, with the authors noting informative censoring as a likely contributing factor. 
• The review identifies the need for standardized methods of BCL2 protein quantification and additional studies on resistance mechanisms and optimal patient selection. 
 
Why this review matters 
This review summarizes evidence evaluating BCL2 inhibitor–based therapy in multiple myeloma with t(11;14), where clinical studies reported higher response rates and longer progression-free survival with venetoclax-based regimens, particularly in patients with t(11;14) and/or high BCL2 expression. The review also describes important safety considerations, including infection risk, and identifies ongoing areas of investigation involving biomarker selection, treatment combinations, sequencing, and the clinical role of next-generation BCL2 inhibitors. 
 
 
Reference: 
Sim S, Dhakal B, Quach H. Translocation t(11;14) and BCL2-inhibition in multiple myeloma. Haematologica 2026; 111(8):2578-2590; https://doi.org/10.3324/haematol.2025.289147. (https://haematologica.org/article/view/13074)   

Research 
 

Global burden of multiple myeloma (1990–2021) and projections up to 2035: a methodical analysis leveraging the global burden of disease 2021 study and Mendelian randomization — Journal of the Egyptian National Cancer Institute (July 2026) 
 

What is the purpose of the study? 
To assess the global burden of multiple myeloma (MM) from 1990 to 2021 using the Global Burden of Disease (GBD) 2021 database. It also evaluates risk factors, investigates the potential causal relationship between body mass index (BMI) and MM using two-sample Mendelian randomization (MR), and projects future disease burden through 2035 using Bayesian Age-Period-Cohort (BAPC) models. 
 
Summary  
Using GBD 2021 data, the study analyzed global and regional trends in MM incidence, mortality, disability-adjusted life years (DALYs), demographic patterns, socioeconomic differences, and risk factors, with temporal trends assessed by Joinpoint regression. In 2021, there were 148,755 incident MM cases, 116,359 deaths, and 2,595,595 DALYs worldwide; age-standardized incidence, mortality, and DALY rates were highest in high-income regions, while global incidence, mortality, and DALY rates increased on average by 0.54%, 0.20%, and 0.18% per year, respectively, between 1990 and 2021. MR analysis supported a positive association between higher BMI and increased MM risk, and BAPC modeling projected declining global age-standardized MM burden through 2035, although the absolute number of cases may continue to increase because of population growth and aging. 
 
Key points 
• The study used the GBD 2021 database to evaluate the global burden of MM from 1990–2021. 
• Methods included: 
 - Analysis of age-standardized incidence, mortality, and DALY rates. 
 - Joinpoint regression for temporal trends. 
 - Two-sample Mendelian randomization (MR) to examine the relationship between BMI and MM
 - Bayesian Age-Period-Cohort (BAPC) modeling to project disease burden through 2035

• 2021 global estimates:
 - 148,755 incident MM cases
 - 116,359 deaths. 
 - 2,595,595 DALYs. 
 - Age-standardized incidence rate: 1.74 per 100,000. 
 - Age-standardized mortality rate: 1.37 per 100,000. 
 - Age-standardized DALY rate: 30.00 per 100,000. 

• Between 1990 and 2021, annual average percentage change (AAPC): 
 - Incidence: 0.54%. 
 - Mortality: 0.20%. 
 - DALYs: 0.18%. 

• The highest age-standardized MM burden was observed in high-income regions. 
• The burden attributable to high BMI was greatest in high-income regions, including Australasia and North America, while lower proportions were observed in South Asia and Southeast Asia. 
• MR analysis identified a positive association between elevated BMI and increased MM risk. 
• Older adults, particularly those aged 70–95 years, accounted for the greatest disease burden. 
• The BAPC model projected declining age-standardized MM burden through 2035, while noting that the absolute number of MM cases may continue to rise because of population growth and aging. 
 
Strengths  
• First comprehensive and systematic global analysis of MM burden. 
• Integrated GBD data with Mendelian randomization to evaluate potential causal relationships between BMI and MM. 
• Examined global, regional, age-specific, and socioeconomic patterns and projected disease burden through 2035. 
 
Limitations  
• Differences in socioeconomic development and healthcare resources across countries may affect the quality and accuracy of GBD estimates. 
• The long study period (1990–2021) may not fully capture short-term changes in disease burden. 
• BAPC projections may be affected by future changes in diagnostics, treatments, demographics, health policies, and risk factor exposure. 
 
Why this study matters 
The study found that the global burden of multiple myeloma increased between 1990 and 2021, with the highest age-standardized burden occurring in high-income regions and faster growth in disease burden in middle-SDI regions. Two-sample Mendelian randomization supported a positive association between elevated BMI and increased MM risk, and BAPC modeling projected declining age-standardized burden through 2035 while indicating that the total number of MM cases may continue to increase because of population growth and aging. 
 
 
Reference: 
Qu, R., Zhang, X., Zou, J. et al. Global burden of multiple myeloma(1990–2021) and projections up to 2035: a methodical analysis leveraging the global burden of disease 2021 study and Mendelian randomization. J Egypt Natl Canc Inst 38, 44 (2026). https://doi.org/10.1186/s43046-026-00377-4  (https://link.springer.com/article/10.1186/s43046-026-00377-4)
 
 

Linvoseltamab versus elranatamab for triple-class exposed relapsed or refractory multiple myeloma: an indirect treatment comparison — Leukemia & Lymphoma (July 2026) 
 

What is the purpose of the study? 
To evaluate the comparative efficacy of linvoseltamab versus elranatamab, two BCMA×CD3 bispecific antibodies, in patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) using an unanchored matching-adjusted indirect comparison (MAIC). Patient-level data from LINKER-MM1 are matched with data from MagnetisMM-3 Cohort A to compare treatment outcomes in the absence of a head-to-head clinical trial. 
 
Summary  
The MAIC included 107 BCMA-targeted therapy-naïve patients from LINKER-MM1 (median follow-up 21.3 months) and 123 patients from MagnetisMM-3 Cohort A (median follow-up 33.9 months). Linvoseltamab was associated with significantly higher overall response rate (71.5% vs. 61.0%; p<0.05) and complete response or better rate (50.5% vs. 37.4%; p<0.05), while the very good partial response or better rate was numerically higher (65.0% vs. 56.1%; p=0.09). Duration of response, progression-free survival, and overall survival hazard ratios numerically favored linvoseltamab but were not statistically significant; however, restricted mean survival time analysis showed a statistically significant overall survival difference of 3.47 months in favor of linvoseltamab (p=0.04). 
 
Key points 
• Study design: Unanchored matching-adjusted indirect comparison (MAIC). 
• Population: Patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) who were BCMA-targeted therapy-naïve. 
• Trials compared: 
 - LINKER-MM1 (linvoseltamab): n=107; data cutoff July 2024; median follow-up 21.3 months. 
 - MagnetisMM-3 Cohort A (elranatamab): N=123; data cutoff September 2024; median follow-up 33.9 months. 

• Efficacy results: 
 - Overall response rate: 71.5% vs. 61.0% (p<0.05). 
 - Complete response or better: 50.5% vs. 37.4% (p<0.05). 
 - Very good partial response or better: 65.0% vs. 56.1% (p=0.09). 
 - Duration of response: HR 0.82 (p=0.54). 
 - Progression-free survival: HR 0.86 (p=0.50). 
 - Overall survival: HR 0.67 (p=0.08). 
 - Restricted mean survival time analysis showed an overall survival difference of 3.47 months favoring linvoseltamab (p=0.04). 

• Sensitivity analyses: Reported results were generally consistent across primary, secondary, and sensitivity analyses. 
 
Strengths  
• Rigorous adjustment for refractory status in accordance with NICE recommendations. 
• Protocol-defined feasibility assessment to evaluate trial comparability. 
• Use of multiple matching strategies to assess consistency. 
• Harmonization of censoring rules for time-to-event outcomes. 
• Consistent findings across analyses, including adjustment for all available prognostic factors. 
 
Limitations  
• Unanchored MAIC may be affected by residual confounding from unmeasured or inconsistently reported prognostic factors. 
• Some baseline variables (e.g., soluble BCMA, β2-microglobulin, time to relapse from first-line therapy) were unavailable or inconsistently reported. 
• Differences between trials in ECOG performance status eligibility, life expectancy criteria, and central nervous system involvement could not be fully adjusted. 
• Reduced effective sample size and wider confidence intervals after matching on all prognostic variables. 
• Potential influence of COVID-19-related mortality, differences in treatment period and supportive care, and differences in cytokine release syndrome management. 
• Shorter follow-up in LINKER-MM1 compared with MagnetisMM-3 may have affected maturity of time-to-event outcomes. 
• Safety and patient-reported outcomes were not evaluated. 
 
Why this study matters 
In this unanchored MAIC, linvoseltamab was associated with significantly higher overall response and complete response or better rates than elranatamab in patients with TCE RRMM. Time-to-event outcomes generally favored linvoseltamab numerically, while restricted mean survival time analysis demonstrated a statistically significant overall survival difference. The authors also reported that elranatamab did not demonstrate numerically or statistically higher efficacy for any evaluated endpoint. These findings should be interpreted in the context of the methodological limitations inherent to indirect comparisons and the absence of a head-to-head trial. 
 
 
Reference: 
Richter, J., Lee, H. C., Jagannath, S., Zonder, J. A., Hoffman, J. E., Zhou, Z. Y., … Bumma, N. (2026). Linvoseltamab versus elranatamab for triple-class exposed relapsed or refractory multiple myeloma: an indirect treatment comparison. Leukemia & Lymphoma, 1–13. https://doi.org/10.1080/10428194.2026.2688561 (https://www.tandfonline.com/doi/full/10.1080/10428194.2026.2688561) 
 

Effectiveness of daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd for transplant-eligible newly diagnosed multiple myeloma — Future Oncology (July 2026) 
 

What is the purpose of the study? 
To evaluate real-world progression-free survival (PFS) in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) treated with frontline daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) followed by daratumumab/lenalidomide (DR) or lenalidomide (R) maintenance (DVRd-DR/R) versus bortezomib, lenalidomide, and dexamethasone (VRd) followed by R maintenance (VRd-R). 
 
Summary  
This retrospective multicenter chart review included 223 adult TE patients with NDMM treated at 10 U.S. sites between January 2020 and June 2022, with 137 patients receiving DVRd-DR/R and 86 receiving VRd-R. After median follow-up of 26.7 months for the DVRd-DR/R group and 39.8 months for the VRd-R group, disease progression or death occurred in 9.1% and 29.7% of patients, respectively; median PFS was not reached in either group. Propensity score-weighted analysis showed that DVRd-DR/R was associated with a lower risk of disease progression or death than VRd-R (weighted hazard ratio [HR] 0.37; 95% confidence interval [CI] 0.17–0.80; p=0.006), and the weighted 48-month PFS rates were 85.2% and 62.6%, respectively. 
 
Key points 
• Study design: Retrospective multicenter chart review conducted at 10 U.S. sites. 
• Population: 223 transplant-eligible adults with newly diagnosed multiple myeloma. 
 - DVRd-DR/R: 137 patients 
 - VRd-R: 86 patients 
• Primary outcome: Progression-free survival (PFS) assessed using Kaplan-Meier analyses and propensity score-weighted Cox regression. 
• Median follow-up: 
 - DVRd-DR/R: 26.7 months 
 - VRd-R: 39.8 months 
• Disease progression or death: 
 - DVRd-DR/R: 11 patients (9.1%) 
 - VRd-R: 32 patients (29.7%) 
• Median PFS: Not reached in either treatment group. 
• Risk of disease progression or death: Weighted HR 0.37 (95% CI 0.17–0.80; p=0.006), corresponding to a lower risk with DVRd-DR/R than VRd-R. 
• Weighted 48-month PFS: 
 - DVRd-DR/R: 85.2% 
 - VRd-R: 62.6% 
• The study reported that the findings were consistent with results from the GRIFFIN and PERSEUS clinical trials. 
 
Strengths 
• Multicenter chart review allowed collection of detailed clinical information not typically available in electronic medical records, including disease progression and transplant eligibility, with data adjudication and quality control. 
• Use of doubly robust inverse probability of treatment weighting (IPTW) improved balance between treatment groups and accounted for measured baseline differences. 
• Patients in both treatment groups initiated frontline therapy during the same time period, reducing potential temporal bias compared with earlier real-world analyses. 
 
Limitations  
• Retrospective, non-randomized observational design with potential for confounding by indication and residual confounding from unmeasured factors. 
• Data were limited to available electronic medical records and charts; some care received outside participating sites, and missing data may not have been captured. 
• Variability in treatment dosing, scheduling, maintenance strategies, and institutional practices may have introduced heterogeneity. 
• Differences in follow-up duration existed between cohorts, although the authors reported analytical approaches intended to minimize their impact. 
• Sample size limited subgroup analyses, institution-level analyses, and robust comparison between DR and R maintenance within the DVRd group. 
• Findings may not be generalizable beyond transplant-eligible patients with NDMM or to patients who experienced earlier disease progression. 
• Safety data, including infection prevention practices and infection-related complications, were not collected. 
 
Why this study matters 
In this real-world retrospective study, frontline DVRd followed by DR or R maintenance was associated with a lower risk of disease progression or death than VRd followed by R maintenance in transplant-eligible patients with newly diagnosed multiple myeloma. Median PFS was not reached in either group, and the weighted 48-month PFS rate was higher with DVRd-DR/R than with VRd-R. The authors reported that these findings were consistent with the GRIFFIN and PERSEUS clinical trials and stated that larger studies with longer follow-up are needed to further evaluate long-term outcomes, safety, and maintenance strategies. 
 
Reference: 
Tan, C. R., Gordan, L., Richter, J., DiLeo, R., Mewawalla, P., Larson, S., … Usmani, S. (2026). Effectiveness of daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd for transplant-eligible newly diagnosed multiple myeloma. Future Oncology, 1–9. https://doi.org/10.1080/14796694.2026.2698699  (https://www.tandfonline.com/doi/full/10.1080/14796694.2026.2698699)
 

Response kinetics and depth of response after idecabtagene vicleucel in relapsed/refractory multiple myeloma — Blood Cancer Journal (July 2026) 
 

What is the purpose of the study? 
To evaluate whether the depth of response after standard-of-care idecabtagene vicleucel (ide-cel) predicts progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma (RRMM), including those who had received many prior lines of therapy. It also examines whether post-infusion response and relapse kinetics, including time to best response (TBR) and duration of best response (DBR), were associated with subsequent clinical outcomes. 
 
Summary  
This registry-based analysis used data from the CIBMTR MM23-01a study and included 821 patients treated with standard-of-care ide-cel in the United States between May 2021 and June 2023 (median 7 prior lines of therapy). The overall response rate was 73%, with 31% achieving very good partial response (VGPR) and 25% achieving complete response (CR); median PFS was 8.75 months (95% CI, 7.8–10.7) and median OS was 15.6 months (95% CI, 13.8–17.8). Deeper responses were associated with longer PFS and OS across all prior line-of-therapy groups, whereas TBR was not independently associated with outcomes after multivariable adjustment; patients with more durable responses had more favorable post-response survival. 
 
 
Key points 
• Study population 
 - Registry-based analysis of 821 patients with RRMM treated with standard-of-care ide-cel
 - Median prior lines of therapy: 7 (IQR 6–9)

• Response outcomes 
 - Overall response rate (ORR): 73%
 - 31% achieved VGPR
 - 25% achieved CR

• Survival outcomes 
 - Median PFS: 8.75 months (95% CI, 7.8–10.7) 
 - Median OS: 15.6 months (95% CI, 13.8–17.8) 

• Depth of response 
 - Best response after ide-cel was significantly associated with both PFS and OS. 
 - Median PFS: 
    • PR: 7.0 months (95% CI, 6.4–9.0) 
    • VGPR: 11.8 months (95% CI, 10.7–not reached) 
    • CR: not reached (95% CI, 13.3–not reached) 
 - The association between deeper response and improved outcomes remained across patients with 4–6, 7–9, and ≥10 prior lines of therapy. 
 - No significant interaction was observed between best response and number of prior therapy lines for PFS (p=0.52) or OS (p=0.61). 

• Response kinetics 
 - Among 503 patients with at least a partial response and complete response-timing data, spline analyses identified cutoffs of: 3 months for TBR; 4 months for DBR. 
 - TBR >3 months was associated with longer post-best-response PFS on univariable analysis but was not independently associated with post-best-response PFS or OS on multivariable analysis. 

• Response and relapse patterns 
 - Patients with a late response/late relapse pattern had the longest post-best-response OS (median not reached). 
 - Patients with an early response/early relapse pattern had the shortest post-best-response OS (median 7.4 months, 95% CI, 5.6–10.7; p<0.001). 
 - Patients achieving VGPR or CR were more likely to have a late response/late relapse pattern. 
 
Limitations  
• Included only patients treated with standard-of-care ide-cel who achieved at least a partial response; findings may not apply to non-responders. 
• Registry-based secondary analysis is susceptible to residual confounding. 
• Relatively short follow-up may have limited assessment of late relapses. 
• Response/relapse trajectory groups incorporated duration of best response and therefore should be interpreted as descriptive rather than as an independent prognostic model. 
• Time to overall response and TBR were identical in patients with both variables available, limiting distinction between initial response timing and response deepening. 
• Findings may not be generalizable to CAR-T products other than ide-cel. 
 
Why this study matters 
In this registry-based analysis of patients with RRMM treated with standard-of-care ide-cel, deeper and more durable responses were associated with longer PFS and OS across all prior lines of therapy. TBR alone was not independently associated with outcomes after multivariable adjustment. The authors conclude that post-infusion response depth and durability may provide useful prognostic information for evaluating outcomes after CAR-T therapy and may inform future studies of risk-adapted post-CAR-T strategies. 
 
Reference: 
Goel, U., Dragomirescu, C., Chedid, R. et al. Response kinetics and depth of response after idecabtagene vicleucel in relapsed/refractory multiple myeloma. Blood Cancer J. 16, 116 (2026). https://doi.org/10.1038/s41408-026-01582-z  (https://www.nature.com/articles/s41408-026-01582-z)
 

Redefining functional high-risk multiple myeloma in the context of upfront quadruplet therapy and autologous stem cell transplantation — Cancer (July 2026) 
 

What is the purpose of the study? 
To identify the most appropriate definition of functional high-risk (FHR) multiple myeloma (MM) in patients receiving quadruplet therapy (QUAD) followed by autologous stem cell transplantation (ASCT). It also evaluates outcomes after second-line therapy and explores factors associated with those outcomes, including the use of T-cell–redirecting therapy (TCRT). 
 
Summary  
The study analyzed 310 patients with newly diagnosed multiple myeloma (NDMM) treated with QUAD plus ASCT, with a median follow-up of 41.8 months and 66 disease progression events. Disease progression within 36 months (FHR36) identified a group representing 16.4% of patients whose median overall survival after starting second-line therapy was 23.8 months, whereas earlier cutoff definitions (<12, <18, or <24 months) were associated with shorter post-progression overall survival than the predefined target of approximately 2 years. The 12-month second progression-free survival (2PFS) rate was 80% in patients who received T-cell–redirecting therapy compared with 23% in those who did not, and multivariable analysis found T-cell–redirecting therapy to be associated with improved 2PFS after adjustment for FHR status. 
 
Key points 
• Study population: 310 patients with NDMM treated with QUAD plus ASCT. 
• Follow-up: Median follow-up was 41.8 months. 
• Progression events: 66 patients experienced disease progression. 
• FHR cutoff points evaluated: Disease progression within 12, 18, 24, and 36 months of treatment initiation. 
• Cumulative incidence of progression: 
 - Within 12 months: 2.6% 
 - Within 18 months: 6.2% 
 - Within 24 months: 10.1% 
 - Within 36 months: 16.4% 

• Median second progression-free survival (2PFS) and overall survival (OS) from second-line therapy: 
 - FHR12: 2PFS 3.0 months; OS 8.1 months 
 - FHR18: 2PFS 2.7 months; OS 8.1 months 
 - FHR24: 2PFS 3.3 months; OS 15.7 months 
 - FHR36: 2PFS 5.8 months; OS 23.8 months 
    
• Based on the predefined criterion of post-progression OS of approximately 2 years, FHR36 was identified as the optimal definition of functional high-risk multiple myeloma in this treatment setting.     
• The 12-month 2PFS rate was 80% among patients who received T-cell–redirecting therapy (CAR T-cell therapy or bispecific T-cell engager) versus 23% among those who did not.     
• In multivariable analysis, T-cell–redirecting therapy was associated with improved 2PFS after adjustment for FHR status. 
 
Limitations  
• Combined clinical trial participants with patients treated according to institutional practice, introducing treatment heterogeneity. 
• Variation existed in induction proteasome inhibitors and post-ASCT consolidation and maintenance strategies. 
• The overall sample size was relatively small, limiting the ability to draw inferences, including in multivariable analyses. 
• Patients who progressed before ASCT were not included. 
• There was substantial heterogeneity in second-line treatments, and only 11 patients received T-cell–redirecting therapy. 
• The use of T-cell–redirecting therapy may have been influenced by treatment availability, patient fitness, and organ function, which could bias comparisons. 
• Findings regarding T-cell–redirecting therapy were based on a small number of progression events and lacked external validation. 
 
Why this study matters 
Among patients with NDMM treated with QUAD plus ASCT, disease progression within 36 months was identified as the study's optimal definition of FHRMM based on the prespecified post-progression overall survival criterion. Patients meeting the FHR36 definition had poor outcomes after conventional second-line therapy, while receipt of T-cell–redirecting therapy was associated with improved second progression-free survival in multivariable analysis. The authors state that these findings provide benchmark data for future clinical trials, while noting the study's limitations, including its small sample size, treatment heterogeneity, and lack of external validation. 
 
Reference: 
Ravi G, Dhakal B, Callander NS, et al. Redefining functional high-risk multiple myeloma in the context of upfront quadruplet therapy and autologous stem cell transplantation. Cancer. 2026;e70478. doi:10.1002/cncr.70478  (https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70478)

Risk factors and clinical impact of bone pain in patients with multiple myeloma – A prospective interdisciplinary study — Journal of Bone Oncology (July 2026) 
 

What is the purpose of the study? 
To evaluate clinical predictors of bone pain in 352 patients with multiple myeloma (MM). It also examines the association between bone pain, quality of life (QoL), and health-related status to identify factors associated with pain. 
 
Summary  
Bone pain was reported by 184 of 352 patients (52%) and was independently associated with osteolytic lesions with fracture risk (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.46–6.40; p=0.003) and pre-existing orthopedic conditions (OR 2.78, 95% CI 1.77–4.36; p<0.0001). Patients with bone pain had significantly lower QoL and health-related status than those without pain (p<0.001), while age, sex, International Staging System (ISS) stage, disease duration, and CRAB-C, CRAB-R, and CRAB-A were not independently associated with bone pain after adjustment. Radiological assessment showed that 71% of reported pain sites corresponded to CT-detected osteolytic lesions, whereas 29% did not, indicating that bone pain may occur without corresponding CT-visible myeloma-related skeletal lesions. 
 
Key points 
• Bone pain occurred in 52% (184/352) of patients with multiple myeloma
• Independent predictors of bone pain: 
 - Osteolytic lesions with fracture risk: OR 3.06 (95% CI 1.46–6.40; p=0.003) 
 - Pre-existing orthopedic conditions: OR 2.78 (95% CI 1.77–4.36; p<0.0001) 

• CRAB-B at initial diagnosis (OR 1.74; p=0.09) and progressive disease (OR 1.68; p=0.09) showed increased odds of bone pain but were not statistically significant after adjustment. 
• Age, sex, ISS stage, disease duration, and CRAB-C, CRAB-R, and CRAB-A were not independently associated with bone pain. 
• Patients with bone pain had significantly lower QoL and health-related status than those without pain (p<0.001). 
• Among patients with bone pain, 71% (130/184) had pain corresponding to CT-detected osteolytic lesions, while 29% (54/184) did not have corresponding CT-visible osteolytic lesions. 
• The findings indicate that bone pain in MM may be related to both myeloma-associated skeletal disease and pre-existing orthopedic conditions, supporting interdisciplinary evaluation to distinguish pain etiology. 
 
Strengths  
• Prospective study design 
• Large sample size (352 patients) 
• Comprehensive assessment of multiple potential predictors 
• Inclusion of patient-reported outcome measures (PROMs) 
• Interdisciplinary approach reflecting real-world clinical practice 
• Median age representative of a real-world patient population 
 
Limitations  
• Single tertiary-center design, limiting generalizability.
• Bone pain assessed at a single time point, providing a cross-sectional rather than longitudinal evaluation.
• Associations should not be interpreted as causal
• Effects of specific myeloma therapies on bone pain were not evaluated as a primary objective.
• PROM instrument used only two adapted global items from the EORTC QLQ-C30 rather than the complete validated questionnaire.
• Assessment of osteolytic lesions at risk of instability was based on routine clinical radiological evaluation without standardized imaging review, formal instability scoring, or inter-reader agreement analysis.
• Etiology of vertebral fractures was not systematically assessed.
 
Why this study matters 
In this prospective cohort, bone pain affected approximately half of patients with multiple myeloma and was independently associated with osteolytic lesions with fracture risk and pre-existing orthopedic conditions. Bone pain was associated with lower quality of life, and nearly one-third of pain cases did not correspond to CT-visible osteolytic lesions, indicating that pain may have multiple contributing factors. The findings support interdisciplinary assessment to differentiate myeloma-related and non-myeloma-related causes of bone pain. 
 
 
Reference: 
Carlotta Pietsch, Monika Engelhardt, Julian P. Maier, Gabriele Ihorst, Hagen Schmal, Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Ralph Wäsch, Georg W. Herget, Risk factors and clinical impact of bone pain in patients with multiple myeloma – A prospective interdisciplinary study, Journal of Bone Oncology, 2026, 100788, ISSN 2212-1374, https://doi.org/10.1016/j.jbo.2026.100788 (https://www.sciencedirect.com/science/article/pii/S2212137426000503?via%3Dihub) 

 
Free Light Chain Monomer—Dimer Pattern Analysis as Non-Invasive Tool in Predicting MGUS and SMM Progression — Cancers (July 2026) 
 

What is the purpose of the study? 
To evaluate whether free light chain monomer–dimer pattern analysis (FLC-MDPA), a non-invasive serum assay, could predict disease progression in patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). It also assesses whether incorporating FLC-MDPA into existing risk stratification models could improve prediction of progression. 
 
Summary  
This prospective cohort study included 108 patients with MGUS (n=68) or SMM (n=40), with 96 patients having complete data for training (n=50) and validation (n=46) analyses. FLC-MDPA was associated with both biochemical progression (sensitivity 0.79, specificity 0.92, negative predictive value [NPV] 0.86; hazard ratio [HR] 19.96, 95% confidence interval [CI] 4.31–92) and clinical progression (sensitivity 0.84, specificity 0.79; HR 13.5, 95% CI 3.68–49.64), with significantly higher progression rates in patients with abnormal FLC patterns (p<0.0001). When incorporated into a modified 2/20/MDPA model, FLC-MDPA improved sensitivity and NPV compared with the original 2/20/20 model, and remained independently associated with biochemical and clinical progression in multivariable analyses. 
 
Key points 
• Study population: 68 patients with MGUS and 40 patients with SMM; 96 patients with complete data were included in training and validation analyses. 
• Intervention: Evaluation of FLC-MDPA, a non-invasive Western blot–based serum assay that detects abnormal free light chain monomer–dimer patterns. 
• Main findings: 
 - Abnormal FLC-MDPA patterns were associated with significantly higher rates of biochemical and clinical progression (p<0.0001). 
 - Biochemical progression prediction: 
    • Sensitivity: 0.79 
    • Specificity: 0.92 
    • NPV: 0.86 
    • HR: 19.96 (95% CI 4.31–92) 
 - Clinical progression prediction: 
    • Sensitivity: 0.84 
    • Specificity: 0.79 
    • HR: 13.5 (95% CI 3.68–49.64) 
 - FLC-MDPA remained independently associated with: 
    • Clinical progression (p=0.001) 
    • Biochemical progression (p=0.04) 
 - Incorporating FLC-MDPA into a modified 2/20/MDPA risk model improved sensitivity and NPV compared with the original 2/20/20 model. 
 
Strengths  
• Prospective cohort design
• Independent training and validation cohorts
• Evaluation of a non-invasive serum-based biomarker as an alternative to bone marrow–based risk assessment
 
Limitations  
• Participants were selected using established high-risk criteria, limiting comparison with unselected patient populations
• Modest cohort size
• Shorter follow-up in the validation cohort, reducing statistical power and precision of effect estimates
• FLC-MDPA has been implemented in a single laboratory; inter-laboratory standardization and reproducibility testing are needed
• Specificity and positive predictive value were more modest than sensitivity and NPV, indicating the assay may be better suited as a rule-out biomarker than a stand-alone rule-in test
 
Why this study matters 
In this study, FLC-MDPA was independently associated with biochemical and clinical progression in patients with MGUS and SMM and improved sensitivity and negative predictive value when incorporated into a modified 2/20/MDPA risk model. The authors conclude that larger independent studies are needed to validate these findings, establish reproducibility across laboratories, refine assay thresholds, and determine the role of FLC-MDPA in monitoring and clinical decision-making. 
 
Reference: 
Serok, A., Kukuy, L., Shaked, O., Weinstein, O., Pick, M., Serok, A., Ostrovsky, A., Goldis, R., Lebel, E., Kaplan, B., & Gatt, M. E. (2026). Free Light Chain Monomer—Dimer Pattern Analysis as Non-Invasive Tool in Predicting MGUS and SMM Progression. Cancers, 18(15), 2409. https://doi.org/10.3390/cancers18152409  (https://www.mdpi.com/2072-6694/18/15/2409)

 
Real-World Treatment Patterns and Physician Perspectives in Relapsed/Refractory Multiple Myeloma: Results From a Nationwide Italian GIMEMA Survey — eJHaem (July 2026) 
 

What is the purpose of the survey? 
To evaluate real-world treatment patterns for relapsed/refractory multiple myeloma (RRMM) across Italian hematology centers and identify clinical challenges and unmet needs in routine practice, including treatment sequencing, refractoriness, and the use of newer therapies. 
 
Summary 
A national cross-sectional survey was conducted between February and March 2025, with complete responses from 71 Italian hematology centers reporting aggregated treatment data from clinical practice during 2024. The survey collected information on treatment lines, therapeutic regimens, patient characteristics, exposure and refractoriness to lenalidomide and anti-CD38 monoclonal antibodies, and physician perspectives on retreatment strategies and anti-BCMA therapies. Daratumumab-based regimens were the most commonly used frontline treatment, while early lenalidomide and anti-CD38 refractoriness limited treatment options in the second and third lines of therapy. Treatment approaches beyond first line varied across centers, and more than 96% of centers supported the use of anti-BCMA therapies by the third treatment line, although access limitations and the absence of robust head-to-head comparative data were reported. 
 
Key points 
• National cross-sectional survey conducted between February and March 2025. 
• Analysis included complete responses from 71 Italian hematology centers. 
• Survey data reflected routine clinical practice during 2024. 
• Data included treatment patterns across first-, second-, and third-line therapy, patient fitness, treatment exposure, refractoriness, and physician perspectives. 
• Daratumumab-based regimens were the most frequently used frontline treatment for transplant-ineligible patients. 
• Lenalidomide maintenance after autologous stem cell transplantation was widely used. 
• Early refractoriness to lenalidomide and anti-CD38 monoclonal antibodies emerged in many patients, reducing treatment options in second- and third-line therapy. 
• Triplet regimens were commonly used in second- and third-line treatment, but regimen selection varied substantially across centers. 
• Increasing use of pomalidomide- and isatuximab-based regimens was observed. 
• More than 96% of participating centers supported the use of anti-BCMA therapies by the third line of treatment. 
• Reported barriers to broader anti-BCMA use included limited access and a lack of robust head-to-head comparative data. 
• Treatment decisions were influenced by disease characteristics, patient factors, prior therapies, refractoriness, frailty, treatment burden, route of administration, expected tolerability, and physician preference. 
 
Strengths  
• Included nearly 15,000 patients, providing a large, nationally representative real-world dataset. 
• Broad geographic participation across Italy was reported to provide a nationwide overview of clinical practice. 
• Authors stated that the large population base increases the robustness, external validity, and representativeness of the observed treatment patterns. 
 
Limitations  
• Aggregate survey design did not allow complete cross-stratified analyses of second-line regimens according to lenalidomide and anti-CD38 exposure or refractoriness. 
• Inferential statistical analyses were not performed because the study was designed as a descriptive overview. 
• Access constraints and the absence of robust head-to-head comparative data limited broader implementation of anti-BCMA therapies. 
 
Why this survey matters 
This national survey describes contemporary multiple myeloma treatment patterns in Italy, showing widespread adoption of novel therapies alongside substantial variability in treatment sequencing for relapsed/refractory disease. Early refractoriness to lenalidomide and anti-CD38 monoclonal antibodies was commonly reported, and participating centers broadly supported earlier use of anti-BCMA therapies, while noting access limitations and limited comparative evidence. The findings also identified variability in retreatment strategies and highlighted the reported need for comparative effectiveness data and shared treatment guidelines. 
 
Reference: 
F. Fazio, A. Piciocchi, P. de Fabritiis, et al. “Real-World Treatment Patterns and Physician Perspectives in Relapsed/Refractory Multiple Myeloma: Results From a Nationwide Italian GIMEMA Survey.” eJHaem 7, no. 4 (2026): e70354. https://doi.org/10.1002/jha2.70354 (https://onlinelibrary.wiley.com/doi/10.1002/jha2.70354) 

When Myeloma Escapes the Bone Marrow: Extramedullary Disease in the Immunotherapy Era — Cancers (July 2026) 
 

What is the purpose of the review? 
This review summarizes the current understanding of the biology, classification, and treatment landscape of extramedullary disease (EMD) in multiple myeloma, including both non-central nervous system (non-CNS) and central nervous system (CNS) involvement. It also reviews emerging evidence on T-cell-redirecting therapies and identifies priorities for future research and prospective clinical trials. 
 
Summary  
EMD is a high-risk manifestation of multiple myeloma characterized by clonal plasma cells growing outside the bone marrow and is associated with aggressive disease biology, treatment resistance, and poor clinical outcomes. The review describes biologic mechanisms underlying EMD, including reduced adhesion molecule expression, high-risk cytogenetic abnormalities (del(17p), gain(1q)), RAS–MAPK pathway activation, EZH2 upregulation, and an immunosuppressive, T-cell-depleted microenvironment. It summarizes current evidence indicating that conventional therapies have limited efficacy, while CAR T-cell therapy and bispecific antibodies have demonstrated clinically meaningful activity in both non-CNS EMD and selected cases of CNS myeloma, although durable disease control remains challenging and outcomes remain inferior compared with patients without EMD. 
 
Key points 

Disease characteristics 
• EMD is defined by clonal plasma cell proliferation in soft tissues without direct bone connection. 
• EMD is associated with aggressive disease biology, treatment resistance, and poorer outcomes than typical multiple myeloma. 
• CNS myeloma represents the most severe form of EMD and has historically been associated with a poor prognosis. 

Biologic mechanisms 
• Proposed mechanisms include: 
 - Downregulation of adhesion molecules. 
 - High-risk cytogenetic abnormalities, including del(17p) and gain(1q). 
 - Activation of the RAS–MAPK signaling pathway. 
 - Epigenetic dysregulation, including EZH2 upregulation. 
- Development of an immunosuppressive, T-cell-depleted tumor microenvironment. 

Current treatment evidence 
• Conventional therapies, including anti-CD38-based regimens, demonstrate limited efficacy in EMD. 
• In triple-class-exposed relapsed/refractory disease, pooled overall response rates with conventional therapies are approximately 20%. 
• CAR T-cell therapy and bispecific antibodies have demonstrated clinically meaningful activity in soft tissue EMD. 
• CAR T-cell therapy has produced the deepest and most durable responses among currently available T-cell-redirecting therapies. 
• Dual-targeting bispecific antibody combinations have shown encouraging efficacy. 
• Emerging retrospective data suggest CAR T-cell therapy and bispecific antibodies can produce meaningful CNS responses with acceptable safety profiles when used within multimodal treatment strategies. 
    
Future research priorities 
• Integrated bone marrow and EMD tissue sampling and liquid biopsy to better characterize disease heterogeneity. 
• Strategies to overcome the immunosuppressive microenvironment. 
• Evaluation of novel therapeutic targets, including CD70, EZH2, CD24, broader RAS/MEK inhibition, and dual-target CAR T-cell approaches. 
• Studies evaluating optimal sequencing of bispecific antibodies and CAR T-cell therapy, maintenance strategies after CAR T-cell therapy, and dual-antigen targeting. 
• Prospective clinical trials specifically enrolling patients with non-CNS EMD and CNS myeloma, incorporating standardized response criteria and correlative biological studies. 

Strength 
• Provides a comprehensive overview of the biology, classification, and evolving treatment landscape of both non-CNS and CNS EMD in the era of T-cell-redirecting immunotherapy. 
 
Limitations  
• Much of the available evidence for CNS myeloma is based on retrospective data. 
• Prospective clinical data remain lacking for several proposed treatment strategies, including maintenaREseaance approaches after CAR T-cell therapy. 
• The review explicitly highlights the need for prospective clinical trials dedicated to patients with EMD and CNS involvement. 
 
Why this review matters 
This review describes EMD as a biologically distinct, high-risk manifestation of multiple myeloma characterized by aggressive disease features and inferior outcomes. Current evidence indicates that CAR T-cell therapy and bispecific antibodies have demonstrated meaningful activity in both non-CNS EMD and selected cases of CNS myeloma, although durable disease control remains difficult. The authors emphasize the need for prospective clinical trials, improved biologic characterization, and investigation of new therapeutic strategies to improve outcomes in this patient population. 
 
Reference: 
Afrough, A., Dillard, C. M., Alsup, A. M., Lee, J., Al Hadidi, S., Sannareddy, A., Abraham, P. R., Turer, L., Dima, D., Khan, A. M., Taasan, S. M., Pasvolsky, O., Patel, K. K., Azab, A. K., Anderson, L. D., Jr., & Gaballa, M. R. (2026). When Myeloma Escapes the Bone Marrow: Extramedullary Disease in the Immunotherapy Era. Cancers, 18(15), 2415. https://doi.org/10.3390/cancers18152415  (https://www.mdpi.com/2072-6694/18/15/2415)

Access to T-Cell Redirecting Therapies in Multiple Myeloma: Patient, Caregiver, and Physician Perspectives on Awareness and Barriers — Cancers (July 2026) 
 

What is the purpose of the study? 
To evaluate awareness, access, utilization, and perceived barriers to T-cell redirecting therapies (TCRTs), including CAR T-cell therapies and bispecific antibodies, among patients with relapsed/refractory multiple myeloma (RRMM), caregivers, and community physicians. The primary objective is to compare TCRT utilization across racial groups among previously treated patients. 
 
Summary  
This cross-sectional survey (June–September 2025) included 428 respondents (346 patients, 51 caregivers, and 31 physicians). Overall, 26% of patients were unfamiliar with TCRTs, with higher unawareness among Black patients (32% vs. 25%) and those with a high school education or less (42% vs. 23%); higher educational attainment was associated with approximately twice the odds of TCRT utilization (p = 0.05), while TCRT utilization among previously treated patients was similar across racial groups (39% Black vs. 38% non-Black). Caregivers frequently reported emotional and time-related burdens, and physicians identified patient hesitancy as the most common barrier to referral, with 71% reporting referral for TCRT but 48% indicating that fewer than one-quarter of referred patients ultimately received treatment. 
 
Key points 
• Study design: Cross-sectional, IRB-approved survey conducted from June to September 2025 using REDCap. 
• Participants: 428 respondents, including: 
 - 346 patients with multiple myeloma 
 - 51 caregivers of TCRT recipients 
 - 31 community physicians 
• Primary objective: Compare TCRT utilization across racial groups among previously treated patients. 

• Patient awareness: 
 - 26% of patients were unfamiliar with TCRTs. 
 - Unawareness was higher among Black patients (32% vs. 25%) and patients with a high school education or less (42% vs. 23%). 

• Treatment utilization: 
 - Higher educational attainment was associated with approximately twice the odds of TCRT utilization (p = 0.05). 
 - Among previously treated patients, TCRT utilization was similar across racial groups (39% Black vs. 38% non-Black). 
 - Among TCRT recipients, Black patients more frequently received therapy through clinical trials than non-Black patients (44% vs. 34%). 

• Caregiver findings: 
 - 53% reported effects on mental or emotional well-being. 
 - 61% reported moderate-to-high stress during treatment. 
 - 33% provided more than 40 hours of care per week during the first month. 
    
• Physician findings: 
 - 71% reported referring patients for TCRT. 
 - 48% reported that fewer than 25% of referred patients ultimately received treatment. 
 - Patient hesitancy was the most commonly reported referral barrier. 
 
Strengths  
• Included perspectives from patients, caregivers, and community physicians, allowing assessment of barriers across multiple stakeholders
• Provided quantitative caregiver data in an area where prior evidence has been largely qualitative
 
Limitations  
• Cross-sectional, single-institution design precludes causal inference and may limit generalizability. 
• Survey instruments were internally developed and not formally validated. 
• Self-reported TCRT utilization was not confirmed by medical records, introducing potential recall and social desirability bias. 
• Possible misclassification of treatment exposure due to inaccurate recall of TCRT modalities. 
• Greater frequency of missing or "I don't know" responses among Black patients and those with lower educational attainment may reduce precision of utilization estimates. 
• Underrepresentation of Black participants and MyChart-based recruitment may have introduced participation and selection bias. 
• Caregiver survey included only caregivers of TCRT recipients and did not distinguish between CAR T-cell therapy and bispecific antibody recipients. 
• Small convenience sample of community physicians may limit generalizability and introduce selection bias. 
 
Why this survey matters 
This survey identified barriers to TCRT awareness, access, and referral among patients with multiple myeloma, caregivers, and community physicians. Awareness was lower among Black patients and those with lower educational attainment, although TCRT utilization among previously treated patients was similar across racial groups at the study center. Caregivers reported substantial emotional and time demands, and physicians identified patient hesitancy as the primary referral barrier; the authors concluded that improvements in patient education, caregiver support, care coordination, and referral pathways warrant further evaluation. 
 
 
Reference: 
Shah, Z., Robinson, M., Prempeh, A., Serapin, N., Ndiaye, A., Voorhees, P. M., & Bhutani, M. (2026). Access to T-Cell Redirecting Therapies in Multiple Myeloma: Patient, Caregiver, and Physician Perspectives on Awareness and Barriers. Cancers, 18(15), 2412. https://doi.org/10.3390/cancers18152412  (https://www.mdpi.com/2072-6694/18/15/2412)

Predictors of post-transplant measurable residual disease negativity and impact on clinical outcomes in multiple myeloma — Blood Advances (July 2026) 
 

What is the purpose of the study? 
To evaluate factors associated with achieving measurable residual disease (MRD) negativity after autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) and examine how MRD status, cytogenetic abnormalities, and residual disease burden were associated with clinical outcomes. 
 
Summary 
This retrospective study included 814 patients with multiple myeloma who achieved at least a very good partial response after ASCT between January 2016 and January 2023 and underwent MRD assessment using next-generation flow cytometry (median sensitivity: 2.4 × 10⁻⁶). Overall, 48% (387/814) achieved MRD negativity. The presence of t(11;14) (OR 2.1, 95% CI 1.4–3.2; p<0.01) and a pre-transplant response of less than complete remission (OR 2.1, 95% CI 1.2–3.7; p<0.01) independently predicted MRD positivity. MRD-positive patients had inferior progression-free survival (PFS) (HR 1.99, 95% CI 1.53–2.58; p<0.001) and overall survival (OS) (HR 1.62, 95% CI 1.10–2.28; p=0.009). Despite a lower MRD-negative rate, patients with t(11;14) had similar 5-year PFS whether they were MRD-positive (58%) or MRD-negative (63%) (p=0.12). Among MRD-positive patients, the presence of ≥2 high-risk cytogenetic abnormalities (HRCA) and a higher residual clonal plasma cell burden were associated with inferior PFS. 
 
Key points 
• Study population: 814 patients with multiple myeloma who achieved at least a very good partial response after ASCT and underwent MRD assessment between January 2016 and January 2023. 
• MRD assessment: Next-generation flow cytometry with a median sensitivity of 2.4 × 10⁻⁶. 
• MRD negativity rate: 48% (387/814) achieved MRD negativity after ASCT. 
• Independent predictors of MRD positivity: 
 - Presence of t(11;14) (OR 2.1, 95% CI 1.4–3.2; p<0.01). 
 - Pre-transplant response less than complete remission (OR 2.1, 95% CI 1.2–3.7; p<0.01). 

• Clinical outcomes: 
 - MRD-positive patients had inferior PFS (HR 1.99, 95% CI 1.53–2.58; p<0.001). 
 - MRD-positive patients had inferior OS (HR 1.62, 95% CI 1.10–2.28; p=0.009). 

• Patients with t(11;14): Despite a lower rate of MRD negativity, 5-year PFS did not differ significantly between MRD-positive (58%) and MRD-negative (63%) patients (p=0.12). 
    
• High-risk cytogenetics: 
 - In MRD-negative patients, 5-year PFS was 73% without ≥2 HRCA versus 55% with ≥2 HRCA (HR 1.9, 95% CI 1.2–3.3; p=0.01). 
 - In MRD-positive patients, 5-year PFS was 53% without ≥2 HRCA versus 17% with ≥2 HRCA (HR 2.4, 95% CI 1.6–3.6; p<0.01). 
    
• Residual disease burden: Within the MRD-positive cohort, a higher residual clonal plasma cell burden was associated with inferior PFS (HR 2.4, 95% CI 1.2–6.9; p=0.002). 
 
Why this study matters 
In this cohort, t(11;14) and a pre-transplant response of less than complete remission were independently associated with MRD positivity after ASCT. MRD-positive patients had inferior progression-free survival (PFS) and overall survival (OS). Within the MRD-positive cohort, the presence of ≥2 high-risk cytogenetic abnormalities (HRCA) and a higher residual clonal plasma cell burden were associated with inferior PFS. Among patients with t(11;14), 5-year PFS did not differ significantly between MRD-positive and MRD-negative patients. 
 
 
Reference: 
Abiola Bolarinwa, Saurabh S. Zanwar, Nadine Abdallah, Madhu Nagaraj, Sukriti Seth, Francis K Buadi, Suzanne R Hayman, Morie A Gertz, Angela Dispenzieri, Eli Muchtar, Prashant Kapoor, Wilson I Gonsalves, Taxiarchis V. Kourelis, David Dingli, Rahma Warsame, Nelson Leung, Joselle Cook, Moritz Binder, Yi Lin, Yi Lisa Hwa, Michelle Genevieve Rogers, Miriam A Hobbs, Amie L Fonder, Dragan Jevremovic, S. Vincent Rajkumar, Shaji K Kumar; Predictors of post-transplant measurable residual disease negativity and impact on clinical outcomes in multiple myeloma. Blood Adv 2026; bloodadvances.2026020294. doi: https://doi.org/10.1182/bloodadvances.2026020294  (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2026020294/569888/Predictors-of-post-transplant-measurable-residual)

Self-Reported Geriatric Impairments and Treatment Toxicity in Older Patients with Multiple Myeloma-A Single Center Prospective Study — Blood Advances (July 2026) 
 

What is the purpose of the study? 
To evaluate patient-reported comprehensive geriatric assessment (CGA) domains, frailty, and their associations with treatment toxicity and patient-reported outcomes (PROs) in adults aged ≥60 years with newly diagnosed (NDMM) or relapsed/refractory multiple myeloma (RRMM) who were starting a new therapy. 
 
Summary 
A total of 90 patients (mean age 72 years) completed electronic CGA and PRO questionnaires at baseline and 4 months. Geriatric impairments, particularly in physical function, were common, and high-grade non-hematological toxicities were significantly associated with older age, comorbidities, patient-reported functional limitations, and anxiety. Frailty, identified in 22% of patients using a cumulative deficit frailty index, was associated with worse baseline health-related quality of life (HRQOL) and increased high-grade non-hematological toxicity, but not with treatment adaptations or healthcare utilization. Patient-reported toxicity measured by PROCTCAE was higher than physician-reported toxicity measured by CTCAE, while average CGA and HRQOL scores remained stable over 4 months despite variation in individual patient trajectories. 
 
Key points 
• Patient-reported geriatric impairments were common in older adults with multiple myeloma, including physical function limitations. 
• The study included 90 patients with a mean age of 72 years who were initiating treatment for NDMM or RRMM. 
• High-grade non-hematological toxicities were significantly associated with: 
 - Older age 
 - Comorbidities 
 - Patient-reported functional limitations 
 - Anxiety 
    
• Frailty was present in 22% of patients based on a cumulative deficit frailty index. 
• Frailty was associated with: 
 - Worse baseline HRQOL 
 - Increased high-grade non-hematological toxicity 
 - No association with treatment adaptations or healthcare utilization 

• Patient-reported toxicity (PROCTCAE) was higher than physician-reported toxicity (CTCAE), indicating discordance between patient- and clinician-reported treatment toxicity. 
• Average CGA and HRQOL scores remained stable over 4 months, although individual patient trajectories varied. 
 
Strengths  
• Prospective study design 
• Use of patient-reported comprehensive geriatric assessment and patient-reported outcome measures 
• Longitudinal assessment with baseline and 4-month follow-up 
 
Limitation  
• Single-center study 
 
Why this study matters 
Patient-reported geriatric impairments were common among older adults with multiple myeloma and were significantly associated with high-grade non-hematological toxicities. Frailty was associated with poorer baseline HRQOL and greater non-hematological toxicity but was not associated with treatment adaptations or healthcare utilization. The study also found higher patient-reported than physician-reported treatment toxicity and observed variability in individual geriatric assessment trajectories over time, supporting the value of longitudinal patient-reported assessments. 
 
 
Reference: 
Nadine Abdallah, Rosalyn Marar, Claire I. Yee, Anna Bodily, Mia Truman, Tanya Wildes, Terri Menser, Megan Weivoda, Sarah Aug, Byron Smith, Francis K Buadi, Prashant Kapoor, Angela Dispenzieri, Suzanne R Hayman, David Dingli, Wilson I Gonsalves, Joselle Cook, Saurabh S. Zanwar, Moritz Binder, Taxiarchis V. Kourelis, Morie A Gertz, Rahma Warsame, Yi Lin, S. Vincent Rajkumar, Amylou C. Dueck, Shaji K Kumar; Self-Reported Geriatric Impairments and Treatment Toxicity in Older Patients with Multiple Myeloma-A Single Center Prospective Study. Blood Adv 2026; bloodadvances.2026020579. doi: https://doi.org/10.1182/bloodadvances.2026020579 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2026020579/569890/Self-Reported-Geriatric-Impairments-and-Treatment) 

MRD dynamics predicts progression and reveals a vulnerable state for immunotherapy interception in multiple myeloma — Blood (July 2026) 
 

What is the purpose of the study? 
To evaluate whether measurable residual disease (MRD) dynamics based on three or more sequential MRD assessments can improve patient stratification and prognosis in newly diagnosed multiple myeloma (MM). It also examines the biological characteristics of MRD resistance and investigated whether treating persistent MRD rather than waiting until clinical relapse affects outcomes in a preclinical mouse model. 
 
Summary 
MRD dynamics were calculated using next-generation flow cytometry and Connector in 539 newly diagnosed MM patients with at least three MRD assessments from the GEM2012MENOS65/GEM2014MAIN and GEM2017FIT trials, comprising 3,610 MRD assessments. Five MRD dynamic subgroups with distinct survival outcomes were identified, including early-sustained and late-sustained MRD response, volatile MRD, primary MRD resistance, and resurgent MRD resistance. The prognostic performance of MRD dynamics exceeded transplant eligibility and the Revised International Staging System (R-ISS), and these findings were validated in an independent cohort of 249 MM patients treated in routine clinical practice. 
 
Multiomics analyses of paired diagnostic and MRD samples, together with mouse models of MRD resistance, identified genomic evolution, transcriptional adaptation, and a pro-inflammatory tumor-immune microenvironment associated with MRD resistance, along with increasing endogenous T-cell clonality and exhaustion during disease progression. In MIcγ1huCRBN mice, administration of anti-BCMA CAR T cells at the stage of MRD resistance prolonged survival compared with administration of the same treatment at relapse. 
 
Key points 
• MRD dynamics were evaluated using 3,610 MRD assessments from 539 newly diagnosed MM patients enrolled in the GEM2012MENOS65/GEM2014MAIN and GEM2017FIT clinical trials. 

• Five MRD dynamic subgroups with different survival outcomes were identified: 
 - Early-sustained MRD response 
 - Late-sustained MRD response 
 - Volatile MRD 
 - Primary MRD resistance 
 - Resurgent MRD resistance 
    
• Patients with late-sustained MRD response had survival outcomes comparable to those with early-sustained MRD response. 
• Patients with volatile MRD, primary MRD resistance, and resurgent MRD resistance had poorer survival outcomes. 
• MRD dynamics demonstrated greater prognostic value than transplant eligibility and the Revised International Staging System (R-ISS). 
• Findings were validated in an independent cohort of 249 MM patients treated in routine clinical practice. 

• Multiomics analyses associated MRD resistance with: 
 - Genomic evolution 
 - Transcriptional adaptation 
 - A pro-inflammatory tumor-immune microenvironment 
 - Increasing endogenous T-cell clonality and exhaustion during disease progression 
    
• In the MIcγ1huCRBN mouse model, anti-BCMA CAR T-cell therapy administered during MRD resistance prolonged survival compared with the same treatment given at relapse. 
 
Why this study matters 
Sequential assessment of MRD dynamics identified five prognostically distinct subgroups of patients with multiple myeloma and demonstrated greater prognostic value than transplant eligibility and the Revised International Staging System (R-ISS) in the studied cohorts. Molecular and immune analyses characterized biological features associated with MRD resistance, and anti-BCMA CAR T-cell treatment administered during MRD resistance prolonged survival compared with treatment at relapse in the MIcγ1huCRBN mouse model. The authors conclude that MRD dynamics may help tailor treatment to prevent additional tumor and immune alterations prior to relapse. 
 
Reference: 
Carmen Gonzalez, Camila Guerrero, Marta Larrayoz, Aintzane Zabaleta, Junfei Zhao, Ioannis V Kostopoulos, Ourania Tsitsilonis, Evangelos Terpos, Norma C. Gutierrez, Manuela Fernandez, Maria J José Calasanz, Paula Rodriguez-Otero, Felipe Prosper, Teresa Lozano, Juan J Lasarte, Benjamin L Ebert, Albert Oriol, Anna Sureda, María-Jesús Blanchard, Yolanda González-Montes, Joan Bargay, Sunil Lakhwani, Rafael Ríos-Tamayo, Laura Rosiñol, Joaquín Martínez-López, Juan-Jose Lahuerta, Joan Bladé, Maria-Victoria Mateos, Jesús San-Miguel, Maria-Teresa Cedena, Noemí Puig, Patrick Ryan Hagner, Maria Ortiz Estevez, Jose A Martínez-Climent, Bruno Paiva; MRD dynamics predicts progression and reveals a vulnerable state for immunotherapy interception in multiple myeloma. Blood 2026; blood.2026033878. doi: https://doi.org/10.1182/blood.2026033878 (https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2026033878/569873/MRD-dynamics-predicts-progression-and-reveals-a?redirectedFrom=fulltext) 

Real-world analyses of bispecific antibodies and CAR-T cell therapy in relapsed or refractory multiple myeloma: a global TriNetX discovery and contemporary validation cohort — Leukemia & Lymphoma (July 2026) 
 

What is the purpose of the study? 
To compare real-world outcomes of bispecific antibodies (BsAbs) and BCMA-directed CAR-T cell therapies in patients with late-line relapsed/refractory multiple myeloma (RRMM). It aims to evaluate overall survival (OS) and time to next treatment (TTNT) using a global propensity-matched TriNetX discovery cohort and a contemporary validation cohort that accounted for treatment line and patient characteristics. 
 
Summary  
The TriNetX discovery cohort included 223,703 patients with multiple myeloma, with propensity matching resulting in 822 BsAb-treated and 822 CAR-T-treated patients. In this cohort, BsAb therapy was associated with inferior OS compared with CAR-T therapy (HR 2.015, 95% CI 1.592–2.551; p<0.001), and cilta-cel showed better outcomes than ide-cel, while teclistamab and talquetamab had comparable outcomes. In the contemporary validation cohort (187 patients, 211 treatment exposures), adjustment for treatment line and patient fitness reduced class-level differences in OS and TTNT between BsAbs and CAR-T therapy, although cilta-cel remained numerically favorable. 
 
Key points 
• The study combined two complementary real-world datasets: 
 - A global propensity-matched TriNetX discovery cohort. 
 - A contemporary treatment-line-aware validation cohort. 

• Discovery cohort: 
 - Identified 223,703 patients with multiple myeloma through April 8, 2026. 
 - Propensity matching produced 822 BsAb-treated and 822 CAR-T-treated patients. 
 - BsAb therapy was associated with inferior OS versus CAR-T therapy: 
   • Hazard ratio (HR): 2.015 
   • 95% confidence interval (CI): 1.592–2.551 
   • p<0.001 
 - Similar survival patterns were observed in several biochemical high-risk subgroups. 
    
• Product-level findings: 
 - Cilta-cel showed better outcomes than ide-cel. 
 - Teclistamab and talquetamab showed comparable outcomes. 
    
• Validation cohort: 
 - Included 187 patients and 211 treatment exposures. 
 - CAR-T therapy was generally administered earlier and to patients with better performance status. 
 - After accounting for treatment exposure and later-line disease, differences in OS and TTNT between BsAbs and CAR-T therapy became smaller. 
 - Cilta-cel remained numerically favorable. 
    
• The findings support individualized treatment selection based on patient and treatment characteristics rather than preference for one treatment class alone. 
 
Strengths 
• Combined a large global propensity-matched discovery cohort with a contemporary validation cohort using different analytical approaches. 
• The validation cohort included additional clinical variables such as treatment sequence, ECOG performance status, prior transplantation, response assessment, and contemporary clinical practice. 
 
Limitations 
• Both cohorts were retrospective and nonrandomized. 
• The TriNetX cohort relied on aggregate platform data with limited matching variables and incomplete biological detail. 
• The validation cohort had short follow-up, few first-exposure OS events, missing laboratory and cytogenetic data in several patients, and repeated treatment exposures in TTNT analyses. 
• The platform did not distinguish true extramedullary disease from paraskeletal disease. 
• Biomarker thresholds differed between the discovery and validation cohorts, limiting direct subgroup comparisons. 
• The authors state that the study should be considered hypothesis-generating rather than a definitive comparative effectiveness study. 
 
Why this study matters 
The propensity-matched TriNetX analysis found an OS advantage for CAR-T cell therapy over BsAbs and favored cilta-cel over ide-cel. In the treatment-line-aware validation cohort, differences in OS and TTNT between BsAbs and CAR-T therapy were attenuated after accounting for treatment line and patient fitness, while cilta-cel remained numerically favorable. Overall, the findings support individualized, risk-adapted, and treatment-sequence-aware decision-making for patients with RRMM. 
 
Reference: 
Leitner, T., Oelschläger, L., Henriquez Mosquera, F., Schaefers, C., Leypoldt, L., Weisel, K., … Khandanpour, C. (2026). Real-world analyses of bispecific antibodies and CAR-T cell therapy in relapsed or refractory multiple myeloma: a global TriNetX discovery and contemporary validation cohort. Leukemia & Lymphoma, 1–10. https://doi.org/10.1080/10428194.2026.2699285 (https://www.tandfonline.com/doi/full/10.1080/10428194.2026.2699285) 

Clinical Characteristics and Prognostic Analysis of Extramedullary Disease in Multiple Myeloma: A 15-Year Retrospective Cohort Study — Cancers (August 2026) 
 

What is the purpose of the study? 
To evaluate the clinical characteristics and outcomes of bone-related extramedullary disease (bEMD) and soft tissue-associated extramedullary disease (sEMD) in patients with multiple myeloma (MM). It also aims to develop a pretreatment risk stratification tool using routinely available baseline clinical parameters for patients with extramedullary disease (EMD). 
 
Summary  
This retrospective single-center study analyzed 118 patients with MM and EMD (72 bEMD and 46 sEMD) treated between 2011 and 2025. Compared with bEMD, patients with sEMD had higher serum β2-microglobulin (β2-MG) levels (6.4 vs. 4.5 mg/L; p = 0.007), a higher proportion of relapsed/refractory disease (41.3% vs. 15.3%; p = 0.002), shorter median progression-free survival (12.0 vs. 29.0 months; p < 0.001), and shorter median overall survival (25.0 vs. 67.0 months; p = 0.009). Multivariable analysis identified thrombocytopenia (platelet count <100 × 10⁹/L), elevated β2-MG, multisite extramedullary involvement, and TP53 deletion as independent adverse prognostic factors, and a risk score based on β2-MG, thrombocytopenia, and multisite involvement separated patients into low-risk (0–2 points) and high-risk (3–4 points) groups with significantly different progression-free survival (27.0 vs. 10.0 months; p < 0.001) and overall survival (54.0 vs. 22.0 months; p = 0.008). 
 
Key points 
• Retrospective analysis of 118 patients with MM and EMD treated at a single center from 2011 to 2025
• Study population included: 
 - 72 patients (61.0%) with bone-related EMD (bEMD)
 - 46 patients (39.0%) with soft tissue-associated EMD (sEMD)

• Compared with bEMD, patients with sEMD had: 
 - Higher serum β2-microglobulin (β2-MG) levels (6.4 vs. 4.5 mg/L; p = 0.007)
 - A higher proportion of relapsed/refractory disease (41.3% vs. 15.3%; p = 0.002)
 - Shorter median progression-free survival (12.0 vs. 29.0 months; p < 0.001)
 - Shorter median overall survival (25.0 vs. 67.0 months; p = 0.009)
    
• Independent adverse prognostic factors identified by multivariable analysis were: 
 - Thrombocytopenia (platelet count <100 × 10⁹/L)
 - Elevated β2-MG
 - Multisite extramedullary involvement
 - TP53 deletion
    
• The proposed pretreatment risk score included: 
 - β2-MG (0–2 points)
 - Thrombocytopenia (1 point)
 - Multisite extramedullary involvement (1 point)
    
• The risk score classified patients into: 
 - Low risk (0–2 points): median progression-free survival 27.0 months; median overall survival 54.0 months
 - High risk (3–4 points): median progression-free survival 10.0 months; median overall survival 22.0 months
 
Strengths  
• Developed using routinely available baseline clinical parameters intended for pretreatment risk stratification
• Internal validation demonstrated model stability
 
Limitations  
• Single-center retrospective study with a relatively small sample size, particularly in the sEMD subgroup, which may limit statistical power and generalizability. 
• Treatment-related variables were not included because of heterogeneous treatment strategies over the 15-year study period. 
• External validation in larger multicenter cohorts with standardized imaging, molecular profiling, and treatment data is still required. 
 
Why this study matters 
In this study, patients with soft tissue-associated extramedullary disease had shorter progression-free and overall survival than patients with bone-related extramedullary disease. Thrombocytopenia, elevated β2-microglobulin, multisite extramedullary involvement, and TP53 deletion were independently associated with poorer outcomes, and a pretreatment risk score based on three routinely available clinical parameters stratified patients into groups with significantly different survival outcomes. The authors state that external validation and incorporation of molecular and immune-related features are needed to further refine prognostic assessment. 
 

Reference: 
Zhao, J., Bai, Q., Qiu, Q., Song, J., Kong, S., Zhu, K., Zhang, Y., Li, S., Ma, Y., Zhang, L., & Qin, X. (2026). Clinical Characteristics and Prognostic Analysis of Extramedullary Disease in Multiple Myeloma: A 15-Year Retrospective Cohort Study. Cancers, 18(15), 2484. https://doi.org/10.3390/cancers18152484 (https://www.mdpi.com/2072-6694/18/15/2484) 

Smoldering multiple myeloma: a multi-country mixed-methods study on disease perceptions and patient treatment preferences — Future Oncology (August 2026) 
 

What is the purpose of the study? 
To examine disease perceptions, psychological and quality-of-life impacts, and treatment preferences among patients with high-risk smoldering multiple myeloma (HR-SMM) and patients with multiple myeloma (MM) that had recently progressed from HR-SMM. It also estimates the minimum progression-free survival (min-PFS) patients required to accept the burden and adverse effects of a hypothetical treatment. 
 
Summary  
The study interviewed 50 patients (25 with HR-SMM and 25 with MM) from the USA, France, Italy, and Spain using qualitative interviews and a quantitative thresholding exercise. Fatigue (68%) and pain (56%) were the most commonly reported symptoms, while 20% of participants were asymptomatic; 61% of patients were willing to begin treatment during the HR-SMM stage, and most treatment-naïve patients (31/44) accepted physician recommendations that treatment was not needed, was burdensome, or was unavailable. Patients most commonly expected treatment to delay disease progression (30%) or increase life expectancy (24%), although 22% expected a cure, and the median minimum progression-free survival required to accept the hypothetical treatment burden was 60 months (61 months for HR-SMM and 59 months for MM). 
 
Key points 
• Study design: Mixed-methods study including qualitative semi-structured interviews and a quantitative thresholding exercise. 
• Participants: 50 patients with HR-SMM or MM that had recently progressed from HR-SMM (1:1 ratio) from the USA, France, Italy, and Spain. 
• Most common symptoms: 
 - Fatigue: 68% 
 - Pain: 56% 
 - Asymptomatic: 20% 
    
• Treatment awareness: 
 - Awareness of HR-SMM treatment options was generally low in both groups. 
 - Most treatment-naïve patients (31/44) accepted physician recommendations that treatment was not needed, was burdensome, or was unavailable. 
    
• Treatment preferences: 
 - 61% of patients were willing to start treatment during the HR-SMM stage.
 - The most commonly expected benefits were delaying disease progression (30%) and increasing life expectancy (24%).
 - 22% expected treatment to cure their disease.
    
• Minimum acceptable benefit: 
 - Median minimum progression-free survival required to accept the hypothetical treatment burden: 60 months
 - HR-SMM: 61 months
 - MM: 59 months
    
• Psychological impact: 
 - Anxiety, worry, and fear related to possible disease progression were commonly reported, including among asymptomatic patients. 
 - Psychological impacts were reported both before and after progression to MM. 
 
Strengths  
• Provides patient perspectives on HR-SMM, a previously underrepresented population. 
• Included patients classified using commonly used IMWG or Mayo Clinic risk criteria at the time of study initiation. 
• Findings supplement existing literature on patient perceptions and treatment preferences. 
 
Limitations 
• Stated preference and thresholding methods may not fully reflect real-world preferences. 
• Results apply only to the hypothetical treatment attributes presented, including a 42% adverse effect risk. 
• Composite adverse-effect measure may have been interpreted differently by participants. 
• Qualitative interviews are subject to response and interview-related biases. 
• Small sample size limited country-level analyses. 
• Generalizability may be limited because many participants were younger and had higher educational attainment than typical HR-SMM populations. 
• Older patients and those with different comorbidity profiles may be underrepresented. 
• Possible selection bias related to ECOG performance status. 
• Only functional scales of the EORTC QLQ-C30 were collected, limiting comparison with studies using the complete instrument. 
• Patient-reported symptoms were not equivalent to clinician-assessed CRAB criteria and may have reflected comorbidities or general health. 
• Differences in diagnostic pathways and treatment availability across countries may have influenced findings. 
 
Why this study matters 
This study found that patients with HR-SMM and MM that had progressed from HR-SMM reported substantial psychological, physical, and functional impacts associated with the possibility of disease progression. Many participants were willing to consider treatment during the HR-SMM stage and indicated a median minimum progression-free survival of 60 months to accept the burden of a hypothetical treatment. The study also identified low awareness of HR-SMM treatment options and highlighted the role of clinician discussions and shared decision-making in treatment planning. 
 
 
Reference: 
Quaife, M., Jimenez-Moreno, C., Gros Otero, B., Asra, A., Gupta-Werner, N., Gries, K. S., … Bathija, S. (2026). Smoldering multiple myeloma: a multi-country mixed-methods study on disease perceptions and patient treatment preferences. Future Oncology, 1–13. https://doi.org/10.1080/14796694.2026.2710562 (https://www.tandfonline.com/doi/full/10.1080/14796694.2026.2710562) 

Validation of the new IMS/IMWG consensus genomic staging (CGS) of high-risk multiple myeloma (HRMM) in a contemporary cohort of 1209 patients — HemaSphere (August 2026) 
 

What is the purpose of the study? 
To evaluate the International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) consensus genomic staging (CGS) criteria for identifying high-risk multiple myeloma (HRMM) and determining their prognostic value. It assesses the criteria in 1,209 consecutive newly diagnosed multiple myeloma (NDMM) patients treated with contemporary regimens at a single tertiary center from 2010 to 2024. 
 
Summary 
The study included 1,209 NDMM patients with complete clinical and FISH-derived cytogenetic data, excluding TP53 mutational status because it was available in very few patients; 25.2% met the IMS/IMWG CGS definition of HRMM. HRMM was associated with shorter overall survival (OS; median 44 vs. 93 months; hazard ratio [HR] 1.81; P<0.001; 5-year OS 40% vs. 61%) and progression-free survival (PFS; median 21.3 vs. 36 months; HR 1.64; P<0.001) compared with standard-risk (SR) disease. Patients with ≥2 high-risk features, representing 4.4% of the cohort, had approximately threefold higher risk of death than SR patients, and CGS remained prognostic across renal-function groups, age groups, transplant eligibility, and treatment eras. 
 
Key points 
• Population: 1,209 consecutive NDMM patients diagnosed and treated at a single tertiary center in Athens, Greece, from 2010–2024. 
• Risk classification: 25.2% were classified as HRMM according to IMS/IMWG CGS criteria. 
• Overall survival: Median OS was 44 months in HRMM vs. 93 months in SR (HR 1.81; P<0.001); 5-year OS was 40% vs. 61%. 
• Progression-free survival: Median PFS was 21.3 months in HRMM vs. 36 months in SR (HR 1.64; P<0.001). 
• Ultra-high-risk group: Patients with ≥2 high-risk features comprised 4.4% of the cohort and had a threefold increased risk of death compared with SR patients. 
• Renal function: CGS remained prognostic in patients with serum creatinine (sCr) >1.2 mg/dL (HR 1.71; P<0.001). 
• Subgroups: Prognostic significance was retained across different age groups, transplant eligibility, and treatment eras, including pre-2020 and post-2020 cohorts. 
• CGS criteria: HRMM was defined by specified combinations involving del(17p), IgH translocations [t(4;14), t(14;16), t(14;20)] with 1q+ and/or del1p32, monoallelic del1p32 with 1q+ or biallelic del1p32, or β2-microglobulin ≥5.5 mg/L with normal renal function (sCr <1.2 mg/dL). 
• Comparison with existing staging: The discussion reports that ISS, R-ISS, and R2-ISS could place many patients with adverse genomic features in intermediate-risk categories, whereas CGS identified a distinct HRMM group. 
• FISH vs. NGS: HRMM prevalence was lower than in several other validation cohorts, and the authors report that without NGS, approximately 5% of patients may be misclassified as SR. 
 
Strengths
The study was conducted in a large cohort of consecutive patients, including patients receiving different contemporary treatment approaches and treatment eras, and provided OS data with a median follow-up of 63 months. 
 
Limitations
TP53 mutation data were largely unavailable, potentially missing double TP53-hit cases and TP53-mutated cases without del17p; chromosome 1p abnormalities were assessed by FISH rather than NGS, so small deletions could have been missed. The study was also conducted at a single tertiary center, and the authors state that further external validation in other populations and healthcare settings is warranted. 
 
Why this study matters 
In this cohort, IMS/IMWG CGS classified 25.2% of patients as HRMM and was associated with significantly shorter PFS and OS, while ≥2 high-risk features identified an ultra-high-risk subgroup comprising 4.4% of patients. The authors conclude that CGS provides prognostic risk stratification across several clinically relevant subgroups, while noting limitations related to unavailable TP53 mutation data, FISH-only assessment of chromosome 1p abnormalities, and the single-center study setting. 
 
Reference: 
Kastritis, E., Filippatos, C., Gavriatopoulou, M., Theodorakakou, F., Solia, E., Ntanasis-Stathopoulos, I., Malandrakis, P., Kanellias, N., Eleutherakis-Papaiakovou, E., Migkou, M., Spiliopoulou, V., Katsadouros, I., Vlachou, A., Fotiou, D., Giannakas, K., Boutakoglou, E., Giannouli, S., Tsirigotis, P., Papanikolaou, A., Terpos, E. and Dimopoulos, M.A. (2026), Validation of the new IMS/IMWG consensus genomic staging (CGS) of high-risk multiple myeloma (HRMM) in a contemporary cohort of 1209 patients. HemaSphere, 10: e70435. https://doi.org/10.1002/hem3.70435 (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70435) 

Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers — British Journal of Haematology (August 2026) 
 

What is the purpose of the study? 
To evaluate whether continuing zoledronic acid (ZOL) beyond 2 years reduces progressive bone disease (PBD) in patients with multiple myeloma (MM) who achieved very good partial response (VGPR) or better. It also assesses whether bone turnover markers could identify patients at increased risk of PBD after ZOL discontinuation. 
 
Summary 
Two Magnolia subgroups were analyzed: patients with VGPR or better after 2 years of monthly ZOL who were randomized to continued ZOL or observation, and patients randomized to observation who underwent serial measurement of C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase isoform 5b (TRAcP) for up to 4 years. Among patients with VGPR or better, continued monthly ZOL was associated with a significantly lower risk of PBD than observation (hazard ratio [HR] 0.40; 95% confidence interval [CI], 0.16–0.92). After ZOL discontinuation, bone turnover markers increased gradually; CTX ≥0.30 μg/L and TRAcP ≥4 U/L were associated with increased 6-month PBD risk of 29% and 15%, respectively. 
 
Key points 
• Treatment: Continued monthly ZOL beyond 2 years was associated with a lower risk of PBD in patients who had achieved VGPR or better. 
• Effect estimate: The HR for PBD with continued ZOL versus observation was 0.40 (95% CI, 0.16–0.92)
• Bone markers: After ZOL discontinuation, bone turnover markers increased gradually, consistent with the study's observation of a prolonged anti-resorptive effect. 
• Risk markers: CTX ≥0.30 μg/L and TRAcP ≥4 U/L were associated with increased risk of PBD within 6 months, with risks of 29% and 15%, respectively. 
• Limits of biomarker interpretation: The study did not identify a low bone-resorption-marker threshold that ensured no risk of PBD. Markedly elevated CTX or TRAcP values occurred in only a minority of patients, and the authors stated that, although the findings demonstrate a biological association, their application to clinical decision-making appears limited. 
• Potential clinical use: The study states that serial monitoring of CTX after ZOL discontinuation might help identify patients at increased risk of PBD and allow timely re-initiation of bisphosphonate therapy; however, the optimal measurement regimen has not been established, and further studies are needed to determine whether this approach prevents skeletal progression. 
 
Limitations  
• The analysis of patients with VGPR or better was a secondary analysis that was not planned in advance, so the risk of type 1 error must be considered. 
• The study was not powered to determine whether the occurrence of medication-related osteonecrosis of the jaw (MRONJ) only in the ZOL-treatment group represented an increased risk. 
• Larger studies were stated to be necessary to clarify the magnitude of benefit from continued ZOL in patients achieving deeper responses, such as complete response (CR), or in patients with VGPR without bone disease at diagnosis. 
• The authors stated that further studies are needed to determine whether monitoring bone-resorption markers and considering ZOL re-initiation can prevent PBD. 
 
Why this secondary analysis matters 
In this secondary analysis of Magnolia data, continuation of ZOL beyond 2 years was associated with a reduced risk of PBD among patients who had achieved VGPR or better. Among patients who discontinued ZOL, markedly elevated CTX and TRAcP levels were associated with a higher risk of PBD within 6 months, but these findings did not establish a biomarker threshold that reliably excluded PBD risk or establish the clinical benefit of marker-guided ZOL re-initiation. Further studies are needed to determine whether serial biomarker monitoring and treatment re-initiation can prevent skeletal progression. 
 
Reference: 
Gundesen MT, Vangsted AJ, Helleberg C, Haukås E, Silkjær T, Madsen JS, et al. Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers. Br J Haematol. 2026; 00: 1–9. https://doi.org/10.1111/bjh.70612 (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70612) 

 
 
Clinical Trials 

A phase 1/1b study of the BCMA-targeting bispecific T-cell engager pavurutamab for relapsed/refractory multiple myeloma — Blood (July 2026) 

What is the purpose of the study? 
To evaluate the safety, tolerability, pharmacokinetics, and efficacy of pavurutamab (AMG 701), a BCMA-targeting bispecific T-cell engager, given as monotherapy in patients with triple-class relapsed/refractory multiple myeloma (RRMM). The study also assesses the recommended phase 2 dose (RP2D) using intravenous weekly administration with step-up dosing. 
 
Summary 
A total of 172 patients with heavily pretreated triple-class RRMM received intravenous pavurutamab at doses ranging from 5 to 18,000 μg weekly with step-up dosing; 73 patients received the RP2D (18,000 μg). Dose-limiting toxicities occurred in 12 patients and included cytokine release syndrome (CRS) and increased transaminases; none occurred at the RP2D. The most common treatment-emergent adverse events were CRS (74.4%), anemia (61.0%), neutropenia (47.1%), and hypophosphatemia (45.3%), while grade ≥3 infections occurred in 34.9% of patients. The overall response rate (ORR) was 46.5% in all treated patients and 65.8% at the RP2D, with 60.3% achieving a very good partial response (VGPR) or better. At a median follow-up of 17.2 months, the median duration of response (DOR) was 36.6 months (95% CI, 22.3 to not estimable), the median progression-free survival (PFS) was 5.5 months overall and 16.8 months at the RP2D. Pavurutamab exposure increased approximately proportionally with dose, and higher soluble BCMA levels were associated with lower drug exposure. 
 
Key points 
• Study design: Phase 1/1b, open-label, dose-exploration and dose-expansion study. 
• Population: 172 patients with RRMM. 
• Intervention: Pavurutamab (AMG 701) administered intravenously once weekly with step-up dosing (5–18,000 μg). 
• Recommended phase 2 dose (RP2D): 18,000 μg; 73 patients received the RP2D. 
• Dose-limiting toxicities: Reported in 12 patients, including cytokine release syndrome (CRS) and increased transaminases; none occurred at the RP2D. 
• Most common treatment-emergent adverse events: 
 - CRS: 74.4% 
 - Anemia: 61.0% 
 - Neutropenia: 47.1% 
 - Hypophosphatemia: 45.3% 
 - Grade ≥3 infections: 34.9% 
    
• Efficacy: 
 - ORR (all patients): 46.5% 
 - ORR (RP2D): 65.8% 
 - VGPR or better (RP2D): 60.3% 
 - Median DOR: 36.6 months (95% CI, 22.3 to not estimable) 
 - Median PFS (all patients): 5.5 months (95% CI, 2.8–10.1) 
 - Median PFS (RP2D): 16.8 months (95% CI, 5.0 to not estimable) 
    
• Pharmacokinetics: Drug exposure generally increased in a dose-proportional manner; higher soluble BCMA levels correlated with lower pavurutamab exposure. 
 
Why this study matters 
In this phase 1/1b study, intravenous pavurutamab (AMG 701) demonstrated an acceptable safety profile with step-up dosing, including no dose-limiting toxicities at the RP2D, while treatment-emergent adverse events included CRS, hematologic toxicities, and infections. At the RP2D, the study reported an ORR of 65.8%, VGPR or better in 60.3% of patients, and a median PFS of 16.8 months. The study also found dose-proportional pharmacokinetics, with higher soluble BCMA levels associated with lower drug exposure. 
 
 
Reference: 
Hans C. Lee, Wouter J. Plattel, Simon J. Harrison, Douglas W. Sborov, Suzanne Lentzsch, Andrew Spencer, Ruben Niesvizky, Suzanne Trudel, Peter Mollee, Ravi Vij, Monique C. Minnema, Leo Rasche, Vijay V. Upreti, Di Zhou, Qing Xia, Mihaela Talpes, Tobias Eggert, Prashant Kapoor, Sikander Ailawadhi; A phase 1/1b study of the BCMA-targeting bispecific T-cell engager pavurutamab for relapsed/refractory multiple myeloma. Blood 2026; 148 (2): 199–212. doi: https://doi.org/10.1182/blood.2025032044  (https://ashpublications.org/blood/article-abstract/148/2/199/567636/A-phase-1-1b-study-of-the-BCMA-targeting?redirectedFrom=fulltext)
 
 

Clinical and Psychological Outcomes After Monoclonal Gammopathy Screening: A Population-Based Screening Study and Subsequent Randomized Trial of Follow-Up — Journal of Clinical Oncology (July 2026) 
 

What is the purpose of the study? 
To evaluate the benefits and harms of the iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma) study and compare different follow-up strategies to determine their effects on disease detection, progression, symptom burden, and psychological well-being. 
 
Summary 
The iStopMM trial (ClinicalTrials.gov: NCT03327597) screened 75,422 individuals in Iceland, identifying 3,541 participants with MGUS who were randomly assigned to no notification, guideline-based follow-up, or intensified follow-up. After a median follow-up of 4.5 years, screening resulted in a 27-fold increase in the detection of smoldering multiple myeloma (SMM) (8.6% vs 0.3%; hazard ratio, 27.46 [95% CI, 10.21–73.86]; P<.001), while rates of active malignancy did not differ between study groups. Active multiple myeloma (MM) and related malignancies were diagnosed approximately 1 year earlier in the intervention groups, with fewer symptomatic presentations and hospitalizations at diagnosis, and MGUS notification was not associated with adverse psychological outcomes. 
 
Key points 
• Study design: Nationwide screening study with a randomized controlled trial of follow-up strategies iStopMM study; ClinicalTrials.gov: NCT03327597
• Participants: 75,422 individuals were screened (53% of those invited); 3,541 participants with MGUS were randomized to: 
 - Arm 1: No notification
 - Arm 2: Guideline-based follow-up
 - Arm 3: Intensified follow-up

• Median follow-up: 4.5 years
• Primary findings: 
 - Screening increased detection of SMM by 27-fold (8.6% vs 0.3%; hazard ratio, 27.46 [95% CI, 10.21–73.86]; P<.001)
 - Rates of active MM and related malignancies did not differ between groups. 
 - Active MM and related malignancies were diagnosed approximately 1 year earlier in the intervention arms. 
 - Earlier diagnosis was associated with fewer symptomatic presentations and fewer hospitalizations at diagnosis. 
 - MGUS notification was not associated with adverse psychological outcomes based on more than 11,000 mental health assessments. 
    
• Comparison of follow-up strategies: 
 - Intensified follow-up increased SMM detection by 65% compared with guideline-based follow-up. 
 - No differences were observed in other study end points between the two follow-up strategies. 

Strengths  
• Randomized study design 
• Wide recruitment criteria 
• High participation rate 
• High-quality registry data with virtually complete capture of disease progression, including the control arm 

Limitations  
• Relatively short follow-up 
• Reliance on end points that do not directly measure clinical benefit and are susceptible to lead-time bias 
• Exclusion of individuals with advanced disease at screening 
• Genetically and ethnically homogeneous population 
 
Why this study matters 
In this randomized controlled trial, population-based screening for monoclonal gammopathies substantially increased detection of SMM and led to earlier diagnosis of active MM and related malignancies without evidence of adverse psychological effects from MGUS notification. The study found no difference in active malignancy rates during the current follow-up period, and the authors stated that longer follow-up is needed to determine effects on survival and cost-effectiveness. 
 
Reference: 
Sæmundur Rögnvaldsson et al. Clinical and Psychological Outcomes After Monoclonal Gammopathy Screening: A Population-Based Screening Study and Subsequent Randomized Trial of Follow-Up. J Clin Oncol 0, JCO-25-02771 DOI:10.1200/JCO-25-02771 (https://ascopubs.org/doi/10.1200/JCO-25-02771) 

Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma — New England Journal of Medicine (July 2026) 

What is the purpose of the study? 
To evaluate whether indefinite-duration (continuous) lenalidomide maintenance therapy improves overall survival compared with fixed-duration lenalidomide maintenance (2 years) in patients with standard-risk newly diagnosed multiple myeloma (NDMM) who did not undergo upfront autologous stem cell transplantation (ASCT) after induction therapy. 
 
Summary 
In the phase III randomized ENDURANCE trial, a total of 516 patients were randomly assigned to receive either indefinite-duration lenalidomide (260 patients) or fixed-duration lenalidomide for 2 years (256 patients) after induction with a proteasome inhibitor–lenalidomide combination. After a median follow-up of 86 months, overall survival at 7 years was similar between the groups (68.6% vs. 69.0%; difference, −0.4 percentage points; 95% CI, −9.0 to 8.3; P=0.93), while progression-free survival at 7 years was 36.1% versus 29.7% (difference, 6.4 percentage points; 95% CI, −2.6 to 15.4). Indefinite-duration lenalidomide was associated with more adverse events, including grade 3 or higher nonhematologic events (48.2% vs. 31.5%), and a 5-year cumulative incidence of second primary cancers (excluding nonmelanoma skin cancer) of 11.2% versus 8.3%. 
 
Key points 
• Study design: Phase III randomized trial. Clinical trial: ENDURANCE (ClinicalTrials.gov: NCT01863550)
• Population: 516 patients with standard-risk NDMM who did not undergo upfront ASCT. 
• Intervention: Indefinite-duration (continuous) lenalidomide maintenance therapy after induction. 
• Comparator: Fixed-duration lenalidomide maintenance therapy for 2 years. 
• Primary endpoint: Overall survival. 
• Median follow-up: 86 months. 
• Overall survival (7 years): 
 - Indefinite duration: 68.6% 
 - Fixed duration: 69.0% 
 - Difference: −0.4 percentage points (95% CI, −9.0 to 8.3; P=0.93). 

• Progression-free survival (7 years): 
 - Indefinite duration: 36.1% 
 - Fixed duration: 29.7% 
 - Difference: 6.4 percentage points (95% CI, −2.6 to 15.4). 

• Second primary cancers (5-year cumulative incidence, excluding nonmelanoma skin cancer): 
 - Indefinite duration: 11.2% 
 - Fixed duration: 8.3%. 
    
• Safety: Grade 3 or higher nonhematologic adverse events: 
 - Indefinite duration: 48.2% 
 - Fixed duration: 31.5%. 
 
Why this study matters 
In this phase III trial, indefinite-duration lenalidomide maintenance therapy did not significantly improve overall survival compared with fixed-duration (2-year) lenalidomide maintenance in patients with standard-risk NDMM who did not undergo upfront ASCT. Indefinite-duration therapy was associated with a higher incidence of adverse events, including grade 3 or higher nonhematologic events, while progression-free survival and second primary cancer incidence were also reported. 
 
Reference: 
Kumar S, Jacobus S, Cohen A, Weiss M, Callander N, Singh A, Parker T, Green M, Thertulien R, Parsons B, Kumar P, Kapoor P, Rosenberg A, Dib E, Almquist D, Zonder J, Faber E, Wei Z, Anderson K, Lonial S, Richardson P, Orlowski R, Wagner L, Rajkumar SV. Continuous or Fixed-Duration Maintenance Therapy in Multiple Myeloma. N Engl J Med. 2026 Jul 16;395(3):221-232. doi: 10.1056/NEJMoa2600157.  (https://www.nejm.org/doi/full/10.1056/NEJMoa2600157)
 
 

SECURE study: baseline findings from a UK prospective cohort of incidentally detected MGUS — Blood Cancer Journal (July 2026) 
 

What is the purpose of the study? 
To characterize incidentally detected Monoclonal Gammopathy of Undetermined Significance (MGUS) in routine clinical practice. It aims to describe epidemiology, monitoring practices, progression risk, patient-reported outcomes, and biomarkers that may support future risk-adapted follow-up. 
 
Summary  
The SECURE study is a UK prospective, multicenter, non-interventional observational cohort (ClinicalTrials.gov NCT05539079) which plans to recruit 2,000 adults with incidentally detected MGUS and follow them for up to 60 months using routine clinical data, patient-reported outcomes, and serial biospecimens. This interim descriptive analysis included 1,133 eligible participants recruited from 35 NHS sites by April 2026; the median age was 71 years, 53.0% were male, 22.3% were diagnosed through primary care and 77.0% through secondary care, and among participants with sufficient data for risk stratification, 30.2% were low risk, 44.8% low-intermediate risk, 23.2% high-intermediate risk, and 1.8% high risk for progression. Ten participants had progressed to multiple myeloma at the time of analysis, while longitudinal time-to-event and biomarker analyses are planned after longer follow-up. 
 
Key points 
• Study design 
 - UK prospective, multicentre, non-interventional observational cohort. 
 - Includes adults (≥18 years) with confirmed incidentally detected MGUS (non-IgM, IgM, and light-chain MGUS). 
 - Planned enrollment: 2,000 participants with follow-up of up to 60 months. 
    
• Data collected 
 - Demographic and clinical characteristics. 
 - Laboratory measurements, including M-protein and free light chain (FLC) parameters. 
 - Patient-reported outcomes (quality of life and psychological assessments). 
 - Serial serum and blood biospecimens for immunology, proteomics, metabolomics, and genomic analyses. 
 - Planned linkage with healthcare datasets for health service utilization analyses. 
    
• Primary outcome: Progression from MGUS to multiple myeloma (MM). 
    
• Secondary outcomes 
 - Route to diagnosis. 
 - Monitoring patterns. 
 - Family history. 
 - Incidence of Monoclonal Gammopathy of Clinical Significance (MGCS). 
 - Quality of life, psychological burden, and healthcare utilization. 
    
• Interim baseline results 
 - 1,244 participants recruited from 35 NHS sites; 1,133 met inclusion criteria. 
 - Median age: 71 years (range 25–95). 
 - 53.0% male. 
 - Diagnosis route available for 1,083 participants: 
   • 22.3% primary care. 
   • 77.0% secondary care. 

 - Among participants with available risk stratification: 
   • 30.2% low risk. 
   • 44.8% low-intermediate risk. 
   • 23.2% high-intermediate risk. 
   • 1.8% high risk. 

 - Baseline progression-related factors among those with measurements: 
   • Abnormal FLC ratio: 52.4%. 
   • Non-IgG MGUS: 29.9%. 
   • M-protein ≥15 g/L: 14.2%. 

 - Light-chain MGUS prevalence: 7.1%. 
   • Common comorbidities included autoimmune disease (16.3%), prior infection requiring hospitalization (16.2%), and osteoporosis (11.1%). 
   • Ten participants had progressed to MM at the time of the interim analysis. 
 
Strengths 
• First UK prospective cohort of incidentally detected MGUS in routine care. 
• Integrates routine clinical data, patient-reported outcomes, serial biospecimens, and planned healthcare data linkage. 
• Serial biosampling enables collection of pre-progression samples for future biomarker analyses. 
 
Limitations  
• Interim descriptive analysis with expected missing data under standard clinical practice. 
• Differences in case capture and testing between sites; standardization is ongoing. 
• Clinically detected cohort is not directly comparable with screened populations. 
• Ethnicity and other subgroup analyses are currently underpowered. 
• Short follow-up has resulted in few progression events, limiting time-to-event analyses. 
• No MGUS-negative comparator group was included. 
 
Why this study matters 
This interim analysis of the SECURE study describes the baseline characteristics of a large UK cohort of patients with incidentally detected MGUS managed in routine clinical practice. The study combines longitudinal clinical data, patient-reported outcomes, and serial biospecimens to evaluate progression, MGCS, monitoring practices, and potential biomarkers, with additional analyses planned after longer follow-up. The authors note that current findings are descriptive and that mature follow-up will be required for time-to-event and multivariable analyses. 
 
Reference: 
Knight, E., Krishnamoorthi, A., Balik, B. et al. SECURE study: baseline findings from a UK prospective cohort of incidentally detected MGUS. Blood Cancer J. 16, 119 (2026). https://doi.org/10.1038/s41408-026-01576-x  (https://www.nature.com/articles/s41408-026-01576-x)
 
 

FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial — Nature Medicine (July 2026) 
 

What is the purpose of the study? 
To evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of cevostamab, a first-in-class FcRH5-targeted bispecific antibody, in patients with late-line multiple myeloma (MM). The study also assesses multiple dosing regimens to determine the recommended phase 2 dose (RP2D). 
 
Summary 
This phase 1 study enrolled heavily pretreated patients with MM, including 95.8% with triple-class refractory disease, 73.7% with penta-drug refractory disease, and 57.5% with prior BCMA-targeted therapy. The maximum tolerated dose was not reached, and 160 mg every 3 weeks (Q3W) with a 0.3/1.2/3.6/160 mg triple step-up dosing regimen was selected as the RP2D based on its benefit-risk profile. At the 160 mg target dose, the objective response rate (ORR) was 44.3% and the very good partial response (VGPR) or better rate was 25.7%, with durable responses observed, particularly among patients achieving VGPR or better. The ORR was 60.6% in patients without prior BCMA-targeted therapy, 17.2%–43.8% in patients with prior BCMA-targeted therapy, 36.2% after prior BCMA-targeted CAR T-cell therapy, and 43.8% after prior BCMA-targeted antibody-drug conjugate (ADC) therapy. The most common grade 3 or 4 adverse events were neutropenia (28.7%), anemia (18.0%), and thrombocytopenia (10.8%), while grade 3 or 4 infections occurred in 15.6% of patients. With the triple step-up regimen, cytokine release syndrome (CRS) occurred primarily during cycle 1, was limited to grade 1 or 2, resolved in all cases, and did not lead to treatment discontinuation. The study also reported that cevostamab did not cause substantial dysgeusia, weight loss, nail changes, desquamation, or ataxia, which are toxicities associated with GPRC5D-targeted therapies. 
 
Key points 
• Study design: Phase 1 evaluation of cevostamab, an FcRH5-targeted bispecific antibody, in patients with late-line multiple myeloma. 
• Multiple dosing schedules were evaluated, including single, double, and triple step-up dosing with target doses ranging from 0.15 mg to 252 mg. 
• The maximum tolerated dose (MTD) was not reached. 
• Recommended phase 2 dose (RP2D): 
 - 160 mg every 3 weeks (Q3W) 
 - Triple step-up dosing: 0.3/1.2/3.6/160 mg
    
• Patient population at the 160 mg target dose: 
 - Median of 6 prior lines of therapy
 - 95.8% triple-class refractory
 - 73.7% penta-drug refractory
 - 57.5% previously treated with BCMA-targeted therapy
    
• Efficacy at the 160 mg target dose: 
 - Objective response rate (ORR): 44.3%
 - VGPR or better: 25.7%
 - Responses were durable, particularly among patients achieving VGPR or better
 - ORR was 60.6% in patients without prior BCMA-targeted therapy
 - ORR was 17.2%–43.8% in patients with prior BCMA-targeted therapy
 - ORR was 36.2% after prior BCMA-targeted CAR T-cell therapy
 - ORR was 43.8% after prior BCMA-targeted ADC therapy
    
• The reported median progression-free survival (PFS) at the 160 mg target dose was short. The authors stated that this was largely driven by the high proportion of patients with prior BCMA-targeted therapy and penta-drug-refractory disease and noted that the relatively short washout period between T-cell-redirecting therapies may also have contributed. They stated that further studies are needed to evaluate the optimal timing and sequencing of these therapies. 
    
• Safety findings: 
 - Grade 3 or 4 neutropenia: 28.7%
 - Grade 3 or 4 anemia: 18.0%
 - Grade 3 or 4 thrombocytopenia: 10.8%
 - Grade 3 or 4 infections: 15.6%
 - Grade 3 or 4 febrile neutropenia: 4.8%
 - With triple step-up dosing, CRS occurred mainly during cycle 1, was limited to grade 1–2, resolved in all cases, and did not cause treatment discontinuation. 
 - The study reported no substantial dysgeusia, weight loss, nail changes, desquamation, or ataxia. 
    
• Fixed-duration treatment of approximately 12 months was evaluated. At the 160 mg target dose, 26 patients completed treatment with a partial response or better, and 17 had ongoing responses after treatment discontinuation at the data cutoff. 
 
Limitations  
• Small patient numbers in the step-up dosing cohorts. 
• Non-uniform follow-up, with relatively short follow-up in the latest cohorts. 
• Heterogeneity in the step-up dosing schedules within the 160 mg target-dose group. 
• Evolution of CRS management and availability of targeted myeloma therapies during the enrollment period. 
• Lack of a standardized approach to anti-infective prophylaxis during the study. 
• Risk status according to the most recent IMWG criteria could not be determined retrospectively because key genetic alterations were not evaluated. 
 
Why this study matters 
In this phase 1 study, cevostamab demonstrated manageable safety in heavily pretreated patients with late-line multiple myeloma, and the 160 mg Q3W triple step-up regimen was selected as the RP2D. The study reported durable responses, particularly among patients achieving VGPR or better, while also reporting a short median PFS in a cohort with a high proportion of prior BCMA-targeted therapy exposure and penta-drug-refractory disease. The authors acknowledged several study limitations, including small cohort sizes, non-uniform follow-up, heterogeneous dosing schedules, evolving supportive care practices, and the inability to retrospectively determine IMWG risk status. 
 
 
Reference: 
Cohen, A.D., Richter, J., Trudel, S. et al. FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04522-3  (https://www.nature.com/articles/s41591-026-04522-3)

Phase 3 MonumenTAL-6 Trial Results: Teclistamab Plus Talquetamab, Talquetamab Plus Pomalidomide Improved PFS and OS vs Standard of Care in RRMM (July 2026) 
 

What is the purpose of the study? 
To evaluate the efficacy and safety of Tecvayli® (teclistamab-cqyv) plus Talvey® (talquetamab-tgvs) and Talvey plus pomalidomide compared with investigator's choice of standard of care (elotuzumab, pomalidomide, and dexamethasone [EPd] or pomalidomide, bortezomib, and dexamethasone [PVd]) in adults with relapsed or refractory multiple myeloma (RRMM) who had received one to four prior lines of therapy, including an anti-CD38 antibody and lenalidomide. 
 
Summary  
According to topline results announced by Johnson & Johnson, the randomized three-arm Phase 3 MonumenTAL-6 trial met its primary endpoint of progression-free survival (PFS) for both investigational treatment arms compared with investigator's choice of standard of care. The teclistamab plus talquetamab (Tec-Tal) combination reduced the risk of disease progression or death by 89% (hazard ratio [HR] 0.11; 95% confidence interval [CI] 0.08–0.16; p<0.0001) and reduced the risk of death by 62% (HR 0.38), while talquetamab plus pomalidomide (Tal-P) reduced the risk of disease progression or death by 73% (HR 0.27; 95% CI 0.20–0.35). Both investigational regimens demonstrated statistically significant improvements in overall survival versus standard treatment, and their overall safety profiles were reported to be consistent with the known safety profiles of the individual monotherapies. 
 
Key points 
• Study design 
 - Global, randomized, three-arm Phase 3 MonumenTAL-6 (NCT06208150) trial. 
 - Enrolled adults with relapsed or refractory multiple myeloma (RRMM) who had received one to four prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. 
 - Compared: 
   • Tecvayli® (teclistamab-cqyv) + Talvey® (talquetamab-tgvs) (Tec-Tal) 
   • Talvey + pomalidomide (Tal-P) 
   • Investigator's choice of EPd or PVd. 
    
• Primary endpoint: Progression-free survival (PFS) assessed independently. 
    
• Main results 
 - Both investigational treatment arms met the primary endpoint of improved PFS versus standard of care. 
 - Tec-Tal: 
   • Reduced risk of disease progression or death by 89%. 
   • HR 0.11 (95% CI 0.08–0.16; p<0.0001). 
   • Reduced risk of death by 62% (HR 0.38). 

 - Tal-P: 
   • Reduced risk of disease progression or death by 73%. 
   • HR 0.27 (95% CI 0.20–0.35). 

 - Both investigational regimens demonstrated statistically significant improvements in overall survival compared with standard treatment. 
 - The overall survival hazard ratio was disclosed only for the Tec-Tal arm. 
    
• Treatment approach 
 - Evaluated a dual-antigen strategy targeting B-cell maturation antigen (BCMA) with teclistamab and G protein-coupled receptor class C group 5 member D (GPRC5D) with talquetamab. 
 - Reported as the first Phase 3 trial evaluating simultaneous targeting of BCMA and GPRC5D in RRMM. 
    
• Safety: Overall safety profiles of Tec-Tal and Tal-P were reported to be consistent with the known safety profiles of each monotherapy. 
• Study status 
 - Based on the interim analysis, the Independent Data Monitoring Committee (IDMC) recommended that the study be unblinded. 
 - Full study results are planned for presentation at a future medical meeting and submission to global health authorities. 
 
Strengths  
• Randomized, global, three-arm Phase 3 trial. 
• First Phase 3 study evaluating dual targeting of BCMA and GPRC5D in RRMM. 
 
Limitations  
• Results reported are topline/interim findings. 
• Full study results have not yet been presented or published. 
• The overall survival hazard ratio was reported only for the Tec-Tal arm. 
 
Why this study matters 
Topline interim results from the Phase 3 MonumenTAL-6 trial showed that both Tecvayli (teclistamab-cqyv) plus Talvey (talquetamab-tgvs) and Talvey plus pomalidomide improved progression-free survival compared with investigator's choice of standard therapy in adults with RRMM. Both investigational regimens also demonstrated statistically significant improvements in overall survival, and their safety profiles were reported to be consistent with the known profiles of the individual agents. Full study results are pending presentation and regulatory submission. 
 
References: 
TECVAYLI® + TALVEY® reduced the risk of disease progression or death by 89% and the risk of death by 62% in earlier-line relapsed/refractory multiple myeloma (https://www.jnj.com/media-center/press-releases/tecvayli-talvey-reduced-the-risk-of-disease-progression-or-death-by-89-and-the-risk-of-death-by-62-in-earlier-line-relapsed-refractory-multiple-myeloma). Johnson & Johnson press release. July 23, 2026. 

A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortezomib, and Dexamethasone in Participants With Relapsed or Refractory Myeloma Who Have Received an Anti-CD3 (https://clinicaltrials.gov/study/NCT06208150). ClinicalTrials.gov. NCT06208150.
 
 

Phase I/II Trial of Evomela for Autologous Transplant in Myeloma: Schedule Optimization and Matched Comparison with MEL200 — Blood Advances (July 2026) 
 

What is the purpose of the study? 
To evaluate the optimal dose and infusion schedule of Evomela and characterized its pharmacokinetics (PK) in patients with newly diagnosed multiple myeloma (NDMM) undergoing autologous hematopoietic stem cell transplantation (ASCT). The study also assesses minimal residual disease (MRD)-negative complete response (CR), toxicity, and progression-free survival (PFS). 
 
Summary 
Sixty patients with NDMM undergoing ASCT were randomized to receive Evomela at 200 or 225 mg/m² by either a short (30–60 minutes) or long (8–9 hours) infusion. No grade ≥4 non-hematologic toxicities or day-100 non-relapse mortality were observed, and MRD-negative stringent (s)CR/CR at day 90 was 45% overall (43% with short infusion and 47% with long infusion), with similar toxicity and PFS between infusion schedules. Higher melphalan area under the concentration-time curve (AUC) was strongly associated with MRD-negative sCR/CR (posterior probability of benefit [PBE] = 0.99) without increased toxicity, but was not associated with PFS. In propensity-matched comparisons, Evomela was associated with longer PFS than melphalan 200 mg/m² (MEL200) (PBE = 0.90). 
 
Key points 
• Study design: Prospective phase I/II trial in 60 patients with newly diagnosed multiple myeloma undergoing ASCT. 
• Patients were randomized to: 
 - Evomela 200 or 225 mg/m² 
 - Short infusion (30–60 minutes) or long infusion (8–9 hours) 

• Primary objectives: 
 - Optimize Evomela dose and infusion schedule using a Bayesian design. 
 - Characterize pharmacokinetics (PK). 
    
• Secondary objectives: 
 - MRD-negative complete response (CR) at day 90
 - Toxicity
 - Progression-free survival (PFS)
    
• Safety results: 
 - No grade ≥4 non-hematologic toxicities 
 - No day-100 non-relapse mortality 
    
• Efficacy results: 
 - Overall MRD-negative sCR/CR at day 90: 45% 
 - Short infusion: 43% 
 - Long infusion: 47% 
 - Toxicity and PFS were similar between infusion schedules. 
    
• Higher melphalan AUC was strongly associated with MRD-negative sCR/CR (PBE = 0.99) without increased toxicity 
• Higher melphalan AUC was not associated with PFS 
• In propensity-matched comparisons, Evomela was associated with longer PFS than MEL200 (PBE = 0.90) 
 
Strengths 
• Prospective phase I/II trial 
• Randomized evaluation of dose and infusion schedule 
• Bayesian dose/schedule optimization with pharmacokinetic characterization 
 
Why this study matters 
In this prospective phase I/II trial, Evomela conditioning for ASCT demonstrated no grade ≥4 non-hematologic toxicities or day-100 non-relapse mortality, with similar safety and PFS across short and long infusion schedules. Higher melphalan AUC was strongly associated with increased MRD-negative sCR/CR without increased toxicity, and, in propensity-matched comparisons, Evomela was associated with longer PFS than MEL200 (PBE = 0.90). These results support Evomela as a platform for safe dose intensification and AUC-guided conditioning in newly diagnosed multiple myeloma patients undergoing ASCT. 
 
Reference: 
Qaiser Bashir, Peter F Thall, Jitesh Kawedia, Xun Xu, Cristina G Knape, Ruby Delgado, Yago Nieto, Neeraj Y Saini, Yosra M. Aljawai, Samer A Srour, Jeremy L. Ramdial, Chitra Hosing, Uday R. Popat, Betul Oran, Partow Kebriaei, Sairah Ahmed, Oren Pasvolsky, Krina K. Patel, Sheeba K. Thomas, Mahmoud R. Gaballa, Jing Christine Ye, Robert Z. Orlowski, Richard E. Champlin, Elizabeth J. Shpall, Muzaffar H Qazilbash; Phase I/II Trial of Evomela for Autologous Transplant in Myeloma: Schedule Optimization and Matched Comparison with MEL200. Blood Adv 2026; bloodadvances.2026020293. doi: https://doi.org/10.1182/bloodadvances.2026020293 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2026020293/569992/Phase-I-II-Trial-of-Evomela-for-Autologous) 
 
 

Talquetamab in patients with relapsed/refractory multiple myeloma: 3-year follow-up of the phase 1/2 MonumenTAL-1 study — Blood (August 2026) 
 

What is the purpose of the study? 
To evaluate the long-term efficacy and safety of talquetamab in patients with relapsed/refractory multiple myeloma, using 3 years of follow-up from the phase 1/2 MonumenTAL-1 study. It assesses response rates, progression-free survival, overall survival, and adverse events over longer follow-up. 
 
Summary 
With median follow-up of 30–38 months, talquetamab produced overall response rates of 67–74% and complete response or better rates of 33–42% across the three study cohorts. Median progression-free survival was 7.5, 11.2, and 7.7 months, while median overall survival was 34.0 months, not reached, and 28.3 months, respectively. The most common adverse events were cytokine release syndrome (73–79%), taste changes (72–76%), and infections (61–78%); no patients died from talquetamab-related adverse events. 
 
Key points 
• Study: Phase 1/2 MonumenTAL-1; NCT03399799 (phase 1) and NCT04634552 (phase 2). 
• Treatment cohorts: 
 - Talquetamab 0.4 mg/kg weekly: n = 143 
 - Talquetamab 0.8 mg/kg every 2 weeks: n = 154 
 - Patients with prior T-cell redirection therapy (TCR) receiving either dose: n = 78 
    
• Median follow-up: 38, 31, and 30 months, respectively, as of September 2024
• Overall response rate: 67–74%
• Complete response or better: 33–42%
• Median progression-free survival: 7.5, 11.2, and 7.7 months, respectively. 
• Median overall survival: 34.0 months, not reached, and 28.3 months, respectively. 
• 36-month overall survival: 49.3%, 60.8%, and 44.6%, respectively. 
• Most common adverse events: 
 - Cytokine release syndrome: 73–79%; grade 3/4: 0.6–2.1% 
 - Taste changes: 72–76% 
 - Infections: 61–78%; grade 3/4: 21–26% 
• Ataxia/balance disorders: 5.3%; no grade 4/5 events. 
• Dose reductions and treatment discontinuations due to adverse events remained low. 
• No deaths were attributed to talquetamab-related adverse events. 
 
Why this study matters 
After 3 years of follow-up, talquetamab continued to show overall response rates of 67–74%, with complete response or better rates of 33–42% across the three cohorts. The safety profile remained comparable with previous results, with cytokine release syndrome, taste changes, and infections among the most common adverse events, and no deaths attributed to talquetamab-related adverse events. 
 
Reference: 
Leo Rasche, Carolina Schinke, Cyrille Touzeau, Monique C Minnema, Niels van de Donk, Paula Rodriguez-Otero, Maria-Victoria Mateos, Jing Christine Ye, Chalmer Tomlinson, Deeksha Vishwamitra, Indrajeet Singh, Xiang Qin, Michela Campagna, Tara Masterson, Veronique Vreys, Bonnie W Lau, Jaszianne Tolbert, Thomas Renaud, Christoph Heuck, Ajai Chari; Talquetamab in patients with relapsed/refractory multiple myeloma: 3-year follow-up of the phase 1/2 MonumenTAL-1 study. Blood 2026; blood.2025031994. doi: https://doi.org/10.1182/blood.2025031994  (https://ashpublications.org/blood/article/doi/10.1182/blood.2025031994/570026/Talquetamab-in-patients-with-relapsed-refractory)
 
 

U.S. Food and Drug Administration 
 

FDA grants accelerated approval to iberdomide, in combination with daratumumab and hyaluronidase-fihj and dexamethasone, as treatment for RRMM 
 

On Thursday, August 13, the U.S. Food and Drug Administration (FDA) granted accelerated approval to ZENBEXUS™ (iberdomide), in combination with Darzalex Faspro® (daratumumab and hyaluronidase-fihj) and dexamethasone as treatment for adults with relapsed/refractory myeloma (RRMM) who have received at least one prior line of therapy — including a proteasome inhibitor and an immunomodulatory agent.     
 

Efficacy results  
The approval was based on efficacy results from EXCALIBER-RRMM (NCT04975997), a two-stage, randomized, multicenter, open-label trial in adults with RRMM who had previously received one or two lines of therapy. Patients whose disease was refractory to prior anti-CD38 monoclonal antibody therapy or prior bortezomib were excluded. 
 
A total of 939 patients were randomized. In stage 1,279 patients were assigned to one of three iberdomide dose levels in combination with daratumumab and hyaluronidase-fihj and dexamethasone (IberDd), or to daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd). In stage 2, 660 patients were assigned to iberdomide 1 mg in combination with daratumumab and hyaluronidase-fihj and dexamethasone (Dd) or DVd. 

The major efficacy outcome measure was minimal residual disease (MRD)-negative complete response at any time. The primary efficacy population consisted of the first 420 patients randomized to iberdomide 1 mg in combination with Dd (207 patients) or DVd (213 patients) across the two stages. MRD-negative complete response at any time occurred in 41% of patients in the IberDd arm (95% confidence interval [CI], 34% to 48%) and 21% of patients in the DVd arm (95% CI, 15% to 27%), with a p-value of less than 0.0001. 
 
Safety information 
The prescribing information contains a boxed warning for embryo-fetal toxicity and serious venous and arterial thromboembolism. Warnings and precautions include neutropenia, infections, and secondary primary malignancies. 

Because of the risk of embryo-fetal toxicity, iberdomide is available only through the ZENBEXUS Risk Evaluation and Mitigation Strategy (REMS) (https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems), a restricted distribution program. 

The recommended iberdomide dose is 1 mg orally once daily, with or without food, on Days 1 through 21 of each 28-day cycle, in combination with daratumumab and hyaluronidase-fihj and dexamethasone. 

Daratumumab and hyaluronidase-fihj is administered subcutaneously at 1,800 mg on Days 1, 8, 15 and 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 through 6; and on Day 1 of Cycle 7 and subsequent cycles. Dexamethasone is administered orally at 20 mg or 40 mg on Days 1, 8, 15 and 22. Treatment is continued until disease progression or unacceptable toxicity. 

The FDA said full prescribing information for Zenbexus (iberdomide) will be posted on Drugs@FDA. (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm)  

Healthcare professionals should report serious adverse events suspected to be associated with medicines or medical devices through the FDA's MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 1-800-FDA-1088. 

Regulatory review 
The FDA review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among international regulatory partners. For this application, the FDA collaborated with Switzerland's Swissmedic. 

The review also used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant intended to facilitate the FDA's assessment. 

The application received priority review, (https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review) and iberdomide previously received breakthrough therapy (https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy) and orphan drug designations. (https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/designating-orphan-product-drugs-and-biological-products) 

A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics). 

Healthcare professionals seeking assistance with single-patient investigational new drug applications for investigational oncology products may contact the FDA Oncology Center of Excellence's Project Facilitate at 240-402-0004 or [email protected] (mailto:[email protected]). 

Reference: 
FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-iberdomide-daratumumab-and-hyaluronidase-fihj-and-dexamethasone). U.S. Food and Drug Administration news release. August 13, 2026. 

European Commission

European Commission approves teclistamab plus daratumumab for the treatment of relapsed/refractory myeloma

The European Commission (EC) has approved Johnson & Johnson’s TECVAYLI® (teclistamab) in combination with daratumumab for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy, expanding its use to patients as early as second-line treatment.  

The decision was based on results from the Phase 3 MajesTEC-3 trial (NCT05083169), which compared subcutaneous teclistamab plus daratumumab with investigator’s choice of daratumumab, dexamethasone and either pomalidomide or bortezomib (DPd/DVd) in patients who had received one to three prior lines of therapy.  

At nearly three years, the combination reduced the risk of disease progression or death by 83.4% versus standard treatment (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.12–0.23; p<0.001).  

Overall survival also favored the combination (HR, 0.46; 95% CI, 0.32–0.65; p<0.0001), with 83.3% of patients alive at three years compared with 65.0% in the standard-of-care group.  

The treatment effect was durable: more than 90% of patients who remained progression-free at six months were still progression-free three years later.

The safety profile was consistent with the known effects of the individual drugs, with no new safety signals; all cases of cytokine release syndrome were Grade 1/2 and did not result in treatment discontinuation.  

Grade 3/4 cytopenia and infections were the most common treatment-emergent adverse events, while discontinuations due to adverse events were similar between groups (4.6% versus 5.5%).  

What is teclistamab? 
Teclistamab is a bispecific antibody that targets BCMA and CD3, redirecting T cells to attack myeloma cells, while daratumumab targets CD38 and helps stimulate an immune response against the cancer.  

The European Medicines Agency continues to classify teclistamab as a medicine under additional monitoring, meaning additional evidence is required to further confirm its benefits and risks.

To view a full list of adverse events and information on dosage and administration, contraindications and other precautions when using teclistamab, please refer to the Summary of Product Characteristics (https://www.ema.europa.eu/en/documents/product-information/tecvayli-epar-product-information_en.pdf).

What is daratumumab and daratumumab SC? 
Daratumumab is a CD38-directed antibody that has become a foundational treatment for multiple myeloma.  

Daratumumab SC (subcutaneous) was the first CD38-directed antibody approved for subcutaneous use in multiple myeloma and the first oncology injectable that, from the fifth dose, may be administered by patients or caregivers after appropriate healthcare-professional training.  

Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) using Halozyme’s ENHANZE® drug-delivery technology. By binding to CD38, which is highly expressed on multiple myeloma cells, daratumumab inhibits tumor-cell growth and promotes myeloma cell death, although it may also affect normal cells. Across 10 Phase 3 clinical trials in frontline and relapsed settings, daratumumab-based regimens significantly improved progression-free survival and/or overall survival.

A Summary of Product Characteristics (https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf) is available for further information on daratumumab.

Reference: 
European Commission approves Johnson & Johnson’s TECVAYLI®▼ (teclistamab) plus daratumumab for relapsed/refractory multiple myeloma, offering a potential new standard of care (https://www.jnj.com/innovativemedicine/emea/media-center/press-releases/european-commission-approves-johnson-johnsons-tecvayli-teclistamab-plus-daratumumab-for-relapsed-refractory-multiple-myeloma-offering-a-potential-new-standard-of-care). Johnson & Johnson press release. August 21, 2026. 

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