New Standards in Multiple Myeloma Treatment: Early Intervention and Precision Response Assessment

This article reviews key research advancements in multiple myeloma (MM) treatment presented at the 2024 American Society of Hematology (ASH) annual meeting, including efficacy of daratumumab in high-risk smoldering MM, MRD-guided treatment cessation strategies, and simplified response assessment methods.

 

Literature Overview
This article, 'Practice-changing updates on multiple myeloma: highlights from the 2024 ASH annual meeting', published in the Journal of Hematology & Oncology, synthesizes and summarizes multiple groundbreaking studies on multiple myeloma (MM) presented at the 2024 ASH annual meeting. It focuses on therapeutic advantages of daratumumab in high-risk smoldering MM, the role of MRD monitoring in treatment discontinuation decisions, and improved efficacy of belantamab mafodotin in early relapse settings. The research team also discusses streamlining response assessment protocols and their potential impact on clinical trial design.

Background Knowledge
Multiple myeloma (MM) is a plasma cell proliferative malignancy that remains incurable but benefits from continuously optimized treatment strategies. High-risk smoldering MM (sMM) patients typically face rapid disease progression, where early intervention may delay transformation. Daratumumab, an anti-CD38 monoclonal antibody, demonstrates significant PFS benefits in first-line treatment. MRD (minimal residual disease) assessment serves as a critical biomarker for treatment response, with sustained MRD negativity indicating potential treatment cessation safety. Belantamab mafodotin, an anti-BCMA antibody-drug conjugate, shows higher MRD negativity rates and extended PFS compared to standard therapies in early relapse settings. Despite these advancements, challenges persist in disease stratification, personalized treatment, and response assessment. This review highlights these key developments and discusses their implications for clinical practice and future research directions.

 

 

Research Methods and Experiments
The research team integrated results from multiple phase 3 clinical trials, including AQUILA, GMMG-HD7, CEPHEUS, and DREAMM-7/8. The studies evaluated efficacy of daratumumab in high-risk sMM, MRD negativity rates between IsaVRd and VRd in transplant-eligible patients, PFS and OS of DaraVRd versus VRd in non-eligible patients, and efficacy/safety of belantamab mafodotin in early relapse settings.

Key Conclusions and Perspectives

• The AQUILA study showed median PFS was not reached in the daratumumab group versus 41.5 months in the active monitoring group, with 60-month PFS rates at 63.1% vs. 40.8%.
• Serious adverse events occurred in 40% of daratumumab-treated patients, including 16.1% infection rates, compared to 4.6% in the active monitoring group.
• In GMMG-HD7, IsaVRd achieved a 66% MRD negativity rate (10−5) versus 48% for VRd, with 3-year PFS rates at 83% vs. 75%.
• The CEPHEUS study reported MRD negativity rates (10−5) of 46.2% for DaraVRd versus 27.3% for VRd, and 54-month PFS rates at 81% vs. 69.5%.
• In DREAMM-7, median PFS for belantamab plus bortezomib/dexamethasone (BelaVd) was 36.6 months versus 13.4 months for daratumumab (HR=0.41).
• The DREAMM-8 study showed a 1-year PFS rate of 80% for BelaPd versus 67% for PVd, with higher MRD negativity rates (24% vs. 5%).
• MRD monitoring demonstrated that 92% of patients maintaining sustained MRD negativity for 3 years remained MRD-negative at 30-month follow-up after treatment cessation.
• Secondary analysis of the STAMINA study revealed 24-hour urine protein contributes less than 1% to response assessment, suggesting potential simplification of protocols.

Research Significance and Prospects
These findings provide critical clinical evidence for early intervention, treatment optimization, and response assessment in multiple myeloma, particularly supporting daratumumab in high-risk sMM, IsaVRd/DaraVRd as first-line regimens, and belantamab's role in early relapse. Future research will focus on precise high-risk patient stratification, refining MRD assessment strategies, and evaluating long-term impacts of combination therapies and personalized treatment cessation.

 

 

Conclusion
This systematic review highlights key advancements in multiple myeloma treatment from the 2024 ASH meeting, emphasizing daratumumab's significant PFS benefits in high-risk sMM, MRD-guided treatment cessation strategies, and superior efficacy of belantamab combination regimens in early relapse. It also advocates for simplified response assessment protocols by reducing redundant urine protein testing. These findings establish new clinical standards and provide a foundation for future personalized treatment strategies.

 

Ioannis Ntanasis-Stathopoulos, Panagiotis Malandrakis, and Maria Gavriatopoulou. Practice-changing updates on multiple myeloma: highlights from the 2024 ASH annual meeting. Journal of Hematology & Oncology.