Highlights
- Significant advances in multiple myeloma therapy promise improved patient outcomes and innovative treatment strategies.
- Personalized treatment plans and novel therapies are redefining management and enhancing survival rates.
Summary and Background
Multiple myeloma treatment in 2025 has advanced significantly, emphasizing early intervention, personalized plans, and novel immunotherapies like CAR T-cell (CAR-T) therapies and bispecific antibodies (BsAbs). First-line regimens commonly use quadruplet combinations including anti-CD38 antibodies, proteasome inhibitors, immunomodulatory drugs, and dexamethasone, followed by autologous stem cell transplantation (ASCT) and maintenance therapy. These approaches increase minimal residual disease (MRD) negativity and prolong survival. CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel target BCMA and are expanding to earlier treatment lines, while BsAbs such as teclistamab and elranatamab offer off-the-shelf immunotherapies.
Recent guidelines support early treatment, particularly for high-risk smoldering myeloma. Maintenance therapies with agents like daratumumab and lenalidomide are standard, with trials indicating improved long-term outcomes. Real-world data confirm the safety and efficacy of CAR-T and antibody-drug conjugates such as belantamab mafodotin in relapsed/refractory cases.
First-Line Treatment and Patient Management
For newly diagnosed multiple myeloma (NDMM), especially transplant-eligible patients under 70, quadruplet induction regimens combining anti-CD38 antibodies with proteasome inhibitors, immunomodulatory drugs, and dexamethasone are standard before ASCT and maintenance. These regimens achieve higher MRD-negative rates and longer remissions compared to earlier therapies. Modified quadruplet regimens also benefit transplant-ineligible patients, including those over 80. Immunotherapies like CAR-T targeting BCMA are integrated from first relapse onward, with referrals to specialized centers encouraged. European and U.S. guidelines now incorporate MRD-guided therapy and risk stratification to personalize treatment.
Treatment decisions increasingly consider transplant eligibility, prior therapies, and patient preferences, balancing efficacy with safety. Collaboration and real-world data sharing are vital for optimizing outcomes and managing immune-related toxicities.
Novel and Emerging Therapies
CAR-T therapies ide-cel and cilta-cel, approved for relapsed/refractory multiple myeloma (RRMM), show improved progression-free and overall survival but are not curative. New CAR-T constructs target alternative antigens like GPRC5D and use dual-targeting methods. Bispecific antibodies engage T cells to kill myeloma cells by binding BCMA or other antigens and CD3, with teclistamab, elranatamab, linvoseltamab, and talquetamab approved for RRMM. These agents demonstrate response rates around 60-70%, with manageable side effects such as cytokine release syndrome (CRS) and neurotoxicity.
Novel targets like GPRC5D and FcRH5 are under evaluation, and combination strategies with immunomodulatory drugs and checkpoint inhibitors aim to deepen responses and overcome resistance. Off-the-shelf BsAbs offer scalable alternatives to personalized CAR-T therapies. Ongoing trials are exploring optimal sequencing and combinations, including antibody-drug conjugates, to enhance durability and safety.
Safety and Adverse Effects
Bispecific antibodies and CAR-T therapies carry distinct safety risks, including CRS, neurotoxicity, infections, anemia, and neutropenia. CRS and neurotoxicity are usually mild to moderate and manageable with supportive care and prophylaxis. Infection rates are high but tend to decrease over time; BsAbs targeting alternative antigens like GPRC5D show fewer severe infections. Dose adjustments and biweekly dosing regimens improve tolerability. Personalized management and vigilant monitoring are essential to balance efficacy and safety, supported by real-world data and collaborative patient care.
Regulatory Approvals and Market Access
Regulatory decisions vary globally, affecting patient access. Linvoseltamab, a BCMA×CD3 bispecific antibody, is approved for patients with at least three prior therapies, showing a 70% response rate with manageable side effects. The FDA is expected to decide on its Biologics License Application by July 2025, while the European Medicines Agency is also reviewing it. Other BsAbs like elranatamab have received accelerated FDA approval.
Market access faces challenges due to the rapid introduction of expensive therapies. The global multiple myeloma drug market is projected to reach $55.7 billion by 2033, driven by new immunotherapies and generics. Pricing and reimbursement decisions must balance clinical benefit, cost-effectiveness, and equitable access. Economic evaluations, including cost-per-responder analyses, inform these decisions amid evolving treatment options.
Future Perspectives and Personalized Medicine
Personalized medicine remains central to multiple myeloma care, with treatment tailored to patient characteristics, preferences, and disease features. Integration of genomic profiling and MRD monitoring guides therapy choices. Ongoing trials are assessing maintenance regimens and frontline use of BsAbs and CAR-T therapies. Combination strategies aim to deepen responses and reduce toxicity.
Challenges include managing immune-related toxicities and addressing disparities in treatment access. Collaborative efforts between clinicians, researchers, and patient advocates are crucial to advance therapy development and ensure broad availability. The future treatment paradigm focuses on maximizing efficacy, minimizing adverse effects, and improving quality of life for multiple myeloma patients.
The content is provided by Jordan Fields, Scopewires
