Multiple Myeloma 2025: Integrating CAR‐T and Bispecifics into an Evolving Treatment Landscape - Tahminakhan123/healthpharma GitHub Wiki

Multiple myeloma (MM) management has entered an era of rapidly expanding therapeutic options. While frontline regimens (proteasome inhibitor + immunomodulatory drug + monoclonal antibody) remain standard for most newly diagnosed patients, relapsed/refractory disease management is being transformed by BCMA-targeted CAR-T cell therapies and bispecific T-cell engagers.

State-of-the-art options. Autologous stem cell transplant (ASCT) still has a role for transplant-eligible patients, but novel agents—daratumumab and next-generation proteasome inhibitors/IMiDs—have improved depth of response and survival. For heavily pretreated or refractory disease, BCMA-directed CAR-T therapies (ide-cel, cilta-cel) produce high response rates and deep remissions in many patients, though durability and access remain considerations. Bispecific antibodies (e.g., teclistamab, elranatamab) recruit T cells to BCMA and offer off-the-shelf alternatives with promising activity in trials and real-world practice.

Clinical evidence and comparative considerations. Recent ASH and peer-reviewed data highlight that CAR-T therapies produce rapid, high-quality responses; however, cytokine release syndrome (CRS), neurotoxicity, and manufacturing/logistics are important constraints. Bispecifics are more immediately accessible and can be dosed in an outpatient setting with step-up regimens to manage CRS risk. Matching-adjusted and indirect comparisons are emerging to guide sequencing decisions, but head-to-head data are limited—treatment choice currently hinges on disease biology, prior therapies, comorbidities, and patient preference.

Safety and monitoring. Both CAR-T and bispecific therapies require vigilant monitoring for CRS and immune effector cell-associated neurotoxicity (ICANS). Prophylaxis and standardized management algorithms (tocilizumab, corticosteroids, ICU pathways) minimize severe events. Infectious risk (hypogammaglobulinemia, prolonged cytopenias) prompts close surveillance and consideration for immunoglobulin replacement in selected patients. Multidisciplinary care—hematology, nursing, infectious disease, and critical care—is essential.

Practical sequencing and future directions. Current practice personalizes sequencing: reserve CAR-T for patients eligible for cell therapy when durable remission is the aim, while bispecifics offer repeated, adaptable outpatient options. Trials exploring combinations (CAR-T + CELMoDs, bispecifics earlier in disease course), BCMA-targeting alternatives, and strategies to extend durability (gamma-secretase inhibitors to increase BCMA density, cellular manufacturing improvements) are active. Ongoing real-world datasets and randomized comparisons will further inform best sequencing.

Bottom line. The multiple myeloma (MM) treatment landscape in 2025 is characterized by unprecedented therapeutic depth and choice. Clinicians must balance efficacy, toxicity, logistics, and patient goals when integrating CAR-T and bispecific agents—while continuing to use established standards (ASCT, triplet/quadruplet induction) to optimize long-term outcomes.