Redefining second-line treatment strategy, sequencing, and real-world implementation in relapsed/refractory multiple myeloma: insights from the 31st Annual Congress of the European Hematology Association.

Abstract

The management of relapsed/refractory (R/R) multiple myeloma (MM) continues to evolve with the introduction of novel therapies and the use of newer therapies in different treatment settings and combinations. Chimeric antigen receptor (CAR) T-cell therapies targeting B-cell maturation antigen (BCMA) and bispecific antibodies targeting BCMA and GPRC5D were initially introduced in the heavily pretreated R/R MM setting but have now demonstrated efficacy benefits in earlier lines of therapy. Encouraging results have recently been reported from 3 major phase 3 trials-MonumenTAL-3, MajesTEC-3, and MajesTEC-9-showing significant progression-free survival (PFS) as well as confirmed or preliminary overall survival (OS) improvements with bispecific-containing regimens over current standard-of-care triplets. Bispecific antibodies are associated with a risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) and on-target, off-tumor toxicities, including infections and hypogammaglobulinemia with BCMA-targeting agents and oral and skin-related toxicities with GPRC5D-targeting agents. Implementation of bispecific antibodies requires proactive monitoring and management by a knowledgeable and prepared interdisciplinary team. Treatment selection is individualized based on disease-related factors, treatment history, and patient-related factors and preferences. Adoption of bispecific antibodies in community-based oncology practices will be essential for maximizing the benefit of these therapies and ensuring they reach the patients in need.