Advancements in multiple myeloma treatment: Integrating quadruplet and dual antigen CAR-T therapy

Multiple myeloma (MM), a type of hematologic malignancy, is characterized by the uncontrolled proliferation of plasma cells in the bone marrow. There have been significant challenges in treating MM due to factors such as relapse, resistance, and antigen escape. Over the past decade, the treatment algorithm has shifted from traditional chemotherapy to immune-based therapies and quadruplet induction regimens. To our knowledge, no published review has yet provided an integrated analysis of current FDA-approved CAR-T therapies and quadruplet therapy regimens for MM. This review examines the mechanistic rationale of combining CAR-T and quadruplet therapy by modulation of the immune microenvironment. Based on findings from recent clinical trials, this review assesses the potential synergistic benefit of combining these approaches to improve long-term outcomes in MM patients. Thereafter, the persistent limitations and areas for further research are highlighted, along with actionable next steps to advance these therapies and improve patient outcomes while addressing real-world barriers that require implementation.