T-Cell-Based Cellular Immunotherapy of Multiple Myeloma: Current Developments

SIMPLE SUMMARY: Over the past two decades, there has been significant progress in the treatment of multiple myeloma. Starting with the approval of bortezomib and lenalidomide, followed by newer agents in the same classes, monoclonal antibodies, and most recently idecabtagene vicleucel and ciltacabtagene autoleucel, which are genetically engineered autologous T-cell-based therapies, our view of this disease has changed from incurable to controllable and potentially curable. In addition to multiple myeloma and B-cell lymphomas, T-cell-based therapies are also actively investigated in various types of hematological and non-hematological malignancies and are considered one of the most impactful evolutions in cancer therapeutics. This review aims to summarize existing data regarding the efficacy, toxicity, and management of unique adverse events in T-cell-based therapies that are both clinically available and under investigation. We will also address undergoing efforts to improve the survival outcomes of multiple myeloma patients through this treatment modality. ABSTRACT: T-cell-based cellular therapy was first approved in lymphoid malignancies (B-cell acute lymphoblastic leukemia and large B-cell lymphoma) and expanding its investigation and application both in hematological and non-hematological malignancies. Two anti-BCMA (B cell maturation antigen) CAR (Chimeric Antigen Receptor) T-cell therapies have been recently approved for relapsed and refractory multiple myeloma with excellent efficacy even in the heavily pre-treated patient population. This new therapeutic approach significantly changes our practice; however, there is still room for further investigation to optimize antigen receptor engineering, cell harvest/selection, treatment sequence, etc. They are also associated with unique adverse events, especially CRS (cytokine release syndrome) and ICANS (immune effector cell-associated neurotoxicity syndrome), which are not seen with other anti-myeloma therapies and require expertise for management and prevention. Other T-cell based therapies such as TCR (T Cell Receptor) engineered T-cells and non-genetically engineered adoptive T-cell transfers (Vγ9 Vδ2 T-cells and Marrow infiltrating lymphocytes) are also actively studied and worth attention. They can potentially overcome therapeutic challenges after the failure of CAR T-cell therapy through different mechanisms of action. This review aims to provide readers clinical data of T-cell-based therapies for multiple myeloma, management of unique toxicities and ongoing investigation in both clinical and pre-clinical settings.