CAR-T cells in multiple myeloma: current status

Abstract

SummaryStarting with the approval of bortezomib, a proteasome-inhibiting drug, tremendous progress has been achieved in the treatment of multiple myeloma (MM) patients during the last 15 years. Due to a plethora of novel drugs such as second generation proteasome inhibitors, immunomodulating agents and monoclonal antibodies the 5‑year survival of MM patients has been extended from 33% at the turn of the millennium to approximately 60% in younger patients (<65–70 years) who were eligible for consolidation with high-dose chemotherapy and autologous stem cell transplantation. Unfortunately, virtually all patients suffer from relapse and ultimately succumb to the disease, indicating the need for additional treatment strategies. Currently there are two promising immunologic approaches. First, bispecific antibodies called BITE (bispecific T-cell enhancer), which act as fusion proteins with two single-chain variable fragments, target antigens on malignant cells and bind the CD3 receptor and thereby recruit T‑cells to the target cells. The second strategy is chimeric antigen receptor (CAR) engineered T‑cell therapy that attacks myeloma cells by recognizing specific targets such as CD138, BCMA (B-cell maturation antigen), light-chains, SLAM-F7 (signaling lymphocytic activation molecule family member 7) or the pan B‑cell antigen CD19.Several early phase clinical trials show encouraging results in patients who have relapsed after modern treatment including proteasome inhibitors, immunomodulating drugs and monoclonal antibodies. Here, we briefly summarize current clinical knowledge about CAR‑T cell treatment in multiple myeloma, including clinical data presented at the 61st American Society of Hematology annual meeting held in December 2019 in Orlando.