BCMA-targeted CAR-T Therapy Associated Adverse Events in Multiple Myeloma: A Systematic Review and Meta-analysis

Abstract

Abstract B cell maturation antigen (BCMA)-targeted chimeric antigen receptor modified (CAR)-T therapy is an emerging treatment option for multiple myeloma (MM) but many severe adverse events (AEs) remain in clinical practice, raising safety concerns regarding this promising therapy. In this systematic review, we searched 4 databases and selected 45 reports from 32 different studies involving a total of 927 patients with MM. Data were extracted and analyzed to assess the efficacy and safety of the therapy. Complete responses (CR) and stringent complete responses (sCR) were achieved in 48% (95% CI, 39%-59%) patients, with partial responses and very good partial responses (VGPR) were achieved in 36% (95% CI, 30%-43%) patients. Of the patients who had MM evaluable for minimal residual disease (MRD), 71% (95% CI: 56%-89%) achieved negative status for bone marrow MRD. Regarding safety, the AE with the highest incidence was cytokine release syndrome (CRS), which occurred in 76% (95% CI, 65%-86%) patients, while severe CRS was observed in 10% (95% CI, 5%-14%) patients. The AE with the second highest incidence was neurotoxicity reported in 9% (95% CI, 5%-14%) patients, with the proportion of severe neurotoxicity being 2% (95% CI, 1%-4%). Notably, hematological toxicities, often manifesting as cytopenia, were a prominent severe AE. Furthermore, 68 (7.34%) of the 927 enrolled patients had died. This study shws that, despite the promising results of BCMA-targeted CAR-T therapy in MM patients, significant and sometimes severe toxicities were observed frequently during treatment. There is an urgent need to place more emphasis on these AEs and solutions. The study was registered in PROSPERO, number CRD42022295858.