Background: Chimeric antigen receptor T (CAR-T) cell therapy targeting B cell maturation antigen (BCMA) is an effective treatment for relapsed/refractory multiple myeloma (r/r MM). However, antigen escape-mediated relapse often occurs. CARs simultaneously targeting two antigens may overcome this limitation. Therefore, we used A proliferation inducing ligand (APRIL) to construct a ligand-base CAR that allows for bispecific targeting of BCMA and transmembrane activator and CAML interactor (TACI) as a novel therapy for r/r MM.
Methods: The APRIL CAR-T was evaluated in a Phase 1 clinical trial (NCT04657861) in patients with BCMA/TACI positive relapsed/refractory multiple myeloma. Safety, efficacy, and APRIL CAR-T cellular kinetics were evaluated.
Results: 9 patients received APRIL CAR-T infusions following a conditioning regimen of cyclophosphamide and fludarabine. The treatment was generally well tolerated, with 6 patients experiencing grade 1 cytokine release syndrome (CRS) and 1 patient experiencing grade 2 CRS, no patient had grades 3-4 CRS , no GvHD and immune effector cell-associated neurotoxicity were observed. The overall response rate was 88.8% (8/9), including 2 (22.2%) with complete remission (CR), 4 (44.4%) with very good partial remission (VGPR), and 2 (22.2%) with partial remission (PR).After a median follow-up of 6.63 months (range, 0.50-13.90 months), 1 patients remained in complete remission,and 1 patient died of a cerebrovascular accident. The median overall survival and relapse-free survival for the patients treated with APRIL CAR-T cells was 8.31 months (95% confidence interval [CI], 0.50-13.90 months) and 2.80 months (95% CI, 0.50-6.63 months), respectively.
Conclusions: The APRIL CAR-T cell-based therapy appeared to be a promising therapeutic approach in r/r MM, based on its antitumor effects and manageable side effects, meanwhile additional strategies are required to sustain the therapeutic response.
No relevant conflicts of interest to declare.
