COSTEM 2021 | Factors associated with treatment response to CD19 CAR T-cell therapy in B-ALL

Peihua Lu, MD, Beijing Lu Daopei Institute of Hematology, Beijing, China, and Hebei Yanda Lu Daopei Hospital, Langfang, China, comments on the results of a study investigating the factors associated with treatment response to CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). To begin with, univariate analysis identified several factors associated with a lower initial complete response (CR) to CAR T-cell therapy including TP53 mutations, bone marrow (BM) blasts above 20%, prior immunotherapy, and severe cytokine release syndrome (CRS) and neurotoxicity after CAR-T. A subsequent multivariate analysis indicated TP53 mutation status and BM blast percentage as independent risk factors for initial CR. Moreover, the study found that prior history of allogeneic hematopoietic stem cell transplantation (alloHSCT) or CAR T-cell therapy, complex cytogenetic abnormalities, TP53 mutations, severe CRS and neurotoxicity, and CAR-T without consolidation were all associated with a lower leukemia-free survival (LFS) and overall survival (OS). Only TP53 mutations, prior CAR-T therapy without consolidation and occurrence of severe CAR-T-related side effects were independently associated with lower LFS and OS. In addition, patients with early loss of CAR T-cells or early B-cell recovery after CAR-T, as well as patients with high lactate dehydrogenase (LDH) levels and a low platelet count prior to conditioning chemotherapy are at a higher risk of recurrence and relapse after CAR T-cell therapy. This interview took place at the 6th Congress on Controversies in Stem Cell Transplantation and Cellular Therapies (COSTEM), which took place virtually.