Safety and efficacy of allogeneic CD19-directed CAR-T therapy CTX110 in relapsed/refractory B-cell non-Hodgkin lymphoma

ABSTRACT: This multicenter, single-arm, phase 1/2 study evaluated the safety and efficacy of CD19-directed allogeneic chimeric antigen receptor (CAR) immunotherapy CTX110 in adult patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). Patients received 1 or 2 treatment courses: standard lymphodepletion, followed by 1 CTX110 infusion at dose levels (DLs) 1 to 4 (3 × 107 to 60 × 107 CAR T cells; dose escalation, N = 32), or 2 infusions at DL4 on days 1 and 35 (cohort expansion, N = 31). Primary end points in dose escalation and cohort expansion were incidence of dose-limiting toxicities and objective response rate, respectively. CTX110 was administered to 63 heavily pretreated patients: 59% primary refractory, 43% with ≥3 previous therapies. Among 57 patients whose first infusion was DL ≥3, rates of objective and complete response (CR) were 65% and 39%, respectively. Among 22 patients achieving CR, 5 (23%) had ongoing CR at data cutoff, with 15 to 50 (median 34) months follow-up. The 2-infusion regimen prolonged response duration vs 1 infusion (hazard ratio, 0.65). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 54% and 13% of treated patients, respectively, including 2 grade ≥3 cases each. The most common grade ≥3 adverse events (AEs) were neutropenia (59%), and anemia and thrombocytopenia (35% each). Serious AEs occurred in 32% of treated patients, including CRS (14%), ICANS (8%), and febrile neutropenia (6%). In this R/R NHL population, CTX110 was well tolerated, resulting in clinically meaningful responses at DL ≥3, with a second infusion demonstrating further clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT04035434.