Inaticabtagene autoleucel in adult relapsed or refractory B-cell acute lymphoblastic leukemia

Abstract

Before November 2023, CD19 chimeric antigen receptor (CAR) T-cell therapies had not been approved in China for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), leaving a significant unmet need. In response, inaticabtagene autoleucel (Inati-cel), a novel CD19 CAR T-cell therapy with a distinct single-chain variable fragment (HI19α), was developed and showed promising efficacy in preliminary clinical research. We conducted a phase 2, single-arm, multicenter study of Inati-cel in adult CD19+ R/R B-ALL in China. The primary end point was the overall remission rate (ORR) at the end of month 3. Forty-eight patients who underwent Inati-cel infusion were evaluated for both efficacy and safety. Among them, 34 patients achieved and maintained remission beyond 3 months, with a 3-month ORR of 70.8% (95% confidence interval [CI], 55.9-83.1). The best ORR was 85.4%, with all responders reaching minimal residual disease negativity. With a median follow-up of 23.7 months, the median duration of remission was 20.7 months (95% CI, 6.4 to not reached), and the median overall survival was not reached (95% CI, 13.0 months to not reached). Additionally, grade ≥3 cytokine release syndrome and neurologic events occurred in 12.5% and 6.2% of patients, respectively. The 2-year follow-up data suggest that Inati-cel demonstrates encouraging and durable responses with manageable safety profiles in R/R B-ALL. Based on the data from this pivotal trial, Inati-cel was approved as the first CAR T-cell therapy for adult R/R B-ALL in China and underscores its potential therapeutic benefits for this patient population. This trial was registered at www.ClinicalTrials.gov as #NCT04684147.

Graphical abstract

Figure 1.

Flow diagram. The reasons for patients not enrolling in the study after screening included 2 patients withdrawing voluntarily, 4 patients not meeting the inclusion criteria (<5% blasts in the bone marrow at the screening), and 19 patients meeting the exclusion criteria (including hepatitis B infection, hepatitis C infection, Epstein-Barr virus infection, cytomegalovirus infection, or uncontrolled infection in 11 patients; physician decision in 4 patients due to rapid disease progression; ineligible for apheresis procedure in 3 patients, and central nervous system leukemia in 1 patient). All patients who completed screening and whose apheresis product was received by the manufacturing facility were enrolled in the study. Reasons for treatment discontinuation before lymphodepletion included: uncontrolled infection (n = 6), voluntary withdrawal (n = 3), physician decision (n = 2; 1 patient remitted after bridging chemotherapy, and 1 patient was diagnosed as mixed-phenotype acute leukemia), and ineligibility (n = 1). After lymphodepletion, 7 patients did not proceed to Inati-cel infusion due to physician decision (n = 2; 1 patient accompanied with teratoma and 1 patient remitted), uncontrolled infection (n = 2), and rapid disease progression (n = 3).

Figure 2.

DOR, RFS, and OS. (A-B) Kaplan-Meier estimates the DOR, with censoring patients at subsequent allogeneic stem cell transplant (A) and without censoring (B). (C) Kaplan-Meier estimate of RFS by investigator assessment, with patients censored at subsequent allogeneic stem cell transplant. (D) Kaplan-Meier estimate of OS. NE, not estimable.