Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia

Abstract

Background: Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence.

Methods: We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease. The primary end point was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A. Secondary end points included event-free survival, overall survival, and safety.

Results: Of the 153 enrolled patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. In cohort 2A (94 patients; median follow-up, 20.3 months), overall remission occurred in 77% (95% confidence interval [CI], 67 to 85), with complete remission in 55% (95% CI, 45 to 66) and complete remission with incomplete hematologic recovery in 21% (95% CI, 14 to 31). The prespecified null hypotheses of overall remission (≤40%) and complete remission (≤20%) were rejected (P<0.001). In the 127 patients who received at least one obe-cel infusion (median follow-up, 21.5 months), the median event-free survival was 11.9 months (95% CI, 8.0 to 22.1); estimated 6- and 12-month event-free survival was 65.4% and 49.5%, respectively. The median overall survival was 15.6 months (95% CI, 12.9 to not evaluable); estimated 6- and 12-month overall survival was 80.3% and 61.1%, respectively. Grade 3 or higher cytokine release syndrome developed in 2.4% of the patients, and grade 3 or higher immune effector cell-associated neurotoxicity syndrome developed in 7.1% of the patients.

Conclusions: Obe-cel resulted in a high incidence of durable response among adults with relapsed or refractory B-cell ALL, with a low incidence of grade 3 or higher immune-related toxic effects. (Funded by Autolus Therapeutics; FELIX ClinicalTrials.gov number, NCT04404660.).

Figure 1.. Screening, Enrollment, and Infusion.

Shown is the disposition of the entire study population. Enrolled patients had met all the inclusion criteria and none of the exclusion criteria and had leukapheresate sufficient for the manufacture of obe-cel. Cohort A included adults (≥18 years of age) with B-cell acute lymphoblastic leukemia (ALL) who had 5% or more bone marrow blasts at enrollment. Cohort B included adults with B-cell ALL who were in morphologic remission with measurable residual disease and had less than 5% bone marrow blasts at enrollment. Cohort C included adults with B-cell ALL who had isolated extramedullary disease at enrollment. Obe-cel denotes obecabtagene autoleucel.

Figure 2 (facing page).. Event-free and Overall Survival.

Panel A shows event-free survival among all the patients who received at least one infusion of obe-cel, Panel B event-free survival among all the patients who received at least one infusion according to bone marrow burden before lymphodepletion, Panel C overall survival among all the patients who received at least one infusion, and Panel D overall survival among all the patients who received at least one infusion according to bone marrow burden before lymphodepletion. NE denotes not evaluable.