CAR T-cell Kinetics, Persistence, and Clinical Outcomes in Adult Patients with Relapsed/Refractory B-cell ALL Treated with Obecabtagene Autoleucel in the FELIX Study
Abstract
Assessments of chimeric antigen receptor (CAR) T-cell pharmacokinetics by flow cytometry (FC) and a droplet digital PCR (ddPCR) assay were compared in adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) following treatment with obecabtagene autoleucel (obe-cel) in the phase Ib/II FELIX study (NCT04404660). CAR T-cell persistence and B-cell aplasia (BCA) were then correlated with event-free survival (EFS). Peripheral blood (PB) samples collected from 127 obe-cel-infused patients were tested by FC and ddPCR. The Spearman correlation coefficient was used to measure the correlation between the number of CAR T-positive cells by FC and ddPCR. The impact of CAR T-cell persistence and BCA (B cells <20 cells/μL by FC in PB) on EFS was assessed using Cox proportional hazards regression. ddPCR was observed to statistically correlate with both the surface (0.60, P < 0.0001) and intracellular FC assays (0.74, P < 0.0001). A higher sensitivity for detecting CAR T-cell positive samples was observed with ddPCR, with 58.8% and 41.3% of samples negative by surface and intracellular FC, respectively, being positive by ddPCR. Loss of CAR T-cell persistence (HR, 2.7; 95% CI, 1.4-5.4) and, to a lesser degree, B-cell recovery (HR, 1.7; 95% CI, 0.7-3.8) as time-dependent variables and at month 3 were associated with poorer EFS. ddPCR demonstrated enhanced sensitivity over FC methods for detection of obe-cel persistence. Additionally, ongoing persistence and BCA…
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Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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