Cancer research communications · 2026
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.
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Roddie Claire, Day William, Raymond Meera, Cluxton Deborah, Caulfield Jason, Dainton-Smith Heather, McElwee Brooke, Hu Yanqing, Sandhu Karamjeet S, Tholouli Eleni, Logan Aaron C, Shaughnessy Paul, Yallop Deborah, Barba Pere, Guerreiro Manuel, Yared Jean A, Hodby Katharine, Shah Bijal D, Brugger Wolfram, Lao-Sirieix Pierre, Bishop Michael R, DeAngelo Daniel J, Jabbour Elias, Park Jae H
Аннотация
UNLABELLED: 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 were associated with longer EFS and may be taken into consideration, together with clinical parameters, in informing decision making.
SIGNIFICANCE: In patients with R/R B-ALL treated with obe-cel, ddPCR assessment of CAR transgene levels produced results consistent with FC while providing superior sensitivity. ddPCR-detected CAR T-cell persistence at month 3 and at any time after infusion correlated with longer EFS versus loss of persistence, therefore potentially informing clinical decision making.
SIGNIFICANCE: In patients with R/R B-ALL treated with obe-cel, ddPCR assessment of CAR transgene levels produced results consistent with FC while providing superior sensitivity. ddPCR-detected CAR T-cell persistence at month 3 and at any time after infusion correlated with longer EFS versus loss of persistence, therefore potentially informing clinical decision making.