FELIX 研究中接受 Obecabtagene Autoleucel 治疗的复发/难治性 B 细胞急性淋巴细胞白血病成人患者 CAR-T 细胞动力学、持久性与临床结局

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/ L 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.