Axicabtagene ciloleucel in vivo expansion and treatment outcome in aggressive B-cell lymphoma in a real-world setting

Abstract

Data on the association between chimeric antigen receptor (CAR)-T-cell kinetics and patient outcome in the nontrial setting are missing, mainly due to the lack of broadly available CAR-T-cell diagnostic quantification tools. We performed prospective quantification of axicabtagene ciloleucel (axi-cel) in 21 patients treated for aggressive B-cell lymphoma at our clinic. Median peak CAR-T-cell count was 16.14 CAR-T cells/µL. Patients with 16.14/μL or higher peak CAR-T cells (strong expanders) had more day-30 objective responses (91% vs 40%, P = .02). In univariate analysis, peak CAR-T cell ≥ 16.14 (P < .001), normal platelet counts at start of lymphodepletion (P < .001), no prior stem cell transplant (P = .04), and peak CAR-T cells as continuous variable (P = .03) were associated with better progression-free survival (PFS). After adjusting for platelet counts and prior stem cell transplantation, peak CAR-T cells below median was still associated with shorter PFS (relative risk, 0.15, 95% confidence interval, 0.04-0.59, P = .007). Low platelet counts also maintained significant impact on PFS. Our data demonstrate association of axi-cel levels and outcome in a nontrial setting and for the first time use a cutoff to segregate weak and strong expanders with respective outcomes.

Figure 1.

“Real-world” axi-cel kinetics in 21 r/r B-NHL patients treated in our clinic. Analysis of peripheral blood mononuclear cells using an axi-cel–specific dPCR assay reveals differences in the CAR-T-cell engraftment kinetics. In vivo persistence of axi-cel T cells in the peripheral blood over time. The horizontal line indicates the median of the peak expansion. Negative values were set to 0.001/µL (limit of detection). (A) Strong expanders had a peak expansion of ≥16.14 cells/µL. (B) Peak expansion values and clinical outcome for individual patients. The median peak value (16.14 CAR T cells/µL) was found for patient 9. The color coding highlights the patients with prolonged persistence in each group. PD, progressive disease. (C-D) Kaplan-Meier curves of 21 patients treated with commercially available axi-cel in the nontrial setting show the OS and PFS during the >1 year of follow-up. (E) Kaplan-Meier curves of 21 axi-cel–treated patients show significantly increased survival of patients in the “strong expanders” group vs the “weak expanders” group. P value compares strong expanders vs weak expanders. (F) Boxplots showing CAR-T cell peak concentrations and correlation with response, CRS, and ICANS. The upper and lower borders of the box represent 25th and 75th percentiles, the line within the box depicts the median, and the bars represent the range. ns, nonsignificant.