Factors associated with long-term outcomes of CD19 chimeric antigen receptor T-cell therapy for relapsedrefractory chronic lymphocytic leukemia 6-year follow-up

In patients with R/R CLL receiving CD19 CAR T-cell therapy, day +28 CR by PET CT, day +28 MRD negativity, higher in vivo peak CAR T-cell expansion, and longer CAR T-cell persistence were associated with long-term outcomes, including DOR.

We observed high efficacy in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) treated on a phase I/II clinical trial with a defined-composition (1:1 ratio of CD8+:CD4+) CD19 CAR T-cell product (NCT01865617). We now report comprehensive analyses of factors associated with duration of response (DOR) with over 6 years of median follow-up.

We included 49 patients with R/R CLL and/or Richter's transformation (n = 9) (Table 1). Response was defined as complete (CR) or partial response (PR) by investigator-assessed 2018 iwCLL criteria at day+28. Measurable residual disease (MRD) in bone marrow (BM) was evaluated by multiparameter flow cytometry (MFC) and IGH next-generation sequencing (NGS; clonoSEQ assay).

In the response-evaluable cohort (n = 47), median follow-up was 79.6 months. Median DOR was 18.9 months (95% CI, 9.66-55.6) (Figure 1A). In NGS MRD-negative responders, the median DOR was 53.4 months (95% CI, 27.1-not reached) (Figure 1B). In all infused patients (n = 49), the 6-year PFS and OS were 17.8% and 31.2%, respectively (Figure 1C-D).

In univariate Cox regression, day +28 CR by PET-CT scan, day +28 MRD negativity by MFC, day +28 MRD negativity by NGS, higher peak CD8+ CAR T-cell expansion, higher peak CD4+ CAR T-cell expansion, and longer CAR T-cell persistence were associated with longer DOR (Table 2). These factors were also associated with longer PFS and OS in univariate Cox regression. In the 7 patients who were progression-free at 5 years, 7 had day +28 MRD negativity by MFC, and 5 (1 missing) had day +28 MRD negativity by NGS.