Factors associated with long-term outcomes of CD19 CAR T-cell therapy for relapsed/refractory CLL.

High response rates have been reported after CD19-targeted chimeric antigen receptor-modified (CD19 CAR) T-cell therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), yet the factors associated with duration of response in this setting are poorly characterized. We analyzed long-term outcomes in 47 patients with R/R CLL and/or Richter transformation treated on our phase I/II clinical trial of CD19 CAR T-cell therapy with an updated median follow-up of 79.6 months. Median progression-free survival (PFS) was 8.9 months and the 6-year PFS was 17.8%. Maximum SUV (HR = 1.15, 95% CI, 1.07-1.23, p < 0.001) and bulky disease (≥5 cm; HR = 2.12, 95% CI, 1.06-4.26, p = 0.034) prior to lymphodepletion were associated with shorter PFS. Day +28 CR by PET-CT scan (HR = 0.13, 95% CI, 0.04-0.40, p < 0.001), day +28 MRD negativity by MFC (HR = 0.08, 95% CI, 0.03-0.22, p < 0.001), day +28 MRD negativity by NGS (HR = 0.21, 95% CI, 0.08-0.51, p < 0.001), higher peak CD8+ CAR T-cell expansion (HR = 0.49, 95% CI, 0.36-0.68, p < 0.001), higher peak CD4+ CAR T-cell expansion (HR = 0.47, 95% CI, 0.33-0.69, p < 0.001), and longer CAR T-cell persistence (HR = 0.56, 95% CI, 0.44-0.72, p < 0.001) were associated with longer PFS. The 6-year duration of response and overall survival were 26.4% and 31.2%, respectively. CD19 CAR T-cell therapy achieved durable responses with curative potential in a subset of R/R CLL patients. This trial was registered at ClinicalTrials.gov (#NCT01865617).