CD19 CAR T-Cell Therapy Achieved Durable Responses Among Specific Subset of Patients With R/R CLL

According to a recent phase 1/2 study which set out to analyze the factors associated with long-term treatment outcomes, CD19 CAR T-cell therapy achieved positive, long-term responses with curative potential among a specific subset of patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).

“Although long-term responses have been reported after CD19 CAR T-cell therapy for CLL, the factors associated with long-term outcomes have not been identified,” explained Emily C. Liang, MD, Fred Hutchinson Cancer Center, Seattle, Washington, and coauthors, “Therefore, we now provide an update of our phase 1/2 clinical trial results with >6 years of median follow-up, including exploratory analyses of factors associated with long-term outcomes.”

In this study, the investigators examined long-term outcomes in 47 patients with R/R CLL and/or Richter transformation treated on a phase 1/2 clinical trial of CD19 CAR T-cell therapy with an updated median follow-up of 79.6 months. The median progression-free survival (PFS) was 8.9 months, and the 6-year PFS was 17.8%.

Results demonstrated that the maximum standardized uptake value (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.07 to 1.23; P < .001) and bulky disease (≥5 cm; HR, 2.12; 95% CI, 1.06 to 4.26; P = .034) before lymphodepletion were associated with shorter PFS. Additionally, Day +28 complete response by positron emission tomography–computed tomography (HR, 0.13; 95% CI, 0.04 to 0.40; P < .001), day +28 measurable residual disease (MRD) negativity by multiparameter flow cytometry (HR, 0.08; 95% CI, 0.03 to 0.22; P < .001), day +28 MRD negativity by next-generation sequencing (HR, 0.21; 95% CI, 0.08 to 0.51; P < .001), higher peak CD8+ CAR T-cell expansion (HR, 0.49; 95% CI; 0.36 to 0.68; P < .001), higher peak CD4+ CAR T-cell expansion (HR, 0.47; 95% CI; 0.33 to 0.69; P < .001), and longer CAR T-cell persistence (HR, 0.56; 95% CI, 0.44 to 0.72; P < .001) were associated with longer PFS. It was noted that the 6-year duration of response and overall survival were 26.4% and 31.2%, respectively.

Liang and colleagues concluded, “This 6-year follow-up update of our phase 1/2 clinical trial demonstrates durable responses in patients with high-risk R/R CLL with MRD-negative response after CD19 CAR T-cell therapy.”

“We identified both pretreatment (maximum SUV and bulky disease) and post-treatment variables (day +28 PET-CT response, day +28 MRD status, peak CAR T-cell expansion, and CAR T-cell persistence) that were strongly associated with PFS,” they added. 

“We expect CD19 CAR T-cell therapy to become a critical addition to the therapeutic armamentarium for high-risk CLL. Pending additional results, the CD19 CAR T-cell product JCAR017 is anticipated to be approved by the US Food and Drug Administration in the near future based on the TRANSCEND CLL 004 clinical trial,” study authors additionally noted. 

Source:

Liang E, Albittar A, Huang J, et al. Factors associated with long-term outcomes of CD19 CAR T-cell therapy for relapsed/refractory CLL. Blood Adv (2023); 7 (22): 6990–7005. doi: 10.1182/bloodadvances.2023011399