In a study reported in the Journal of Clinical Oncology by Noelle V. Frey, MD, and colleagues, a higher dose of anti-CD19 chimeric antigen receptor (CAR) T cells was associated with a higher rate of complete response in patients with relapsed or refractory chronic lymphocytic leukemia, with long-term follow-up showing that complete response—irrespective of dose—was associated with improved progression-free and overall survival.
Noelle V. Frey, MD
Study Details
The study enrolled patients between January 2013 and June 2016. In part 1 of the study, 28 patients were randomly assigned to receive a low-dose (5 x 107) or high-dose (5 x 108) infusion of anti-CD19 CAR T-cells, with 24 being evaluable for response. After an interim analysis, 10 additional patients received a high-dose infusion, with 8 being evaluable for response.
Key Findings
At 4 weeks, overall and complete response rates were 44% and 22% among all 32 evaluable patients, respectively.
Among the total of 19 evaluable patients receiving the high-dose infusion, response was observed in 10 (53%), with complete response observed in 7 (37%). Responses were observed in 4 (31%) of 13 evaluable patients in the low-dose group, with complete response observed in 2 (15%).
KEY POINTS
- At 4 weeks, among the total of 19 evaluable patients receiving the high-dose infusion, response was observed in 10, with complete response observed in 7. Responses were observed in 4 of 13 evaluable patients in the low-dose group, with complete response observed in 2.
- Achievement of complete response, irrespective of dose, was associated with significantly longer overall survival vs no complete response.
At a median follow-up was 31.5 months, no significant difference in overall survival was observed between patients receiving a low dose vs a high dose of anti-CD19 CAR T-cell therapy (median = 64 vs 68 months, P = .84).
Achievement of complete response, irrespective of dose, was associated with significantly longer overall survival vs no complete response (median = not reached vs 64 months, P = .035).
Median progression-free survival was 40.2 months in patients with complete response vs 1 month in those without complete response (P < .0001).
Toxicity after lymphodepleting chemotherapy and anti-CD19 CAR T-cell infusion was similar to previously reported findings, and similar in the low-dose and high-dose groups.
The investigators concluded, “In patients with advanced chronic lymphocytic leukemia, a 5 x 108 dose of [anti-CD19 CAR T-cell therapy] may be more effective than [a] 5 x 107 [dose] at inducing complete response without excessive toxicity. Attainment of a complete response after infusion, regardless of cell dose, is associated with longer overall survival and progression-free survival in patients with relapsed chronic lymphocytic leukemia.”
David L. Porter, MD, of the University of Pennsylvania, Perelman Center for Advanced Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Leukemia & Lymphoma Society and Novartis. For full disclosures of the study authors, visit ascopubs.org.
