CAR T-Cell Therapy for CLL: Comparing Doses and Outcomes
Posted: Friday, June 12, 2020
According to a phase II dose-optimization trial published in the Journal of Clinical Oncology, patients with advanced chronic lymphocytic leukemia (CLL) who are treated with a higher dose of chimeric antigen receptor (CAR)-modified T cells targeting CD19 (CART-19) may experience a more effective induction of complete remission than those who are treated with a lower dose. David L. Porter, MD, of the University of Pennsylvania, Philadelphia, and colleagues also noted that complete remission appears to be correlated with an increased length of both overall and progression-free survival, independent of the cell dosage.
A total of 38 patients with relapsed or refractory disease were randomly assigned and subsequently received CART-19 infusion of either 5 x 108 cells/kg (high dose) or 5 x 107 cells/kg (low dose). Thirty-two patients were deemed evaluable for response. All patients who received CART-19 infusion were eligible for toxicity assessments. Follow-up data were provided for an average of 31.5 months.
The high-dosage group achieved a longer median progression-free survival than the low-dosage group (1.8 vs. 1 month). However, the difference in overall survival between the groups did not appear to be statistically significant (P = .84). Notably, the two dosages exhibited similar toxicity profiles. Of the evaluable patients, 28% achieved a complete response, and 44% achieved an overall response at 4 weeks post-treatment. Prolonged survival appeared to be associated with complete remission (P = .035), irrespective of the assigned dosage. The median progression-free survival for patients with and without complete remission was 40.2 months and 1 month, respectively (P < .0001).
“[Other strategies to increase the complete remission rate to CART cells] could include prospective selection of patients who are most likely to benefit from CART cells, such as those exhibiting a CD27+PD-1- IL-6R+CD8+ T-cell phenotype, or rationally combining CART cells with small-molecule inhibitors,” the investigators proposed.
Disclosure: For full disclosures of the study authors, visit ascopubs.org
