Long-term data from a phase 1 study investigating anti-CD19 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy in patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) showed that the product appeared to be safe, and that lymphodepleting chemotherapy is necessary. The data, published in JCI Insight, also brought to the forefront ibrutinib as a possible means of enhancing CAR-T’s efficacy in CLL, an indication for which CAR-T has thus far proven elusive.1
“We don’t have a lot of published data on CAR-T cells in CLL,” Tanya Siddiqi, MD, hematologist/oncologist at City of Hope, Duarte, California, told Cancer Therapy Advisor. Dr Siddiqi has consulted for Juno Therapeutics and led trials funded by the company, but she was not involved in the current trial, which was funded by Juno Therapeutics. “The little we do have does seem to suggest that the CAR-T cells directed against CD19 in CLL patients may not have as great responses as we’ve seen in acute lymphoblastic leukemia.”
Approximately a quarter of patients with relapsed or refractory CLL achieve durable responses to anti-CD19 CAR-T, whereas more than 70% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) achieve durable responses.2
The long-term data are based on an analysis of a phase 1 trial that treated patients with anti-CD19 CAR-T containing a CD28 costimulatory domain between June 2007 and April 2017 (ClinicalTrials.gov Identifier: NCT00466531). The trial included 16 patients with relapsed or refractory CLL, and although all received anti-CD19 CAR-T, the circumstances varied on the basis of the stage at which patients were enrolled.
The trial had 3 stages, and for stage 1, 3 patients received an infusion of CAR-T at a dose of 1.2 to 3.0 × 107 CAR-T cells/kg without lymphodepleting chemotherapy. For stage 2A, one patient received cyclophosphamide as lymphodepleting chemotherapy followed by an infusion of CAR-T cells at 3.0 × 107 CAR-T cells/kg, but the patient died within 48 hours of receipt and was considered nonevaluable in the analysis. The protocol was modified to use a lower CAR-T cell dose and to split the infusion over 2 days.