All-grade CRS and neurotoxicity were reported in 74% (n = 14) and 32% (n = 6), respectively, of patients receiving concurrent ibrutinib versus 92% (n = 22) and 42% (n = 10) in those who did not receive the BTK inhibitor (P
= .21; P
= .42). Severe cases of CRS occurred in 0% of patients on the concurrent ibrutinib cohort and in 25% (n = 6) of those not treated with ibrutinib (P
There was 1 death in each cohort; 1 was presumed as cardiac arrhythmia in the ibrutinib cohort and CRS/neurotoxicity in the no-ibrutinib cohort. “To our knowledge, these are the most encouraging results that have been seen to date in humans with a combination of CAR T cells and a targeted agent,” said Gauthier. “While the CAR T cells expanded robustly in both groups and led to high rates of response, we did not observe a single case of severe CRS in patients receiving ibrutinib during CAR T therapy.”
These findings must be validated in a larger, prospective trial, Gauthier concluded. In the ongoing, prospective phase I/II TRANSCEND-CLL 17004 study (NCT03331198), investigators will evaluate the safety and efficacy of the CD19-targeted JCAR017 CAR T-cell therapy alone and in combination with ibrutinib in patients with relapsed or refractory CLL or small lymphocytic lymphoma.
Ibrutinib was approved by the FDA as a frontline treatment for patients with CLL in March 2016; prior to that, it was approved for previously treated patients.
<<< 2018 ASH Annual Meeting
- Gauthier J, Hirayama AV, Hay KA, et al. Efficacy and toxicity of CD19 CAR-T cells alone or in combination with ibrutinib for relapsed and/or refractory CLL. Presented at 60th American Society of Hematology Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 299.
- Turtle CJ, Hay KA, Hanafi LA, et al. Durable molecular remission in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol. 2017;35(26):3010-3020. doi: 10.1200/JCO.2017.72.8519.