A new pilot study is suggesting that CD19-targeted chimeric antigen receptor (CAR) T-cell (CAR-T) engineered therapy combined with concurrent ibrutinib is well tolerated in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). The researchers, who published their findings in the journal Blood, demonstrated that this combination approach for patients with R/R CLL was feasible in most patients, resulting in high response rates without severe cytokine release syndrome (CRS).
The study included patients with CLL (median age was 65 years) who received ibrutinib, and 18 of the 19 patients received 1 CAR-T. One patient received a second CAR-T infusion for persistent disease 50 days after the first infusion. Combining ibrutinib and CD19-directed CAR T cells resulted in high response rates by the 2018 International Workshop on CLL (iwCLL) criteria. The iwCLL overall response rate (ORR) was 83% and these responses included high rates of minimal residual disease (MRD)-negative marrow response by flow cytometry (72%) and high lymph node response rates (71%).
The median number of prior therapies was 5, and 89% of the patients (17 individuals) had high-risk cytogenetics (17p deletion and/or complex karyotype). Ibrutinib was started 2 weeks prior to leukapheresis and continued for 3 months after CAR-T infusion. The combination therapy was found to be well tolerated and 68% of the patients (13 individuals) received ibrutinib as planned without dose reductions.
The study showed that 61% of the patients achieved a MRD-negative marrow response by immunoglobulin heavy chain sequencing. The 1-year overall survival (OS) rate probability was 86% and progression-free survival (PFS) rate probability was 59%.
One patient died 4 days after infusion from a presumed ibrutinib-related cardiac arrhythmia, and 18 of 19 patients were evaluable for response 4 weeks after CAR-T infusion.
Gauthier J, Hirayama AV, Purushe J, et al. Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood. 2020; 135(19):1650-1660