CAR-T and ibrutinib vs CLL: Sequential or simultaneous?

In this issue of Blood, Gauthier and colleagues present the results of a pilot study evaluating the safety and feasibility of administrating ibrutinib concurrently with CD3zeta, 4-1BB-signaling anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory chronic lymphocytic leukemia (CLL).1 Minimal residual disease (MRD) assessment was performed on bone marrow (BM) at an early time point (4 weeks) following CAR T-cell infusion. The study enrolled 19 CLL patients, one of whom died 4 days after infusion from a presumed ibrutinib-related cardiac arrhythmia during grade 2 cytokine release syndrome (CRS). At the 4-week time point, 15 of the remaining 18 patients responded, with 4 patients achieving a complete response. Remarkably, 11 patients had undetectable BM MRD as measured by IGH sequencing. One-year progression-free survival (PFS) of the 18 evaluable patients was 38%. The authors compared these results to 19 CLL patients who were previously treated with a very similar regimen but without concurrent ibrutinib2 and found that severity of CRS was lower with concomitant ibrutinib, but PFS was unchanged.