CD19 CAR T-Cells With Concurrent Ibrutinib Well-Tolerated in Relapsed/Refractory CLL

The use of CD19 CAR-T cells with concurrent ibrutinib was well-tolerated and yielded low cytokine release syndrome (CRS) severity in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL; Blood. 2020 Feb 19. Epub ahead of print).

“We previously reported durable responses in…R/R…CLL…patients treated with CD19-targeted chimeric antigen receptor-engineered T (CD19 CAR-T) cell immunotherapy after ibrutinib failure,” explained Jordan Gauthier, MD, MSc, University of Washington, Seattle, and co-investigators.

Citing preclinical data demonstrating that ibrutinib could improve CAR-T cell antitumor efficacy and reduce CRS, Dr Gauthier et al conducted a pilot study assessing the safety and feasibility of ibrutinib administered concurrently with CD19 CAR-T cell immunotherapy in 19 patients with CLL.

Patients had previously received a median of 5 therapies, and 17 (89%) patients had high-risk cytogenetics, including 17p deletion and/or complex karyotype. Ibrutinib therapy was slated to begin at least 2 weeks before leukapheresis and continue at least 3 months after CAR-T cell infusion.

Ultimately, CD19 CAR-T cell immunotherapy administered concurrently with ibrutinib was well-tolerated, and 13 (68%) patients received ibrutinib without any dose reductions.

According to the International Workshop Group on CLL criteria, the 4-week overall response rate was 83%, with 61% of patients achieving minimal residual disease–negative marrow response via IGH sequencing. The 1-year overall and progression-free survival probabilities in this subset were 86% and 59%, respectively.

The use of CAR-T cells with concurrent ibrutinib led to lower CRS severity and lower serum concentrations of CRS-associated cytokines despite equivalent in vivo CAR-T cell expansion than in patients treated only with CAR-T cells.

According to Dr Gauthier and colleagues, the 1-year PFS probabilities in all evaluable patients given CD19 CAR-T therapy with and without concurrent ibrutinib were 38% and 50%, respectively (P = .91).

“CD19 CAR-T cells with concurrent ibrutinib for R/R CLL were well tolerated, with low CRS severity, and led to high rates of MRD-negative response by IGH sequencing,” they concluded.—Hina Porcelli