Concurrent Ibrutinib and CD19 CAR-T Therapy Well-Tolerated in Relapsed/Refractory CLL

The administration of CD19-targeted chimeric antigen receptor (CD19 CAR) T-cells and concurrent ibrutinib was well-tolerated and yielded high response rates in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to findings from a pilot study (Blood. 2020;135[19]:1650-1660).

“Because preclinical studies showed that ibrutinib could improve CAR T cell-antitumor efficacy and reduce cytokine release syndrome (CRS), we conducted a pilot study to evaluate the safety and feasibility of administering ibrutinib concurrently with CD19 CAR T-cell immunotherapy,” wrote lead investigator Jordan Gauthier, MD, MSc, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, and colleagues.

Overall, 19 patients with CLL were included in the study (median prior therapies, 5), including 17 (89%) with high-risk cytogenetics (17p deletion and/or complex karyotype).

Patients being given ibrutinib were scheduled to initiate receipt of the drug ≥2 weeks before leukapheresis and continue receiving ibrutinib for ≥3 months after CAR-T cell infusion.

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

As per 2018 International Workshop on CLL criteria, the 4-week overall response rate was 83%, and 61% of patients achieved a minimal residual disease (MRD)-negative marrow response according to IGH sequencing. Probabilities of 1-year overall survival and progression-free survival (PFS) for this subset of patients were 86% and 59%, respectively.

Patients given CAR-T cells and concurrent ibrutinib had lower CRS severity and lower serum concentrations of CRS-associated cytokines than those not given ibrutinib, regardless of equivalent in vivo CAR-T cell expansion.

After receiving CD19 CAR T-cell therapy, evaluable patients who did and did not receive concurrent ibrutinib had 1-year PFS probabilities of 38% and 50%, respectively (P = .91).

“CD19 CAR T cells with concurrent ibrutinib for [relapsed or refractory] CLL were well tolerated, with low CRS severity, and led to high rates of MRD-negative response by IGH sequencing,” Dr Gauthier et al concluded.—Hina M. Porcelli