CAR T Cell/Ibrutinib Combination May Improve CLL Response Rates

Despite immune-related adverse events, concurrent ibrutinib and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy may improve response rates in patients with chronic lymphocytic leukemia (CLL), according to early results (abstract 7509) from a small study presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.

Among high-risk CLL patients on the combination, 89% had complete responses with minimal residual disease (MRD) negativity in the marrow, reported lead author Saar Gill, MD, PhD, of the University of Pennsylvania in Philadelphia, and colleagues.

Ten patients were included in the study. Eight of nine evaluable patients “have no CLL in the marrow by flow and/or MRD testing,” at a median follow-up of 6 months, they reported. “Radiologic responses are less clear-cut and may require longer follow-up.”

Nine patients developed cytokine release syndrome (grade 1/2 in eight patients and grade 3 in one patient). However, treatment was nevertheless “well tolerated,” the authors reported, noting that none of these patients required therapy for cytokine release syndrome. One patient developed grade 4 tumor lysis syndrome.

Alone, anti-CD19 CAR T-cell immunotherapy induces durable complete tumor responses in between 25% and 45% of patients with CLL, the authors noted. Preclinical research suggests possible synergism for this immunotherapy and ibrutinib. The authors sought to evaluate complete response rates for CLL patients treated with ibrutinib prior to and concurrent with anti-CD19 CAR T-cell immunotherapy.

Adult patients who had not achieved a complete response after 6 months or more of ibrutinib therapy were enrolled. Bendamustine or fludarabine and cyclophosphamide were used for lymphodepletion 1 week before treatment. Patients were administered CAR T cells and ibrutinib, and marrow CLL burden was measured with flow cytometry and next-generation deep sequencing for IGH gene rearrangement. Radiographic evaluations of lymph nodes and the spleen were conducted using computed tomography.

Five patients had complete responses in the spleen, and two patients each experienced partial responses and stable disease.

The team plans to treat 25 patients with the combination.

“Longer follow-up will reveal the durability of these results and could support evaluation of a first-line combination approach in an attempt to obviate the need for chronic therapy,” they reported.

Novartis funded the study.