The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

The combination of chimeric antigen receptor (CAR) T-cell (CAR-T) therapy lisocabtagene maraleucel (liso-cel) and ibrutinib demonstrated antitumor activity with a tolerable safety profile, including low rates of grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity, among patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), according to the results of the phase 1 study presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

“Clinical trials with CD19-directed CAR T-cell therapy and ibrutinib suggested improved efficacy and reduced toxicity profile,” William G Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and presenter of the study, said. The purpose of this study was to evaluate such a combination among patients with relapsed/refractory CLL/SLL.


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The phase 1 study treated 19 patients with relapsed/refractory CLL/SLL with 2 different doses of liso-cel plus ibrutinib. All patients had received prior ibrutinib.  Lymphodepletion was performed with fludarabine and cyclophosphamide prior to treatment with liso-cel and ibrutinib. The present analysis included initial safety and preliminary efficacy data.

At baseline, the patient median age was 61 years. High-risk cytogenetics was present among 95% of patients, and the median number or prior therapies was 4 (range, 1-10). In addition to prior ibrutinib, 58% had received a prior Bruton tyrosine kinase (BTK) inhibitor and venetoclax.

The ORR was 95%, with all patients responding to the highest liso-cel dose, and 75% responding to the lower dose. Responses were ongoing for 89% of patients at 6-month follow-up. All responses occurred within 30 days after liso-cel infusion.

Among evaluable patients, 89% achieved undetectable minimal residual disease by flow cytometry of peripheral blood and 79% by next-generation sequencing analysis of bone marrow.

CAR T cells persisted for at least 6 months in 38% of patients and for at least 12 months among 20% of patients.

There were no dose-limiting toxicities. Neutropenia, anemia, and febrile neutropenia ere the most common grade 3 to 4 treatment-emergent adverse events (TEAEs). There were no grade 5 TEAEs. CRS developed among 74% of patients, with only 1 grade 3 event. There were 32% of patients who developed neurotoxicity, including 3 grade 3 to 4.

Treatment discontinuation due to TEAEs occurred among 21% of patients, and a dose reduction of ibrutinib was required among 11% of patients.

Dr Wierda concluded, “preliminary data show the tolerability and safety of liso-cel combined with ibrutinib for patients with relapsed or refractory CLL.” He added analyses of efficacy and safety of the liso-cel plus ibrutinib combination from this trial are ongoing.

Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.

Reference

Wierda WG, Dorritie KA, Munoz J, et al. Transcend CLL 004: phase 1 cohort of lisocabtagene maraleucel (liso-cel) in combination with ibrutinib for patients with relapsed/refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-9, 2020. Abstract 544.

This article originally appeared on Cancer Therapy Advisor