The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy 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.

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.


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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.

Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.

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.