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Jennifer R. Brown, MD, PhD


Addition of Novel BTK Inhibitor Pirtobrutinib to Combination Therapy May Improve Resistant CLL

By: Joshua D. Madera, MS
Posted: Wednesday, May 4, 2022

For patients with relapsed or refractory chronic lymphocytic leukemia (CLL), combination treatment with the non-covalent Bruton’s tyrosine kinase (BTK) inhibitor pirtobrutinib and venetoclax was well tolerated without any additional toxicity, according to the phase I/II BRUIN study presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 138/5). These benefits occurred whether rituximab was added to the treatment regimen or not, explained Lindsey E. Roeker, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues.

A total of 25 patients with advanced B-cell malignancies were recruited for the study. Patients received six cycles of therapy with either pirtobrutinib plus venetoclax (n = 15) or pirtobrutinib plus venetoclax and rituximab (n = 10). No patients had a history of treatment with venetoclax. However, most patients had received prior treatment with a CD20 monoclonal antibody (n = 18), chemotherapy (n = 14), or treatment with covalent BTK inhibitors (n = 17).

The study findings did not reveal any dose-limiting toxicities in either treatment group. The most common adverse effects reported across both treatment groups were decreased neutrophil count (36%), fatigue (32%), nausea (32%), diarrhea (28%), and constipation (24%). In addition, there was one reported case of tumor-lysis syndrome with acute kidney injury during the escalation of venetoclax dosage. Furthermore, the overall risk ratio was 95.5%, and the median duration of follow-up was 9 months.

Disclosures: For full disclosures of the study authors, visit

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