1. Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.
- Author
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Roeker, Lindsey E, Coombs, Catherine C, Shah, Nirav N, Jurczak, Wojciech, Woyach, Jennifer A, Cheah, Chan Y, Patel, Krish, Maddocks, Kami, Wang, Yucai, Zinzani, Pier Luigi, Munir, Talha, Koh, Youngil, Thompson, Meghan C, Muehlenbein, Catherine E, Wang, Chunxiao, Sizelove, Richard, Abhyankar, Sarang, Hasanabba, Safarulla, Tsai, Donald E, Eyre, Toby A, and Wang, Michael
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Patient Safety ,Infectious Diseases ,Cancer ,Clinical Trials and Supportive Activities ,Rare Diseases ,Hematology ,Clinical Research ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,B-cell malignancies ,Bruton tyrosine kinase inhibitor ,Long-term safety ,Toxicity ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - Abstract
IntroductionPirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.MethodsHere we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).ResultsOf 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy.ConclusionsPirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.
- Published
- 2024