Safety of extended pirtobrutinib exposure in relapsed and/or refractory B-cell malignancies Journal Article
| Authors: | Roeker, L. E.; Coombs, C. C.; Shah, N. N.; Jurczak, W.; Woyach, J. A.; Cheah, C. Y.; Patel, K.; Maddocks, K.; Wang, Y.; Zinzani, P. L.; Munir, T.; Koh, Y.; Thompson, M. C.; Muehlenbein, C. E.; Wang, C.; Sizelove, R.; Abhyankar, S.; Hasanabba, S.; Tsai, D. E.; Eyre, T. A.; Wang, M. |
| Article Title: | Safety of extended pirtobrutinib exposure in relapsed and/or refractory B-cell malignancies |
| Abstract: | INTRODUCTION: Pirtobrutinib, 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. METHODS: Here 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). RESULTS: Of 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. CONCLUSIONS: Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals. INTRODUCTION: Pirtobrutinib, 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. METHODS: Here 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). RESULTS: Of 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. CONCLUSIONS: Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals. © 2024 The Author(s). Published by S. Karger AG, Basel. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; clinical trial; protein kinase inhibitor; recurrence; pyrimidines; protein kinase inhibitors; b cell lymphoma; lymphoma, b-cell; pyrazole derivative; multicenter study; pyrazoles; recurrent disease; drug therapy; toxicity; pyrimidine derivative; b cell leukemia; bruton tyrosine kinase; leukemia, b-cell; long-term safety; very elderly; humans; human; male; female; agammaglobulinaemia tyrosine kinase; b-cell malignancies; bruton tyrosine kinase inhibitor; btk protein, human |
| Journal Title: | Acta Haematologica |
| Volume: | 148 |
| Issue: | 2 |
| ISSN: | 0001-5792 |
| Publisher: | S. Karger AG |
| Date Published: | 2025-03-01 |
| Start Page: | 180 |
| End Page: | 197 |
| Language: | English |
| DOI: | 10.1159/000539587 |
| PUBMED: | 38824917 |
| PROVIDER: | scopus |
| PMCID: | PMC11617602 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Lindsey Roeker -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work