Lindsey E Roeker, Catherine C Coombs, Nirav N Shah, Wojciech Jurczak, Jennifer A Woyach, Chan Y Cheah, Krish Patel, Kami Maddocks, Yucai Wang, Pier Luigi Zinzani, Talha Munir, Youngil Koh, Meghan C Thompson, Catherine E Muehlenbein, Chunxiao Wang, Richard Sizelove, Sarang Abhyankar, Safarulla Hasanabba, Donald E Tsai, Toby A Eyre, Michael Wang
{"title":"在复发和/或难治性B细胞恶性肿瘤中延长帕托布替尼暴露期的安全性。","authors":"Lindsey E Roeker, Catherine C Coombs, Nirav N Shah, Wojciech Jurczak, Jennifer A Woyach, Chan Y Cheah, Krish Patel, Kami Maddocks, Yucai Wang, Pier Luigi Zinzani, Talha Munir, Youngil Koh, Meghan C Thompson, Catherine E Muehlenbein, Chunxiao Wang, Richard Sizelove, Sarang Abhyankar, Safarulla Hasanabba, Donald E Tsai, Toby A Eyre, Michael Wang","doi":"10.1159/000539587","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"1-17"},"PeriodicalIF":1.7000,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617602/pdf/","citationCount":"0","resultStr":"{\"title\":\"Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.\",\"authors\":\"Lindsey E Roeker, Catherine C Coombs, Nirav N Shah, Wojciech Jurczak, Jennifer A Woyach, Chan Y Cheah, Krish Patel, Kami Maddocks, Yucai Wang, Pier Luigi Zinzani, Talha Munir, Youngil Koh, Meghan C Thompson, Catherine E Muehlenbein, Chunxiao Wang, Richard Sizelove, Sarang Abhyankar, Safarulla Hasanabba, Donald E Tsai, Toby A Eyre, Michael Wang\",\"doi\":\"10.1159/000539587\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Pirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.</p>\",\"PeriodicalId\":6981,\"journal\":{\"name\":\"Acta Haematologica\",\"volume\":\" \",\"pages\":\"1-17\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617602/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Haematologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000539587\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Haematologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000539587","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Safety of Extended Pirtobrutinib Exposure in Relapsed and/or Refractory B-Cell Malignancies.
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.
期刊介绍:
''Acta Haematologica'' is a well-established and internationally recognized clinically-oriented journal featuring balanced, wide-ranging coverage of current hematology research. A wealth of information on such problems as anemia, leukemia, lymphoma, multiple myeloma, hereditary disorders, blood coagulation, growth factors, hematopoiesis and differentiation is contained in first-rate basic and clinical papers some of which are accompanied by editorial comments by eminent experts. These are supplemented by short state-of-the-art communications, reviews and correspondence as well as occasional special issues devoted to ‘hot topics’ in hematology. These will keep the practicing hematologist well informed of the new developments in the field.