Page 100 - Haematologica Vol. 110 - January 2025

ARTICLE - Chronic Lymphocytic Leukemia
Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: results of the phase I/II BRUIN trial
Nirav N. Shah,1* Michael Wang,2* Lindsey E. Roeker,3 Krish Patel,4 Jennifer A. Woyach,5 William G. Wierda,6 Chaitra S. Ujjani,7 Toby A. Eyre,8 Pier Luigi Zinzani,9 Alvaro J. Alencar,10 Paolo Ghia,11,12 Nicole Lamanna,13 Marc S. Hoffmann,14 Manish R. Patel,15 Ian Flinn,16 James N. Gerson,17 Shuo Ma,18 Catherine C. Coombs,19 Chan Y. Cheah,20 Ewa Lech-Maranda,21 Bita Fakhri,22 Won Seog Kim,23 Minal A. Barve,24 Jonathon B. Cohen,25 Wojciech Jurczak,26 Talha Munir,27 Meghan C. Thompson,3 Donald E. Tsai,28 Katherine Bao,28 Nicholas A. Cangemi,28 Jennifer F. Kherani,28 Richard A. Walgren,28 Hongmei Han,28 Amy S. Ruppert29 and Jennifer R. Brown30
1Medical College of Wisconsin, Milwaukee, WI, USA; 2MD Anderson Cancer Center, Houston, TX, USA; 3Memorial Sloan Kettering Cancer Center, New York, NY, USA; 4Swedish Cancer Institute, Center for Blood Disorders and Cellular Therapy, Seattle, WA, USA; 5The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 6Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7University of Washington / Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 8Oxford University Hospitals NHS Foundation Trust, Churchill Cancer Center, Oxford, UK; 9Institute of Hematology “Seràgnoli” University of Bologna, Bologna, Italy; 10University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA; 11Università Vita-Salute San Raffaele, Milano, Italy; 12IRCCS Ospedale San Raffaele, Milano, Italy; 13New York-Presbyterian Columbia University Medical Center, New York, NY, USA; 14Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA; 15Florida Cancer Specialists / Sarah Cannon Research Institute, Sarasota, FL, USA; 16Sarah Cannon Research Institute, Nashville, TN, USA; 17Lymphoma Program, Abramson Cancer Center, Philadelphia, PA, USA; 18Robert H. Lurie Comprehensive Cancer Center, Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 19University of California Irvine, Irvine, CA, USA; 20Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia; 21Institute of Hematology and Transfusion Medicine, Warsaw, Poland; 22Division of Hematology at Stanford University School of Medicine, Stanford, CA, USA; 23Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 24Mary Crowley Cancer Research Center, Dallas, TX, USA; 25Winship Cancer Institute, Emory University, Atlanta, GA, USA; 26Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland; 27Department of Haematology, St. James’s University Hospital, Leeds, UK; 28Loxo@ Lilly, Indianapolis, IN, USA; 29Eli Lilly and Company, Indianapolis, IN, USA and 30Chronic Lymphocytic Leukemia Center, Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
*NNS and MW contributed equally as first authors.
Abstract
Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment of B-cell malignancies, but intolerance has often led to their discontinuation. The phase I/II BRUIN study evaluated pirtobrutinib, a highly selective non-covalent (reversible) BTKi, in patients with relapsed / refractory B-cell malignancies (clinicaltrials.gov 03740529). Pirtobrutinib was investigated in 127 patients with intolerance to at least one prior BTKi therapy in the absence of progressive disease. The most common adverse event (AE) leading to BTKi discontinuation was cardiac disorders (N=40, 31.5%), specifically atrial fibrillation (N=30, 23.6%). The median follow-up was 17.4 months and the median time on pirtobrutinib was 15.3 months. The most common
Haematologica | 110 January 2025
Correspondence: Nirav N. Shah nishah@mcw.edu
Received: Accepted: Early view:
April 26, 2024. September 27, 2024. October 3, 2024.
https://doi.org/10.3324/haematol.2024.285754
©2025 Ferrata Storti Foundation Published under a CC BY-NC license
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