Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma.

Autor:	Wang ML; MD Anderson Cancer Center, Houston, TX., Jurczak W; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland., Zinzani PL; IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia 'Seràgnoli,' Bologna, Italy.; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy., Eyre TA; Oxford University Hospitals NHS Foundation Trust, Churchill Cancer Center, Oxford, United Kingdom., Cheah CY; Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, WA, Australia.; Medical School, University of Western Australia, Perth, WA, Australia., Ujjani CS; Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington., Koh Y; Seoul National University Hospital, Seoul, Korea., Izutsu K; Department of Hematology, National Cancer Center Hospital, Tokyo, Japan., Gerson JN; University of Vermont, Burlington, VT., Flinn I; Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN., Tessoulin B; Haematology Department, University Hospital, Nantes, France., Alencar AJ; Sylvester Comprehensive Cancer Center, Miami, FL., Ma S; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL., Lewis D; Plymouth Hospitals NHS Trust-Derriford Hospital, Plymouth, United Kingdom., Lech-Maranda E; Institute of Hematology and Transfusion Medicine, Warsaw, Poland., Rhodes J; Donald and Barbara Zucker School of Medicine at Northwell/Hofstra, Uniondale, NY.; Northwell Health Cancer Institute Lake Success, New Hyde Park, NY., Patel K; Center for Blood Disorders and Cellular Therapy, Swedish Cancer Institute, Seattle, WA., Maddocks K; The Ohio State University Comprehensive Cancer Center, Columbus, OH., Lamanna N; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY., Wang Y; Division of Hematology, Mayo Clinic, Rochester, MN., Tam CS; Peter MacCallum Cancer Centre, Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia., Munir T; Department of Haematology, St James's University Hospital, Leeds, United Kingdom., Nagai H; Department of Hematology, National Hospital Organization Nagoya Medical Center, Aichi, Japan., Hernandez-Ilizaliturri F; Roswell Park Comprehensive Cancer Center, Buffalo, NY., Kumar A; Memorial Sloan Kettering Cancer Center, New York, NY., Fenske TS; Medical College of Wisconsin, Milwaukee, WI., Seymour JF; Peter MacCallum Cancer Centre, Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia., Zelenetz AD; Memorial Sloan Kettering Cancer Center, New York, NY., Nair B; Loxo@Lilly, Indianapolis, IN., Tsai DE; Loxo@Lilly, Indianapolis, IN., Balbas M; Loxo@Lilly, Indianapolis, IN., Walgren RA; Loxo@Lilly, Indianapolis, IN., Abada P; Loxo@Lilly, Indianapolis, IN., Wang C; Eli Lilly and Company, Indianapolis, IN., Zhao J; Loxo@Lilly, Indianapolis, IN., Mato AR; Memorial Sloan Kettering Cancer Center, New York, NY., Shah NN; Medical College of Wisconsin, Milwaukee, WI.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Aug 20; Vol. 41 (24), pp. 3988-3997. Date of Electronic Publication: 2023 May 16.
DOI:	10.1200/JCO.23.00562
Abstrakt:	Purpose: Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis. Methods: Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety. Results: The median patient age was 70 years (range, 46-87), the median prior lines of therapy was 3 (range, 1-8), 82.2% had discontinued a prior cBTKi because of disease progression, and 77.8% had intermediate- or high-risk simplified MCL International Prognostic Index score. The ORR was 57.8% (95% CI, 46.9 to 68.1), including 20.0% complete responses (n = 18). At a median follow-up of 12 months, the median DOR was 21.6 months (95% CI, 7.5 to not reached). The 6- and 12-month estimated DOR rates were 73.6% and 57.1%, respectively. In the MCL safety cohort (n = 164), the most common treatment-emergent adverse events (TEAEs) were fatigue (29.9%), diarrhea (21.3%), and dyspnea (16.5%). Grade ≥3 TEAEs of hemorrhage (3.7%) and atrial fibrillation/flutter (1.2%) were less common. Only 3% of patients discontinued pirtobrutinib because of a treatment-related adverse event. Conclusion: Pirtobrutinib is a first-in-class novel noncovalent (reversible) BTKi and the first BTKi of any kind to demonstrate durable efficacy after prior cBTKi therapy in heavily pretreated R/R MCL. Pirtobrutinib was well tolerated with low rates of treatment discontinuation because of toxicity.
Databáze:	MEDLINE
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