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

Wang, ML; Jurczak, W; Zinzani, PL; Eyre, TA; Cheah, CY; Ujjani, CS; Koh, Y; Izutsu, K; Gerson, JN; Flinn, I; Tessoulin, B; Alencar, AJ; Ma, S; Lewis, D; Lech-Maranda, E; Rhodes, J; Patel, K; Maddocks, K; Lamanna, N; Wang, Y; Tam, CS; Munir, T; Nagai, H; Hernandez-Ilizaliturri, F; Kumar, A; Fenske, TS; Seymour, JF; Zelenetz, AD; Nair, B; Tsai, DE; Balbas, M; Walgren, RA; Abada, P; Wang, C; Zhao, J; Mato, AR; Shah, NN

Author(s): Wang, ML; Jurczak, W; Zinzani, PL; Eyre, TA; Cheah, CY; Ujjani, CS; Koh, Y; Izutsu, K; Gerson, JN; Flinn, I; Tessoulin, B; Alencar, AJ; Ma, S; Lewis, D; Lech-Maranda, E; Rhodes, J; Patel, K; Maddocks, K; Lamanna, N; Wang, Y; Tam, CS; Munir, T; Nagai, H; Hernandez-Ilizaliturri, F; Kumar, A; Fenske, TS; Seymour, JF; Zelenetz, AD; Nair, B; Tsai, DE; Balbas, M; Walgren, RA; Abada, P; Wang, C; Zhao, J; Mato, AR; Shah, NN;
Details: Publication Year 2023-08-20,Volume 41,Issue #24,Page 3988-3997
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: 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.
Publisher: American Society of Clinical Oncology
Keywords: Adult; Humans; Middle Aged; Aged; Aged, 80 and over; *Lymphoma, Mantle-Cell/drug therapy/pathology; Tyrosine Protein Kinase Inhibitors; Neoplasm Recurrence, Local/drug therapy; Protein Kinase Inhibitors/adverse effects
Department(s): Clinical Haematology
PubMed ID: 37192437
Publisher's Version: https://doi.org/10.1200/JCO.23.00562
Open Access at Publisher's Site: https://doi.org/10.1200/jco.23.00562
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-11-14 12:42:04

Last Modified: 2023-11-14 12:43:26