Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma.
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Wang Michael L, Jurczak Wojciech, Zinzani Pier Luigi, Eyre Toby A, Cheah Chan Y, Ujjani Chaitra S, Koh Youngil, Izutsu Koji, Gerson James N, Flinn Ian, Tessoulin Benoit, Alencar Alvaro J, Ma Shuo, Lewis David, Lech-Maranda Ewa, Rhodes Joanna, Patel Krish, Maddocks Kami, Lamanna Nicole, Wang Yucai, Tam Constantine S, Munir Talha, Nagai Hirokazu, Hernandez-Ilizaliturri Francisco, Kumar Anita, Fenske Timothy S, Seymour John F, Zelenetz Andrew D, Nair Binoj, Tsai Donald E, Balbas Minna, Walgren Richard A, Abada Paolo, Wang Chunxiao, Zhao Junjie, Mato Anthony R, Shah Nirav N
Аннотация
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.