A phase I trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma.

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A phase I trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma.

Blood. 2019 Jan 28;:

Authors: Martin P, Bartlett NL, Blum KA, Park S, Maddocks K, Ruan J, Ridling L, Dittus C, Chen Z, Huang X, Inghirami G, DiLiberto M, Chen-Kiang S, Leonard JP

Abstract
Single-agent ibrutinib is active in patients with previously treated mantle cell lymphoma (MCL); however, nearly half of all patients experience treatment failure during the first year. We previously demonstrated that prolonged early G1 cell cycle arrest induced by the oral, specific CDK4/6 inhibitor palbociclib can overcome ibrutinib resistance in primary human MCL cells and MCL cell lines expressing wild-type BTK. Therefore, we conducted a phase I trial to evaluate the dosing, safety and preliminary activity of palbociclib plus ibrutinib in patients with previously treated mantle cell lymphoma (NCT02159755). From August 2014 to June 2016 a total of 27 patients (21 males, 6 females) were enrolled. The maximum tolerated doses were ibrutinib 560 mg daily plus palbociclib 100 mg days 1-21 of each 28-day cycle. The dose limiting toxicity was grade 3 rash. The most common grade 3-4 toxicities included neutropenia (41%), thrombocytopenia (30%), hypertension (15%), febrile neutropenia (15%), and lung infection (11%). The overall and complete response rates were 67% and 37%, and with a median follow-up of 25.6 months, the 2-year progression-free survival was 59.4% and the 2-year response duration was 69.8%. A phase II multicenter clinical trial to further characterize efficacy is now ongoing.

PMID: 30692121 [PubMed - as supplied by publisher]

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