A phase 1 trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma

Peter Martin, Nancy L. Bartlett, Kristie A. Blum, Steven Park, Kami Maddocks, Jia Ruan, Le Ann Ridling, Christopher Dittus, Zhengming Chen, Xiangao Huang, Giorgio Inghirami, Maurizio DiLiberto, Selina Chen-Kiang, John P. Leonard

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


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 Bruton's tyrosine kinase (BTK). Therefore, we conducted a phase 1 trial to evaluate the dosing, safety, and preliminary activity of palbociclib plus ibrutinib in patients with previously treated mantle cell lymphoma. From August 2014 to June 2016, a total of 27 patients (21 men, 6 women) were enrolled. The maximum tolerated doses were ibrutinib 560 mg daily plus palbociclib 100 mg on days 1 to 21 of each 28-day cycle. The dose-limiting toxicitywas grade 3 rash. The most common grade 3 to 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 2 multicenter clinical trial to further characterize efficacy is now ongoing.

Original languageEnglish
Pages (from-to)1201-1204
Number of pages4
Issue number11
StatePublished - 2019


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