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Blood. 2019 Mar 14;133(11):1201-1204. doi: 10.1182/blood-2018-11-886457. Epub 2019 Jan 28.

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

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Meyer Cancer Center, Weill Cornell Medicine, New York, NY.
Department of Medicine, New York Presbyterian Hospital, New York, NY.
Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO.
The Ohio State University Comprehensive Cancer Center, Columbus, OH.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and.
Department of Healthcare Policy and Research and.
Department of Pathology, Weill Cornell Medicine, New York, NY.


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 toxicity was 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. The current trial was registered at as #NCT02159755.

[Available on 2020-03-14]

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