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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.

Author information

1
Meyer Cancer Center, Weill Cornell Medicine, New York, NY.
2
Department of Medicine, New York Presbyterian Hospital, New York, NY.
3
Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO.
4
The Ohio State University Comprehensive Cancer Center, Columbus, OH.
5
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and.
6
Department of Healthcare Policy and Research and.
7
Department of Pathology, Weill Cornell Medicine, New York, NY.

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 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 www.clinicaltrials.gov as #NCT02159755.

PMID:
30692121
PMCID:
PMC6418474
[Available on 2020-03-14]
DOI:
10.1182/blood-2018-11-886457

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