Title | A phase 1 trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Martin P, Bartlett NL, Blum KA, Park S, Maddocks K, Ruan J, Ridling LA, Dittus C, Chen Z, Huang X, Inghirami G, Diliberto M, Chen-Kiang S, Leonard JP |
Journal | Blood |
Volume | 133 |
Issue | 11 |
Pagination | 1201-1204 |
Date Published | 2019 03 14 |
ISSN | 1528-0020 |
Keywords | Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Female, Follow-Up Studies, Humans, Lymphoma, Mantle-Cell, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Recurrence, Local, Piperazines, Prognosis, Pyrazoles, Pyridines, Pyrimidines, Survival Rate |
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. |
DOI | 10.1182/blood-2018-11-886457 |
Alternate Journal | Blood |
PubMed ID | 30692121 |
PubMed Central ID | PMC6418474 |
Grant List | K24 CA201524 / CA / NCI NIH HHS / United States UM1 CA186712 / CA / NCI NIH HHS / United States |
Related Faculty:
Giorgio Inghirami, M.D. Selina Chen-Kiang, Ph.D.