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

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

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Piperazines / administration & dosage
  • Prognosis
  • Pyrazoles / administration & dosage
  • Pyridines / administration & dosage
  • Pyrimidines / administration & dosage
  • Survival Rate

Substances

  • Piperazines
  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • ibrutinib
  • palbociclib

Associated data

  • ClinicalTrials.gov/NCT02159755