Palbociclib combined with ibrutinib in patients with previously treated mantle cell lymphoma (MCL) showed an overall response rate of 67% and a complete response rate of 37% after median follow-up of more than 2 years (25.6 months) in a phase 1 trial (ClinicalTrials.gov Identifier: NCT02159755). The trial assessed dosing, safety, and preliminary activity of the combination, and its results were published in Blood.
Although the Bruton’s tyrosine kinase inhibitor ibrutinib has shown activity in patients with previously treated MCL, approximately half of all patients will experience treatment failure within the first year. Previous research in cell cultures and primary human MCL cells indicated that the CDK4/6 inhibitor palbociclib could overcome resistance to ibrutinib.
This phase 1 trial investigating the combination of palbociclib with ibrutinib in patients with previously treated MCL enrolled 27 patients between August 2014 and June 2016. The maximum tolerated doses (MTD) were palbociclib 100 mg on days 1 to 21 of a 28 day cycle and ibrutinib 560 mg daily. The median number of cycles administered was 15 (range, 1-51).
Response to treatment was seen in 18 patients. The 2-year progression-free survival was 59.4% (95% confidence interval [CI], 37.9%-80.9%), and the 2-year duration of response was 69.8%. The 2-year overall survival was 60.6% (95% CI, 41.1%-80.1%).
Grade 3 rash was the dose-limiting toxicity, and the most common grade 3 and 4 adverse events were neutropenia (41%), thrombocytopenia (30%), hypertension (15%), febrile neutropenia (15%), and lung infection (11%).
The authors noted that a phase 2 multicenter trial further evaluating efficacy of palbociclib with ibrutinib in patients with previously treated MCL is ongoing (ClinicalTrials.gov Identifier: NCT03478514).
1. Martin P, Bartlett NL, Blum KA, et al. A phase I trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma [published online January 28, 2019]. Blood. doi: 10.1182/blood-2018-11-886457