The oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has become a mainstay in the treatment of mantle cell lymphoma (MCL), producing a response in nearly 70 percent of all patients. Yet, the majority of MCL patients treated with ibrutinib develop resistance to the drug within about a year.
Preclinical research conducted at Weill Cornell Medicine demonstrated that sustained inhibition of CDK4 (a protein that promotes growth of MCL cells) by the oral drug palbociclib can not only prevent proliferation of MCL cells, but also make them more sensitive to attack by ibrutinib.
Based on these findings, Weill Cornell Medicine and NewYork-Presbyterian Lymphoma Program Chief Dr. Peter Martin and colleagues initiated a phase I study of palbociclib plus ibrutinib (PALIBR) in patients with previously treated MCL. Results from the all-oral regimen were recently published online in the American Society of Hematology (ASH) Blood Journal.
The addition of palbociclib to ibrutinib appeared to produce deeper, more durable responses compared to what is traditionally produced by ibrutinib alone, with over half of all patients remaining free of disease progression at the two-year post-treatment mark. The most prevalent side effect was low blood counts.
“The first person to be treated on the study in August of 2014 achieved a complete response within three months and remains in a complete response today,” said Dr. Martin. “We were all excited by the results.”
Physicians and researchers at the Lymphoma Program look forward to learning more about the efficacy of PALIBR in the ongoing AFT-32 phase II trial, which incorporates genetic profiling that may help to identify the features associated with drug resistance.