Dr. Martin on Ibrutinib/Palbociclib Combo in Ibrutinib-Resistant MCL

Peter Martin, MD, associate professor of medicine, chief, the Lymphoma Program, Meyer Cancer Center, Weill Cornell Medicine, discusses a phase I trial examining the ibrutinib (Imbruvica) plus palbociclib (Ibrance) combination in ibrutinib-resistant patients with mantle cell lymphoma (MCL).

While looking at cells belonging to patients who were resistant to ibrutinib, Martin and his colleagues found that some of the active pathways were passing the BTK blockade. The study exposed those ibrutinib-resistant cells to palbociclib, a CDK4/6 inhibitor, which does not have significant single-agent activity. However, the cells that had a cell-cycle arrest due to palbociclib were subsequently sensitized to killing ibrutinib, allowing the ibrutinib-resistant cells to be resensitized to ibrutinib, explains Martin.

Overall, the phase I trial showed the combination was well-tolerated in patients with MCL. There was more myelosuppression, which is expected with palbociclib, says Martin. There also might be some immunological adverse events, such as rash. About 30% of patients were not responsive to the ibrutinib/palbociclib combination, according to Martin. Those patients who were likely to be refractory to ibrutinib were still refractory to a combination of ibrutinib/palbociclib, whereas the patients who were sensitive to ibrutinib had a rapid and deep response, concludes Martin.