CDK4 Inhibition With Palbociclib in MCL

Selina Chen-Kiang, PhD, professor of pathology and immunology, Weill Cornell Medicine, discusses CDK4 inhibition with palbociclib (Ibrance) in mantle cell lymphoma (MCL).

The CDK4/6 inhibitor palbociclib has been shown to overcome ibrutinib (Imbruvica) resistance in primary human samples and MCL cell lines with the mutated BTKC481S protein. Targeting CDK4 is a rational approach in MCL, says Chen-Kiang, as dysregulation of CDK4 and cyclin D1 underlies unrestrained proliferation of MCL cells.

In a phase I clinical trial of 6 patients, palbociclib was administered to patients with MCL for 12 days, and bortezomib (Velcade) was given in prolonged early G1 arrest after synchronous S phase reentry. One patient progressed and 1 patient has been in complete remission for 6 years, suggesting that CDK4 inhibition reprograms MCL for therapy vulnerability. The follow-up clinical trial combined palbociclib together with ibrutinib. The combination looked durable with low toxicity, and induced impressive complete responses by preliminary analysis, says Chen-Kiang.