MCL Patients Respond to CDK4/6 Inhibition Available to Purchase

Mantle cell lymphoma (MCL) is a poor-prognosis subtype of B-cell lymphoma molecularly characterized by an oncogenic t(11;14) translocation that causes aberrant cyclin D1 expression. Mechanistically, cyclin D1 complexes with cyclin-dependent kinases (CDK) 4 and 6 to phosphorylate the retinoblastoma protein (RB) and drive cell-cycle progression. Leonard and colleagues performed a multicenter phase Ib study of the CDK4/6 inhibitor PD0332991 in 17 relapsed MCL patients, using positron emission tomography (PET) and immunohistochemical assessment of RB phosphorylation in lymph node biopsies to measure pharmacodynamic tumor responses at baseline and during the first month of treatment. PD0332991 treatment resulted in an objective response rate of 18%, with 1 complete response and 2 partial responses. Seven additional patients achieved stable disease, and 5 patients achieved more than 1 year of progression-free survival. PET scanning with 2-deoxy-2-[¹⁸F]fluoro-D-glucose showed a metabolic response in 7 patients, and 3-deoxy-3[¹⁸F]fluorothymidine-PET scanning demonstrated a proliferative response...