panobinostat + carfilzomib

Panobinostat + carfilzomib is an investigational combination regimen for relapsed or refractory multiple myeloma that pairs the histone deacetylase inhibitor panobinostat with the second‑generation proteasome inhibitor carfilzomib to exploit synergistic cytotoxicity observed between HDAC inhibition and proteasome blockade. Panobinostat is a pan-HDAC inhibitor that increases acetylation of histones and other proteins, disrupting oncogenic signaling and the aggresome–proteasome protein degradation pathway; carfilzomib irreversibly inhibits the chymotrypsin-like activity of the 20S proteasome, inducing apoptosis in myeloma cells. Multiple phase I/II studies have reported that the doublet is tolerable and shows clinically meaningful responses in heavily pretreated RRMM, with common grade 3/4 toxicities including thrombocytopenia, fatigue, and gastrointestinal adverse events. Schedules explored include panobinostat given thrice weekly on intermittent cycles alongside carfilzomib on days 1, 2, 8, 9, 15, and 16 of 28‑day cycles, with objective response rates around 39–67% depending on cohort and the addition of dexamethasone.[1][2][3]

Other names

panobinostat and carfilzomibCarPan