Panobinostat plus lenalidomide and dexamethasone phase I trial in multiple myeloma (MM)

8542 Background: Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), affecting with epigenetic and non-epigenetic pathways of cancer. In vivo experiments demonstrated potent MM cytotoxicity of the triplet panobinostat + lenalidomide + dexamethasone. Methods: Trial started with 5 mg panobinostat (po, TIW) combined with fixed doses of lenalidomide (25 mg po, QD, Days 1–21) and dexamethasone (40 mg po, Days 1–4, 9–12, 17–20, Cycles 1–4), in a 28-day cycle. MTD of panobinostat in this combination for second-line MM will be established based on data from cohorts of ≥6 evaluable patients (pts). Safety, tolerability, PK/PD, and preliminary efficacy will be assessed. Results: Twenty-two pts with relapsed or relapsed refractory MM were treated in three dose levels to date. Dose escalation started at 5 mg panobinostat (po, thrice weekly) combined with fixed doses of 25 mg lenalidomide (po, qd, Days 1–21) and 40 mg of dexamethasone (po, Days 1–4, 9–12, 17–20, Cycles 1–4), in a 28-day cycle...