A phase I/II trial of melphalan (MEL) combined with panobinostat (PAN) for patients with relapsed or refractory (R/R) multiple myeloma (MM).

• DOI: 10.1200/jco.2012.30.15_suppl.e18558
• Publication Date: 2020-03-11T15:23:35Z
• Authors: Ori Yellin; James R. Berenson; Ralph V. Boccia; Allen Lee Cohn; Paul Berard; Hassan Ghazal; Saad Jamshed; Edwin Kingsley; Wael A. Harb; Stephen J. Noga; Youram Nassir; Regina A. Swift; Robert A. Vescio
• Keywords: Panobinostat; Melphalan; Refractory (planetary science)

e18558 Background: PAN, a potent histone deacetylase inhibitor, significantly inhibits the growth of MM cells in vitro and enhances cytotoxicity standard chemotherapy. Studies with our SCID-hu models show an increased inhibition cell when PAN was combined MEL compared to treatment either drug alone. These preclinical studies provided rationale for evaluating combination oral patients R/R disease. Methods: This Phase 1/2, open-label, dose‑escalation study treat initially using every Monday, Wednesday Fridayin (0.05 mg/kg) on days 1-5 28‑day cycle. Results: Thirty-seven were enrolled into 1 portion this study. The median number prior regimens received 4 (range, 1-17) 22 previously treated MEL. Following amendments dose schedule because toxicity including cytopenias fatigue, both administered only 1, 3 5 28-day maximum tolerated defined as at 20 mg 0.05 mg/kg 5. Overall, (11%) showed objective responses complete (3%) partial (8%) occurred among receiving throughout An additional 18 (49%) had stable disease while 15 (41%) progressed Eighteen experienced grade or adverse events (AEs) 6 these meeting definition dose-limiting toxicity. AEs included reversible thrombocytopenia (n=11), neutropenia (n=10), worsening anemia (n=3), one case each forearm rash, fatigue/weakness, pneumonia, hypokalemia hyponatremia. Three more who are not yet evaluable have been 2 planned 40 trial. Conclusions: intermittent & low-dose shows modest activity heavily pretreated MM. Continuous doses yielded better efficacy but tolerable.