Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma.

8510^ Background: Panobinostat (PAN) is a potent pan-deacetylase inhibitor that demonstrates synergistic antimyeloma activity when combined with bortezomib (BTZ) + dexamethasone (Dex). Early studies demonstrated durable responses in patients (pts) with relapsed (Rel) and relapsed/refractory (RR) multiple myeloma (MM) treated with PAN + BTZ + Dex. This initiated the PANORAMA 1 study, presented herein. Methods: Eligible pts had Rel or RR (excluding BTZ- and primary-ref MM) following 1-3 prior regimens. Pts received oral PAN (20 mg) or placebo (pbo) 3 ×/wk + IV BTZ (1.3 mg/m2; D 1, 4, 8, 11) during wks 1-2 with oral Dex (20 mg) on the days of and after BTZ in treatment phase (TP) 1, eight 3 wk cycles. Pts demonstrating benefit could proceed to TP2, with PAN dosing maintained and BTZ/Dex less frequent. The primary endpoint was progression free survival (PFS) with response assessed by modified EBMT criteria. Other endpoints included overall survival (OS), overall response rate (ORR), near complete/complete response (nCR/CR) rate, duration of response (DOR), and safety. PFS/ORR was confirmed by an independent review committee. Results: A total of 768 pts (PAN + BTZ + Dex [n = 387]; pbo + BTZ + Dex [n = 381]) were randomized. Median age was 63 y (42% ≥ 65 y) and 48% received ≥ 2 prior regimens. Prior therapies included BTZ (43%), thalidomide (51%), lenalidomide (20%), and 25% received both prior BTZ + IMiDs. The primary endpoint was met with median PFS of 12 mo vs 8.1 mo (P < .0001; HR 0.63, 95% CI [0.52, 0.76]) for pts treated on the PAN vs pbo arm. In the PAN and pbo arms, ORR was 61% vs 55% and nCR/CR rate was 28% vs 16%, with DOR of 13.1 mo vs 10.9 mo, respectively. OS data is not mature. Adverse events (AEs) led to discontinuation in 36% in the PAN arm and 20% in the pbo arm. Common grade 3/4 lab abnormalities and AEs (regardless of study drug relationship) in the PAN vs pbo arms included thrombocytopenia (67% vs 31%), neutropenia (35% vs 11%), and diarrhea (26% vs 8%); these were generally manageable with dose reduction/supportive care. On-treatment deaths occurred in 8% and 5%, respectively. Conclusions: PAN + BTZ/Dex significantly improves PFS in pts with Rel or RR MM, with manageable toxicity. Clinical trial information: NCT01023308.