Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial

摘要: Summary Background Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, dexamethasone placebo, patients relapsed or refractory multiple myeloma. Methods PANORAMA1 multicentre, randomised, placebo-controlled, double-blind phase 3 trial of myeloma who have received between one three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based voice response system, stratified by number lines use receive 21 day cycles placebo panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both combination (1·3 mg/m 2 4, 11, intravenously) mg 2, 9, orally). Patients, physicians, the investigators did data analysis masked allocation; crossover was not permitted. The primary endpoint progression-free survival (in accordance modified European Group for Blood Marrow Transplantation criteria based investigators' assessment) analysed intention treat. study ongoing, but no longer recruiting, registered at ClinicalTrials.gov, NCT01023308. Findings 768 enrolled Jan 21, 2010, Feb 29, 2012, 387 381 Median follow-up 6·47 months (IQR 1·81–13·47) group 5·59 (2·14–11·30) group. significantly than (11·99 [95% CI 10·33–12·94] vs 8·08 [7·56–9·23]; hazard ratio [HR] 0·63, 95% 0·52–0·76; p 208 [54·6%, 49·4–59·7] placebo; p=0·09); however, proportion complete near higher (107 [27·6%, 23·2–32·4] 60 [15·7%, 12·2–19·8]; p=0·00006). Minimal responses noted 23 (6%) 42 (11%) duration (partial better) 13·14 (95% 11·76–14·92) 10·87 (9·23–11·76) group, median time 1·51 (1·41–1·64) 2·00 (1·61–2·79) Serious adverse events reported 228 (60%) 157 (42%) 377 Common grade 3–4 laboratory abnormalities (irrespective association drug) included thrombocytopenia (256 [67%] 118 [31%] group), lymphopenia (202 [53%] 150 [40%]), diarrhoea (97 [26%] 30 [8%]), asthenia fatigue (91 [24%] 45 [12%]), peripheral neuropathy (67 [18%] 55 [15%]). Interpretation Our results suggest could be useful addition armamentarium Longer follow up will necessary determine whether there any effect overall survival. Funding Novartis Pharmaceuticals.