Quisinostat, bortezomib, and dexamethasone combination therapy for relapsed multiple myeloma. Issue 7 (2nd July 2016)

• Record Type: Journal Article
• Authors: Moreau, Philippe; Facon, Thierry; Touzeau, Cyrille; Benboubker, Lotfi; Delain, Martine; Badamo-Dotzis, Julie; Phelps, Charles; Doty, Christopher; Smit, Hans; Fourneau, Nele; Forslund, Ann; Hellemans, Peter; Leleu, Xavier
• Is Part Of: Leukemia & lymphoma. Volume 57:Issue 7(2016:Jul.)
• Page Start: 1546
• Page End: 1559
• Publication Date: 2016-07-02
• Subjects: Bortezomib -- dexamethasone -- histone deacetylase inhibitor -- multiple myeloma -- quisinostat; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2015.1117611
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: The maximum tolerated dose (MTD) of quisinostat + bortezomib + dexamethasone in patients with relapsed multiple myeloma was evaluated in a phase-1b, open-label, multicenter, '3 + 3' dose-escalation study. Patients received escalating doses of oral quisinostat (6 mg [ n = 3], 8 mg [ n = 3], 10 mg [ n = 6], and 12 mg [ n = 6] on days 1, 3, and 5/week) plus subcutaneous bortezomib (1.3 mg/m 2 ) and oral dexamethasone (20 mg) in cycles of 21 (cycles 1–8) or 35 d (cycles 9–11) until MTD was determined. No dose-limiting toxicities were reported in 6/8 mg groups except ventricular fibrillation (Grade 4 cardiac arrest, n = 1 [10 mg] cycle 6) and clinically significant cardiac toxicities (Grade 3 QTc prolongation, Grade 3 atrial fibrillation, n = 2 [12 mg]). Thrombocytopenia ( n = 11), asthenia ( n = 10), and diarrhea ( n = 12) were most common adverse events. Overall, 88.2% patients achieved treatment response, median duration of response, and median progression-free survival were 9.4 and 8.2 months, respectively. The MTD of quisinostat was established as 10 mg thrice weekly oral dose with bortezomib + dexamethasone.