The multicenter, open-label, phase I/II MUK-six trial found that 91 percent of patients (n=42/46) with relapsed multiple myeloma (MM) who were treated with panobinostat in addition to a regimen of bortezomib, thalidomide, and dexamethasone achieved partial response or better (primary endpoint; 80% CI 83.4-96.2). Rakesh Popat, MD, and authors published the findings in The Lancet Haematology.
The study involved a rolling six-escalation design (defined as allowing for accrual of two to six patients concurrently onto a dose level in an effort to reduce the overall time to study completion) to determine the maximum-tolerated dose (MTD) of panobinostat. Patients received the following for sixteen 21-day cycles:
- subcutaneous bortezomib: 1.3 mg/m2 on days 1 and 8
- oral thalidomide: 100 mg daily
- dexamethasone: 20 mg on days 1, 2, 8, and 9
- panobinostat: 10, 15, or 20 mg on days 1, 3, 5, 8, 10, and 12
The recommended dose of panobinostat was 20 mg, though the MTD was not reached.
The most common grade ≥3 treatment-related adverse events (AEs) in the overall population (n=57) were neutropenia (26%), hypophosphatemia (19%), and thrombocytopenia (14%).
Forty-six cases of serious AEs were observed, 14 of which were deemed treatment-related.
Source: Popat R, Brown SR, Flanagan L, et al. Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): A multicentre, open-label, phase 1/2 trial. Lancet Haematol. 2016;3:e572-80.
