Addition of Panobinostat to Multiple Myeloma Regimen Improves Patient Response to Treatment

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.

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