An Expanded Treatment Protocol of Panobinostat Plus Bortezomib and Dexamethasone in Patients With Previously Treated Myeloma.

ABSTRACT

BACKGROUND: Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability. PATIENTS AND METHODS: In treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1.3 mg/m2 twice weekly with dexamethasone 20 mg on the days of and after bortezomib treatment. Patients with no change or better in treatment phase 1 proceeded to treatment phase 2, when bortezomib was reduced to once weekly. Unlike in the phase III trial, PANORAMA-1 (panobinostat or placebo with bortezomib and dexamethasone in patients with relapsed multiple myeloma), bortezomib could be administered either subcutaneously or intravenously. RESULTS: Thirty-nine patients with a median number of previous treatments of 4 (range, 1-12) were enrolled; most received subcutaneous bortezomib (87%). The overall response rate (partial response or better) was 56%. Grade 3/4 adverse events included thrombocytopenia (47%), fatigue (31%), dehydration (26%), and diarrhea (18%). Among the patients who received subcutaneous bortezomib, relatively low rates of peripheral neuropathy (all grade, 15%) and notable grade 3/4 adverse events (thrombocytopenia, 47%; diarrhea, 12%) were observed. CONCLUSION: Overall, data from the PANEX trial support regulatory approval of panobinostat plus bortezomib and dexamethasone and suggest the potential tolerability benefits of subcutaneous bortezomib in this regimen.