PANORAMA 2: A phase II study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma.

Abstract

8012 Background: Patients (pts) with multiple myeloma (MM) refractory to bortezomib (BTZ) and an immunomodulatory drug have limited treatment options and a poor prognosis. In a phase I study of pts with relapsed or relapsed/refractory MM treated with panobinostat (PAN) + BTZ, clinical responses were observed overall and in pts with BTZ-refractory disease. We report results in PANORAMA 2, a trial in relapsed and BTZ-refractory pts. Methods: PANORAMA 2 is a single-arm, phase II study of PAN + BTZ + dexamethasone (Dex) in pts with relapsed and BTZ-refractory MM. Treatment phase 1 (TP1) consists of eight 3-week cycles of oral PAN + intravenous BTZ + oral Dex. Pts demonstrating clinical benefit enter treatment phase 2 (TP2) which consists of four 6-week cycles of PAN + BTZ + Dex. The primary endpoint is overall response (≥ partial response [PR]) in TP1. Results: Fifty-five pts with BTZ-refractory MM were enrolled with 10 pts ongoing and 28 in follow-up. The median age was 61 years (range 41-88 years). Pts were heavily pretreated: the median number of prior regimens was 4 (range 2-11), and most pts (64%) received prior autologous stem cell transplant. Twenty-seven (49%) and 36 (65%) pts had BTZ and Dex in their most recent prior line of therapy, respectively. Eighteen pts achieved ≥ PR for an overall response rate of 33% (1 near complete response and 17 PR), and 13 pts achieved MR for a clinical benefit rate of 56%. Three pts achieved a VGPR. Eighteen pts completed TP1 and entered TP2, and 2 have completed ≥ 12 cycles. Common adverse events (AEs) of any grade included thrombocytopenia (66%), fatigue (64%), diarrhea (62%), nausea (58%), dyspnea (40%), anemia (38%), decreased appetite (36%), and dizziness (36%). Common grade 3/4 AEs included thrombocytopenia (58%), fatigue (17%), anemia (15%), pneumonia (15%), neutropenia (13%), and diarrhea (13%). Only 1 pt (2%) experienced grade 3/4 peripheral neuropathy. Conclusions: PAN synergizes with BTZ in recapturing responses in heavily pretreated, BTZ-refractory MM pts. The combination of PAN and BTZ is a promising treatment for pts with BTZ-refractory MM that is generally well tolerated, with several pts receiving therapy long term.