Phase III study of panobinostat with bortezomib and dexamethasone in patients with relapsed multiple myeloma (PANORAMA 1).

e18572^ Background: Multiple myeloma (MM) is an incurable disease, and significant unmet need remains in the relapsed (Rel) and refractory (Ref) settings. Thus, effective agents and combination strategies are of continued interest. Clinical activity was observed in a phase Ib study of the novel pan-deacetylase inhibitor panobinostat (PAN) and the proteasome inhibitor bortezomib (BTZ) in patients (pts) with Rel or Rel/Ref MM. We report the results of a blinded safety analysis from PANORAMA 1, an international, randomized, double-blind, phase III study of PAN (or placebo) + BTZ + dexamethasone (Dex). Methods: Pts with Rel or Rel/Ref MM (1-3 prior lines of therapy) were enrolled. Pts with BTZ-ref MM were not eligible. The study was comprised of 2 treatment phases, and follow up was to be continued during and after treatment until progressive disease or relapse. Treatment phase 1 consisted of eight 3-week cycles of PAN or placebo administered thrice weekly and BTZ administered twice weekly for 2 weeks. Dex was administered on days of and after BTZ. Pts who achieved clinical benefit proceeded to treatment phase 2, which consisted of four 6-week cycles with BTZ and Dex administered at a reduced frequency. Results: Preliminary demographic and blinded safety data from 536 randomized pts were available with treatment ongoing in 257 pts (47.9%). Median age was 63 years (32-84 y). Approximately half of pts (51.7%) received 2-3 prior lines of therapy and 57.3% received prior stem cell transplant. Any-grade adverse events (AEs) included thrombocytopenia (47.6%), diarrhea (45.7%), fatigue (32.6%), anemia (30.5%), constipation (24.8%), and nausea (24.4%). Common grade 3/4 AEs were thrombocytopenia (36.2%), diarrhea (14.5%), anemia (13.0%), fatigue (12.2%), neutropenia (11.4%), and hypokalemia (11.0%). Of interest, peripheral neuropathy was observed in 24.6% at any grade and 5.3% at grade 3/4. Conclusions: Preliminary analysis in 525 pts treated in PANORAMA 1 demonstrated a comparable safety profile to clinical experience with BTZ + Dex. The data monitoring committee recommended the study continue as planned. Enrollment completion is anticipated for Feb 2012 (N = 762). Updated blinded safety data will be presented.