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Purpose The long-term impact of thalidomide plus dexamethasone (thal/dex) as primary therapy for newly diagnosed multiple myeloma (MM) is unknown. The goal of this study was to compare thalidomide plus dexamethasone versus placebo plus dexamethasone (placebo/dex)as primary therapy for newly diagnosed MM. Patients and Methods In this double-blind, placebo-controlled trial, patients with untreated symptomatic MM were randomized to thal/dex (arm A) or to placebo plus dexamethasone (dex) (arm B). Patients in arm A received oral thalidomide 50 mg daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2 (28-day cycles). Oral dex 40 mg was administered on days 1 through 4, 9 through 12, and 17 through 20 during cycles 1 through 4 and on days 1 through 4 only from cycle 5 onwards. Patients in arm B received placebo and dex, administered as in arm A. The primary end point of the study was time to progression. This study is registered at http://ClinicalTrials.gov ( NCT00057564 ). Results A total of 470 patients were enrolled (235 randomly assigned to thal/dex and 235 to placebo/dex). The overall response rate was significantly higher with thal/dex compared with placebo/dex (63% v 46%), P < .001. Time to progression (TTP) was significantly longer with thal/dex compared with placebo/dex (median, 22.6 v 6.5 months, P < .001). Grade 4 adverse events were more frequent with thal/dex than with placebo/dex (30.3% v 22.8%). Conclusion Thal/dex results in significantly higher response rates and significantly prolongs TTP compared with dexamethasone alone in patients with newly diagnosed MM.

8575 Background: Panobinostat (PAN) is the first pan-deacetylase inhibitor (pan-DACi) to demonstrate a statistically significant and clinically relevant increase in median progression-free survival...

8526 Background: Panobinostat (PAN) is a potent pan-deacetylase inhibitor (pan-DACi) that targets key biological aberrations in multiple myeloma (MM), including epigenetics and protein metabolism. PAN + bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) led to a clinically relevant and statistically significant increase in progression-free survival (PFS) of ≈4 months compared with placebo + BTZ and Dex (Pbo-BTZ-Dex) in patients (pts) with relapsed or relapsed and refractory MM in the PANORAMA 1 phase 3 clinical trial. Methods: The study design was described previously (San-Miguel. Lancet Oncol. 2014;15:1195-206). For this subanalysis, pts who received prior BTZ and IMiDs (lenalidomide or thalidomide) were analyzed for outcomes and safety. Results: A total of 193 pts (25%) received prior BTZ and IMiDs (PAN-BTZ-Dex [n = 94] or Pbo-BTZ-Dex [n = 99]). Median PFS as determined by investigator assessment for the PAN arm was 10.6 mo (95% CI, 7.6-13.8) vs 5.8 mo (95% CI, 4.4-7.1) for the Pbo arm (HR 0.56 [95% ...

8510^ Background: Panobinostat (PAN) is a potent pan-deacetylase inhibitor that demonstrates synergistic antimyeloma activity when combined with bortezomib (BTZ) + dexamethasone (Dex). Early studie...

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.

TPS227 Background: The development of novel agents, including the proteasome inhibitor bortezomib (BTZ), has resulted in significant improvements in survival for patients (pts) with multiple myelom...