Analysis of outcomes based on response for patients with relapsed or relapsed and refractory multiple myeloma in the phase 3 PANORAMA 1 study.

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 (PFS) in patients (pts) with relapsed or relapsed and refractory multiple myeloma (MM) in a phase 3 clinical trial. In the PANORAMA 1 trial, pts randomized to receive PAN + bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) demonstrated a median PFS of 12.0 months vs 8.1 months for pts who received placebo + BTZ and Dex (Pbo-BTZ-Dex; HR, 0.63; P < .0001). Here, we present a detailed analysis of the effect of response on clinical outcomes. Methods: Response outcomes, including rate of near complete/complete response (nCR/CR) and duration of response (DOR), were analyzed. A landmarkanalysis at 6, 12, 18, and 24 weeks using a Cox regression model was conducted to determine PFS in pts who achieved nCR/CR or partial response (PR) per mEBMT and IMWG criteria. Results: The nCR/CR rate was significantly higher with PAN-BTZ-Dex vs Pbo-BTZ-Dex (27.6% vs 15.7%; P = .00006 post hoc testing).The DOR for pts with nCR/CR and PR was 18.4 and 9.0 months, respectively, in the PAN-BTZ-Dex arm and 14.5 and 8.8 months, respectively, in the Pbo-BTZ-Dex arm. The landmark analysis by mEBMT criteria at 12 weeks demonstrated a median PFS of 16.5 months for pts with CR/nCR and 10.3 months for pts with PR in the PAN-BTZ-Dex arm (HR, 0.40; 95%CI, 0.25-0.65) and a median PFS of 14.1 months for pts with CR/nCR and 9.7 months for pts with PR in the Pbo-BTZ-Dex arm (HR, 0.62; 95%CI, 0.36-1.07). By IMWG criteria, the landmark analysis at 12 weeks demonstrated a median PFS of 15.9 months for pts with ≥ very good PR (VGPR) and 8.1 months for pts with PR in the PAN-BTZ-Dex arm (HR, 0.36; 95%CI, 0.21-0.62) and a median PFS of 14.4 months for pts with ≥ VGPR and 7.6 months for pts with PR in the Pbo-BTZ-Dex arm (HR, 0.39; 95% CI, 0.22-0.68). Similar results were observed the other landmarks tested. Conclusions: A higher proportion of pts in the PAN-BTZ-Dex arm achieved higher-quality responses, which are associated with longer PFS. Overall, these data support achievement of higher-quality responses as a treatment goal in relapsed/refractory MM. Clinical trial information: NCT01023308.