Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment

Abstract

Panobinostat is a potent pan-deacetylase inhibitor that affects the growth and survival of multiple myeloma (MM) cells through alteration of epigenetic mechanisms and protein metabolism. Panobinostat plus bortezomib and dexamethasone (PAN-BTZ-Dex) led to a significant increase in progression-free survival (PFS) vs placebo plus bortezomib and dexamethasone (Pbo-BTZ-Dex) in patients with relapsed or relapsed and refractory MM in the phase 3 PANORAMA 1 trial. This subgroup analysis evaluated outcomes in patients in the PANORAMA 1 trial based on prior treatment: a prior immunomodulatory drug (IMiD; n = 485), prior bortezomib plus an IMiD (n = 193), and ≥2 prior regimens including bortezomib and an IMiD (n = 147). Median PFS with PAN-BTZ-Dex vs Pbo-BTZ-Dex across subgroups was as follows: prior IMiD (12.3 vs 7.4 months; hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.43-0.68), prior bortezomib plus IMiD (10.6 vs 5.8 months; HR, 0.52; 95% CI, 0.36-0.76), and ≥2 prior regimens including bortezomib and an IMiD (12.5 vs 4.7 months; HR, 0.47; 95% CI, 0.31-0.72). Common grade 3/4 adverse events and laboratory abnormalities in patients who received PAN-BTZ-Dex across the prior treatment groups included thrombocytopenia, lymphopenia, neutropenia, diarrhea, and asthenia/fatigue. Incidence of on-treatment deaths among patients who received prior bortezomib and an IMiD (regardless of number of prior regimens) was similar between treatment arms. This analysis demonstrated a clear PFS benefit of 7.8 months with PAN-BTZ-Dex among patients who received ≥2 prior regimens including bortezomib and an IMiD, a population with limited treatment options and poorer prognosis. This trial was registered at www.clinicaltrials.gov as #NCT01023308.

© 2016 by The American Society of Hematology.

Figures

Figure 1

PFS based on prior treatment. Kaplan-Meier analysis of PFS for each prior treatment subgroup. (A) Kaplan-Meier analysis of PFS among patients who received prior treatment with an IMiD. (B) Kaplan-Meier analysis of PFS among patients who received prior treatment with bortezomib and an IMiD. (C) PFS among patients who received ≥2 prior regimens including bortezomib and an IMiD.

Figure 2

Response rate based on prior treatment. Response rate as demonstrated by ORR and nCR/CR is shown for each treatment arm, PAN-BTZ-Dex and Pbo-BTZ-Dex, and for each prior treatment subgroup analyzed: prior treatment with an IMiD, prior treatment with bortezomib and an IMiD, and patients who received ≥2 prior regimens including bortezomib and an IMiD. Statistical analyses were conducted for comparison of ORR between treatment arms.

Figure 3

TFI by prior treatment. TFIs determined by subtracting the mean treatment duration from the mean PFS. TFIs are shown for each treatment arm for the overall treatment population and each prior treatment subgroup.