Panobinostat plus bortezomib and dexamethasone in relapsed/relapsed and refractory myeloma: outcomes by prior treatment
Richardson PG (1), Hungria VT (2), Yoon SS (3), Beksac M (4), Dimopoulos MA (5), Elghandour A (6), Jedrzejczak WW (7), Guenther A (8), Na Nakorn T (9), Siritanaratkul N (10), Schlossman RL (11), Hou J (12), Moreau P (13), Lonial S (14), Lee JH (15), Einsele H (16), Sopala M (17), Bengoudifa BR (17), Corrado C (17), Binlich F (18), San-Miguel JF (19).
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 of patients in the PANORAMA 1 trial based on prior treatment: prior IMiD (n = 485); prior bortezomib plus IMiD (n = 193); and ≥ 2 prior regimens including bortezomib and an IMiD (n = 147). Median PFS for PAN-BTZ-Dex vs Pbo-BTZ-Dex across subgroups were as follows: prior IMiD (12.3 vs 7.4 months; hazard ratio [HR] 0.54; 95% 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 IMiD (regardless of number of prior regimens) were similar between treatment arms.
This analysis demonstrated a clear PFS benefit of 7.8 months for PAN-BTZ-Dex among patients who received ≥ 2 prior regimens including bortezomib and an IMiD, a population with limited treatment options and poorer prognosis.