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

• Published in: Blood Vol. 127; no. 6; pp. 713 - 721
• Main Authors: Richardson, Paul G., Hungria, Vânia T.M., Yoon, Sung-Soo, Beksac, Meral, Dimopoulos, Meletios Athanasios, Elghandour, Ashraf, Jedrzejczak, Wieslaw W., Guenther, Andreas, Nakorn, Thanyaphong Na, Siritanaratkul, Noppadol, Schlossman, Robert L., Hou, Jian, Moreau, Philippe, Lonial, Sagar, Lee, Jae Hoon, Einsele, Hermann, Sopala, Monika, Bengoudifa, Bourras-Rezki, Corrado, Claudia, Binlich, Florence, San-Miguel, Jesús F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.02.2016; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bortezomib - administration & dosage; Chemotherapy, Adjuvant; Clinical Trials and Observations; Dexamethasone - administration & dosage; Female; Humans; Hydroxamic Acids - administration & dosage; Indoles - administration & dosage; Male; Middle Aged; Multiple Myeloma - drug therapy; Multiple Myeloma - epidemiology; Panobinostat; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-09-665018

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. •Benefit from panobinostat-dexamethasone-bortezomib was greatest in patients who received ≥2 prior regimens including bortezomib and IMiDs.