title: 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.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.affiliation: Irmandade da Santa Casa de Misericordia de São Paulo, São Paulo, Brazil;
authors.forename: Vânia T M
authors.initials: VT
authors.lastname: Hungria
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea;
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Ankara University School of Medicine, Ankara, Turkey;
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.affiliation: National and Kapodistrian University of Athens, Athens, Greece;
authors.forename: Meletios Athanasios
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Alexandria University, Alexandria, Egypt;
authors.forename: Ashraf
authors.initials: A
authors.lastname: Elghandour
authors.affiliation: Medical University of Warsaw, Warsaw, Poland;
authors.forename: Wieslaw W
authors.initials: WW
authors.lastname: Jedrzejczak
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, University Hospital Schleswig-Holstein and University of Kiel, Kiel, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Guenther
authors.affiliation: King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand;
authors.forename: Thanyaphong Na
authors.initials: TN
authors.lastname: Nakorn
authors.affiliation: Siriraj Hospital, Bangkok, Thailand;
authors.forename: Noppadol
authors.initials: N
authors.lastname: Siritanaratkul
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schlossman
authors.affiliation: Chang Zheng Hospital, Shanghai, China;
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.affiliation: University Hospital of Nantes, Nantes, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA;
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.affiliation: Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Republic of Korea;
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany;
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Novartis Pharma AG, Basel, Switzerland;
authors.forename: Monika
authors.initials: M
authors.lastname: Sopala
authors.affiliation: Novartis Pharma AG, Basel, Switzerland;
authors.forename: Bourras-Rezki
authors.initials: BR
authors.lastname: Bengoudifa
authors.affiliation: Novartis Pharma AG, Basel, Switzerland;
authors.forename: Claudia
authors.initials: C
authors.lastname: Corrado
authors.affiliation: Novartis Pharma SAS, Rueil-Malmaison, France; and.
authors.forename: Florence
authors.initials: F
authors.lastname: Binlich
authors.affiliation: Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San-Miguel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000453:epidemiology; D000077767:Panobinostat; D016896:Treatment Outcome
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D000069286:Bortezomib; D003907:Dexamethasone; D000077767:Panobinostat