@article{3001521,
    title = "Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by prior treatment",
    author = "Richardson, P.G. and Hungria, V.T.M. and Yoon, S.-S. and Beksac, M. and Dimopoulos, M.A. and Elghandour, A. and Jedrzejczak, W.W. and Guenther, A. and Na Nakorn, T. and Siritanaratkul, N. and Schlossman, R.L. and Hou, J. and Moreau, P. and Lonial, S. and Lee, J.H. and Einsele, H. and Sopala, M. and Bengoudifa, B.-R. and Corrado, C. and Binlich, F. and San-Miguel, J.F.",
    journal = "Blood advances",
    year = "2016",
    volume = "127",
    number = "6",
    pages = "713-721",
    publisher = "American Society of Hematology",
    doi = "10.1182/blood-2015-09-665018",
    keywords = "bortezomib;  dexamethasone;  lenalidomide;  panobinostat;  placebo;  thalidomide;  antineoplastic agent;  bortezomib;  dexamethasone;  hydroxamic acid;  indole derivative;  panobinostat, abdominal pain;  abnormal laboratory result;  acute kidney failure;  adult;  aged;  anemia;  Article;  asthenia;  brain hemorrhage;  cancer combination chemotherapy;  cancer survival;  cardiopulmonary insufficiency;  cerebrovascular accident;  constipation;  coughing;  decreased appetite;  diarrhea;  double blind procedure;  drug dose reduction;  drug efficacy;  drug safety;  fatigue;  female;  fever;  gastrointestinal hemorrhage;  heart infarction;  heart muscle ischemia;  human;  hypokalemia;  intestine ischemia;  leukopenia;  lung embolism;  lung hemorrhage;  lung infection;  lymphocytopenia;  major clinical study;  male;  multicenter study (topic);  multiple cycle treatment;  multiple myeloma;  nausea;  necrotizing fasciitis;  neutropenia;  outcome assessment;  peripheral edema;  peripheral neuropathy;  phase 3 clinical trial (topic);  pneumonia;  priority journal;  progression free survival;  respiratory failure;  sepsis;  septic shock;  thrombocytopenia;  treatment duration;  treatment response;  upper respiratory tract infection;  vomiting;  adjuvant chemotherapy;  clinical trial;  controlled study;  middle aged;  multicenter study;  multiple myeloma;  phase 3 clinical trial;  randomized controlled trial;  treatment outcome;  very elderly, Adult;  Aged;  Aged, 80 and over;  Antineoplastic Combined Chemotherapy Protocols;  Bortezomib;  Chemotherapy, Adjuvant;  Dexamethasone;  Female;  Humans;  Hydroxamic Acids;  Indoles;  Male;  Middle Aged;  Multiple Myeloma;  Treatment Outcome",
    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 refractoryMMin the phase 3PANORAMA1 trial. This subgroup analysis evaluated outcomes in patients in the PANORAMA 1 trial based on prior treatment: A prior immunomodulatory drug (IMiD; n 5 485), prior bortezomib plus an IMiD (n 5 193), and ≥2 prior regimens including bortezomib and an IMiD (n5147). 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."
}