TY - JOUR
TI - Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by prior treatment
AU - Richardson, P.G.
AU - Hungria, V.T.M.
AU - Yoon, S.-S.
AU - Beksac, M.
AU - Dimopoulos, M.A.
AU - Elghandour, A.
AU - Jedrzejczak, W.W.
AU - Guenther, A.
AU - Na Nakorn, T.
AU - Siritanaratkul, N.
AU - Schlossman, R.L.
AU - Hou, J.
AU - Moreau, P.
AU - Lonial, S.
AU - Lee, J.H.
AU - Einsele, H.
AU - Sopala, M.
AU - Bengoudifa, B.-R.
AU - Corrado, C.
AU - Binlich, F.
AU - San-Miguel, J.F.
JO - Blood advances
PY - 2016
VL - 127
TODO - 6
SP - 713-721
PB - American Society of Hematology
SN - null
TODO - 10.1182/blood-2015-09-665018
TODO - 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
TODO - 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.
ER -