Τίτλος:
Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by prior treatment
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Richardson, P.G.
Hungria, V.T.M.
Yoon, S.-S.
Beksac, M.
Dimopoulos, M.A.
Elghandour, A.
Jedrzejczak, W.W.
Guenther, A.
Na Nakorn, T.
Siritanaratkul, N.
Schlossman, R.L.
Hou, J.
Moreau, P.
Lonial, S.
Lee, J.H.
Einsele, H.
Sopala, M.
Bengoudifa, B.-R.
Corrado, C.
Binlich, F.
San-Miguel, J.F.
Περιοδικό:
Blood advances
Εκδότης:
American Society of Hematology
Λέξεις-κλειδιά:
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
DOI:
10.1182/blood-2015-09-665018
