@article {7094, title = {Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by prior treatment}, journal = {Blood}, volume = {127}, year = {2016}, note = {Cited By :18Export Date: 18 February 2017References: Kumar, S.K., Rajkumar, S.V., Dispenzieri, A., Improved survival in multiple myeloma and the impact of novel therapies (2008) Blood, 111 (5), pp. 2516-2520;Kumar, S.K., Dispenzieri, A., Lacy, M.Q., Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients (2014) Leukemia, 28 (5), pp. 1122-1128; Kumar, S.K., Lee, J.H., Lahuerta, J.J., Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study (2012) Leukemia, 26 (1), pp. 149-157. , International Myeloma Working Group; Atadja, P., Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges (2009) Cancer Lett, 280 (2), pp. 233-241; Hideshima, T., Richardson, P.G., Anderson, K.C., Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma (2011) Mol Cancer Ther, 10 (11), pp. 2034-2042; San-Miguel, J.F., Hungria, V.T., Yoon, S.S., Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: A multicentre, randomised, double-blind phase 3 trial (2014) Lancet Oncol, 15 (11), pp. 1195-1206; Blade, J., Samson, D., Reece, D., Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation (1998) Br J Haematol, 102 (5), pp. 1115-1123. , Myeloma Subcommittee of the EBMT. 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Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma (2005) Blood, 106 (12), pp. 3777-3784 }, month = {2016}, pages = {713 - 721}, 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 {\textdaggerdbl}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. {\textcopyright} 2016 by The American Society of Hematology.}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959357825\&doi=10.1182\%2fblood-2015-09-665018\&partnerID=40\&md5=b78bd086d16101d09f5bb27e5a444c69}, 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.} }