Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by prior treatment

Paul G. Richardson, Vania T.M. Hungria, Sung Soo Yoon, Meral Beksac, Meletios Athanasios Dimopoulos, Ashraf Elghandour, Wieslaw W. Jedrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert L. Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Monika Sopala, Bourras Rezki Bengoudifa, Claudia Corrado, Florence BinlichJes̈us F. San-Miguel

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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.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalBlood
Volume127
Issue number6
DOIs
StatePublished - 11 Feb 2016

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Multiple Myeloma
Dexamethasone
Disease-Free Survival
Hazards
Confidence Intervals
Bortezomib
panobinostat
Placebos
Therapeutics
Asthenia
Growth Inhibitors
Lymphopenia
Neutropenia
Metabolism
Epigenomics
Thrombocytopenia
Fatigue
Diarrhea
Fatigue of materials

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Richardson, P. G., Hungria, V. T. M., Yoon, S. S., Beksac, M., Dimopoulos, M. A., Elghandour, A., ... San-Miguel, J. F. (2016). Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by prior treatment. Blood, 127(6), 713-721. https://doi.org/10.1182/blood-2015-09-665018
Richardson, Paul G. ; Hungria, Vania T.M. ; Yoon, Sung Soo ; Beksac, Meral ; Dimopoulos, Meletios Athanasios ; Elghandour, Ashraf ; Jedrzejczak, Wieslaw W. ; Guenther, Andreas ; Na Nakorn, Thanyaphong ; Siritanaratkul, Noppadol ; Schlossman, Robert L. ; Hou, Jian ; Moreau, Philippe ; Lonial, Sagar ; Lee, Jae Hoon ; Einsele, Hermann ; Sopala, Monika ; Bengoudifa, Bourras Rezki ; Corrado, Claudia ; Binlich, Florence ; San-Miguel, Jes̈us F. / Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma : Outcomes by prior treatment. In: Blood. 2016 ; Vol. 127, No. 6. pp. 713-721.
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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.",
author = "Richardson, {Paul G.} and Hungria, {Vania T.M.} and Yoon, {Sung Soo} and Meral Beksac and Dimopoulos, {Meletios Athanasios} and Ashraf Elghandour and Jedrzejczak, {Wieslaw W.} and Andreas Guenther and {Na Nakorn}, Thanyaphong and Noppadol Siritanaratkul and Schlossman, {Robert L.} and Jian Hou and Philippe Moreau and Sagar Lonial and Lee, {Jae Hoon} and Hermann Einsele and Monika Sopala and Bengoudifa, {Bourras Rezki} and Claudia Corrado and Florence Binlich and San-Miguel, {Jes̈us F.}",
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Richardson, PG, Hungria, VTM, Yoon, SS, Beksac, M, Dimopoulos, MA, Elghandour, A, Jedrzejczak, WW, Guenther, A, Na Nakorn, T, Siritanaratkul, N, Schlossman, RL, Hou, J, Moreau, P, Lonial, S, Lee, JH, Einsele, H, Sopala, M, Bengoudifa, BR, Corrado, C, Binlich, F & San-Miguel, JF 2016, 'Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by prior treatment', Blood, vol. 127, no. 6, pp. 713-721. https://doi.org/10.1182/blood-2015-09-665018

Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma : Outcomes by prior treatment. / Richardson, Paul G.; Hungria, Vania T.M.; Yoon, Sung Soo; Beksac, Meral; Dimopoulos, Meletios Athanasios; Elghandour, Ashraf; Jedrzejczak, Wieslaw W.; Guenther, Andreas; Na Nakorn, Thanyaphong; Siritanaratkul, Noppadol; Schlossman, Robert L.; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae Hoon; Einsele, Hermann; Sopala, Monika; Bengoudifa, Bourras Rezki; Corrado, Claudia; Binlich, Florence; San-Miguel, Jes̈us F.

In: Blood, Vol. 127, No. 6, 11.02.2016, p. 713-721.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma

T2 - Outcomes by prior treatment

AU - Richardson, Paul G.

AU - Hungria, Vania T.M.

AU - Yoon, Sung Soo

AU - Beksac, Meral

AU - Dimopoulos, Meletios Athanasios

AU - Elghandour, Ashraf

AU - Jedrzejczak, Wieslaw W.

AU - Guenther, Andreas

AU - Na Nakorn, Thanyaphong

AU - Siritanaratkul, Noppadol

AU - Schlossman, Robert L.

AU - Hou, Jian

AU - Moreau, Philippe

AU - Lonial, Sagar

AU - Lee, Jae Hoon

AU - Einsele, Hermann

AU - Sopala, Monika

AU - Bengoudifa, Bourras Rezki

AU - Corrado, Claudia

AU - Binlich, Florence

AU - San-Miguel, Jes̈us F.

PY - 2016/2/11

Y1 - 2016/2/11

N2 - 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.

AB - 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.

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