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

Jesús F. San-Miguel, Vânia T M Hungria, Sung Soo Yoon, Meral Beksac, Meletios Athanasios Dimopoulos, Ashraf Elghandour, Wieslaw Wiktor Jedrzejczak, Andreas Günther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Paolo Corradini, Suporn Chuncharunee, Je Jung Lee, Robert L. Schlossman, Tatiana Shelekhova, Kwee Yong, Daryl Tan, Tontanai Numbenjapon, Jamie D. Cavenagh, Jian HouRichard LeBlanc, Hareth Nahi, Lugui Qiu, Hans Salwender, Stefano Pulini, Philippe Moreau, Krzysztof Warzocha, Darrell White, Joan Bladé, WenMing Chen, Javier de la Rubia, Peter Gimsing, Sagar Lonial, Jonathan L. Kaufman, Enrique M. Ocio, Ljupco Veskovski, Sang Kyun Sohn, Ming Chung Wang, Jae Hoon Lee, Hermann Einsele, Monika Sopala, Claudia Corrado, Bourras Rezki Bengoudifa, Florence Binlich, Paul G. Richardson

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Abstract

Background: Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Methods: PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1·3 mg/m2 on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators' assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308. Findings: 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6·47 months (IQR 1·81-13·47) in the panobinostat group and 5·59 months (2·14-11·30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11·99 months [95% CI 10·33-12·94] vs 8·08 months [7·56-9·23]; hazard ratio [HR] 0·63, 95% CI 0·52-0·76; p

Original languageEnglish
Pages (from-to)1195-1206
Number of pages12
JournalThe Lancet Oncology
Volume15
Issue number11
DOIs
Publication statusPublished - Oct 1 2014

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ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

San-Miguel, J. F., Hungria, V. T. M., Yoon, S. S., Beksac, M., Dimopoulos, M. A., Elghandour, A., Jedrzejczak, W. W., Günther, A., Nakorn, T. N., Siritanaratkul, N., Corradini, P., Chuncharunee, S., Lee, J. J., Schlossman, R. L., Shelekhova, T., Yong, K., Tan, D., Numbenjapon, T., Cavenagh, J. D., ... Richardson, P. G. (2014). 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. The Lancet Oncology, 15(11), 1195-1206. https://doi.org/10.1016/S1470-2045(14)70440-1