1. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial
- Author
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Richardson, Paul G, Oriol, Albert, Beksac, Meral, Liberati, Anna Marina, Galli, Monica, Schjesvold, Fredrik, Lindsay, Jindriska, Weisel, Katja, White, Darrell, Facon, Thierry, San Miguel, Jesus, Sunami, Kazutaka, O'Gorman, Peter, Sonneveld, Pieter, Robak, Pawel, Semochkin, Sergey, Schey, Steve, Yu, Xin, Doerr, Thomas, Bensmaine, Amine, Biyukov, Tsvetan, Peluso, Teresa, Zaki, Mohamed, Anderson, Kenneth, Dimopoulos, Meletios, OPTIMISMM trial investigators, Abildgaard N, Adler H, Altuntas F, Akay OM, Amin B, Anagnostopoulos A, Anderson L, Anttila P, Araujo C, Arce-Lara C, Aydin Y, Basu S, Battini R, Beeker T, Benboubker L, Ben-Yehuda D, Bladé J, Blau IW, Boccia R, Burke L, Byeff P, Cascavilla N, Cavo M, Chantry A, Charles Y, Chaudhry A, Corso A, Coyne M, De Arriba F, Delimpasi S, Desjardins P, Dhakal B, Di Bartolomeo P, Di Raimondo F, Dürig J, Engelhardt M, Escoffre-Barbe M, Esteves G, Flogegard M, Gabrail N, Gamberi B, Garrison M, Gay J, Gisslinger H, Goldschmidt H, Goncalves C, Gressot L, Grosicki S, Hanna W, Hayden P, Henriques Bernardo MM, Hermann R, Holden V, Honkalehto K, Huben M, Huffman J, Hunter H, Hus M, Jagasia M, Jagganath S, Janakiram M, Jaiyesimi I, Jenner M, João C, Johnson P, Jurcyszyn A, Kalayoğlu Beşişik S, Kambhampati S, Kanate A, Karadoğan I, Khojasteh A, Kirkel D, Komarnicki M, Krauth MT, Kuriakose P, Larocca A, Lauri B, Leleu X, Lucio P, Luppi M, Mangiacavalli S, Mariette C, Matsue K, Mellqvist UH, Mendeleeva L, Meshad M, Miller C, Mohrbacher A, Moreau P, Morelli AM, Müldür E, Naassan A, Nahi H, Nair R, O'Dwyer M, Öngören Aydin S, Openshaw T, O'Rourke T, Osswald M, Overton L, Pati A, Pavic M, Pegourie B, Pehlivan M, Pierola AA, Plesner T, Pluta A, Rabin N, Ramasamy K, Rambaldi A, Rodriguez P, Röllig C, Rosenblatt J, Rosenbluth J, Salomo M, Samoylova O, Sastre Moral J, Sati H, Selleri C, Shafeek S, Shinagawa A, Sleckman B, Smith C, Sonmez M, Stone C, Streetly M, Suzuki K, Taetle R, Tafuri A, Takezako N, Teke HÜ, Vapaatalo M, Vassilopoulos G, Verma A, Vidito S, Viterbo L, Vural F, Wang XS, Yağci M, Yee A., Richardson, Paul G, Oriol, Albert, Beksac, Meral, Liberati, Anna Marina, Galli, Monica, Schjesvold, Fredrik, Lindsay, Jindriska, Weisel, Katja, White, Darrell, Facon, Thierry, San Miguel, Jesu, Sunami, Kazutaka, O'Gorman, Peter, Sonneveld, Pieter, Robak, Pawel, Semochkin, Sergey, Schey, Steve, Yu, Xin, Doerr, Thoma, Bensmaine, Amine, Biyukov, Tsvetan, Peluso, Teresa, Zaki, Mohamed, Anderson, Kenneth, Dimopoulos, Meletio, OPTIMISMM trial investigator, Abildgaard N, Adler H, Altuntas F, Akay OM, Amin B, Anagnostopoulos A, Anderson L, Anttila P, Araujo C, Arce-Lara C, Aydin Y, Basu S, Battini R, Beeker T, Benboubker L, Ben-Yehuda D, Bladé J, Blau IW, Boccia R, Burke L, Byeff P, Cascavilla N, Cavo M, Chantry A, Charles Y, Chaudhry A, Corso A, Coyne M, De Arriba F, Delimpasi S, Desjardins P, Dhakal B, Di Bartolomeo P, Di Raimondo F, Dürig J, Engelhardt M, Escoffre-Barbe M, Esteves G, Flogegard M, Gabrail N, Gamberi B, Garrison M, Gay J, Gisslinger H, Goldschmidt H, Goncalves C, Gressot L, Grosicki S, Hanna W, Hayden P, Henriques Bernardo MM, Hermann R, Holden V, Honkalehto K, Huben M, Huffman J, Hunter H, Hus M, Jagasia M, Jagganath S, Janakiram M, Jaiyesimi I, Jenner M, João C, Johnson P, Jurcyszyn A, Kalayoğlu Beşişik S, Kambhampati S, Kanate A, Karadoğan I, Khojasteh A, Kirkel D, Komarnicki M, Krauth MT, Kuriakose P, Larocca A, Lauri B, Leleu X, Lucio P, Luppi M, Mangiacavalli S, Mariette C, Matsue K, Mellqvist UH, Mendeleeva L, Meshad M, Miller C, Mohrbacher A, Moreau P, Morelli AM, Müldür E, Naassan A, Nahi H, Nair R, O'Dwyer M, Öngören Aydin S, Openshaw T, O'Rourke T, Osswald M, Overton L, Pati A, Pavic M, Pegourie B, Pehlivan M, Pierola AA, Plesner T, Pluta A, Rabin N, Ramasamy K, Rambaldi A, Rodriguez P, Röllig C, Rosenblatt J, Rosenbluth J, Salomo M, Samoylova O, Sastre Moral J, Sati H, Selleri C, Shafeek S, Shinagawa A, Sleckman B, Smith C, Sonmez M, Stone C, Streetly M, Suzuki K, Taetle R, Tafuri A, Takezako N, Teke HÜ, Vapaatalo M, Vassilopoulos G, Verma A, Vidito S, Viterbo L, Vural F, Wang XS, Yağci M, Yee A., and Hematology
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Population ,Dexamethasone ,Bortezomib ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,education ,Survival rate ,Lenalidomide ,Multiple myeloma ,Aged ,Salvage Therapy ,education.field_of_study ,business.industry ,Pomalidomide, bortezomib, dexamethasone ,Middle Aged ,Pomalidomide ,medicine.disease ,Prognosis ,Thalidomide ,Survival Rate ,Regimen ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Female ,Neoplasm Recurrence, Local ,business ,Multiple Myeloma ,030215 immunology ,medicine.drug ,Follow-Up Studies - Abstract
Background As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. Methods We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged >= 18 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of beta(2) microglobulin at screening. Bortezomib (1.3 mg/m(2)) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1,4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled. Findings Between Jan 7, 2013, and May 15,2017,559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15.9 months (IQR 9.9-21.7). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11.20 months [95% CI 9.66-13-73] vs 7.10 months [5.88-8-48]; hazard ratio 0.61, 95% CI 0.49-0-77; p
- Published
- 2019