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Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial
Grosicki, Sebastian Simonova, Maryana Spicka, Ivan Pour, Ludek Kriachok, Iryrna Gavriatopoulou, Maria Pylypenko, Halyna Auner, Holger W. Leleu, Xavier Doronin, Vadim
Grosicki, Sebastian
Simonova, Maryana
Spicka, Ivan
Pour, Ludek
Kriachok, Iryrna
Gavriatopoulou, Maria
Pylypenko, Halyna
Auner, Holger W.
Leleu, Xavier
Doronin, Vadim
Authors
Grosicki, Sebastian
Simonova, Maryana
Spicka, Ivan
Pour, Ludek
Kriachok, Iryrna
Gavriatopoulou, Maria
Pylypenko, Halyna
Auner, Holger W.
Leleu, Xavier
Doronin, Vadim
Usenko, Ganna
Bahlis, Nizar
Hajek, Roman
Benjamin, Reuben
Dolai, Tuphan K.
Sinha, Dinesh K
Venner, Christopher P.
Garg, Mamta
Gironella, Mercedes
Jurczyszyn, Artur
Robak, Pawel
Galli, Monica
Wallington-Beddoe, Craig
Radinoff, Atanas
Salogub, Galina
Stevens, Don A.
Basu, Supratik
Liberati, Anna M.
Quach, Hang
St Goranova-Marinova, Vesselina
Bila, Jelena
Katodritou, Eirini
Oliynyk, Hanna
Korenkova, Sybiryna
Kumar, Jeevan
Jagannath, Sundar
Moreau, Phillipe
Levy, Moshe
White, Darrell
Gatt, Moshe E.
Facon, Thierry
Mateos, Maria V.
Cavo, Michele
Reece, Donna
Anderson, Larry D.
Saint-Martin, Jean-Richard
Jeha, Jacqueline
Joshi, Anita A.
Chai, Yi
Li, Lingling
Peddagali, Vishnuvardhan
Arazy, Melina
Shah, Jatin
Shacham, Sharon
Kauffman, Michael G.
Dimopoulos, Meletios
Richardson, Paul G.
Delimpasi, Sosana
Simonova, Maryana
Spicka, Ivan
Pour, Ludek
Kriachok, Iryrna
Gavriatopoulou, Maria
Pylypenko, Halyna
Auner, Holger W.
Leleu, Xavier
Doronin, Vadim
Usenko, Ganna
Bahlis, Nizar
Hajek, Roman
Benjamin, Reuben
Dolai, Tuphan K.
Sinha, Dinesh K
Venner, Christopher P.
Garg, Mamta
Gironella, Mercedes
Jurczyszyn, Artur
Robak, Pawel
Galli, Monica
Wallington-Beddoe, Craig
Radinoff, Atanas
Salogub, Galina
Stevens, Don A.
Basu, Supratik
Liberati, Anna M.
Quach, Hang
St Goranova-Marinova, Vesselina
Bila, Jelena
Katodritou, Eirini
Oliynyk, Hanna
Korenkova, Sybiryna
Kumar, Jeevan
Jagannath, Sundar
Moreau, Phillipe
Levy, Moshe
White, Darrell
Gatt, Moshe E.
Facon, Thierry
Mateos, Maria V.
Cavo, Michele
Reece, Donna
Anderson, Larry D.
Saint-Martin, Jean-Richard
Jeha, Jacqueline
Joshi, Anita A.
Chai, Yi
Li, Lingling
Peddagali, Vishnuvardhan
Arazy, Melina
Shah, Jatin
Shacham, Sharon
Kauffman, Michael G.
Dimopoulos, Meletios
Richardson, Paul G.
Delimpasi, Sosana
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2020-11-14
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Abstract
Background Selinexor with dexamethasone has demonstrated activity in patients with heavily pretreated multiple myeloma (MM). In a phase 1b/2 study, the combination of oral selinexor with the proteasome inhibitor (PI) bortezomib, and dexamethasone (SVd) induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. The aim of this trial was to evaluate the clinical benefit of weekly SVd versus standard bortezomib and dexamethasone (Vd) in patients with previously treated MM. Methods This phase 3, randomised, open label trial was conducted at 123 sites in 21 countries. Patients who were previously treated with one to three lines of therapy, including PIs were randomised (1:1) to selinexor (100 mg once-weekly) plus bortezomib (1·3 mg/m2 once-weekly) and dexamethasone (20 mg twice-weekly) [SVd] or bortezomib (1·3 mg/m2 twice-weekly) and dexamethasone (20 mg 4 times per week) [Vd]. Randomisation was done using interactive response technology and stratified by previous PI therapy, lines of treatment, and MM stage. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. Findings Between June 2017 and February 2019, 402 patients were randomised: 195 to SVd and 207 to Vd. Median PFS was 13·93 (95% CI 11·73–NE) with SVd versus 9·46 months (8·11–10·78) with Vd; HR 0·70, [95% CI 0·53–0·93]; P=0.0075. Most frequent grade ≥3 adverse events (SVd vs Vd) were thrombocytopenia (77 [40%] vs 35 [17%]), fatigue (26 [13%] vs 2 [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy rates (overall, 32·3% vs 47·1%; OR 0·52, [95% CI 0·35-0·79]; P=0.0010 and grade ≥2, 21·0% vs 34·3%; OR 0·50, [95% CI 0·32-0·79]; P=0.0013) were lower with SVd. There were 47 (24%) deaths on SVd and 62 (30%) on Vd. Interpretation Once-weekly SVd is a novel, effective, and convenient treatment option for patients with MM who have received 1-3 prior therapies.
Citation
Grosicki, S., Simonova, M., Spicka, I. et al. (2020) Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label phase 3 trial, The Lancet, 396 (10262), pp. 1563-1573
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Journal article
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en
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This is an accepted manuscript of an article published by Elsevier in The Lancet.
The accepted version of the publication may differ from the final published version.
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0140-6736
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Karyopharm Therapeutics Inc.