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

Sebastian Grosicki, Maryana Simonova, Ivan Spicka, Ludek Pour, Iryrna Kriachok, Maria Gavriatopoulou , Halyna Pylypenko , Holger W Auner, Xavier Leleu, Vadim Doronin, Vadim Doronin, Ganna Usenko, Nizar J Bahlis, Roman Hajek, Reuben Benjamin, Tuphan K Dolai, Dinesh K Sinha, Christopher P Venner, Mamta Garg, Mercedes Gironella Artur Jurczyszyn , Pawel Robak, Monica Galli, Craig Wallington-Beddoe, Atanas Radinoff, Galina Salogub, Don A Stevens, Supratik Basu, Anna Liberati, Hang Quach, Vesselina S Goranova-Marinova , Jelena Bila, Eirini Katodritou , Hanna Oliynyk, Sybiryna Korenkova, Jeevan Kumar, Sundar Jagannath, Phillipe Moreau, Moshe Levy, Darrell White, Moshe E Gatt, Thierry Facon, Maria V Mateos, Michele Cavo, Donna Reece, Larry D Anderson Jr, Jean-Richard Saint-Martin, Jacqueline Jeha, Anita A Joshi, Yi Chai, Lingling Li, Vishnuvardhan Peddagali, Melina Arazy, Jatin Shah, Sharon Shacham, Michael G Kauffman, Meletios A Dimopoulos, Paul G Richardson, Sosana Delimpasi

Research output: Contribution to journalArticlepeer-review

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/m 2 once-weekly) and dexamethasone (20 mg twice-weekly) [SVd] or bortezomib (1·3 mg/m 2 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. Overall response rate (76·4% vs 62·3%, P=0·0012), and rates of very good partial response or better (44·6% vs 32·4%, P=0·0082) were higher with SVd. 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%, P=0.0010 and grade ≥2, 21·0% vs 34·3%, P=0.0013) were lower with SVd. There were 47 (24%) deaths on SVd and 61 (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.
Original languageEnglish
Pages (from-to)1563-1573
Number of pages11
JournalThe Lancet
Volume396
Issue number10262
DOIs
Publication statusPublished - 14 Nov 2020

Keywords

  • Multiple myeloma
  • Selinexor
  • Bortezomib
  • Dexamethasone
  • Patients
  • Treatment

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