Overall survival with oral selinexor plus low-dose dexamethasone versus real-world therapy in triple-class-refractory multiple myeloma.

• Type of Material: Article
• Authors: Paul G Richardson, Jerome Lipper Multiple Myeloma Center Department of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School Boston Massachusetts.; Sundar Jagannath, Mount Sinai Medical Center New York New York.; Ajai Chari, Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York New York.; Dan T Vogl, Abramson Cancer Center University of Pennsylvania Philadelphia Pennsylvania.; Meletios A Dimopoulos, National and Kapodistrian University of Athens School of Medicine Athens Greece.; Philippe Moreau, CHU de Nantes-Hôtel Dieu Nantes France.; David Dingli, Mayo Clinic Rochester Minnesota.; Lee-Jen Wei, Harvard T.H. Chan School of Public Health Boston Massachusetts.; Joshua Richter, Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack New Jersey.; Noa Biran, Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack New Jersey.; David Siegel, Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack New Jersey.; William Reichmann, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Lingling Li, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Shijie Tang, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Jean-Ricjard Saint-Martin, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Anita Joshi, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Michael Kauffman, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Jatin Shah, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Sharon Shacham, Karyopharm Therapeutics Inc. Newton Massachusetts USA.; Sagar Lonial, Emory University
• Language: English
• Date: 2021-02
• Publisher: British Society for Haematology and John Wiley & Sons Ltd.
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/jha2.120
• Title of Journal or Parent Work: EJHaem
• Volume: 2
• Issue: 1
• Start Page: 48
• End Page: 55
• Keywords: selinexor; multiple myeloma; selective inhibitor of nuclear export; triple‐class‐refractory multiple myeloma
• Research Categories: Health Sciences, Public Health

Abstract

Triple-class-refractory multiple myeloma (MM) describes MM refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. In the Phase IIb STORM study (NCT02336815), oral selinexor plus low-dose dexamethasone (Sel-dex) demonstrated a 26.2% overall response rate in triple-class-refractory MM. Here, we compare overall survival (OS) of 122 patients with triple-class-refractory MM who received Sel-dex in STORM Part 2 with that of 64 similar patients treated with other available therapies in a Flatiron Health Analytic Database (FHAD) cohort. OS from the date that the patients' MM became triple-class-refractory was longer in STORM versus FHAD, with an unadjusted hazard ratio (HR) of 0.43 (P =  .0002; adjusted HR 0.35 [P  =  .011]). In a subset analysis of highly resistant patients receiving further therapies after their MM first became at least triple-class-refractory (i.e., who received Sel-dex in STORM, n = 64, and non-Sel-dex in FHAD, n = 36), the OS was significantly longer in STORM with an unadjusted HR of 0.52 (P = .0331; adjusted HR 0.33 [P = .041]). Within the limits of this analysis, the OS of patients with at least triple-class-refractory MM was significantly better with Sel-dex versus available therapies, suggesting that Sel-dex may be associated with a meaningful OS benefit in these patients.