Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk

Abstract

In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1-3 prior regimens were randomized to once-weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib-dexamethasone (XVd) or twice-weekly bortezomib-dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high-risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard-risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high-risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard-risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.

Conflict of interest statement

Ajai Chari reports grants and personal fees from Janssen, Celgene, Novartis, Amgen, Seattle Genetics, and Millenium/Takeda; personal fees from Bristol Myers Squibb, Karyopharm, Sanofi, Oncopeptides, Antengene, Glaxo Smith Kline, Secura Bio, and Shattuch Labs.

Ivan Spicka reports personal fees from Janssen‐Cilag, Takeda, Sanofi Aventis and Novartis; personal fees and non‐financial support from Colgene, BMS and Amgen.

Iryna Kriachok reports a consulting role, an advisory role, and a speaker's bureau role for Takeda, Janssen, Roche, Abbvie and MSD; Travel support by Takeda, MSD, Roche, Abbvie and Janssen.

Holger W. Auner reports an advisory role for Takeda and Karyopharm; grant from Amgen; and a speaker's bureau role for Janssen.

Roman Hajek has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda.

Christopher P. Venner has received honoraria from BMS/Celgene, Janssen, Sanofi, Amgen, GSK, and Takeda.

Mamta Garg reports support for attending conferences from Takeda; an advisory role for Amgen, Takeda, Jansen, Novartis and Celgene; and a speaker's bureau role for Janssen.

Hang Quach reports grants from and an advisory board role for Amgen, Celgene, Karyopharm, GlaxoSmithKline; non‐financial support and research drug supply from Sanofi; an advisory board role for Janssen Cilag and Specialized therapeutics.

Sundar Jagannath reports consulting services for AbbVie, Bristol‐Myers Squibb, Janssen Pharmaceuticals, Merck & Co. PM reports personal fees from Celgene, Amgen, Takeda, Janssen and Abbvie.

Moshe Levy reports receiving consulting fees and lecture fees from Takeda, Celgene, Seattle Genetics, AbbVie, Jazz Pharmaceuticals, Gilead Sciences, Bristol‐Myers Squibb, Amgen, Spectrum Pharmaceuticals, and Janssen.

Larry D. Anderson, Jr. reports honoraria from advisory board activity from the following: GSK, Amgen, Janssen, BMS/Celgene, Karyopharm, and Oncopeptides.

Nizar J. Bahlis reports grants and personal fees from Celgene; personal fees from Janssen, Amgen, Takeda, Abbvie, GSK and Karyopharm.

Thierry Facon reports an advisory board role for Karyopharm, Amgen, Roche and Oncopeptides; an advisory board role and a speaker bureau role for Janssen, Celgene/BMS, and Takeda.

Maria Victoria Mateos has served as member of advisory boards or received honoraria from Janssen, BMS‐Celgene, Takeda, Amgen, Sanofi, Oncopeptides, GSK, Adaptive, Pfizer, Regeneron, Roche and Sea‐Gen.

Hua Chang, Yosef Landesman, Yi Chai, Melina Arazy, Jatin Shah and Michael G. Kauffman are salaried employees and stockholders of Karyopharm Therapeutics Inc.

Sharon Shacham reports being employed by and owning stock in Karyopharm Therapeutics, holding patents (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide‐containing nuclear transport modulators and uses, and holding pending patents (PCT/US12/048319, 499/2012, PI20102724, and 2012000928) on hydrazide‐containing nuclear transport modulators and uses.

Paul G. Richardson reports receiving grant support and honoraria from Oncopeptides, Celgene, and Takeda, grant support from Bristol‐Myers Squibb, and honoraria from Amgen, Janssen, and Karyopharm Therapeutics.

© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.

Figures

FIGURE 1

Progression‐free survival. Patients with A, high‐risk and B, standard‐risk cytogenetics. CI, confidence interval; HR, hazard ratio; PFS, progression‐free survival; Vd, bortezomib and dexamethasone; XVd, selinexor, bortezomib, and dexamethasone [Color figure can be viewed at wileyonlinelibrary.com]