Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk
Shambavi Richard, Ajai Chari, Sosana Delimpasi, Maryana Simonova, Ivan Špıčka, Luděk Pour, Iryna Kriachok, Meletios Α. Dimopoulos, Halyna Pylypenko, Holger W. Auner, Xavier Leleu, Ganna Usenko, Roman Hájek, Reuben Benjamin, Tuphan Kanti Dolai, Dinesh Kumar Sinha, Christopher P. Venner, Mamta Garg, Don A. Stevens, Hang Quach, Sundar Jagannath, Philippe Moreau, Moshe Levy, Ashraf Badros, Larry D. Anderson, Nizar J. Bahlis, Thierry Façon, María‐Victoria Mateos, Michèle Cavo, Hua Chang, Yosef Landesman, Yi Chai, Melina Arazy, Jatin J. Shah, Sharon Shacham, Michael Kauffman, Sebastian Grosicki, Paul G. Richardson
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.