• Effect of Age and Frailty on the Efficacy and Tolerability of Once-Weekly Selinexor, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma

      Auner, Holger W; Gavriatopoulou, Maria; Delimpasi, Sosana; Simonova, Maryana; Spicka, Ivan; Pour, Ludek; Dimopoulos, Meletios A; Kriachok, Iryna; Pylypenko, Halyna; Leleu, Xavier; et al. (Wiley-Blackwell, 2021-03-23)
      Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (<65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p =.024), ≥VGPR (OR, 1.68, p =.027), PFS (HR 0.55, p =.002), and improved OS (HR 0.63, p =.030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p =.08) and OS (HR 0.62, p =.062). Significant improvements were also observed in patients <65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year-old (22% vs. 37%; p =.0060) and frail patients (15% vs. 44%; p =.0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients <65 and ≥65 and in nonfrail and frail patients with previously treated MM. © 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
    • Selinexor, bortezomib, and dexamethasone versus bortezomib and dexamethasone in previously treated multiple myeloma: Outcomes by cytogenetic risk

      Richard, Shambavi; Chari, Ajai; Delimpasi, Sosana; Simonova, Maryana; Spicka, Ivan; Pour, Ludek; Kriachok, Iryna; Dimopoulos, Meletios A; Pylypenko, Halyna; Auner, Holger W; et al. (Wiley-Blackwell, 2021-06-01)
      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. © 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.