• 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.