Survival among older patients with previously treated multiple myeloma treated with selinexor, bortezomib, and dexamethasone (XVd) in the BOSTON study.
Authors: Thierry Facon, Holger W. Auner, Maria Gavriatopoulou, Sosana Delimpasi, Maryana Simonova, Ivan Spicka, Luděk Pour, Meletios A. Dimopoulos, Iryna Kriachok, Halyna Pylypenko, Xavier Leleu, Hang Quach, Benjamin Reuben, Tuphan Kanti Dolai, Dinesh Kumar Sinha, Mamta Garg, Don A. Stevens, Jatin J. Shah, Paul G. Richardson, Sebastian Grosicki
Journal: Journal of Clinical Oncology (2021)

8019 Background: Multiple myeloma (MM) typically affects older populations, which are more vulnerable to toxicity with anti-MM treatments. These patients (pts) have significant morbidity and mortality, resulting in a need for dose modifications or alternative suboptimal treatment options. Significant improvements were observed in the BOSTON study with XVd vs Vd in median progression-free survival (PFS), overall response rate (ORR), and rates of peripheral neuropathy (PN); median overall survival (OS) trended in favor of XVd. Methods: The phase 3 randomized BOSTON trial (NCT03110562) is a controlled, open-label study of once weekly XVd vs. twice weekly standard Vd in pts with MM and 1-3 prior treatment regimens. We performed post-hoc analyses to compare survival benefits in pts ≥65 vs &lt; 65 years of age. Results: The BOSTON study enrolled a total of 402 pts between June 2017 and February 2019 that were randomized into XVd or Vd arms. The numbers of pts treated with XVd or Vd who were ≥65 were 109/132 and 86/75 who were &lt; 65, respectively. Baseline characteristics were similar by age although pts ≥65 years were less likely to have received ASCT than those &lt; 65 years (48.4% vs. 25.3%). Median PFS was prolonged with XVd compared with Vd, across both age groups: ≥65 (HR, 0.55 [95% CI, 0.37-0.83] P = 0.002) and &lt; 65, (HR, 0. 74 [95% CI, 0.49-1.11], P = 0.07). Vd was associated with a lower ORR (64.4%) than treatment with XVd (76.1%) (OR, 1.77 [95% CI, 1.00-3.11], P = 0.024) in pts ≥65, while the ORR in those &lt; 65 was 76.7% with XVd and 58.7% (OR, 2.33 [95% CI, 1.18-4.59], P = 0.007) with Vd. As of Jan 2021, the median OS for the overall population was not reached for both arms (HR = 0.86; p = 0.193), with 61 and 75 deaths in the XVd and Vd arms, respectively. Median OS was not reached in pts ≥65 with XVd and was 28.6 months with Vd (HR = 0.60; 95% CI, 0.38-0.94; p = 0.012), while there was no difference in the OS for pts &lt; 65 (HR = 1.52; 95% CI, 0.86-2.68; p = 0.926). Pts ≥65 had a lower incidence of death with XVd as compared to Vd (29 vs 56) and there were 32 deaths with XVd and 19 with Vd in pts &lt; 65. Grade ≥3 treatment-emergent adverse events were not observed more often in older compared to younger pts. Amongst pts ≥65, PN of any grade was lower with XVd (32.1%) compared to Vd (46.5%); (OR 0.57 [95% CI 0.34-0.97], p = 0.017), including a lower incidence of grade ≥3 PN (XVd 4.6% vs. Vd 11.6%). Pts &lt; 65 followed a similar trend of PN AEs of any grade: XVd, 32.6%; Vd, 48.0% (OR 0.42 [95% CI 0.21-0.82], p = 0.006). Conclusions: In an older patient population with a poor prognosis, XVd was associated with a significant survival benefit, improved PFS and OR with reduced PN, and requires relatively short and infrequent clinic visits. XVd may be a simple, effective regimen for pts ≥65 years of age. Clinical trial information: NCT03110562.