Background
Phase 3, open-label, randomized controlled trial (BOSTON). N=402 patients with relapsed or refractory multiple myeloma after 1–3 prior lines including at least one PI. Randomized 1:1. Key eligibility: ECOG PS ≤2; prior selinexor not allowed; prior bortezomib permitted if not refractory. XPO1 (exportin 1) is a nuclear export protein; selinexor is a first-in-class oral SINE compound.
Interventions and follow up
Arm A (XVd): Selinexor 100 mg PO weekly (days 1, 8, 15, 22) + bortezomib 1.3 mg/m² SC (days 1, 8, 15) + dexamethasone 20 mg PO (days 1, 2, 8, 9, 15, 16, 22, 23), 35-day cycles.
Arm B (Vd): Bortezomib 1.3 mg/m² SC (twice-weekly schedule, days 1, 4, 8, 11, 22, 25, 29, 32) + dexamethasone 20 mg PO, 35-day cycles.
Primary endpoint: Progression-free survival
Median follow-up: 13.2 months
Arm B (Vd): Bortezomib 1.3 mg/m² SC (twice-weekly schedule, days 1, 4, 8, 11, 22, 25, 29, 32) + dexamethasone 20 mg PO, 35-day cycles.
Primary endpoint: Progression-free survival
Median follow-up: 13.2 months
Results
mPFS: 13.93 vs 9.46 months, HR 0.70 (95% CI 0.53–0.93), P=.0075
ORR: 76.4% vs 62.3%
≥VGPR rate: 44.6% vs 32.4%
OS: Not significant at primary analysis
ORR: 76.4% vs 62.3%
≥VGPR rate: 44.6% vs 32.4%
OS: Not significant at primary analysis
Adverse events
Hematologic (XVd vs Vd): Grade ≥3 thrombocytopenia 39.8% vs 17.1%.
GI / constitutional: Grade ≥3 fatigue 13.9% vs 1.5%; grade ≥3 nausea 9.0% vs 1.5%; grade ≥3 anorexia 4.5% vs 1.5%.
Neurologic / discontinuation: Peripheral neuropathy grade ≥3 4.5% vs 6.1% (less neuropathy with once-weekly bortezomib); discontinuation 26.4% vs 26.2%.
GI / constitutional: Grade ≥3 fatigue 13.9% vs 1.5%; grade ≥3 nausea 9.0% vs 1.5%; grade ≥3 anorexia 4.5% vs 1.5%.
Neurologic / discontinuation: Peripheral neuropathy grade ≥3 4.5% vs 6.1% (less neuropathy with once-weekly bortezomib); discontinuation 26.4% vs 26.2%.
Conclusions
Selinexor + once-weekly bortezomib + dexamethasone (XVd) significantly improved PFS and response rates compared with twice-weekly Vd in 1–3 line RRMM, with notably less peripheral neuropathy — a potential advantage of the once-weekly bortezomib schedule.
Key Limitations
The comparator (twice-weekly Vd) is more toxic in terms of neuropathy than the now-standard once-weekly or subcutaneous regimens, potentially inflating the apparent advantage of XVd. Significant GI toxicities (nausea, anorexia, weight loss) with selinexor require active antiemetic prophylaxis. OS benefit was not demonstrated. Selinexor's mechanism and toxicity profile differ substantially from anti-CD38 or IMiD agents, making patient selection and sequencing complex.
Clinical Context
XVd was FDA-approved in 2020 for RRMM after ≥1 prior line including a PI; selinexor + dexamethasone (STORM) was already approved for penta-refractory myeloma. ASCO and ESMO guidance recognize selinexor-based regimens as later-line options. XVd provides an oral + SC combination for patients who have failed multiple prior therapies; the once-weekly bortezomib schedule notably reduces neuropathy. The GI toxicity profile of selinexor limits broad use but fills a niche for heavily pretreated patients.