Background
Phase 2b, open-label, single-arm trial (STORM Part 2). N=122 patients with penta-refractory multiple myeloma: refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab (triple-class refractory including anti-CD38). Median prior lines: 7. All patients were refractory to their most recent PI, IMiD, and daratumumab.
Interventions and follow up
Regimen: Selinexor 80 mg PO twice weekly (days 1 and 3) + dexamethasone 20 mg PO twice weekly, until progression or unacceptable toxicity.
Primary endpoint: Overall response rate (ORR)
Median follow-up: 6.0 months
Primary endpoint: Overall response rate (ORR)
Median follow-up: 6.0 months
Results
ORR: 26.2% (95% CI 18.8–35.3%); all PR or better
Clinical benefit rate (≥MR): 39.3%
mDOR: 4.4 months
mPFS: 3.7 months
mOS: 8.6 months
Clinical benefit rate (≥MR): 39.3%
mDOR: 4.4 months
mPFS: 3.7 months
mOS: 8.6 months
Adverse events
Hematologic: Grade ≥3 thrombocytopenia 58.8%; grade ≥3 anemia 28.7%.
Constitutional / metabolic: Grade ≥3 fatigue 23.5%; grade ≥3 hyponatremia 22.5%.
GI / discontinuation: Grade ≥3 nausea 9.2%; discontinuation for AEs 18.0%.
Constitutional / metabolic: Grade ≥3 fatigue 23.5%; grade ≥3 hyponatremia 22.5%.
GI / discontinuation: Grade ≥3 nausea 9.2%; discontinuation for AEs 18.0%.
Conclusions
Selinexor + low-dose dexamethasone achieved a 26% ORR in penta-refractory myeloma — a population with no approved treatment options and historically near-zero response rates to chemotherapy — demonstrating that XPO1 inhibition is an active mechanism even after exhaustion of PI, IMiD, and anti-CD38 therapy.
Key Limitations
Single-arm, non-randomized design without a control comparator limits interpretation of the magnitude of benefit. Response duration was short (mDOR 4.4 months) and median PFS only 3.7 months, reflecting transient disease control. Substantial hematologic and constitutional toxicity (grade ≥3 thrombocytopenia 59%, fatigue, hyponatremia) required dose modification and supportive care. The heavily pretreated population (median 7 prior lines) limits generalizability to earlier-line settings.
Clinical Context
STORM led to accelerated FDA approval of selinexor + dexamethasone in 2019 for penta-refractory multiple myeloma (after ≥4 prior therapies, refractory to ≥2 PIs, ≥2 IMiDs, and an anti-CD38 antibody). ASCO and ESMO guidance recognize selinexor as a later-line option for triple-class-refractory disease. The subsequent BOSTON trial moved selinexor (with bortezomib) into earlier relapse. With BCMA-directed CAR-T and bispecific antibodies now available, selinexor-dexamethasone is generally reserved for patients ineligible for or who have exhausted those options.
References