- Selinexor plus low-dose dexamethasone induces response for 1 in 4 patients with multiple myeloma (MM) who are refractory to multiple lines of prior therapy.
Why this matters
- The oral exportin 1 (XPO1) inhibitor is the first investigational drug to show activity in this patient population.
- Expected median OS in heavily pretreated patients with disease progression is only ~1.7 months, and there are currently no therapies with clinical benefit in triple class refractory MM.
- STORM Part 2 study, a single-group trial of 122 patients (median age, 65 years) with MM previously treated with bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, an alkylator, and/or glucocorticoids.
- 100% were quad-refractory; 68% were penta-refractory (including anti-CD38 agent); and 96% were refractory to all 3 drug classes represented by carfilzomib, pomalidomide, and daratumumab.
- Median number of prior regimens, 7 (over the course of 6.6 years).
- 29.5% received ≥9 prior lines.
- Selinexor (80 mg)+dexamethasone (20 mg) was administered twice weekly on days 1 and 3 of a 28-day cycle.
- Funding: Karyopharm
- Overall response rate, 26.2%.
- 19.7% with very good partial response (PR).
- 6.5% with very good or better PR, including 2 patients with stringent complete responses.
- Median PFS, 3.7 months (5.3 months in patients with at least a PR).
- Median OS, 8.6 months (15.6 months in patients with at least a minimal response).
- 79.7% required dose modification because of adverse events (AEs), mostly during the first 2 cycles.
- Two patients with progression after CAR-T therapy had a PR.
- Nonhematologic AEs included nausea (69.1%), fatigue (56.1%), and anorexia (52.0%).
- Hematologic AEs included thrombocytopenia (67.5%), anemia (48.0%), neutropenia (36.6%), and leukopenia (29.3%).
- Single-group study.