Safety and efficacy of reduced selinexor doses in patients with relapsed/refractory multiple myeloma

A recent study suggests that appropriate dose modifications in selinexor in response to adverse events (AEs) were associated with improved efficacy, reduced AE rates and improved quality of life (QoL) in patients with relapsed/refractory multiple myeloma. The study’s findings were published in the journal, Clinical Lymphoma, Myeloma & Leukemia. 
The BOSTON study, a phase III, open label, randomized, controlled trial included 195 patients with relapsed/refractory multiple myeloma. They were randomized either to once-weekly (QW) 100 mg of selinexor, QW subcutaneous bortezomib (1.3 mg/m2), QW with 20 mg of twice-weekly dexamethasone or to a standard subcutaneous bortezomib and dexamethasone twice-weekly. Primary endpoint was progression-free survival (PFS). Secondary endpoints included Overall response rate (ORR), ≥ very good partial response (VGPR) rate, overall survival (OS), duration of response (DoR), time to next treatment (TTNT), and time to response (TTR) 
Of the total 195 patients enrolled, 126 patients had selinexor dose reductions. The median progression-free survival for patients who received dose reductions was 16.6 months (95% CI 12.9 – NR), while it was 9.2 months (95% CI 6.8, 15.5) for those who did not with a hazard ratio of 0.57 (95% CI 0.36, 0.89). The ORR was 81.7% (95% CI 73.9%, 88.1%) vs 66.7% (95% CI 54.3%, 77.6%) for patients with dose reductions vs in those without dose reductions, respectively. DOR was not reached (95% CI 13.8, NE) in the dose reduction group and was 12.0 months (95% CI 8.3, NE) in the group without reduction (HR = 0.59 [95% CI 0.34, 1.04]). TTNT was 22.6 months (95% CI 14.6, NE) for patients who received selinexor dose reductions, whereas it was 10.5 months (95% CI 6.3, 18.2) for patients who did not receive dose reductions.  
On the EORTC QLQ-C30 Global Health Status/QoL scale, the mean best change from baseline was 10.0 ± 20.5 (95% CI 6.3, 13.7) in the dose reduction group as opposed to 4.0 ± 20.9 (95% CI −1.4, 9.3) in those without dose reduction. After selinexor dose reduction, AE rates that were lower included thrombocytopenia (62.5% before vs. 47.6% after), fatigue (28.1% before vs. 9.9% after), nausea (31.6% before vs. 7.3% after), anemia (17.9% before vs. 10.3% after), diarrhea (12.9% before vs. 5.2% after), and diarrhea (21.5% before vs. 6.4% after).
Based on the above results, it can be concluded that appropriate dose reductions of 100 mg selinexor starting dose may be associated with improved efficacy, reduced AE rates and improved QoL