Preliminary Results from the Launch Study-a Multicenter, Open-Label Study of Selinexor, Dexamethasone and Chemotherapy Drugs in Relapsed/ Refractory Multiple Myeloma

Background: Selinexor is a novel, oral selective inhibitor of nuclear export inhibiting exportin 1 (XPO1). In STORM study, selinexor (80mg biweekly) plus dexamethasone (20mg biweekly) (Xd) have demonstrated activity against relapsed/refractory multiple myeloma. In pre-clinical studies, selinexor played a synergistic anti-tumor role with chemotherapy drugs, but there is still a lack of clinical data on combined treatment.

Methods: The LAUNCH study is a multicenter, open-label study (NCT04877275) enrolled patients with relapsed/refractory MM who had at least one prior treatment. There are two arms in this study, and 25 patients will be enrolled in each arm. XDd Arm: Selinexor 80mg d1,8,15,22, Dexamethasone 40mg d1,8,15,22, and Liposome Doxorubicin 25mg/m² d1; XCd Arm: Selinexor 100mg d1,8,15,22, Dexamethasone 40mg d1,8,15,22, and Cyclophosphamide 300mg/m² d1,8,15,22. 28d per cycle in both arms. The primary endpoint is Objective Response Rate (ORR), secondary endpoints including clinical benefit rate (CBR), Duration of Response (DOR) and 1yesr Progression-Free-Survival (PFS).

Results: As of July 31 2022, 20 patients were enrolled (15 in XDd and 5 in XCd). Of these, 9 patients were male and 11 were female. The median age was 54 years (range: 54-73years). The median time since initial diagnosis was 3.2 years (range: 1.2-15years). The median number of prior treatments was 3 (range: 1- 7). There were 7 patients (35%) with high-risk cytogenetic abnormalities, 3 patients (15%) with extramedullary disease (EMD), 3 patients (15%) received prior autologous stem cell transplantation. 19 of 20 patients (95%) were exposed to bortezomib, 17 patients (85%) were exposed to lenalidomide, 3 patients (15%) exposed to daratumumab, 4 patients (20%) exposed to cyclophosphamide and liposome doxorubicin.

The median treatment time of all patients was 20 weeks (range: 1-41weeks), 18 patients were evaluated for efficacy. The ORR was 55.6% (53.8% in 13 XDd arm and 60% in 5 XCd arm) including 1 VGPR and 9 PRs . Five patients had stable disease. As of July 31, 5 patients still remained on treatment.

The most common hematological adverse events (All Grades, Grade ≥3) were leukopenia (65%, 35%), thrombocytopenia (55%, 25%), and anemia (45%, 20%). The most common non-hematological adverse events (All Grades, Grade ≥3) were vomiting (60%, 10%), fatigue (55%, 5%) and nausea (45%, 0%). Most treatment related adverse events were observed in the first 8 weeks.

Conclusion: In this study, the combination of selinexor, dexamethasone and chemotherapy drugs showed encouraging efficacy and manageable safety in relapsed/refractory MM. Long-term efficacy and safety data remain to be explored.

No relevant conflicts of interest to declare.