Selinexor-Based Triplet Regimens in Patients With Multiple Myeloma Previously Treated With Anti-CD38 Monoclonal Antibodies

We analyzed the efficacy and safety of selinexor-containing triplet regimens (selinexor-bortezomib-dexamethasone, selinexor-pomalidomide-dexamethasone, and selinexor-carfilzomib-dexamethasone) in a subset of STOMP and BOSTON study patients (n = 62) with multiple myeloma enrolled after a median of 4 prior lines, which included an anti-CD38 monoclonal antibodies-containing regimen. The results suggest that selinexor-containing triplets may provide prolonged disease control with generally acceptable tolerability in these patients.Background: The increasing use of anti-CD38 monoclonal antibodies (alpha CD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing alpha CD38 mAb-refractory disease earlier in the treatment course with fewer treatment options. Patients and methods: We analyzed the efficacy and safety of selinexor-based triplets (selinexor +dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with alpha CD38 mAbs. Results: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.3% refractory to alpha CD38 mAb) were included. Overall response rates (ORR) in the SPd, SVd and SKd cohorts were 52.2%, 56.3%, and 65.2%, respectively. Overall response rate was 47.4% among patients who had MM refractory to the third drug reintroduced in the Sd-based triplet. Median progression-free survival in the SPd, SVd, and SKd cohorts was 8.7, 6.7, and 15.0 months, respectively, and median overall survival was 9.6, 16.9, and 33.0 months, respectively. Median time to discontinuation in the SPd, SVd, and SKd cohorts was 4.4, 5.9, and 10.6 months, respectively. The most common hematological adverse events were thrombocytopenia, anemia, and neutropenia. Nausea, fatigue, and diarrhea were pr imar ily grade 1/2. Adverse events were generally manageable with standard supportive care and dose modifications. Conclusion: Selinexor-based regimens may offer effective and well -tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or refractory to alpha CD38 mAb therapy and could help address the unmet clinical need in these high-risk patients.