PB2096: SELINEXOR COMBINED REGIMEN FOR MULTIPLE MYELOMA WITH EXTRAMEDULLARY DISEASE(EMD)

Abstract Topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Background: To the best of our knowledge, there is no established approach for treatment of multiple myeloma with extramedullary disease(EMD) to date. Therefore, identifying new treatment strategies for patients suffering from EMD still represents an urgent medical need. Selinexor is a first-in-class Selective Inhibitor of Nuclear Export compound that selectively binds and inactivates XPO1, which leads to accumulation of tumor suppressor proteins in the nucleus and re-activation of cell cycle regulators such as p53, FOXO, IkB. In the STORM study( NCT02343042 ), 122 patients(pts) with penta-exposed, triple-class refractory multiple myeloma were enrolled to receive Selinexor combined with dexamethasone. Twenty-seven pts with extramedullary plasmacytoma at baseline, median age 64 years, had previously received median 7 line therapy, and eight had high risk cytogenetics. Follow-up evaluation of plasma cell tumor was performed in 16 cases, and complete disappearance or shrinkage of extramedullary lesions was observed in 9 cases. It indicates that Selinexor has clinical activity in the treatment of plasma cell tumor or EMD.

Aims: To evaluate the efficacy and safety of Selinexor combined regimen for multiple myeloma with extramedullary disease.

Methods: Eligible pts were aged≥18 years, and had a diagnosis of multiple myeloma with EMD since January 2022 in our center, and an Eastern Cooperative Oncology Group performance status of 0-2. Selinexor was administered orally (60 mg per week) combination with bortezomib and dexamethasone (XVd), bortezomib, lenalidomide and dexamethasone (XVRd), Daratumumab and dexamethasone(XDd) as per physician’s choice. The primary endpoint is overall response rates (ORR).The secondary endpoints are complete response (CR), duration of response (DOR), progression free survival (PFS), overall survival (OS) and toxicity.

Results: A total of 17 pts were enrolled in the study, 5(29.4%) pts with new diagnosed multiple myeloma(NDMM) with EMD from our clinical study(ChiCTR2200062860),12(70.6%) pts with relapsed/refractory multiple myeloma(RRMM) with EMD. The median age was 61.1(Table 1). According to IMWG criteria, the ORR of 5 pts with NDMM was 100%, including 3 stringent complete response(sCR) and 2 very good partial response (VGPR). The ORR of 12 pts with RRMM was 66.7%, including 1(8.3%) sCR, 1(8.3%) complete response(CR) and 6(50%) partial response(PR), as shown in Table 2. These results established that Selinexor combined regimen has a prospective response for multiple myeloma with EMD. Overall, the severe toxicities are manageable. The most common treatment-related adverse events were grade 1 or 2, including nausea (29.1%), fatigue (52.9%), and anorexia (17.6%).The most common grade 3 or 4 adverse events were fatigue, which occurred in less than 5% of patients. If combined with chemotherapy drugs, the hematological toxicities were common. These adverse events were largely reversible and manageable with supportive care and dose modifications. One patient with plasma cell leukemia after interim evaluation with VGPR stopped treatment for one month due to COVID-19 and had disease progression.

Conclusion:

Despite a small sample size, these results highlight the potential utility of Selinexor-based regimen as a treatment regimen for multiple myeloma with EMD. It is worthy of further study based on the preliminary efficacy results. Long-term results still require more patients to be enrolled and further follow-up. Safety data from the study demonstrates that Selinexor-based regimen has a favorable tolerance profile in patients for multiple myeloma with EMD.

Keywords: Multiple myeloma, Plasma cells