Selinexor Combined with Daratumumab, Thalidomide, and Dexamethasone in Patients with First Relapsed Multiple Myeloma: A Single-Arm, Multicenter, Prospective Study

Background:

Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable, thus necessitating the exploration of new therapies.Selinexor(X), a selective inhibitor of nuclear export protein 1 (XPO1), has shown promise in STOMP study（NCT02343042）, with the XDd regimen demonstrating an overall response rate (ORR) of 69% in Relapsed /Refractory patients. The most common adverse events associated with selinexor are nausea and vomiting, which can be effectively prevented and treated with thalidomide. It is anticipated that the combination of thalidomide and selinexor will effectively mitigate the adverse effects of selinexor on the gastrointestinal system.This study aims to evaluate the efficacy and safety of a regimen combining selinexor with daratumumab (Dara), thalidomide, and dexamethasone for patients with first relapsed MM. The Clinical Ethics Committee of the First Hospital of Zhejiang University School of Medicine approved the protocol.

Methods:

Patients aged 18 to 75 years with a confirmed diagnosis of MM and experiencing their first relapse after front-line therapy were eligible for enrollment.The treatment regimen comprised selinexor 60 mg qw, Dara 16mg/kg, four injections per cycle, weekly for cycles 1-2, biweekly for cycles 3-6, and every four weeks for subsequent cycles, thalidomide 100 mg qn, and dexamethasone 20 mg, with one cycle administered every 28 days.Efficacy was assessed at each cycle, with a systematic assessment conducted after 4 cycles. The study was terminated if stable disease (SD) or progressive disease (PD) was not achieved. The primary endpoint was the overall response rate ORR (PR+ VGPR+CR) in patients who completed at least one cycle of treatment; secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety.

Results

From July 2022 to Jun 2024, 23 patients (64.3% male, median age 66.5 years) were enrolled in our study and 9 patients were excluded due to protocol violation and other reasons.

According to the Mayo myeloma stratification and risk-adjusted treatment criteria, two patients had one risk factor, while twelve patients had two or more risk factors. Of these, twelve had prior exposure to bortezomib and lenalidomide, four were exposed to Dara, and two had undergone autologous stem cell transplantation (ASCT). At the data cutoff on Jun 30, 2024, eight patients completed one cycle of treatment, five patients completed three or more cycles of treatment.Of the eleven patients, eight had efficacy evaluated as PR and better outcomes, two had stable disease, and one exhibited progressive disease. The effectiveness of the XDTd regimen, with an ORR of 72.7%, surpassed that of previous regimen evaluations, with an ORR of 28.6%. Common treatment-related adverse events (all grades, Grades 3/4) included: thrombocytopenia (61.5%, 53.8%), nausea (84.6%,0%), fatigue (92.3%, 0%), neutropenia (61.5%, 53.8%), anemia (38.5%, 7.7%), and leukopenia (30.8%, 30.8%).

Conclusion

The modified XDTd regimen demonstrated effective ORR and tolerable AE, with an effective reduction in grade 3/4 vomiting and AE-related loss compared to the phase III BOSTON study. Further data regarding PFS will be reported.

No relevant conflicts of interest to declare.