KEY TAKEAWAYS
- The BOSTON phase III trial aimed to analyze the impact of LEN-refractoriness on SVd efficacy (PFS, OS) and safety in RRMM.
- The results demonstrated that SVd significantly outperforms Vd in survival and response rates, highlighting the benefit of a multi-mechanism approach.
Lenalidomide (LEN) dominates frontline (MM) therapy, but treatments for patients with LEN-resistant MM are limited. Early BOSTON trials showed SVd significantly beat Vd (bortezomib + dexamethasone) in previously treated MM median progression-free survival (mPFS) and overall response rate(ORR).
For the study, patients with RRMM with a history of 1-3 prior therapies were randomly assigned to receive either SVd (selinexor 100 mg once a week, bortezomib 1.3 mg/m2 once a week, and dexamethasone 20 mg twice a week) or standard Vd twice a week. A post-hoc stratified analysis assessed PFS OS with crossover adjustment using the two-stage method, response rates, and safety outcomes in subgroups based on refractory status to lenalidomide (LEN).
Of 402 patients, 106 were identified as LEN-refractory (SVd=53, Vd=53). In the SVd arm, 30.2% became LEN-refractory after one prior line of therapy (LOT), and 69.8% after two or more LOT. In the Vd group, 26.4% became LEN-refractory after one prior LOT and 73.6% after two or more LOT. The median age was 65 years (range 40-87) in the SVd arm and 66 years (range 45-85) in the Vd arm. At the time of analysis, the median follow-up was 28.7 months for the SVd arm and 28.6 months for the Vd arm.
The mPFS was 10.2 months (95% CI 5.8-NR) with SVd compared to 7.1 months (95% CI 3.5-9.8) with Vd, indicating a significant improvement (HR 0.52; 95% CI 0.31-0.88, p=0.012). The median overall survival (mOS) was 26.7 months (95% CI 19.9-NR) with SVd versus 18.6 months (95% CI 13.9-29.0) with Vd, demonstrating a statistically significant and clinically meaningful enhancement in OS (HR 0.53; 95% CI 0.30-0.95, P=0.03).
The response rates for SVd and Vd were as follows: ORR 67.9% vs 47.2%, and very good partial response (VGPR) or better 35.8% vs 24.5%, respectively. Among 105 lenalidomide (LEN)-refractory patients in the safety population, the most common (≥25%) treatment-emergent adverse events(TRAEs) with SVd vs Vd included thrombocytopenia (71.7% vs 40.4%), nausea (50.9% vs 11.5%), fatigue (45.3% vs 21.1%), diarrhea (43.4% vs 19.2%), anemia (39.6% vs 25.0%), and peripheral neuropathy (30.2% vs 38.5%).
The results demonstrated that SVd significantly outperforms Vd in survival and response rates, highlighting the benefit of a multi-mechanism approach.
Clinical Trial: https://clinicaltrials.gov/study/NCT03110562
Mateos MV. Efficacy, Survival, and Safety of Selinexor, Bortezomib, and Dexamethasone (SVd) in Patients with Lenalidomide-Refractory Multiple Myeloma: Subgroup Data from the BOSTON Trial. Presented at the IMS 20th Annual Meeting and Exposition, September 2023.
