The Menarini Group presented compelling new subgroup data from the Phase 3 BOSTON trial at the European Hematology Association (EHA) Congress 2023, demonstrating significant survival benefits for selinexor-based combination therapy in specific relapsed refractory multiple myeloma (RRMM) patient populations.
Substantial Survival Improvements in Key Patient Subgroups
The updated analyses from the BOSTON study (NCT03110562) revealed particularly striking results in proteasome inhibitor (PI)-naïve patients, where the combination of selinexor, bortezomib, and dexamethasone (SVd) achieved a median progression-free survival (mPFS) of 29.5 months compared to 9.7 months with bortezomib and dexamethasone (Vd) alone, representing a hazard ratio of 0.29.
In patients with just one prior line of treatment, the SVd combination demonstrated an mPFS of 21 months versus 10.7 months for Vd alone (HR 0.62). For patients refractory to lenalidomide, overall survival reached 26.7 months in the SVd arm compared to 18.6 months in the Vd arm (HR 0.53).
"The data presented today emphasize the synergy between selinexor and bortezomib, highlighting the importance of a double mode of action switch," said Professor Maria-Victoria Mateos, MD, PhD, from University Hospital Salamanca, Spain. "These results are particularly relevant considering the increased use of the daratumumab lenalidomide dexamethasone combination in clinical practice today."
Safety Profile Consistent Across Subgroups
The safety analysis revealed that the most common treatment-emergent adverse events (≥25%) with SVd versus Vd in patients with one prior line of treatment were thrombocytopenia (61.6% vs 28.6%), nausea (52.5% vs 11.2%), fatigue (45.4% vs 17.3%), peripheral neuropathy (38.4% vs 52.0%), diarrhea (34.3% vs 24.5%), and anemia (30.3% vs 26.5%).
Safety findings were similar across the PI-naïve, bortezomib-naïve, and lenalidomide refractory subgroups, with data consistent with those observed in the overall BOSTON study population.
Clinical Implications for Treatment Strategy
These efficacy analyses were based on the final data cut from the BOSTON trial in February 2021, representing a one-year update of previously presented data from 2020. The findings support the use of selinexor in combination with bortezomib in PI/bortezomib-naïve or lenalidomide-refractory RRMM patients, as well as for patients at first relapse.
"We are proud to present these new subgroup data on selinexor," said Elcin Barker Ergun, CEO of the Menarini Group. "We are committed to bringing transformative new therapeutic options to the patients and families affected by cancer, including multiple myeloma."
Addressing Unmet Medical Need
Multiple myeloma remains an incurable cancer and the second most common hematologic malignancy. According to the World Health Organization, in 2020, there were approximately 51,000 new cases and 32,000 deaths from multiple myeloma in Europe. While treatment has improved over the last 20 years and overall survival has increased considerably, the disease remains incurable, and nearly all patients will eventually relapse and develop disease that is refractory to all approved anti-myeloma therapies.
The BOSTON study was a multi-center, randomized study that evaluated 402 adult patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy, comparing once-weekly SVd versus twice-weekly Vd with progression-free survival as the primary endpoint.
