Outcomes With Selinexor, Bortezomib And Dexamethasone (svd) In Patients

Topic: Myeloma and other monoclonal gammopathies — Clinical

Background:Selinexor is a first-in-class, orally bioavailable XPO-1 inhibitor which binds to exportin 1, inhibiting nuclearexport of tumor suppressor proteins. The phase 3 BOSTON trial (NCT03110562) randomized participants withRRMM (1–3 prior lines) to 100 mg selinexor once weekly (QW), bortezomib QW (1.3 mg/m2) and 20 mg ofdexamethasone twice weekly (BIW; SVd) or standard BIW bortezomib and dexamethasone (Vd). BOSTONincluded 402 patients (pts) from 21 countries, spanning diverse geographical regions. The study met its primaryendpoint with an improvement in progression free survival (mPFS), HR 0.70, p=0.0075 (mPFS for SVd 13.93 mvs. Vd 9.46 m). Demographics in Region 4 (R4) indicated a population that was younger with poorer prognosisas measured by ECOG status and disease stage, as well as a much lower rate of prior stem cell transplantation,likely reflecting differences in clinical practice and standards of care in that region.

Aims:To understand outcomes in patients receiving SVd in countries with similar clinical practices and standards ofcare (Regions 1–3; R1–3), with reference to R4 and the intention-to-treat (ITT) population.

Methods:A retrospective, post-hoc, subgroup analysis of the SVd cohort in R1–3 and R4 was conducted to assessdifferences in outcomes across subgroups with reference to the ITT population. Efficacy analyses were based onthe February 2021 data cut and safety analyses on June 2022 data cut.

Results:263 pts from R1–3 were randomized in the BOSTON trial (126 to SVd, 137 to Vd). The overall treatment effectfor SVd vs. Vd in R1–3 was consistent with the ITT population, with a favourable trend: HR of 0.54 for PFS andodds ratio (OR) of 2.29 for ORR, in reference to a HR of 0.70 and OR of 1.96 for the ITT population,respectively. There were some differences in baseline characteristics for SVd pts from R1–3 in reference to R4and the ITT population. The SVd cohort from R1–3 were slightly older (median age of 68 vs. 61 and 66 years,respectively) and included a lower proportion of pts with ECOG 2 (6% vs. 17% and 10%, respectively), as well asa smaller proportion with R-ISS stage III disease at screening (3% vs. 12% and 6%, respectively). There weredifferences in use of prior treatments, particularly stem cell transplantation in the SVd cohorts from R1–3 (52%),R4 (15%) and the ITT population (39%). Efficacy in the SVd cohort from R1–3 included an ORR of 78% and amPFS of 16.6m (Figure 1). The mPFS in clinically relevant subpopulations from R1–3 receiving SVd was 21.0m in≥65 years of age and 12.2m in lenalidomide refractory. The overall AE profile for the SVd cohort in R1–3 wasalso consistent with the overall population, but there was a higher incidence of decreased appetite and newonset cataract rates in R4.

Summary/Conclusion:BOSTON results are reflective of a diverse and global RRMM population with differences in baselinecharacteristics, including an older population with a lower proportion of participants with poor performancestatus, higher rates of prior transplantation and less advanced disease observed in R1–3. Some of thesedifferences may have contributed to the favorable efficacy reported with SVd for pts in R1–3. Undescribeddifferences in clinical care and patient education may also have contributed to outcomes. This subgroupanalysis highlights the importance of better understanding regional differences and the potential impact onclinical outcomes in the context of clinical trials. It also supports the need for patient education, closemonitoring, supportive care and dose modifications to ensure optimal outcomes.

Figure 1: Region 1–3 PFS Kaplan Meier Curves, SVd vs Vd

Keywords: relapsed/refractory, Multiple myeloma

https://clin.larvol.com/abstract-detail/EHA 2024/70979653