Medical Resident Hackensack University Medical Center Hackensack, New Jersey, United States
Introduction: Selinexor is a first in class, oral selective inhibitor of nuclear export compound, which inhibits XPO-1 causing accumulation of tumor suppressor proteins in the cellular nucleus leading to apoptosis. It is currently approved for use in patients(pts) with multiple myeloma (MM) and non-Hodgkin’s lymphoma. In clinical trials, in combination with other agents, selinexor produced an objective response rate (ORR) ranging from 26% to 78%. In the ‘STORM’ trial, for pts with triple-class refractory disease, ORR was found to be 26% with a median progression-free survival (PFS) of 3.7 months (mos). We report our single-center experience with the use of selinexor in various combinations in pts with heavily pre-treated MM.
Methods: All pts with MM who were treated with selinexor-based combinations were included in the institutional review board approved study. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. Survival analysis was performed using the Kaplan-Meir method including PFS and overall survival (OS). The IMWG response criteria were utilized for response assessment.
Results: We identified 101 pts who were treated consecutively between May 2019 and March 2023 with selinexor-based combinations. 58.4% (n=59) were male, median age was 68.9 years, median time from diagnosis to treatment initiation was 5.9 yrs. Pts had received a median of 4 prior lines of therapies (range 2-13). 85.1% (n=86) were triple class refractory, 97% (n=98) were anti-CD38 refractory. 91.1% (n=92) had received at least 1 autologous stem cell transplant. 67% of the FISH evaluable pts had high risk genetic profiles, defined as those with t(4;14), t(14;16), 17p(-), 1q(+) or t(14;20), 21.7% pts were ISS-3, at diagnosis. Baseline characteristics are summarized in Table 1. Combination agents included pomalidomide (31.6%, n=32), carfilzomib (31.6%, n=32), bortezomib (12.8%, n=13), daratumumab (15.8%, n=16), ixazomib (0.9%, n=1) and dexamethasone (6.9%, n=7). Median starting dose of selinexor was 80 mg (range 40mg to 100mg). Dose reduction for toxicity was necessary in 19 pts (18.8%). The most common reasons for dose reduction were fatigue and thrombocytopenia. Overall response rate (ORR) (partial remission or better) for the entire cohort was 32.7%. The median PFS was 3.0 mos (Graph 1), the median OS was 14.1 mos (Graph 2) and median duration of response (DOR) was 7.8 mos. Median time to best response was 30 days. Efficacy data are summarized in Table 1
Conclusions: In our single-center experience, selinexor-based combinations were overall well tolerated, with few pts needing dose modifications. Similar to the real-world outcomes reported by Kastritis et al., a low response rate was observed in our larger cohort of pts with the use of selinexor in several combinations. However, clinical benefit with a moderate duration of response was observed.
