Best Practices That Target Selinexor Treatment Improve MM-Related Outcomes

Patient outcomes among those receiving selinexor, an oral selective nuclear export inhibitor, for relapsed/refractory multiple myeloma (RRMM) improved on 3 important fronts in a new analysis that evaluated the impact of a best practices program at Florida Cancer Specialists & Research Institute (FCS): Time to treatment failure (TTF) and treatment duration increased and drug-limiting toxicities decreased. Overall survival was the fourth study end point.

According to the retrospective, observational study’s findings published in Current Oncology, outcomes were compared between 2 patient groups: cohort 1 (pre-implementation) had 68 patients initiated on a selinexor-based regimen before March 1, 2022, which is when FCS implemented the BP program, and cohort 2 (post implementation) had 41 patients who started their selinexor-based regimen between March 1, 2022, and March 1, 2023. In the program, selinexor treatment was started at a once-weekly dose of 80 mg or less, as its package insert has this as the first dose-reduction recommendation, and electronic health record (EHR) data were used for patient outcomes. In addition, selinexor-related data gathered for the study encompassed concomitant drugs, line of therapy, doses at therapy initiation and conclusion, and dose modifications, delays, schedule changes and discontinuations.

“Despite the emergence of new therapies, most patients will relapse due to residual resistant MM clones,” the study authors wrote. “To prolong duration of response and overall survival, the optimal strategy is to maximize the clinical utility of currently available agents.”

Patients in the postimplementation cohort were slightly older at diagnosis and selinexor initiation, at 67 vs 64 years and 71 vs 69.5 years, respectively. Most patients in the pre-implementation group were White (64.7%) or Black (22.1%), and in the postimplementation group, White (65%) or Other (27.5%). Stage III MM was the most common diagnosis in 38.2% of the pre-implementation group and 31.7% of the postimplementation group, and ECOG performance status of 0 or 1 in 79.4% and 75.6%, respectively.

More than 95% of patients in each group had prior exposure to lenalidomide, pomalidomide, bortezomib, and daratumumab. However, in the pre-implementation group, 91.2% had exposure to carfilzomib and 11.8% to isatuximab vs 70.7% and 7.3%, respectively, of the postimplementation group.

The most common selinexor regimens included dexamethasone only (42.7%) and dexamethasone and bortezomib (30.9%) in cohort 1 and dexamethasone and bortezomib (48.8%%) and dexamethasone and carfilzomib (22%) in cohort 2.

Equivalent groups of patients in each cohort (86.8%, pre-implementation; 85.4%, postimplementation) initiated selinexor as a fifth or greater line of therapy, but its use in double therapy dropped and in triplet therapy jumped: 42.7% to 14.6% ad 54.5% to 85.5%. For the recommended starting dose of once-weekly 80 mg or less, 78% of patients in the postimplementation period started at this dose vs 48.5% of patients in the pre-implementation cohort.

Median (IQR) follow-up was 72% shorter in the postinmplementation vs the pre-implementation cohort, at 6.7 (1.3-11.3) vs 24.0 (13.8-41.6%), even though median treatment duration was longer in cohort 2 vs cohort 1: 4.4 (1.1-9.4) vs 2.5 (1.2-2.2 months). Further, more patients in the postimplementation group were projected to still be alive at 6 and 12 months after selinexor initation vs the pre-implementation group:

• 6 months: 73.6% (55.1%-85.4%) vs 57.0% (44.3%-67.8%)
• 12 months: 51.6% (24.8%-73.0%) vs 38.2% (26.6%-50.0%)

Dose modifications (44.1% vs 43.9%), dosing schedule changes (17.7% and 14.6%), and treatment discontinuations (66.2% vs 29.3%) were more common in the pre-implementation group, while dose delays (16.2% and 19.5%) and treatment interruptions (36.8% and 48.8%) were more common in the postimplementation group. Disease progression was the most common reason for treatment discontinuation in cohort 1 (45.6%) and “other” (36.6%) in cohort 2, while adverse events that led to the same were experienced by almost 4 times as many patients in cohort 1 (n = 30) vs cohort 2 (n = 8).

Median TTF was more than 3 times longer in the postimplementation vs the pre-implementation group, at 7.1 (1.2-not reached) vs 2.3 (1.2-4.4) months, and the investigators saw that starting at a dose of 100 or at least 120 mg correlated with 2.5- and 5.4-times greater likelihood of treatment failure compared with patients who initiated selinexor treatment with a maximum dose of 60 mg.

“These findings support the hypothesis that a BP program designed around specific anticancer drugs can optimize prescribing practices,” the authors concluded, “leading to better disease control and improvements in a patient’s cancer care journey.”

Potential limitations on these findings being applied to a wider patient population include the retrospective nature of the study, risk of selection bias, and that the pre-implementation cohort had a much longer follow-up period vs the postimplementation cohort.

Reference

Gordon LN, Ray D, Ijioma SC, et al. Impact of a best practices program in patients with relapsed/refractory multiple myeloma receiving selinexor. Curr Oncol. 2024;31(1):501-510. doi:10.3390/curroncol31010034