Selinexor once weekly can be safely combined with pomalidomide and dexamethasone in heavily pretreated patients with multiple myeloma (MM), according to the results of a study presented at the 2021 American Society of Clinical Oncology Annual Meeting.
In the multi-arm phase 1b/2 STOMP study (ClinicalTrials.gov Identifier: NCT02343042), investigators evaluated selinexor at 60 mg, 80 mg, or 100 mg weekly, or 60 mg or 80 mg twice weekly in combination with pomalidomide plus dexamethasone. The researchers sought to determine the maximum tolerated dose and recommended phase 2 dose (RP2D), as well as to assess the safety and activity of the selinexor with dexamethasone and pomalidomide regimen including in patients who had received the RP2D.
A total of 65 patients were enrolled (median age, 64 years [range, 37-85 years]; 33 male) through January 4, 2021. Participants had a median of 3 (range, 1-10) previous lines of therapy. Participants’ previously treated and refractory rates, respectively, were lenalidomide 100%/85%, bortezomib 92%/49%, carfilzomib 43%/37%, pomalidomide 31%/29%, and daratumumab 26%/26%. The RP2D was selinexor 60 mg weekly, pomalidomide 4 mg (Days 1-21), and dexamethasone 40 mg weekly.
The most frequently occurring hematologic, treatment-related adverse events (all grades, grades ≥3, respectively) were neutropenia (63%, 55%), anemia (58%, 32%), and thrombocytopenia (54%, 31%). Nausea (62%, 2%), fatigue (55%, 11%), and decreased appetite (45%, 2%) were the observed nonhematologic TRAEs.
In patients with MM who were pomalidomide-naive or nonrefractory (n=44), the overall response rate (ORR) was 57% (1 stringent complete response [sCR]). There was 1 complete response, 8 very good partial response (VGPR), and 15 partial responses (PRs), and the median progression-free survival (PFS) was 12.2 months.
Among participants who received the RP2D (n=20), the ORR was 65% (1 sCR, 5 VGPR, and 7 PR), and the median PFS was not reached with a median follow-up of 3.9 months. In patients who were pomalidomide-refractory and in those with previous daratumumab use, the ORR was 44% (7/16) and 60% (9/15), respectively.
“No new safety signals were identified,” noted the study authors. “The all-oral combination of [selinexor + pomalidomide + dexamethasone] is highly active with an ORR of 65% at RP2D (compared with expected ORR ≤30% for [pomalidomide plus dexamethasone]) and produces durable responses with a [median] PFS of 12.2 months overall.”
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White D, Chen C, Baljevic M, et al. Oral selinexor, pomalidomide, and dexamethasone (XPd) at recommended phase 2 dose in relapsed refractory multiple myeloma (MM). J Clin Oncol. 2021;39:(suppl 15; abstr 8018). doi:10.1200/JCO.2021.39.15_suppl.8018