Recommended Phase 2 Dose of Selinexor Plus Pomalidomide and Dexamethasone Effective for Relapsed/Refractory Multiple Myeloma

Treatment with 60 mg of selinexor (Xpovio) plus pomalidomide (Pomalyst) and dexamethasone (XPd-60) produced stronger and deeper responses than the 40 mg dose regimen (XPd-40) for patients with relapsed/refractory multiple myeloma who were previously treated with an anti-CD38 monoclonal antibody, according to results from the multi-arm phase 1b/2 STOMP study (NCT02343042) presented at the 2021 American Society of Hematology (ASH) Annual Meeting and Exposition.

In the XPd-60 arm, the overall response rate (ORR) was 65.0% compared with 48.1% in the XPd-40 arm. Responses were notably deeper in the XPd-60 arm, with a complete response (CR)/stringent CR rate of 5.0% and a very good partial response rate of 25.0% compared with 3.7% and 7.4% in the XPd-40 arm, respectively. The clinical benefit rate was 75.0% and 70.4% in the XPd-60 and XPd-40 arms, respectively.

“There is a need for effective and well-tolerated therapies to treat multiple myeloma that has progressed after treatment with [anti-CD38 monoclonal antibodies], as well as with lenalidomide (Revlimid) and bortezomib (Velcade),” poster presenter, Darrell White, MD, a hematologist; professor of medicine in the Division of Hematology, Department of Medicine; and the senior associate dean at the Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada, said in his presentation of the data.

Eligible patients had relapsed/refractory multiple myeloma and were previously treated with at least 2 cycles of lenalidomide and a proteasome inhibitor. Although prior pomalidomide (Pomalyst) treatment was allowed, patients who had pomalidomide-refractory multiple myeloma were only eligible for the dose escalation phase.

The primary end points of the trial included determining the maximum tolerated dose, recommended phase 2 dose, and ORR. Secondary end points included safety and tolerability, progression-free survival (PFS), and overall survival (OS).

The XPd-60 arm featured the recommended phase 2 dose, was 60 mg of selinexor once weekly combined with 4 mg of pomalidomide once daily from days 1 to 21 and 40 mg of dexamethasone once weekly. The XPd-40 arm received 40 mg of selinexor with the same pomalidomide/dexamethasone backbone.

At the October 8, 2021, cutoff date, 27 patients were enrolled in the XPd-40 arm and 20 were included in the XPd-60 arm. The median age was 67.0 years (range, 48-78). Additionally, 63% of patients were male, and 51.9% had an ECOG performance status of 1. For the XPd-60 arm, patients had a median age of 65.5 years (range, 37-85). Sixty-five percent of patients were female and 70% had an ECOG performance status of 1.

All patients underwent prior therapy with lenalidomide and a proteasome inhibitor. Moreover, 59.3% of patients in the XPd-40 arm received prior therapy with daratumumab compared with 30.0% of patients in the XPd-60 arm.

The median PFS was 10.9 months (95% CI, 7.6–not evaluable [NE]) in the XPd-60 arm and was NE (95% CI, 5.7-NE) in the XPd-40 arm. The median duration of response was 10.0 months (95% CI, 3.9-NE) and NE (95% CI, NE-NE) in the XPd-60 and XPd-40 arms, respectively. The median time to response was 1.0 months in both arms, respective.

For patients who underwent prior therapy with an anti–CD38 monoclonal antibody, the ORR was 100% in the XPd-60 arm compared with 5.00% in the XPd-40 arm. The clinical benefit rate for this population was 100% and 68.8% in the XPd-60 and XPd-40 arms, respectively. Moreover, the median PFS for those previously treated with an anti-CD38 monoclonal antibody was 8.9 months (95% CI, 7.6-NE) in the XPd-60 arm and NE (95% CI, 3.3-NE) in the XPd-40 arm.

The most common any grade hematologic treatment-emergent adverse effects (TEAEs) in both the XPd-60 and XPd-40 arms, respectively were neutropenia (75.0% vs 63.0%), anemia (65.0% vs 33.3%), and thrombocytopenia (45.0% vs 29.6%). Common any grade non-hematologic TEAEs in the XPd-60 and XPd-40 arms, respectively, were fatigue (75.0% vs 40.7%), nausea (70.0% vs 25.9%), diarrhea (35.0% vs 18.5%), constipation (10.0% vs 25.9%), reduced appetite (30.0% vs 11.0%), and decreased weight (25.0% vs 11.1%).

Common grade 3 TEAEs in the XPd-60 and XPd-40 arms, respectively, included neutropenia (35.0% vs 25.9%), anemia (25.0% vs 7.4%), and thrombocytopenia (15.0% vs 11.1%). Grade 4 neutropenia was observed in both arms (25.0% vs 25.9%), respectively, and grade 4 thrombocytopenia was seen in the XPd-60 arm only (10.0%).

Reference

White D, Chen CI, Baljevic M, et al. Once Weekly Oral Selinexor, Pomalidomide, and Dexamethasone in Relapsed Refractory Multiple Myeloma. Presented at: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021; Virtual. Abstract 2748.