Efficacy and Safety of Selinexor, Pomalidomide, and Dexamethasone (SPd) for Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM)
Authors: Baljevic Muhamed , Bahlis Nizar J. , Kotb Rami , Schiller Gary J. , Lipe Brea , Madan Sumit , Sutherland Heather J. , Lentzsch Suzanne , Callander Natalie , Biran Noa , Van Domelen Dane , Mark Tomer , White Darrell 
Published: December 2024

Introduction: Multiple myeloma (MM) remains incurable; despite the promise of T-cell engaging therapies, no standard of care has been established for patients with RRMM after prior treatment with immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), or anti-CD38 monoclonal antibodies (αCD38). Large observational studies, such as LocoMMotion, have reported short median progression free survival (mPFS) of approximately 4.5 months in triple-class-exposed (TCE) RRMM with commonly used anti-MM agents; however, the vast majority of these patients did not receive selinexor treatment. Selinexor, an oral exportin 1 (XPO1) inhibitor approved in combination with dexamethasone (d) in penta-refractory MM and with d and bortezomib in RRMM after ≥1 prior therapy, is being evaluated with pomalidomide (P) and d (SPd) for the treatment of RRMM in the Phase 1b/2 STOMP trial (NCT02343042). Updated clinical and safety data for the cohorts that received SPd regimens with 40 mg or 60 mg once weekly (QW) selinexor are presented.

Methods: The SPd arm of the multi-arm STOMP study evaluated selinexor at multiple doses and schedules in combination with Pd (P doses tested consisted of 2 mg, 3 mg, or 4 mg QD) in patients with RRMM. Study objectives were to determine the maximum tolerated dose and the recommended Phase 2 dose to assess safety and to examine the efficacy of the SPd regimen. Response assessments were investigator-determined per International Myeloma Working Group criteria.

Results:

Patient Demographics

As of March 25, 2024, 81 patients had been enrolled in the SPd arm, including 20 in the 60 mg QW (SPd60) and 16 in the 40 mg QW (SPd40) groups. Of all patients treated with SPd, 53.1% were male, the median age was 65, and patients had a median 3 prior lines of therapy. Percentage of patients with prior exposure/refractory status to IMiD was 100%/86.4%; PI 100%/80.2%, αCD38 33.3%/30.9%, and TCE: 33.3%/25.9%.

Efficacy

The investigator-assessed overall response rate (ORR) was 39.5% (95% CI 28.8, 51.0) for the entire cohort, 55.0% (95% CI 31.5, 76.9) for SPd60, and 43.8% (95% CI 19.8, 70.1) for SPd40. The very good partial response or better rate was 19.8% (95% CI 11.7, 30.1) in the entire cohort, 30.0% (95% CI 11.9, 54.3) in SPd60, and 31.3% (95% CI 11.0, 58.7) in SPd40. There were 2 stringent complete responses (CRs; 1 in SPd60 and 1 in SPd40, both TCE) and 1 CR (SPd40). For the entire cohort, the median time to response was 1.1 months (95% CI 1.0, 2.0).

Updated PFS and duration of response results will be presented.

Safety

The most common treatment emergent adverse events (TEAEs) were:

Neutropenia Entire cohort: 67.9% any grade/60.5% G3-4SPd60: 75.0%/60.0%SPd40: 68.8%/68.8%

Fatigue Entire cohort: 64.2%/13.6%SPd60: 75.0%/15.0%SPd40: 62.5%/6.3%

Nausea Entire cohort: 61.7%/1.2%SPd60: 70.0%/0SPd40: 50.0%/0

Anemia Entire cohort: 54.3%/33.3%SPd60: 65.0%/25.0%SPd40: 31.3%/18.8%

Thrombocytopenia Entire cohort: 49.4%/29.6%SPd60: 45.0%/25.0%SPd40: 25.0%/18.8%

Median duration of exposure in weeks was 19.0 (range 1, 260) in the entire cohort, 22.0 (7, 114) in SPd60, and 28.0 (4, 176) in SPd40. Median relative selinexor dose intensity was 86.4% (57.5 mg/week) for the entire cohort, 77.5% (46.5 mg/week) for SPd60, and 93.2% (37.3 mg/week) for SPd40.

Conclusions: The all-oral combination of SPd showed signs of preliminary efficacy and was generally tolerable in patients with RRMM. Although the ORR was greater in the SPd60 cohort, TEAEs were less frequent, duration of exposure was longer, and higher dose intensity was achieved for patients treated with SPd40. These data support the further evaluation of low-dose weekly selinexor in the ongoing EMN29 trial (NCT05028348) of SPd40 versus elotuzumab and Pd in TCE RRMM progressing immediately after a αCD38-containing line of therapy.