Objective: To identify the optimal dose of selinexor in combination with pomalidomide and dexamethasone (SPd).
Methods: An analysis of efficacy and safety of 2 once-weekly selinexor regimens (60 mg and 40 mg) with pomalidomide and dexamethasone (SPd-60 and SPd-40, respectively) given to patients with relapsed/refractory multiple myeloma (RRMM) in the STOMP (NCT02343042) and XPORT-MM-028 (NCT04414475) trials.
Results: Twenty-eight patients (60.7% males, median age 67.5 years) and 20 patients (35.0% males, median age 65.5 years) were analyzed in the SPd-40 and SPd-60 cohorts, respectively. Overall response rate was 50% (95% confidence interval [CI] 30.6-69.4%) and 65% (95% CI 40.8-84.6%), respectively. Very good partial response or better was reported in 28.6% (95% CI 13.2-48.7%) and 30.0% (95% CI 11.9-54.3%) of patients, respectively. Among 27 responders in both cohorts, the 12-month sustained response rate was 83.3% (95% CI 64.7-100.0%) for SPd-40 and 28.1% (95% CI 8.9-88.8%) for SPd-60. Median progression-free survival was 18.4 months (95% CI 6.5 months, not evaluable [NE]) and 9.5 months (95% CI 7.6 months-NE) for SPd-40 and SPd-60, respectively. Twenty-four-month survival rates were 64.2% (95% CI 47.7-86.3%) for SPd-40 and 51.1% (95% CI 29.9-87.5%) for SPd-60. Treatment-emergent adverse events (TEAEs) included neutropenia (all grades: SPd-40 64.3% versus SPd-60 75.0%), anemia (46.4% versus 65.0%), thrombocytopenia (42.9% versus 45.0%), fatigue (46.4% versus 75.0%), nausea (32.1% versus 70.0%) and diarrhea (28.6% versus 35.0%).
Conclusion: The all-oral combination of SPd exhibited preliminary signs of efficacy and was generally tolerable in patients with RRMM. The overall risk-benefit profile favored the SPd-40 regimen.
Competing Interests: DW: honoraria: Amgen, Antengene, Bristol Myers Squibb/Celgene, Forus, GSK, Janssen, Karyopharm, Sanofi, Takeda. SL: advisory board: Janssen, GSK, Takeda, Sanofi, Oncopetide, Pfizer, Regeneron; research funding: Zentalis, Sanofi; member of the board of directors and shareholder: Caelum Biosciences. MB: consultancy: Pfizer, AbbVie; advisory boards: Janssen Research, Bristol Myers Squibb/Celgene, Sanofi-Genzyme. OB, DV, CZ: employment and equity holders: Karyopharm. EC: employment: Clalit Health Services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. These studies were supported by research funding from Karyopharm Therapeutics, Inc. Medical writing and editorial assistance was funded by Karyopharm Therapeutics, Inc. Karyopharm had the following involvement in the study: study design, collection, analysis, writing, editorial assistance and submission of the article.
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