NCT07514052

Predicting Response to Selinexor-Based Therapy in Relapsed/Refractory Multiple Myeloma: A Multicenter Prospective Study

Efficacy Prediction of Selinexor-Based Regimens in Relapsed/Refractory Multiple Myeloma Based on Differential Multigene Expression: A Multicenter Prospective Clinical Study

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 127 (estimated)
• Sponsor: Shanxi Bethune Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Background: Relapsed/refractory multiple myeloma (RRMM) remains a major clinical challenge due to treatment resistance and disease heterogeneity. Selinexor-based regimens have demonstrated promising efficacy; however, predictive biomarkers for treatment response are still lacking. This study aims to evaluate the predictive value of differential multigene expression in RRMM patients treated with selinexor-based therapy. Methods: This is a multicenter, prospective clinical study enrolling 127 patients with RRMM. Eligible patients are aged ≥18 years, have a confirmed diagnosis of multiple myeloma based on International Myeloma Working Group (IMWG) criteria, and have received 2-4 prior lines of therapy. Key exclusion criteria include unresolved toxicities from prior treatments, severe comorbidities, prior bone marrow transplantation within 6 months, hypersensitivity to study drugs, HIV infection, pregnancy or lactation, and participation in other clinical trials within 30 days. All patients receive a selinexor-based regimen consisting of selinexor 60 mg orally once weekly (Day 1 of each week) in combination with standard agents. Each treatment cycle lasts 28 days. Treatment response is assessed every two cycles using bone marrow examination, M-protein quantification, and imaging studies. After treatment completion, patients are followed every 3 months for up to 2 years. Endpoints: The primary endpoint is overall response rate (ORR) after two treatment cycles. Secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints focus on the association between the expression levels of candidate genes (hnRNPU, IRF3, ALB2RP, ZBTB17, ATRX, ABCC4, ASB8, and E2F1) and ORR following two cycles of selinexor-based therapy. Statistical Analysis: Statistical analyses are performed using Excel 2019 and SPSS 26.0. Continuous variables are tested for normality using the Shapiro-Wilk test and Q-Q plots. Normally distributed data are presented as mean ± standard deviation, while non-normally distributed data are described using median and interquartile range (IQR). Categorical variables are expressed as counts and percentages. Logistic regression analysis is used to evaluate factors associated with ORR. Survival outcomes (PFS and OS) are estimated using the Kaplan-Meier method. All statistical tests are two-sided, and a P-value \<0.05 is considered statistically significant. Ethics and Timeline: The study is conducted in accordance with ethical principles, and all patients provide written informed consent. Patient enrollment is planned from January 2026 to January 2027, with final data analysis expected in 2027. The total study duration is 2 years. Conclusion: This study aims to identify potential gene expression biomarkers predictive of response to selinexor-based therapy in RRMM, which may contribute to individualized treatment strategies and improved clinical outcomes.

Detailed description

Background: Relapsed/refractory multiple myeloma (RRMM) remains an incurable hematologic malignancy characterized by clonal heterogeneity and progressive drug resistance. Although selinexor-based regimens have demonstrated encouraging clinical activity in heavily pretreated patients, treatment response varies significantly across individuals. The identification of reliable predictive biomarkers is therefore essential to optimize patient selection and improve therapeutic outcomes. Emerging evidence suggests that gene expression profiling may provide valuable insights into treatment sensitivity. This study aims to evaluate the predictive value of differential multigene expression for response to selinexor-based therapy in patients with RRMM. Methods: This is a multicenter, prospective clinical study enrolling a total of 127 patients with RRMM. Eligible participants are aged ≥18 years, have a confirmed diagnosis of multiple myeloma based on International Myeloma Working Group (IMWG) criteria, and have received 2-4 prior lines of therapy. All patients provide written informed consent prior to enrollment. Key exclusion criteria include: unresolved toxicities from prior chemotherapy, presence of other active malignancies or severe systemic diseases that may interfere with study outcomes, prior bone marrow transplantation or therapies affecting the bone marrow microenvironment or immune function within 6 months prior to study entry, known hypersensitivity to selinexor or related agents (e.g., ixazomib), HIV infection, pregnancy or lactation, participation in another clinical trial within 30 days prior to enrollment or during the study period, and inability to comply with study procedures due to psychiatric or other conditions. All enrolled patients receive a selinexor-based combination regimen consisting of selinexor administered orally at a dose of 60 mg once weekly (Day 1 of each week) in combination with standard therapeutic agents. Each treatment cycle is defined as 28 days. Treatment response is assessed every two cycles using bone marrow examination, quantification of M-protein, and imaging studies where appropriate. After completion of treatment, patients are followed up every 3 months for a total duration of 2 years. Endpoints: The primary endpoint is the overall response rate (ORR) after two cycles of selinexor-based therapy. Secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety profile. Safety assessments are conducted according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Exploratory endpoints focus on the association between the expression levels of candidate genes-including hnRNPU, IRF3, ALB2RP, ZBTB17, ATRX, ABCC4, ASB8, and E2F1-in bone marrow samples and treatment response, particularly ORR after two cycles of therapy. These analyses aim to identify potential molecular biomarkers predictive of response to selinexor-based regimens. Statistical Analysis: All data are managed using a double data entry system to ensure accuracy and integrity. Statistical analyses are performed using Excel 2019 and SPSS version 26.0. Continuous variables are first assessed for normality using the Shapiro-Wilk test and Q-Q plots. Normally distributed variables are summarized using mean, standard deviation, median, minimum, and maximum values, while non-normally distributed variables are described using median and interquartile range (IQR), along with minimum and maximum values. Categorical variables are presented as frequencies and percentages. Baseline demographic and clinical characteristics are summarized descriptively. Study completion, including withdrawals and dropouts, is documented and analyzed in detail. Logistic regression analysis is used to evaluate factors associated with ORR. Survival outcomes (PFS and OS) are estimated using the Kaplan-Meier method. All statistical tests are two-sided, and a P-value \<0.05 is considered statistically significant unless otherwise specified. Ethics and Study Timeline: This study is conducted in accordance with the principles of medical ethics and relevant regulatory requirements. All participants provide written informed consent prior to inclusion. Patient enrollment is scheduled from January 2026 to January 2027, with final data analysis expected to be completed in 2027. The total study duration is 2 years. Conclusion: This multicenter prospective study aims to investigate the predictive role of multigene expression profiling in determining response to selinexor-based therapy in RRMM. The findings are expected to facilitate the development of personalized treatment strategies and improve clinical outcomes in this challenging patient population.

Conditions

• Multiple Myeloma of Bone

Interventions

Type	Name	Description
DRUG	Selinexor-Based Regimen	Patients received a selinexor-based combination regimen consisting of selinexor 60 mg administered orally once weekly (QW, on Day 1 of each week) in combination with standard agents. Each treatment cycle lasted 28 days. Treatment response was assessed every two cycles using bone marrow examination, M-protein quantification, and imaging studies. After completion of treatment, patients were followed up every 3 months for 2 years.

Timeline

• Start date: 2026-01-01
• Primary completion: 2027-01-31
• Completion: 2027-04-30
• First posted: 2026-04-07
• Last updated: 2026-04-07

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study