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

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.

Eligibility

Inclusion Criteria:

1. Patients with a confirmed diagnosis of multiple myeloma (MM) based on bone marrow aspiration or biopsy, in accordance with the International Myeloma Working Group (IMWG) criteria.
2. Patients with relapsed/refractory MM after 2-4 prior lines of therapy.
3. Age ≥18 years.
4. Provision of written informed consent, with willingness to participate in the study and to provide relevant clinical samples and follow-up information.

Exclusion Criteria:

1. Patients with relapsed MM whose toxicities from prior chemotherapy have not recovered to baseline or ≤ Grade 1.
2. Presence of other active malignancies or severe systemic diseases (e.g., significant cardiovascular or cerebrovascular disease, hepatic or renal insufficiency) that may affect study outcomes or limit tolerance to treatment or follow-up.
3. Prior history of bone marrow transplantation or other treatments that may affect the bone marrow microenvironment or immune function within 6 months before study initiation.
4. Known hypersensitivity to selinexor, ixazomib, or any components of the study drugs, or a history of severe allergic reactions.
5. Known human immunodeficiency virus (HIV) infection (HIV antibody positive).
6. Participation in another clinical trial within 30 days prior to study initiation or during the study period.
7. Pregnant or breastfeeding women.
8. Patients with psychiatric disorders or those unable to comply with study procedures.

Conditions2

Interventions1

Browse More Trials