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

March 31, 2026 updated by: Weiwei Tian, Shanxi Bethune Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

127

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with multiple myeloma (MM) were enrolled if they had a confirmed diagnosis by bone marrow examination, relapsed/refractory disease after 2-4 prior lines of therapy, were aged ≥18 years, and provided written informed consent. Patients were excluded if they had unresolved toxicities from prior chemotherapy, severe comorbidities, or hypersensitivity to study drugs.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
RRMM Patients Receiving Selinexor-Based Therapy
Patients with multiple myeloma (MM) were enrolled if they had a confirmed diagnosis by bone marrow examination, relapsed/refractory disease after 2-4 prior lines of therapy, were aged ≥18 years, and provided written informed consent. Patients were excluded if they had unresolved toxicities from prior chemotherapy, severe comorbidities, or hypersensitivity to study drugs. All patients received a selinexor-based 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.reatment response was evaluated every two cycles, including bone marrow assessment, M-protein quantification, and imaging studies.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the overall response rate (ORR) after two cycles of selinexor-based therapy.
Time Frame: After 2 treatment cycles (approximately 8 weeks)
Overall response rate (ORR) after two cycles of selinexor-based therapy, assessed according to standard response criteria using bone marrow examination, M-protein quantification, and imaging studies.
After 2 treatment cycles (approximately 8 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanxi Bethune Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2026

Primary Completion (Estimated)

January 31, 2027

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

March 22, 2026

First Submitted That Met QC Criteria

March 31, 2026

First Posted (Actual)

April 7, 2026

Study Record Updates

Last Update Posted (Actual)

April 7, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT-2025-043

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared due to privacy concerns, ethical restrictions, and institutional policies regarding sensitive clinical and genetic data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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