SENTRY Trial Data Demonstrate Significant Spleen Volume Reduction With Selinexor in Myelofibrosis

The phase 3 SENTRY trial (NCT04562389) evaluating selinexor (Xpovio; Karyopharm Therapeutics Inc) in combination with ruxolitinib (Jakafi; Incyte Corporation) has met its first co–primary end point, demonstrating a statistically significant improvement in spleen volume reduction among patients with Janus kinase (JAK) inhibitor–naive myelofibrosis (MF).^1,2

Addressing Unmet Needs in MF

MF is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, and painful constitutional symptoms. JAK inhibitors, such as ruxolitinib, are the current standard of care. However, less than half of patients gain a significant therapeutic effect, such as a spleen volume reduction of at least 35%, and many eventually experience disease progression or loss of response.³

Given these limitations, it is necessary to have therapies that can deepen responses and improve long-term disease control. The main objective of the SENTRY trial was to test whether the combination of ruxolitinib and selinexor, a first-in-class selective inhibitor of nuclear export, would improve clinical outcomes.

SENTRY Design and End Points

SENTRY is a randomized, phase 3 trial enrolling approximately 350 JAK inhibitor–naive patients with MF and adequate platelet counts. Patients were randomly assigned in a 2:1 ratio to receive once-weekly selinexor plus ruxolitinib or placebo plus ruxolitinib.^1,2,4

The trial’s co–primary end points include the proportion of patients achieving at least a 35% reduction in spleen volume (SVR35) at week 24 and the absolute change in total symptom score (TSS) over the same period.^1,2 These end points reflect both objective disease burden and patient-reported symptom improvement, aligning with clinically meaningful outcomes in MF.

“For patients with myelofibrosis, improvements in spleen and symptoms are expected outcomes from JAK inhibitors such as ruxolitinib. The SENTRY topline results suggest that the combination of selinexor and ruxolitinib delivers superior spleen reduction, which may predict overall survival, while offering similar symptom improvement, and may offer an important advance for our patients,” said Claire Harrison, MD, professor of myeloproliferative neoplasms and deputy chief medical officer of research, data, and analytics at Guy’s and St. Thomas’ NHS Foundation Trust in England.¹

The trial met its first co–primary end point by showing that patients who received selinexor plus ruxolitinib experienced significant improvements in SVR35 compared with those who received ruxolitinib alone. This outcome reveals the potential of selinexor to improve spleen responses to a greater extent than is normally achieved with JAK inhibition alone.¹

Spleen volume reduction is a critical end point in MF trials, as splenomegaly contributes significantly to symptom burden and reduced quality of life. Achieving SVR35 has been associated with improved clinical outcomes and is widely considered a benchmark for therapeutic efficacy.⁴

Supporting Evidence From Earlier-Phase Studies

Positive findings from phase 3 trials have further validated results from earlier-phase studies in which selinexor was used with ruxolitinib. For example, in data from a phase 1 trial, 79% of patients achieved SVR35 at week 24, along with significant relief from symptoms measured by TSS. This result implied that the combination may provide a stronger and longer-lasting response than ruxolitinib alone.⁵

Additionally, data from exploratory analyses of previous studies revealed that the drug combination may have an impact on the progression of the disease, such as lowering levels of inflammatory cytokines and molecular indicators of disease activity. Although these results need to be validated in larger studies, they provide biological justification for combining selinexor with JAK inhibition.⁴

Implications for Clinical Practice

The achievement of the first co–primary end point in the SENTRY trial represents an important step toward expanding treatment options for patients with MF. If the combination also demonstrates meaningful improvements in symptom burden and maintains a manageable safety profile, it could emerge as a new frontline therapeutic strategy.

For pharmacists, these findings underscore the importance of staying informed about emerging combination therapies that may reshape treatment paradigms. Pharmacists play a key role in managing adverse events, optimizing adherence, and educating patients on novel treatment approaches.

As additional data from the SENTRY trial, including symptom outcomes and safety analyses, become available, they will further clarify the clinical role of selinexor in MF management. Nonetheless, the demonstrated improvement in spleen volume reduction marks a promising development in a field with significant unmet need.

REFERENCES

1. Karyopharm’s phase 3 SENTRY trial in myelofibrosis met first co–primary end point, demonstrating statistically significant improvement in spleen volume reduction. Press release. Karyopharm Therapeutics Inc. March 24, 2026. Accessed March 31, 2026. https://investors.karyopharm.com/2026-03-24-Karyopharms-Phase-3-SENTRY-Trial-in-Myelofibrosis-Met-First-Co-Primary-Endpoint,-Demonstrating-Statistically-Significant-Improvement-in-Spleen-Volume-Reduction

2. Study of selinexor in combination with ruxolitinib in myelofibrosis (SENTRY). ClinicalTrials.gov. Updated October 3, 2025. Accessed March 31, 2026. https://clinicaltrials.gov/study/NCT04562389

3. Advancing myelofibrosis treatment: the promise of the SENTRY trial. HealthTree. December 2, 2024. Accessed March 31, 2026. https://healthtree.org/myelofibrosis/community/articles/sentry-trial-update

4. Mascarenhas J, Maher K, Rampal R, et al. Selinexor plus ruxolitinib in JAK inhibitor treatment-naive myelofibrosis: SENTRY phase 3 study design. Future Oncol. 2025;21(7):807-813. doi:10.1080/14796694.2025.2461393

5. Karyopharm announces presentation of updated phase 1 selinexor data in patients with treatment-naive myelofibrosis at AACR 2023. Press release. Karyopharm Therapeutics Inc. April 18, 2023. Accessed March 31, 2026. https://investors.karyopharm.com/2023-04-18-Karyopharm-Announces-Presentation-of-Updated-Phase-1-Selinexor-Data-in-Patients-with-Treatment-Naive-Myelofibrosis-at-AACR-2023