Phase 3 SENTRY Trial Shows Progress in Myelofibrosis Care

New findings from the phase 3 SENTRY trial offer encouraging news for patients with myelofibrosis, a rare form of blood cancer. The study met one of its co-primary end points, demonstrating a statistically significant improvement in spleen volume reduction at week 24 in patients treated with Xpovio (selinexor) in combination with Jakafi (ruxolitinib) compared with Jakafi alone, according to a news release which detailed the update.

Spleen enlargement, or splenomegaly, is a hallmark of myelofibrosis and can lead to abdominal discomfort, early satiety, and reduced quality of life. Achieving meaningful spleen volume reduction is a key goal of treatment. The results from this trial suggest that adding Xpovio to standard therapy may enhance disease control in patients who have not yet received prior JAK inhibitor treatment.

"The results from SENTRY are an important development for patients as the combination of Xpovio plus Jakafi meaningfully improved spleen response and we observed a promising signal in overall survival. Reducing spleen volume remains one of the most important treatment goals in myelofibrosis since [it] is associated with improvement in overall survival," Dr. John Mascarenhas, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of the Center of Excellence for Blood Cancers and Myeloid Disorders, said in the release.

Xpovio combination improves key clinical outcome

The SENTRY trial evaluated Xpovio, an oral selective inhibitor of nuclear export, in combination with Jakafi, a commonly used JAK inhibitor. Patients receiving the combination therapy experienced significantly higher rates of spleen volume reduction of at least 35% compared with those receiving Jakafi plus placebo.

This end point, commonly referred to as SVR35, is widely used in myelofibrosis clinical trials and reflects a meaningful reduction in spleen size that can correlate with symptom relief. In addition to spleen response, the trial also includes a second co-primary end point evaluating changes in total symptom score over 24 weeks.

Although full data are still being evaluated, these early findings indicate that the combination approach may provide improved disease control compared with standard therapy alone. For patients, this could translate into better management of symptoms and potentially improved day-to-day functioning.

Understanding myelofibrosis and unmet needs

Myelofibrosis is a rare blood cancer affecting approximately 20,000 patients in the United States. It develops when scar tissue forms in the bone marrow, impairing the body’s ability to produce healthy blood cells.

Common symptoms include fatigue, weakness, night sweats, bone pain, and discomfort caused by an enlarged spleen. Many patients also develop anemia, which may require frequent blood transfusions and is associated with poorer outcomes.

Currently, JAK inhibitors such as Jakafi are the standard treatment option. Although these therapies can reduce symptoms and spleen size, they do not work for all patients, and more than 30% discontinue treatment due to side effects such as anemia. This highlights a clear need for new and more effective treatment strategies.

SENTRY trial design and information

The phase 3 SENTRY trial (XPORT-MF-034) is a randomized, global study evaluating once-weekly Xpovio in combination with Jakafi compared with placebo plus Jakafi in patients with JAK inhibitor–naïve myelofibrosis.

Participants were randomized to receive either the Xpovio combination or the control regimen. The trial focuses on patients with platelet counts greater than 100 × 10⁹/L, representing a population suitable for standard JAK inhibitor therapy.

The co-primary end points include spleen volume reduction of at least 35% at week 24 and changes in total symptom score over the same period. These end points are designed to capture both physical disease burden and patient-reported symptom improvement.

The trial enrolled approximately 350 patients with myelofibrosis, reflecting a broad population of individuals who had not previously been treated with JAK inhibitors.

This patient group is particularly important, as early intervention strategies may influence long-term outcomes. By focusing on JAK inhibitor–naïve patients, the study aims to determine whether adding Xpovio upfront can improve treatment response compared with standard therapy alone.

Patients included in the trial experienced typical features of myelofibrosis, such as enlarged spleen and symptom burden, making the findings relevant to real-world clinical practice.

Additional findings and future outlook

Beyond the primary end point, earlier studies of Xpovio have suggested additional potential benefits, including symptom improvement, stabilization of hemoglobin levels, and possible disease-modifying effects.

These findings support the rationale for combining Xpovio with Jakafi to address multiple aspects of the disease. Investigators continue to evaluate whether the combination can improve not only spleen size but also overall symptom burden and long-term outcomes.

As additional data from the SENTRY trial become available, including results for symptom improvement and safety, the oncology community will gain a clearer understanding of the therapy’s full impact.

For patients with myelofibrosis, these results represent an important step forward. The potential to enhance standard treatment with a novel agent may expand options and improve disease management in a setting where unmet need remains high.

"The myelofibrosis community is waiting for new treatment options that can build upon the benefit of JAK inhibitors. Improving overall survival is the ultimate goal for people living with myelofibrosis and I am incredibly encouraged by these results," Kapila Viges, CEO of the MPN Research Foundation, concluded in the news release. "These results are an exciting development for the myelofibrosis community."

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

1. Karyopharm's Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint, Demonstrating Statistically Significant Improvement in Spleen Volume Reduction, by Karyopharm Therapeutics Inc. News release; March 24, 2026.

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