Translating SENTRY Data into Clinical Practice / Myelofibrosis 09/02/2026

Ep. 3: Incorporating the SENTRY Regimen and Managing Side Effects in Myelofibrosis

Professional portrait of a man in a suit and tie, wearing glasses, smiling confidently against a neutral background. Nikolai Podoltsev, MD, PhD Research scientist in a laboratory setting focusing on oncological advancements and cancer research at OncUpdates. Raajit Rampal, MD, PhD Smiling professional man in a black vest with a blue shirt and red tie, standing indoors with a blurred background. Srinivas Tantravahi, MBBS, MRCP Professional portrait of a man in a dark suit and white shirt against a gray background, suitable for medical or healthcare-related content. Pankit Vachhani, MD Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD

Key Points

  • The SENTRY trial showed that selinexor plus ruxolitinib improved spleen volume reduction responses without worsening symptom response in patients with myelofibrosis.
  • Until longer-term data are available, the doublet regimen may initially be favored for bridging to transplant in patients with substantial splenomegaly who aren’t responding to Janus kinase (JAK) inhibitor monotherapy.
  • Anti-nausea prophylaxis is critical when using selinexor, and dose reductions appeared to be more effective than dose holds for managing side effects in the SENTRY trial.

Managing Side Effects of Selinexor Plus Ruxolitinib in Myelofibrosis

During a broader discussion about the treatment paradigm for myelofibrosis and the impact of the phase 3 SENTRY trial on the Oncology Brothers podcast, four myelofibrosis experts weighed in on the potential place of selinexor plus ruxolitinib in the myelofibrosis treatment paradigm and highlighted important strategies for managing side effects of the combination.

Selinexor Plus Ruxolitinib in the Myelofibrosis Treatment Paradigm

If selinexor plus ruxolitinib is approved, it likely won’t replace JAK inhibitor monotherapy for most patients, at least until longer-term data demonstrate an overall survival (OS) benefit, said Nikolai Podoltsev, MD, PhD, of Yale School of Medicine, who was an author on the phase 3 SENTRY trial. Instead, the doublet may initially become an important frontline option for maximizing spleen reduction in select patients, such as high-risk patients with significant splenomegaly who aren’t responding adequately to JAK inhibitor monotherapy. In this population, selinexor plus ruxolitinib could be an attractive strategy for bridging to transplant, Dr. Podoltsev said. 

For many years, myelofibrosis studies have correlated spleen volume responses with OS, suggesting that spleen volume correlates to burden of disease and that reducing spleen volume is indicative of disease control, said Srinivas Tantravahi, MBBS, MRCP, of Huntsman Cancer Institute at the University of Utah. In SENTRY, spleen response rates at weeks 12 and 24 were similar in the selinexor plus ruxolitinib arm, which may explain the early signal for an OS benefit, Dr. Tantravahi said. In addition, SENTRY data showed the spleen response benefit with the doublet was consistent across subgroups. If the regimen is approved, the paradigm may be to offer selinexor plus ruxolitinib to all patients unless there is a specific reason not to, Dr. Tantravahi said. 

Side Effects of Selinexor Plus Ruxolitinib and Management Strategies

Selinexor has been approved for the treatment of multiple myeloma for several years, and its side effects are well established. Selinexor is commonly associated with nausea and other gastrointestinal (GI) side effects, as well as cytopenias and fatigue. Discussing expected side effects with patients and preparing them with antiemetic prophylaxis is crucial, Dr. Podoltsev said. SENTRY required patients in the combination arm to receive two different antiemetics before each selinexor dose for the first 2 cycles. Ideally GI side effects subside over time and antiemetics can be dropped, but if nausea persists, oncologists should reduce or hold doses of selinexor, Dr. Podoltsev said. 

According to Raajit Rampal, MD, PhD, of Memorial Sloan Kettering Cancer Center, another author on the SENTRY trial, the data did not suggest a direct correlation between dose and response, and many patients maintained responses when dropping from 60 mg once weekly to 40 mg once weekly dosing. In Dr. Rampal’s clinical experience, dose reductions often yielded a steady improvement in side-effect burden without compromising disease control, whereas dose holds without reductions seemed to result in the same side effects recurring. 

Notably, there are overlapping side effects between selinexor, ruxolitinib, and the underlying disease, particularly fatigue and dizziness, said Pankit Vachhani, MD, of the University of Alabama at Birmingham. In the SENTRY trial, neutropenia and thrombocytopenia appeared to be more common with the doublet. However, there did not seem to be an increased rate of complications or deaths related to these events, said Dr. Vachhani. Dr. Vachhani also noted that SENTRY used a lower ruxolitinib dose in the combination arm than in the control arm, and generally suggested that doses of either selinexor or ruxolitinib can be reduced based on a patient’s defining toxicities.