Translating SENTRY Data into Clinical Practice / Myelofibrosis 08/11/2026

Selinexor Combination Therapy in Myelofibrosis: SENTRY Trial Insights

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

  • Janus kinase (JAK) inhibitors are the primary treatment for patients with myelofibrosis.
  • The SENTRY trial showed that adding selinexor, an oral XPO1 inhibitor, to ruxolitinib improved spleen volume responses.
  • Anti-nausea prophylaxis is crucial when starting selinexor, although gastrointestinal toxicities may subside over time.
  • Combination regimens for myelofibrosis may serve as effective bridging therapies prior to allogeneic stem cell transplant, and may even allow previously ineligible patients to proceed to transplant.

Myelofibrosis Treatment Paradigm and the SENTRY Trial

Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, moderated a panel discussion on myelofibrosis treatment, focusing on the recent data from the SENTRY trial. The panel featured Nikolai Podoltsev, MD, PhD, of Yale School of Medicine; Raajit Rampal, MD, PhD, of Memorial Sloan Kettering Cancer Center; Srinivas Tantravahi, MBBS, MRCP, of Huntsman Cancer Institute, University of Utah; and Pankit Vachhani, MD, of University of Alabama at Birmingham.

Treatment Options for Myelofibrosis

Myelofibrosis is a myeloproliferative neoplasm characterized by constitutional symptoms and splenomegaly, and conventional treatments are focused on reducing symptom burden and spleen volume. JAK inhibitors have been the cornerstone of myelofibrosis treatment since the approval of ruxolitinib in 2011. Three additional JAK inhibitors have been approved since then: fedratinib in 2019, pacritinib in 2022, and momelotinib in 2023. In addition to JAK inhibitor therapy, allogeneic stem cell transplant is often pursued for patients with high-risk disease or severe cytopenias.  

Currently, the majority of patients with myelofibrosis are still treated with ruxolitinib monotherapy in the frontline setting, although pacritinib and momelotinib are preferred for patients with thrombocytopenia and anemia, respectively. When approaching a new patient with myelofibrosis, Dr. Podoltsev uses PASS (prognosis, anemia, spleen, and symptoms) as a mnemonic device to stratify patients and guide treatment decisions. 

SENTRY Study: Frontline Treatment With Selinexor Plus Ruxolitinib for Myelofibrosis

The phase 3 SENTRY trial evaluated the addition of selinexor to frontline ruxolitinib in JAK inhibitor–naïve patients with myelofibrosis. Participants were required to have a Dynamic International Prognostic Scoring System score of intermediate-1 or higher, spleen volume of 450 cm3 or higher, and platelet count of 100×109/L or higher. The dual primary end points were spleen volume reduction of 35% or more (SVR35) and absolute mean change in total symptom score (TSS) excluding fatigue at week 24. Safety and overall survival (OS) were secondary end points, and variant allele frequency (VAF) and circulating peripheral blasts were exploratory end points. 

SENTRY enrolled 353 patients in total and randomized 235 to selinexor plus ruxolitinib and 118 to placebo plus ruxolitinib. Overall, 49.8% of patients in the selinexor plus ruxolitinib arm versus 28% in the ruxolitinib arm achieved SVR35 by week 24 (OR, 2.58; 95% CI, 1.6-4.17; P < .0001). Selinexor plus ruxolitinib was favored for spleen response versus ruxolitinib alone at week 12 (49.4% vs 20.3%), week 36 (46.9% vs 23%), and any time (67.7% vs 44.9%). The mean change in spleen volume at week 24 was -40% with selinexor plus ruxolitinib versus -26.7% with ruxolitinib. The absolute mean change in TSS at week 24 was -9.9 (95% CI, -11.2 to -8.6) and -10.9 (95% CI, -12.6 to -9.1) for selinexor plus ruxolitinib and ruxolitinib alone, respectively (mean difference, 0.97; 95% CI, -1.07 to 3.02; P = .825). TSS changes were consistent across all six symptom domains, according to the authors.

After a median follow-up of 11.6 months in the selinexor plus ruxolitinib arm and 12.6 months in the ruxolitinib arm, 95.3% and 89.8% of patients were alive. OS favored selinexor plus ruxolitinib versus ruxolitinib alone (HR, 0.43; 95% CI, 0.19-1; P = .022). In a 24-week landmark analysis, achieving SVR35 predicted improved OS, and 98% of patients who achieved SVR35 versus 88% of nonresponders were alive at week 72. 

Driver mutation VAF reduction of 20% or more at week 24 was 32% with selinexor plus ruxolitinib versus 23.9% with ruxolitinib, and was associated with SVR35 (OR, 3.22; 95% CI, 1.81-5.72). In addition, selinexor plus ruxolitinib reduced circulating peripheral blasts in patients with baseline blasts and maintained 0% blasts in patients without baseline blasts, while ruxolitinib alone did not. 

Treatment-emergent adverse events (TEAEs) occurred in 99.1% of the selinexor plus ruxolitinib arm and 97.4% of the ruxolitinib arm, including grade 3 or higher TEAEs in 70.1% and 50%, respectively. TEAEs led to discontinuation in 14.5% and 8.6% of patients in each arm. TEAEs leading to mortality occurred in 0.9% versus 2.6% of patients in each arm. 

The positive signal for OS is a promising finding for the trial, and represents an evolution from spleen volume and symptom responses as the only end points in myelofibrosis trials, said Dr. Rampal.

Frontline Treatment Selection for Myelofibrosis 

The doctors discussed how selinexor plus ruxolitinib might be incorporated into the treatment paradigm for myelofibrosis. If approved, the selinexor doublet likely won’t replace JAK inhibitor monotherapy for all patients. However, it will be an important frontline option for selected patients in whom maximizing spleen volume reduction is a priority, said Dr. Podoltsev. The selinexor doublet or other intensified regimens may also be used as a bridging therapy to get patients to transplant. The improved spleen response outcomes may even allow patients that were ineligible for transplant to proceed to transplant after treatment, said Dr. Vachhani. 

In SENTRY, the selinexor combination was favored across subgroups, supporting its consideration for all patients with the possible exception of those that are elderly, frail, or with relevant comorbidities. 

Side Effects of Selinexor Plus Ruxolitinib 

Selinexor has been approved for multiple myeloma since 2019 and although it has largely been relegated to late-relapse treatment settings, its side effects have been well described. The most common non-hematological adverse events associated with selinexor include nausea, fatigue, decreased appetite, and weight loss. Nausea can be especially prominent, and robust anti-nausea prophylaxis is needed. The SENTRY protocol required that patients receive two antiemetics with different mechanisms before each selinexor dose for the first two treatment cycles. Typically, gastrointestinal toxicities subside over time, at which point the antiemetic regimen can be held. 

If a patient has persistent nausea, reducing dose may improve tolerability without compromising responses. In Dr. Rampal’s experience, dose reductions were more successful at managing nausea than dose holds. With the SENTRY regimen, either the selinexor and ruxolitinib dose can be modified. Notably, the combination arm in the trial used a lower ruxolitinib dose than the control arm. 

Ongoing Trials and the Future of Myelofibrosis Treatment

Looking forward, researchers are exploring more combinations like selinexor plus ruxolitinib for myelofibrosis treatment. As more combinations emerge, the question may become whether patients will immediately start on combinations, or whether novel agents will be added to JAK inhibitor backbones to improve response, said Dr. Vachhani. The POIESIS trial is exploring the latter strategy by adding navtemadlin in patients who have a suboptimal response to ruxolitinib alone. Conversely, trials are also exploring non-JAK inhibitor treatments in the frontline setting, including the SENTRY-2 trial on frontline selinexor. 

As treatment options expand, the treatment paradigm may shift towards earlier treatment in lower-risk patients to prevent myelofibrosis–related sequelae from developing in the first place. For now, however, the doctors emphasized that treatment selection for myelofibrosis should be a shared decision with each patient based on their characteristics, disease features, and treatment goals.