Translating SENTRY Data into Clinical Practice / Myelofibrosis 08/26/2026

Ep. 2: Phase 3 SENTRY Trial: Selinexor Plus Ruxolitinib 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 phase 3 SENTRY trial showed selinexor plus ruxolitinib significantly improved spleen volume reduction responses compared with ruxolitinib alone in patients with myelofibrosis.
  • Symptom responses were comparable between the arms, but associations between spleen responses and improved survival support the potential value of the selinexor doublet.

SENTRY Trial Phase 3 Data on Selinexor Plus Ruxolitinib in Myelofibrosis

Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, cohosts of the Oncology Brothers podcast, hosted a panel discussion on the current treatment landscape in myelofibrosis. During the discussion, Raajit Rampal, MD, PhD, of Memorial Sloan Kettering Cancer Center, and Pankit Vachhani, MD, of the University of Alabama at Birmingham, reviewed the phase 3 SENTRY trial findings and considered the data’s possible impact on the myelofibrosis treatment paradigm. 

The phase 3 SENTRY trial compared selinexor plus ruxolitinib with placebo plus ruxolitinib as frontline therapy in Janus kinase (JAK) inhibitor–naive patients with intermediate-1 or higher-risk myelofibrosis. The co-primary endpoints were a 35% or greater reduction in spleen volume (SVR35) and an improvement in the absolute mean change in total symptom score (Abs-TSS), excluding fatigue, at week 24. Additional endpoints included safety, overall survival (OS), variant allele frequency, and circulating blast count.

Overall, 49.8% of patients in the selinexor arm versus 28% in the placebo arm achieved SVR35 at week 24 (OR, 2.58; 95% CI, 1.60-4.17; P < .0001). Spleen responses were more rapid and durable in the selinexor arm, with 12-week and 36-week SVR35 rates of 49.4% versus 20.3% and 46.9% versus 23.0%, respectively. SVR35 rates at any time were 67.7% with selinexor and 44.9% with placebo. Notably, selinexor was favored for spleen responses across all analyzed subgroups, Dr. Vachhani said. 

The mean change in Abs-TSS at week 24 was −9.9 (95% CI, −11.2 to −8.6) with selinexor and −10.9 (95% CI, −12.6 to −9.1) with placebo (mean difference, 0.97; 95% CI, −1.07 to 3.02;  P = .825). Changes in Abs-TSS were consistent across all 6 symptom domains. To explain the lack of Abs-TSS benefit with the addition of selinexor, Dr. Rampal suggested that in patients with myelofibrosis, there may be a ceiling to the degree of symptom improvement achievable with current therapies. Importantly, adding selinexor did not worsen symptoms while still providing a significant SVR35 advantage in the study, Dr. Rampal said. 

Previous myelofibrosis trial analyses suggested an association between achievement of SVR35 and improved OS, and phase 3 and earlier phase 1 SENTRY data support this. Although the data are not yet mature, patients treated with selinexor showed a trend toward improved OS compared with those treated with placebo. The positive signal for OS is promising and hopefully represents growth beyond spleen and symptom response endpoints in myelofibrosis clinical trials, Dr. Rampal said.