John Mascarenhas MD; ASCO 2026: New Janus Kinase Inhibitor Improves Myelofibrosis Outcomes When Added to Ruxolitinib Initial Therapy
CHICAGO, USA—Outcomes were improved for patients with myelofibrosis in the phase 3 SENTRY trial who were randomized to have the new Janus kinase inhibitor selinexor added to their ruxolitinib initial therapy.Findings were reported at the 2026 Annual Meeting of the American Society of Clinical Oncology.Peter Goodwin got the details from first author John Mascarenhas MD, Professor of Medicine and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at the Tisch Cancer Institute, Icahn School of Medicine, in Mount Sinai, New York, NY.
New Janus Kinase Inhibitor Improves Myelofibrosis Outcomes When Added to Ruxolitinib Initial Therapy
An interview with:
John Mascarenhas MD, Professor of Medicine, Director, Center of Excellence for Blood Cancers and Myeloid Disorders, Tisch Cancer Institute, Icahn School of Medicine, Mount Sinai, New York, NY
CHICAGO, USA—Outcomes were improved for patients with myelofibrosis in the phase 3 SENTRY trial who were randomized to have the new Janus kinase inhibitor selinexor added to their ruxolitinib initial therapy.Findings were reported at the 2026 Annual Meeting of the American Society of Clinical Oncology.Peter Goodwin got the details from first author John Mascarenhas MD, Professor of Medicine and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at the Tisch Cancer Institute, Icahn School of Medicine, in Mount Sinai, New York, NY.
AUDIO JOURNAL OF ONCOLOGY: John Mascarenhas MD
IN:“Peter Goodwin here …..
OUT:….Audio Journal of Oncology, I’m Peter Goodwin12: 53secs
Source:
https://ascopubs.org/doi/10.1200/JCO-26-01080
ASCO, 2026
Abstract #: LBA6500 Oral Abstract Session
Selinexor plus ruxolitinib in JAK inhibitor–naïve myelofibrosis: Phase 3 SENTRY trial.
Authors:
John Mascarenhas, Haris Ali, Haifa K. Al-Ali, Jose Valentin Garcia-Gutierrez, Sebastian Grosicki, Zhanet Grudeva, Claire Harrison, Jushik Hong, Hsin-An Hou, Michal Kwiatek, Michael Loschi, Francesco Passamonti, Andrea Patriarca, Nikolai A. Podoltsev, Raajit Rampal, Srinivas K. Tantravahi, Laura G. Urian, Reshma Rangwala, Pankit J. Vachhani, Prithviraj Bose
Organizations:
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, City of Hope, Duarte, CA, Universitaetsklinik Halle, Halle, Germany, Hospital Universitario Instituto Ramón y Cajal de Investigación Sanitaria, Universidad de Alcalá, Madrid, Spain, Department of Hematology, Independent Public Healthcare Facility Municipal Hospitals, Katowice, Poland, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Plovdiv, Poland, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea, National Taiwan University Children's Hospital, Taipei, Taiwan, Poznan University of Medical Sciences, Poznan, N/A, Poland, Centre Hospitalier Universitaire de Nice, Nice, France, University of Milano, Milano, Italy, Hematology Unit, Department of Translational Medicine, University of Eastern Piedmont and AOU Maggiore della Carità, Novara, Italy, Yale School of Medicine, New Haven, CT, Memorial Sloan Kettering Cancer Center, New York, NY, Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania, Karyopharm, Newton Center, MA, University of Alabama at Birmingham, Birmingham, AL, The University of Texas MD Anderson Cancer Center, Houston, TX
Background:
Myelofibrosis (MF) is a debilitating myeloproliferative neoplasm marked by splenomegaly, constitutional symptoms, and reduced life expectancy. JAK inhibitors (JAKi), such as ruxolitinib (R), are standard frontline therapy; however, only ~1/3 of R-treated patients (pts) achieve spleen volume reduction ≥35% (SVR35). Despite observed symptom improvements, durable modification of underlying disease biology, including reductions in variant allele frequency (VAF), is limited. Importantly, gains in overall survival remain modest, highlighting a critical unmet need. Selinexor (S), an inhibitor of XPO1-mediated nuclear export, has biologic activity in MF and synergy with R in MPN models. SENTRY evaluated S+R in pts with JAKi–naïve MF.
Methods:
Pts with JAKi-naïve MF were randomized 2:1 to S 60 mg weekly plus R (per label) or placebo plus R, stratified by DIPSS risk, spleen volume, and baseline platelet count. Eligibility included spleen volume ≥450 cm3, active symptoms, DIPSS Int-1 or higher and platelets ≥100×109/L. Co-primary endpoints were SVR35 and absolute mean change in TSS (AbsTSS; excluding fatigue) at Week 24. SVR35 used a stratified Cochran–Mantel–Haenszel test; TSS used a mixed-effects model for repeated measures. Hierarchical testing (one-sided α=0.025) evaluated SVR35 then AbsTSS. Secondary endpoints included safety and overall survival (OS). Changes in VAF were exploratory.
Results:
353 pts were randomized (S+R n=235; R n=118). Baseline characteristics were balanced.
At Week 24 SVR35 was achieved in 49.8% of pts in S+R vs 28.0% in R (difference, 21.8%; OR 2.58; 95% CI 1.60 to 4.17; P < .0001). Responses occurred early and were sustained, with SVR35 rates of 49.4% vs 20.3% at Week 12 and 46.9% vs 23.0% at Week 36. SVR35 was achieved at any time in 67.7% vs 44.9%. Mean percent change in spleen volume at Week 24 was −40.0% vs −26.7%. Mean (95% CI) AbsTSS change at Week 24 was −9.9 (−11.2 to −8.6) vs −10.9 (−12.6 to −9.1); adjusted mean difference 0.97 (95% CI -1.07 to 3.02; P = .825).
As of Feb 20, 2026, 224 (95.3%) pts in S+R and 106 (89.8%) in R were alive. With median follow- up of 11.6 and 12.6 months, OS favored S+R (HR 0.43; 95% CI 0.19 to 1.00; nominal P = .022) with early separation of Kaplan–Meier curves emerging around Month 9. VAF reduction ≥20% at Week 24 occurred in 32.0% vs 23.9% and correlated with SVR35 response.
TEAEs occurred in 99.1% in S+R and 97.4% in R (grade ≥3 in 70.1% vs 50.0%); however, TEAEs leading to treatment discontinuation were low (14.5% and 8.6%). TEAEs leading to death occurred in 0.9% vs 2.6%. Confirmed leukemic transformation was 1.7% in each arm.
Conclusions:
S+R significantly improved spleen response vs R alone with earlier, deeper, and sustained response rates, comparable symptom improvement from baseline, and a manageable safety profile. The improved spleen response, early OS signal, and VAF reductions observed in SENTRY position S+R as a novel combination approach for frontline treatment of MF.
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