In patients with Janus kinase inhibitor (JAKi)-naïve myelofibrosis, the addition of selinexor to ruxolitinib significantly improves the incidence of spleen volume reduction of ≥35 percent (SVR35) compared with ruxolitinib alone, according to the SENTRY trial presented at ASCO 2026.
The trial achieved its first co-primary endpoint, showing a significantly higher SVR35 rate at week 24 with the combination regimen vs ruxolitinib alone, according to Dr John Mascarenhas from Icahn School of Medicine at Mount Sinai, New York, US.
Approximately half (49.8 percent) of the participants in the combination group achieved SVR35 at week 24. With ruxolitinib, only 28 percent achieved this endpoint. A comparison between groups yielded an odds ratio of 1.60 (one-sided p<0.0001). [ASCO 2026, abstract LBA6500]
Notably, a greater proportion of patients in the combination vs the ruxolitinib monotherapy group achieved SVR35 as early as week 12 (49.4 percent vs 20.3 percent). This effect was maintained through week 36 (46.9 percent vs 23 percent).
The improvement in SVR35 rate with the combination regimen over ruxolitinib monotherapy was consistent across all prespecified subgroups.
Second co-primary endpoint
The symptom improvements in both treatment groups were comparable. From baseline to week 24, the absolute mean change in total symptom score (AbsTSS) was –9.9 in the combination group and –10.9 in the ruxolitinib-only group. A comparison between groups yielded an adjusted mean difference of 0.97; however, this did not reach statistical significance (one-sided p=0.825).
Nonetheless, the reductions in TSS were consistent across symptom domains, Mascarenhas noted.
Other outcomes
At a median follow-up of approximately 12 months, a promising early overall survival (OS) signal was observed with selinexor-ruxolitinib compared with ruxolitinib alone (hazard ratio, 0.43; one-sided pnominal=0.022).
In the published manuscript, Mascarenhas and colleagues noted that the early OS signal is “a notable finding in MF, where early survival has not been seen in randomized trials so far.” [J Clin Oncol 2026 2:JCO2601080]
Ninety-eight percent of SVR35 responders were alive at week 72. The corresponding rate among nonresponders was 88 percent. According to Mascarenhas, these results suggest that SVR35 may predict OS.
Of note, a higher percentage of patients treated with selinexor plus ruxolitinib achieved a Variant allele frequency (VAF) reduction of ≥20 percent compared with those treated with ruxolitinib alone (32 percent vs 23.9 percent).
In a post hoc analysis comparing SVR35 responders with nonresponders regardless of treatment group, patients who achieved a VAF reduction of ≥20 percent at week 24 were more likely to achieve SVR35 (odds ratio, 3.22; one-sided pnominal<0.001).
Safety profile
The combination group had a slightly higher incidence of grade ≥3 treatment-emergent adverse events (TEAEs) compared with the ruxolitinib alone group (70.1 percent vs 50 percent).
In the combination group, the most frequently reported TEAEs were thrombocytopenia (59 percent) and anaemia and nausea (57 percent each). Mascarenhas noted that these AEs were mostly manageable and consistent with known profiles of both agents.
Rapid, deep, sustained responses
This global, double-blind, placebo-controlled, phase III trial analysed 353 patients (median age 67 years, 57.5 percent male) with JAKi-naïve myelofibrosis. The participants were randomized in a 2:1 ratio to receive selinexor plus ruxolitinib (n=235) or placebo plus ruxolitinib (n=118). The co-primary endpoints of the study were SVR35 and AbsTSS (excluding fatigue) from baseline to week 24.
“Overall, selinexor and ruxolitinib achieved a rapid, deep, and sustained SVR compared with ruxolitinib alone, and this was consistent across all subgroups of patients,” said Mascarenhas.
“Selinexor plus ruxolitinib represents a novel treatment strategy in JAKi-naïve myelofibrosis,” he added.