Selinisol combined with ruxolitinib tablets shows activity in ruxolitinib pretreatment for myelofibrosis

According to Phase 2 SENTRY trial data submitted in 2024, Selinexor (Selinexor) combined with ruxolitinib tablets (JAKAFI) showed encouraging efficacy and controllable safety in myelofibrosis (MF) patients who had previously received ruxolitinib tablets.

Preliminary results of the study show that among patients evaluable for efficacy (n=30), 26 patients (86.67%) experienced symptom relief, 9 patients (40.91%) experienced a 50% reduction in total symptom score (TSS) or clinically assessed symptom relief rate, and 1 patient (3.33%) experienced symptom relief. In addition, 4 of 9 transfusion-dependent patients achieved transfusion independence after receiving combination therapy.

In the trial data, promising efficacy and safety data of selinesol plus ruxolitinib tablets in a real-world setting in patients with myelofibrosis were demonstrated. Here, the efficacy and safety of this regimen in patients previously treated with ruxolitinib tablets will be reported in a prospective clinical trial.

This prospective, open-label, multicenterPhase 2 study enrolled a total of 38 patients. Paragraph 1 stated that all 38 patients received at least 1 dose of selinesol, and in the 6-month analysis, 88% experienced a reduction in spleen length and 36% achieved a splenic response. Splenic response was defined as a greater than 50% reduction in length according to the International Working Group on Research and Treatment of Myeloproliferative Neoplasms and the European Leukemia Network response criteria.

A total of27 patients received the 60 mg dose of selinesol, 10 patients received the 40 mg dose, and 1 patient received the 20 mg dose. All doses are administered once weekly. The primary endpoint of the trial is splenic response. This is assessed by palpation or CT and MRI. Secondary endpoints were anemic response, symptomatic response, and safety. The median age of all patients was 65.5 years (range 22-84 years), and 17 patients (44.74%) were male. The mean duration of prior ruxolitinib therapy was 20.5 months (range, 3.6-138.0).

At allAmong 38 patients, 25 (65.79%) carried JAK2 gene mutations, 5 (13.16%) carried CALR mutations, 1 (2.63%) carried MPL mutations, and 2 patients (5.26%) had triple-negative myelofibrosis. Data were missing for 3 patients (7.89%) and unknown for the remaining patients. According to the Dynamic International Prognostic Scoring System model, 23 patients (60.53%) were classified as intermediate risk, 10 patients (26.32%) as high risk, and 5 patients (13.16%) as unknown. In addition, 36 patients (94.74%) had splenomegaly at diagnosis.

Regarding safety, the median treatment duration of selinesol was 151 days (range, 16-696 days), which was consistent with the 40-mg and 60-mg doses. A total of 18 patients discontinued treatment: six due to disease progression, four to enroll in another trial, five due to toxicity, two for financial reasons, and one to undergo a transplant. The most common adverse reactions (AEs) of any grade were anemia and nausea (both 36.8%), followed by vomiting (23.7%). For grade 3 or 4 adverse events, the most common were anemia (18.4%), thrombocytopenia (5.3%), and gastrointestinal symptoms, including nausea and vomiting (both 2.6%).

Unlike the [Phase 2] basic study [NCT03627403], which showed that selinexole produced sustained splenic responses as a single agent in inhibitor-refractory myelofibrosis, this combination of selinexole and ruxolitinib tablets may achieve similar therapeutic effects without the need for higher doses. Patients with myelofibrosis require a more comprehensive approach to assessing response than a 35% reduction in spleen volume or a 50% reduction in total symptom score. The Phase 3 SENTRY trial (NCT04562389) is currently recruiting patients with myelofibrosis who are first to JAK inhibitors.

Reference materials:https://www.onclive.com/view/selinexor-plus-ruxolitinib-displays-activity-in-ruxolitinib-pretreated-myelofibrosis