Is the treatment of selineiso in Laos good

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by anemia, splenomegaly, constitutional symptoms, etc. Allogeneic hematopoietic stem cell transplantation is the only possible cure for MF, but its use is limited by a variety of reasons, including age restrictions, patient performance status, and post-transplant complications.

As a new targeted drug, selinexor has been approved for the treatment of multiple myeloma, and some studies have shown that selinexor also performs well in MF. As the world's first novel mechanism of oral selective nuclear export protein inhibitor, it can cause intranuclear storage and activation of tumor suppressor proteins and other growth regulatory proteins, as well as downregulate the intracytoplasmic levels of various oncogenic proteins, and induce apoptosis of a large number of solid and hematological tumor cells.

Background:

According to data from the Phase 1/3 XPORT-MF-034 trial (NCT04562389) presented at the 2023AS Annual Meeting, adverse effects of the oral XPO1 inhibitor selinexor in combination with ruxolitinib were tolerated and manageable and showed signs of clinical efficacy in patients with myelofibrosis (MF) who were not treated with JAK inhibitors.

Research Methods:

The first phase of XPORT-MF-034 (NCT04562389) is an open-label study of patients treated with 40 mg (n=3) or 60 mg (n=3) selinexor once weekly and 15 mg or 20 mg ruxolitinib twice daily, beginning in a Phase 1a dose-escalation phase. Subsequently, the study moved into a Phase 1b dose expansion part, in which selinexor (40 mg or 60 mg once weekly) was combined with ruxolitinib (n=18). This led the researchers to conduct a randomized phase 1/3 trial of 306 patients who were randomized in a 2:1 ratio to receive once-weekly oral selinexor 60 mg plus ruxolitinib and placebo plus ruxolitinib. Data as of August 1, 2023, and the investigators assessed patient safety, drug persistence, and disease improvement as assessed by biomarkers. The primary endpoint includes determining the maximum tolerated dose or recommended Phase 3 dose, and safety. Secondary endpoints included SVR35, TSS50, anemia reactions, and adverse effects (AEs).

Findings:

As of April 10, 2023, a total of 24 patients (PTS) have received at least one dose of selinexor (40 mg: n=10; 60 mg:n=14)。 At any grade, the most common adverse events (AEs) were nausea (75% mostly grade 1-2), fatigue (58%), anemia (54%), and thrombocytopenia (54%). Patients who received prophylactic anti-vomiting reported a lower incidence and severity of nausea AEs compared with those who did not receive prophylactic antiemetic; The median weight of the patients increased by 3.3 kg at week 24. Two patients discontinued treatment due to treatment-related AEs (thrombocytopenia and neuropathy). Generally stable hemoglobin levels were observed in 48% of patients who were not transfusion-dependent. The median was 10.1 g/dL at baseline, 9.3 g/dL at week 12, and 10.2 g/d L at week 24. Median platelet counts remained generally stable, with a median of 258 k/u L at baseline, 164 k/u L at week 14, and 193 k/u l at stage 24. The Intent-to-Treat (ITT) population achieved an SVR35 of 40% at week 24.