KEY TAKEAWAYS
- The study aimed to evaluate the efficacy of SEL plus RUX in patients with MF in a real-world setting.
- The study included 20 patients with MF who received SEL plus RUX treatment. The dosage of SEL and RUX was determined at the investigator’s discretion.
- The median age of the patients was 66 years, and the median time from MF diagnosis to study enrollment was 3 years.
- In this preliminary analysis, the combination of SEL and RUX demonstrated promising clinical activity and had a tolerable adverse effect profile in patients with myelofibrosis.
Selinexor (SEL) is a first-in-class, orally administered, selective inhibitor of nuclear export agent that binds karyopherin protein export protein exportinelofibrosis (MF) is a neoplasm of hematopoietic progenitor cells characterized activation of the JAK/STAT signaling decreased viable cells and colony formation in newly diagnosed and Ruxolitinib(RUX)-exposed MF cells, according to preclinical studies. In a phase I study, 92% of patients with treatment-naive MF who received SEL plus RUX achieved SVR35, 69% had symptom response, and 65% had stable or impossible levels.
Additionally, the ESSENTIAL trial demonstrated the sustained spleen responses of SEL as a sole agent in JAKi-refractory MF. Assess the efficacy and tolerability of SEL plus RUX in patients with MF. This is a prospective, investigator-initiated, multi-center cohort study examining the effectiveness of SEL plus RUX in MF patients in a real-world setting. MF Patients were administered SEL plus RUX (dosage per investigator judgment). According to IWG-MRT and ELN, the response criteria efficacy endpoint was spleen response assessed by palpation or CT/MRI. Critical secondary endpoints included anemia response, symptom response as defined by TSS or physician judgment, and safety. About 20 patients had received at least one dose of oral weekly SEL (20 mg, n=1; 40 mg, n=7; 60 mg, n=12) with RUX twice daily as determined by investigator discretion as of February 2023.
The median age was 66 (range: 43-75). 13 patients had primary MF, 2 patients had post-PV MF, and 5 patients had post-ET MF. Around 11 of 14 patients (79%) had peripheral blood bursts; 1-4% (6 patients) were undetermined. The median time from MF diagnosis to study enrollment was 3 years (range 1-33), and the median duration of prior RUX treatment was 22 months (0 to 77 months), with 1 RUX-naive and 19 suboptimal (n=5) or intolerable (n=14) patients. Patients with JAK2, CALR, and MPL mutations numbered 14, 2, and 1, respectively. 17 patients had splenomegaly, and 4 patients had anemia depenanemia-packed red blood cell (PRBC) transfusions.
Int-2 (n = 16) and high-risk (n high-risk unknown (n = 3) were the DIPSS risk categories. The median duration of treatment was 154 days (range: 26-378). 6/13 (46%) patients who were evaluated attained SVR35 or palpable spleen reduction. 15 patients with available data and at least 8 weeks of treatment were assessed for symptom response; 13/15 (87%) had symptom relief (10 patients achieved a 50% reduction in TSS or significant symptom response as determined by a physician, and 1 patient achieved symptom resolution). 15/16 (94%)PRBC transfusion-independent patients had stable hemoglobin (Hgb, 20g/L; n=10, 63%) or increased Hgb levels (>20g/L increase; n=5, 31%) at the most recent follow-up. 3/4 (75%) of PRBC transfusion-dependent patients became independent of PRBC transfusions (n=1) or reduced their PRBC transfusion frequency (n=1). 11 points (55%) stopped using SEL.
About 5 patients discontinued treatment due to mortality (2 from COVID-19, 1 from sepsis, and 2 unknown), participation in a clinical trial by 1, unsatisfactory response by 2, transplantation by 1, and toxicity by 2. Nausea (11/20, 55%), vomiting (8/20, 40%), decreased appetite (6/20, 30%), and anemia (5/20, 25%) were the most prevalent treatment-emergent adverse events (TEAEs). The most pervasive TEAEs of Grade 3 were anemia and thrombocytopenia. In this preliminary analysis, the combination of SEL and RUX in patients with myelofibrosis exhibits promising clinical activity. To date, the mixture has a tolerable adverse effect profile.
Minghui Duan, Lan Ma, Qiuling Wu, Hong Liang, Wei Wang, Shaoling Wu, Lijun Mu, Hai Lin, Hebing Zhou, Hongxia Shi, Hongmei Jing/A REAL-WORLD STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SELINEXOR IN COMBINATION WITH RUXOLITINIB IN PATIENTS WITH MYELOFIBROSIS/Inc, M. G. (n.d.). A REAL-WORLD STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SELINEXOR… by Minghui Duan. Library.ehaweb.org. Retrieved July 18, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/385502/minghui.duan.a.real-world.study.to.evaluate.the.efficacy.and.safety.of.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27888%2Atrend%3D4016%2Amarker%3D4178
