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4578 The Efficacy and Safety of Selinexor in Combination with Ruxolitinib in Ruxolitinib-Treated Myelofibrosis Patients: the Interim Analysis of a Prospective, Open-Label, Multicenter, Parallel-Cohort, Phase 2 Study

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, adult, MPN, Clinical Research, Combination therapy, Chronic Myeloid Malignancies, Diseases, Therapies, Myeloid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Minghui Duan1*, Lan Ma2*, Qiuling Wu, PhD3*, Hong Liang4*, Wei Wang, MD5*, Shaoling Wu6*, Lijun Mu7*, Hai Lin8*, Hebing Zhou9*, Hong-Xia Shi, MD10*, Jinghua Wang11* and Hongmei Jing2

1Department of Hematology, Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
2Peking University Third Hospital, Beijing, China
3Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, AL, China
4Department of Hematology & Oncology,Harbin Institute of Hematology & Oncology, haerbin, China
5The Affiliated Hospital of Qingdao University, Qingdao, China
6Department of Hematology, The Hospital Affiliated of Qingdao University, Qingdao, China
7The Second Hospital of Dalian Medical University, Dalian, China
8Department of hematology, First Hospital of Jilin University, Jilin, China
9Department of Hematology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
10Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
11The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China, Harbin, China

Background: Myelofibrosis is a chronic hematologic malignancy characterized by constitutional symptoms, bone marrow fibrosis, extramedullary hematopoiesis resulting in splenomegaly and a propensity toward leukemic progression. Although JAK inhibitors have improved patients’ splenomegaly and symptom burden, the clinical management of MF is still challenging for its limited treatment options, especially when patients become less responsive or intolerable to Ruxolitinib (RUX) treatment. Selinexor (SEL) is a novel, first-in-class, oral selective inhibitor of nuclear export agent that binds the karyopherin protein exportin 1 (XPO1). Preclinical studies showed SEL decreased viable cells and colony formation both in newly diagnosed and RUX-exposed MF cells. ESSENTIAL trial showed SEL’s sustained spleen responses as a single agent in JAKi refractory MF. Besides, a phase I study reported, with SEL plus RUX in treatment-Naïve MF, 92% patients(pts) achieved SVR35, 69% had symptom response and 65% had stable or improved Hgb levels. We have presented promising efficacy and safety data in real-world setting of SEL plus RUX regimen in MF patients in 2023 EHA. Here we are to report the efficacy and safety of the regimen in RUX-treated patients in a prospective clinical trial.

Methods: This is a prospective, open-label, multi-center, parallel-cohort phase 2 study, examining SEL plus RUX regimen in RUX-treated MF pts. The study includes MF pts with suboptimal RUX responses or intolerable to RUX treatment. Pts are given SEL 40mg or 60mg QW plus RUX (dosage per investigator judgement, RUX intolerable pts will receive reduced dose of RUX). A total of 40 pts will be included into the study. The primary endpoint is spleen response assessed by palpation or CT/MRI scan per IWG-MRT and ELN response criteria. Key secondary endpoints include anemia response, symptom response defined as symptom resolution or alleviation according to TSS or physician's judgement, and safety.



As of July 2023, 28 pts had received at least one dose of oral weekly SEL, including 12 suboptimal RUX responses pts and 16 RUX intolerable pts. The median age was 65 years old. Mean duration of prior RUX treatment was 24.5 months (range: 4-77). 18 pts had primary MF, 4 had post-PV MF, and 6 had post-ET MF. Median time from MF diagnosis to study enrollment was 5 years (0.25-29). JAK2, CALR and MPL mutations were present in 18 (64.28%), 5 (17.85%) and 1 (3.57%) pts respectively. All pts presented constitutional symptoms, 25 (89.29%) had splenomegaly, and 7 (25.00%) had packed red blood cell (PRBC) transfusion-dependent anemia. DIPSS risk category was intermediate 23 (82.14%), high risk 3 (10.71%) and unknown 2 (7.14%). Median treatment duration was 134 days (14-525) (Table 1). 15 pts (53.57%) discontinued SEL. Reasons for treatment discontinuation were death in 4 pts (3 from covid-19, 1 sepsis), participation in clinical trial in 2 pts, unsatisfactory response in 2, transplantation in 1, toxicity in 2, economic burden in 1 patient and lost to follow-up in 3.

Efficacy Analysis

The analysis of spleen response included 21 pts with spleen length assessment data by either palpation or CT/MRI. Spleen response is defined as length reduction more than 50% per IWG-MRT and ELN response criteria. 15 (71.42%) pts had a reduction in spleen volume and 8 (38.09%) achieved spleen response (Figure 1). For symptom response, 27 pts are with available data. 23 (85.18%) pts had symptom alleviation, 9 (33.33%) achieved ≥50% reduction in TSS or symptom response assessed by physician, of which 1 achieved symptom resolution. There are 12 pts with PRBC transfusion-independent anemia (Hgb≤100g/L) at baseline and had received study treatment for at least 28 days. 10 (83.33%) pts had maintained stable or improved Hgb levels at the last follow up. 5/7 (71.42%) PRBC transfusion-dependent pts became transfusion independent (1 pt) or had reduced transfusion frequency (4 pts), and 2 pts remained stable.


The most common TEAEs were nausea 14 (50.00%), vomiting 9 (32.14%), decreased appetite 8 (28.57%), and anemia 7 (25.00%). The most frequent TEAEs ≥ Grade 3 were anemia 3(10.71%) and thrombocytopenia 2(7.14%).

Conclusion: In this preliminary analysis, the combination of SEL and RUX showed encouraging efficacy and manageable safety in RUX-treated pts with myelofibrosis.

Disclosures: No relevant conflicts of interest to declare.

OffLabel Disclosure: Selinexor is a novel, oral, fi rst-in-class selective inhibitor of XPO1 was approved by NMPA for treatment in patients with Relapsed/ RefractoryMultiple Myeloma in China. Preclinical and clinical studies showed selinexor's activity in MF patients. As the treatment options are limited for MF patients, especially when patients become less responsive or intolerable to Ruxolitinib (RUX) treatment. In our study, we explored selinexor in RUX-treated MF patients in a prospective clinical trial.

*signifies non-member of ASH