Selinexor in combination with azacitidine or ruxolitinib in myelodysplastic/myeloproliferative neoplasm overlap syndromes: A multicenter prospective study
Xijuan Lin, Ziwei Liu, Chen Yang, Junling Zhuang, Na Wei, Tingting Cui, Wenqi Zheng, Fang Ye, Xiaoqing Ding, Miao Chen, Bing HanAbstract
Background
Therapeutic strategies for myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs) remain suboptimal. Selinexor, an oral selective inhibitor of exportin 1, represents a mechanism‐based therapeutic approach. Preclinical and clinical evidence indicated synergistic antileukemic effects when selinexor was combined with hypomethylating agents or janus kinase inhibitors.
Methods
A prospective, single‐arm trial was conducted to evaluate selinexor plus either azacitidine (for MDS‐dominant features) or ruxolitinib (for MPN‐dominant features) in patients with MDS/MPN. The primary end point was the overall response rate at 6 months, which was assessed according to 2015 International Working Group criteria. Secondary end points included safety, progression, and survival.
Results
Twenty patients were enrolled (four with MDS‐dominant features, 16 with MPN‐dominant features). The median age was 66 years in the MDS group and 62.5 years in the MPN group. The overall response rate was 60% (12 of 20 patients; 95% confidence interval [CI], 36.1%–80.5%) overall, 75% (three of four patients; 95% CI, 31.1%–95.4%) in the MDS group, and 56.3% (nine of 16 patients; 95% CI, 33.2%–76.9%) in the MPN group. In the MDS group, clinical benefits included improvements in the total symptom score, erythroid response, platelet response, and spleen response (one in each of four patients; 25% for each response). In the MPN group, partial responses occurred in two of 16 patients (12.5%), and partial bone marrow responses occurred in three of 16 (18.8%), with additional benefits including spleen response (five of 16; 31.3%), total symptom score improvement (two of 16; 12.5%), erythroid response (two of 16; 12.5%), and platelet response (one of 16; 6.3%). Adverse events occurred in 14 patients (70%). Three patients experienced grade 3 or greater events, including two disease‐related fatalities. After a median follow‐up of 6 months (range, 2–15 months), one patient's disease transformed to acute myeloid leukemia.
Conclusions
Selinexor combined with azacitidine or ruxolitinib showed encouraging efficacy with a manageable safety profile in patients with MDS/MPN.