No abstract

PC. Baseline characteristics between the arms included lower baseline ANC (<0.5 x 10 9 /L, 42.4% vs. 21.1%); greater TP53 abnormalities (11.9% vs 5.3%); and increased proportion of prior MDS (11.0% vs 5.3%) in the selinexor group. The median OS for selinexor versus PC was 94 days versus 170 days, (HR = 1.18 [95% CI 0.79-1.75]; P = 0.4221). CR/CRi was observed in 12% of patients on selinexor, and 4% of the PC-treated patients. The most common TEAEs in the selinexor arm included nausea (59.1%), decreased appetite (55.7%), fatigue (46.1%), diarrhea (40.0%), thrombocytopenia (33.9%), vomiting and pyrexia (27.8%). In PC-treated patients, the most common TEAEs included febrile neutropenia (35.6%), constipation (33.3%), fatigue (28.9%), pyrexia (28.9%), anemia (26.7%), thrombocytopenia (24.4%), and dyspnea (22.2%). The most common SAEs in the selinexor and PC groups were febrile neutropenia and pneumonia. Febrile neutropenia occurred at a lower rate in the selinexor group (17.4%) than in the PC group (35.6%). The incidence of TEAE leading to death was identical in each arm (20%). Summary/Conclusion: The primary endpoint was not met and selinexor treatment did not show a significant difference in median OS compared with treatment of PC in this patient population. There was no increased TEAE of death between the 2 arms. There were several factors that may have led to this result. First, the trial was designed to allow DNMTI-experienced patients, but not necessarily DNMTi-refractory patients, so the survival estimates in the PC were subsequently influenced by responses to SOC DNMTi therapy in patients who were not refractory to DNMTi therapy. Second, the imbalances in the presence ofTP53, depth of neutropenia at enrollment, and transformed MDS indicate a higher risk population in the selinexor arm. Therefore, the results of this study support further investigation of selinexor in carefully selected populations of AML patients.