This article reviews interim results from a randomized phase 2 study of induction and consolidation with or without selinexor (SEL), a small-molecule inhibitor of exportin (XPO1), in newly diagnosed patients with acute myeloid leukemia (AML) aged ≥60 years.
Patients enrolled in this study were aged >60 years with newly diagnosed de novo AML and were randomized (3:1) to receive cytarabine 100 mg/m2/day by continuous infusion for 7 days and daunorubicin 60 mg/m2 on days 1 to 3 (7+3) plus SEL, or 7+3 alone. Patients responding to treatment could move to high-dose cytarabine consolidation with or without SEL (as initially randomized). In the SEL arm, patients who completed all consolidation could go on maintenance therapy with SEL alone. Induction consisted of 7+3. Consolidation was cytarabine 1.5 mg/m2 given every 12 hours on days 1 to 3 with granulocyte colony-stimulating factor administered 24 hours after the final dose of cytarabine. During induction and consolidation, SEL was dosed at 60 mg orally on days 1, 3, 8, 10, 15, and 17, and on days 1 and 8 every 21 days during maintenance.
A total of 28 patients were enrolled at the time of data cutoff. Twenty-one patients were randomized to the SEL arm and 7 were randomized to the control arm. The median age was 69 years (range, 60-75 years) and 43% were male. In the control arm, the 60-day mortality rate was 14% (1/7). In the SEL arm, the 60-day mortality rate was 10% (2/21). In the control arm, 43% (3/7) of patients achieved either a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). Of the 3 responders in the control arm, 1 had undergone allogeneic stem-cell transplantation (allo-SCT). In the SEL arm, 86% (18/20) of patients achieved either CR or CRi and, 7 of the 18 responders had proceeded to allo-SCT. Despite the small sample size of this trial, progression-free survival (PFS) and overall survival (OS) both favor the SEL arm with trends toward significance. Median OS was 265 days in the control arm and 839 days in the SEL arm (P = .0472). Median PFS was 108 days in the control arm and 558 days in the SEL arm (P = .1319). No unexpected adverse events (AEs) were observed. Seven (33%) patients in the SEL arm had prolonged thrombocytopenia (>4 weeks following neutrophil recovery, transfusion-dependent in 1). Diarrhea was the most common AE resulting in dose holding or dose modification.
In conclusion, SEL in combination with standard induction and consolidation therapy appears highly active in older patients with de novo AML. Enrollment in this study is ongoing.
Reference
Pardee TS, Pladna KM, Lyerly S, et al. Frontline Selinexor and Chemotherapy Is Highly Active in Older Adults with Acute Myeloid Leukemia (AML). Presented at: 62nd American Society of Hematology Annual Meeting & Exposition; December 5-8, 2020. Abstract 633.