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Selinexor plus 7+3 and HDAC Consolidation Is Highly Active in Older Adults with Newly Diagnosed Acute Myeloid Leukemia

Conference Correspondent

Selinexor is a small-molecule inhibitor of exportin (XPO1). Results are presented here from a randomized phase 2 study of induction and consolidation with or without selinexor among newly diagnosed acute myeloid leukemia (AML) patients.

Patients included in this study were aged ≥60 years with newly diagnosed de novo AML. Eligible patients were randomized (3:1) to receive cytarabine 100 mg/m2 daily by continuous infusion for 7 days and daunorubicin 60 mg/m2 on days 1 to 3 (7+3) plus selinexor, or 7+3 alone. Patients were allowed to move to high-dose cytarabine consolidation with or without selinexor (as initially randomized) if they responded to treatment. In the selinexor arm, patients could go on maintenance therapy with selinexor alone if they completed all consolidation. Induction was comprised of 7+3. Consolidation consisted of cytarabine 1.5 gm/m2 administered every 12 hours on days 1 to 3 and granulocyte colony-stimulating factor administered 24 hours following the final dose of cytarabine. Selinexor was dosed at 60 mg orally on days 1, 3, 8, 10, 15, and 17 during induction and consolidation, and on days 1 and 8 every 21 days during maintenance.

At data cutoff, 28 patients had been enrolled. A total of 21 patients were randomized to the selinexor arm and 7 to the control arm. The median age was 69 years (range, 60-75 years) and 43% of patients were male. The 60-day mortality rate was 14% (1/7) in the control arm and 10% (2/21) in the selinexor arm. Three of the 7 patients in the control arm (43%) achieved either a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). One of these 3 responders moved on to allogeneic stem-cell transplantation (allo-SCT). In the selinexor arm, 86% (18/21) of patients achieved either CR or CRi with 7 of these responders moving on to allo-SCT. Both progression-free survival (PFS) and overall survival (OS) favor the selinexor arm with trends toward significance despite the small sample size. In the control arm, the median OS was 265 days compared with 839 days in the selinexor arm (P = .0472). In the control arm, the median PFS was 108 days compared with 558 days in the selinexor arm (P = .1319). There were no unexpected adverse events (AEs) observed to date. There were 7 (33%) patients in the selinexor arm who had prolonged thrombocytopenia (>4 weeks following neutrophil recovery, transfusion dependent in 1). The most common AE resulting in dose holding or dose modification was diarrhea.

In older patients with de novo AML, the addition of selinexor to standard induction and consolidation therapy appears to result in high activity. 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.

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