Frontline Selinexor and Chemotherapy Is Highly Active in Older Adults with Acute Myeloid Leukemia

2020 Year in Review - AML - Leukemia

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.

Related Items
Tibsovo Received a New Indication, in Combination with Azacitidine, for Newly Diagnosed Patients with AML and IDH1 Mutation
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Leukemia
Vidaza Received New Indication for Patients with Newly Diagnosed Juvenile Myelomonocytic Leukemia
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Leukemia, Pediatric Cancer
Arsenic Trioxide–Induced QTc Interval Prolongation and the Potential Benefit of Beta-Blockers in Patients with Acute Promyelocytic Leukemia: Case Series
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in Case Reports, Leukemia, Adverse Events
Effect of Concomitant Azole Antifungals on Duration of Myelosuppression in Newly Diagnosed Patients with AML Receiving Venetoclax in Combination with Cladribine and Low-Dose Cytarabine
JHOP - March 2022 Vol 12 Special Feature published on March 22, 2022 in HOPA Abstracts, Leukemia
Dasatinib-Induced Gynecomastia in 2 Patients with Chronic Myeloid Leukemia: Case Reports and Review of the Literature
Jessie Signorelli, PharmD, BCOP, Amir T. Fathi, MD, Gabriela Hobbs, MD
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Case Reports, Leukemia, Adverse Events
Lidocaine plus Tetracaine–Medicated Patch Used for Propofol Sedation During Lumbar Punctures in Pediatric Patients with Blood Cancer
Lisa R. Garavaglia, PharmD , Frank Casey, MD, Lesley Cottrell, PhD, Claudiu Faraon-Pogaceanu, MD, Stephan Paul, MD, Melvin Lee Wright, DO
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Original Article, Pediatric Cancer, Leukemia, Lymphoma
Myeloablative and Reduced-Intensity Preparative Regimens for Allogeneic Transplant in the Outpatient versus Inpatient Setting in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes
Gretchen Pardo, PharmD, Beth Eddy, PharmD, BCOP, Zahra Mahmoudjafari, PharmD, BCOP, Dennis Grauer, PhD, MS, Joseph McGuirk, DO
JHOP - August 2021 Vol 11, No 4 published on August 17, 2021 in Original Article, Transplant, Leukemia, Myelodysplastic Syndromes, Conditioning Regimen
Pharmacy Resident–Led Medication Reconciliation and Patient Education Service in Adults with Leukemia Receiving Anticancer Oral Agents: A Pilot Study
Lily Y. Jia, PharmD, BCOP, Jessie Signorelli, PharmD, BCOP, Samantha O. Luk, PharmD, BCOP, E. Bridget Kim, PharmD, BCPS, BCOP, Gayle C. Blouin, PharmD, BCOP
JHOP - June 2021 Vol 11, No 3 published on June 16, 2021 in Original Article, Leukemia, Oncology Pharmacy Programs
Pegaspargase-Induced Diabetic Ketoacidosis in a Patient with Acute Lymphoblastic Leukemia
Ellen Madarang, PharmD, BCOP, Leslie Gallardo, PharmD, BCPS, Terrence Bradley, MD
JHOP - June 2021 Vol 11, No 3 published on June 16, 2021 in Case Reports, Acute Lymphoblastic Leukemia, Leukemia, Adverse Events
Oral Azacitidine Prolongs Survival in Patients with Acute Myeloid Leukemia
Robert J. Ignoffo, PharmD, FASHP, FCSHP, FHOPA
JHOP - April 2021 Vol 11, No 2 published on April 27, 2021 in From the Literature, Leukemia
© Amplity Health. All rights reserved.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: