Published in:
01-06-2021 | Acute Myeloid Leukemia | Original Article
A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory/relapsed adult acute myeloid leukemia patients
Authors:
María P. Martínez Sánchez, Juan Eduardo Megías-Vericat, Rebeca Rodríguez-Veiga, Susana Vives, Juan Miguel Bergua, Anna Torrent, Sara Suárez-Varela, Blanca Boluda, Joaquín Martínez-López, Isabel Cano-Ferri, Evelyn Acuña-Cruz, Laura Torres-Miñana, Beatriz Martín-Herreros, Alfons Serrano, Amparo Sempere, Eva Barragán, Claudia Sargas, Miguel Sanz, David Martínez-Cuadrón, Pau Montesinos, on behalf of the PETHEMA group
Published in:
Annals of Hematology
|
Issue 6/2021
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Abstract
Prognosis for relapsed or refractory (R/R) acute myeloid leukemia (AML) despite salvage therapy is dismal. This phase I dose-escalation trial assessed the safety and preliminary clinical activity of selinexor, an oral exportin-1 (XPO1) inhibitor, in combination with FLAG-Ida in younger R/R AML patients. The aim was to find the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD). Fourteen patients were included, and selinexor dosage was 60 mg (3 patients), 80 mg (3 patients), and 100 mg (7 patients) weekly. No dose-limiting toxicities were reported. Grade ≥3 non-hematologic adverse events (AEs) occurred in 78.6% of patients. Two patients were non MTD evaluable due to early death, and overall, 3 out of 14 patients (21.4%) had fatal AEs. Five out of 12 (42%) response and MTD evaluable patients achieved a complete remission (CR;
n=4) or CR with incomplete hematologic recovery (CRi,
n=1), and 4 patients (33%) subsequently underwent allogeneic transplantation. The median overall survival (OS) and event-free survival (EFS) were 6.0 (range 0.9-19.3) and 1.1 months (range 0.7-19.3), respectively. Using selinexor 100 mg/weekly, CR/CRi rate of 66.7%, OS 13.6 months (range, 1.6-19.3), and EFS 10.6 months (range, 0.9-19.3). At last follow-up, 3 patients were alive. Selinexor 100 mg/weekly with FLAG-Ida combination in R/R AML showed acceptable tolerability and efficacy, establishing the RP2D of this regimen in future clinical trials.
ClinicalTrials.gov Identifier: NCT03661515