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A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory/relapsed adult acute myeloid leukemia patients

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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

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Acknowledgements

We are grateful to all participating institutions and clinicians in the PETHEMA group, and all the patients included.

Funding

This investigator-sponsored study was granted by Karyopharm.

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Authors and Affiliations

  1. Servicio de Hematología y Hemoterapia, Hospital Universitario 12 de Octubre, UCM, CNIO, CIBERONC, Madrid, Spain

    María P. Martínez Sánchez & Joaquín Martínez-López

  2. Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Valencia, Spain

    Juan Eduardo Megías-Vericat

  3. Servicio de Hematología y Hemoterapia, Hospital Universitari i Politècnic La Fe, Valencia, Spain

    Rebeca Rodríguez-Veiga, Blanca Boluda, Isabel Cano-Ferri, Evelyn Acuña-Cruz, Laura Torres-Miñana, Alfons Serrano, Amparo Sempere, Eva Barragán, Claudia Sargas, Miguel Sanz, David Martínez-Cuadrón & Pau Montesinos

  4. Servicio de Hematología y Hemoterapia, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain

    Susana Vives & Anna Torrent

  5. Servicio de Hematología y Hemoterapia, Hospital San Pedro de Alcántara, Cáceres, Spain

    Juan Miguel Bergua & Sara Suárez-Varela

  6. Grupo de investigación en Hematología, Instituto de Investigación Sanitaria La Fe (IISLAFE), Valencia, Spain

    Beatriz Martín-Herreros

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  1. María P. Martínez Sánchez
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  2. Juan Eduardo Megías-Vericat
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Correspondence to Pau Montesinos.

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Martínez Sánchez, M.P., Megías-Vericat, J.E., Rodríguez-Veiga, R. et al. A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory/relapsed adult acute myeloid leukemia patients. Ann Hematol 100, 1497–1508 (2021). https://doi.org/10.1007/s00277-021-04542-8

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