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Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

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Abstract

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

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Data availability

Data are property of the PETHEMA foundation. Data may be available from the corresponding author, upon reasonable request.

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Acknowledgements

The authors would like to thank all the physicians and data managers from the PETHEMA group.

Funding

This research received no external funding.

Author information

Author notes

  1. Juan Manuel ALonso-Dominguez and Pau Monteisnos are senior authors.

Authors and Affiliations

  1. Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain

    E. U. Suárez, J. L. López-Lorenzo, A. Lázaro-García & J. M. Alonso-Dominguez

  2. Hospital Universitari I Politécnic-IIS La Fe, Valencia, Spain

    B. Boluda, E. Barragán, D. Martínez-Cuadrón & P. Montesinos

  3. Hospital Universitario Lucus Augusti, Lugo, Spain

    E. Lavilla

  4. Hospital Clínico Universitario de Valencia, Valencia, Spain

    M. Tormo

  5. INCLIVA, Valencia, Spain

    M. Tormo

  6. Hospital General Universitario de Alicante, Alicante, Spain

    C. Botella & C. Gil

  7. ICO-Hospital Germans Trias I Pujol, Badalona, Spain

    S. Vives

  8. Hospital Universitario Dr Negrín, Las Palmas, Spain

    C. Rodríguez

  9. Hospital Universitario Reina Sofía, Córdoba, Spain

    J. Serrano

  10. IMIBIC, Córdoba, Spain

    J. Serrano

  11. Hospital Universitario Dr. Peset, Valencia, Spain

    M. J. Sayas

  12. Hospital Universitario 12 de Octubre, Madrid, Spain

    P. Martínez-Sánchez

  13. Hospital Universitario de León, León, Spain

    F. Ramos

  14. Hospital Universitario Central de Asturias, Oviedo, Spain

    T. Bernal

  15. Hospital Universitario General de Albacete, Albacete, Spain

    L. Algarra

  16. Hospital San Pedro de Alcántara, Cáceres, Spain

    J. M. Bergua-Burgues

  17. Hospital Universitario Virgen del Rocío, Seville, Spain

    J. A. Pérez-Simón

  18. Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Seville, Spain

    J. A. Pérez-Simón

  19. Hospital Universitario Puerta de Hierro, Majadahonda, Spain

    P. Herrera

  20. Hospital Regional Universitario de Málaga, Málaga, Spain

    M. Barrios

  21. Hospital Universitario de A Coruña, A Coruña, Spain

    V. Noriega-Concepción

  22. Hospital Universitario Puerta del Mar de Cádiz, Cádiz, Spain

    J. A. Raposo-Puglia

  23. Haematological Malignancies Clinical Research Unit, Hospital 12 de Octubre Universidad Complutense, CNIO, CIBERONC, Madrid, Spain

    R. Ayala

  24. Spanish National Cancer Research Center (CNIO), Madrid, Spain

    R. Ayala

  25. Hospital General Universitario Morales Meseguer, Murcia, Spain

    M. L. Amigo

  26. Centro Hospitalar São João, Oporto, Portugal

    J. E. Guimaraes

  27. Hospital Universitario Marqués de Valdecilla, Santander, Spain

    M. Colorado

  28. Hospital General Universitario de Castellón, Castellón de La Plana, Spain

    R. García-Boyero

  29. Hospital Universitario Miguel Servet, Saragossa, Spain

    B. De Rueda-Ciller

  30. Hospital Universitario Infanta Leonor, Madrid, Spain

    M. Foncillas-García

  31. Hospital Universitario Doctor José Molina Orosa, Arrecife, Spain

    A. Hong

  32. Hospital Universitario de Burgos, Burgos, Spain

    J. Labrador

Authors
  1. E. U. Suárez
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  2. B. Boluda
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  3. E. Lavilla
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  5. C. Botella
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  6. C. Gil
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  7. S. Vives
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  9. J. Serrano
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  11. P. Martínez-Sánchez
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  13. T. Bernal
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  14. L. Algarra
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  15. J. M. Bergua-Burgues
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  16. J. A. Pérez-Simón
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  17. P. Herrera
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  18. M. Barrios
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  19. V. Noriega-Concepción
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  20. J. A. Raposo-Puglia
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  23. D. Martínez-Cuadrón
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  24. M. L. Amigo
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  27. J. E. Guimaraes
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  28. M. Colorado
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  29. R. García-Boyero
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  30. B. De Rueda-Ciller
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  31. M. Foncillas-García
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  32. A. Hong
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  33. J. Labrador
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  34. J. M. Alonso-Dominguez
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  35. P. Montesinos
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Consortia

on behalf of the PETHEMA group

Contributions

Conceptualization, E.U., J.M.A., and P.M.; methodology, J.M.A., and P.M; formal analysis, J.M.A., and P.M.; investigation, E.U., B.B., E.L., M.T., C.B., C.G., S.V., C.R., J.S., M.J., P.M., F.R., L.A., JM., J.A., P.H., M.B., V.N.C., J.A.R., R.A., E.B., D.M.C., M.L., J.L.L.,, A.L., J.E., M.C., R.G.B., B.R.C., M.F.G., A.H., J.L., J.M.A., and P.M.; data curation, E.U., J.M.A., and P.M.; writing original draft preparation, E.U., J.M.A., and P.M.; writing review and editing, E.U., J.M., and P.M. All authors have read and agreed to the published version of the manuscript.

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Correspondence to J. M. Alonso-Dominguez.

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Suárez, E.U., Boluda, B., Lavilla, E. et al. Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05840-7

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