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Duchmann M, Micol JB, Duployez N, et al. Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study. Blood. 2021;137(20):2827-2837doi: 10.1182/blood.2020010165.
Duchmann, M., Micol, J. B., Duployez, N., Raffoux, E., Thomas, X., Marolleau, J. P., Braun, T., Adès, L., Chantepie, S., Lemasle, E., Berthon, C., Malfuson, J. V., Pautas, C., Lambert, J., Boissel, N., Celli-Lebras, K., Caillot, D., Turlure, P., Vey, N., Pigneux, A., Recher, C., Terré, C., Gardin, C., Itzykson, R., Preudhomme, C., Dombret, H., & de Botton, S. (2021). Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study. Blood, 137(20), 2827-2837. https://doi.org/10.1182/blood.2020010165
Duchmann, Matthieu, et al. "Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study." Blood vol. 137,20 (2021): 2827-2837. doi: https://doi.org/10.1182/blood.2020010165
Duchmann M, Micol JB, Duployez N, Raffoux E, Thomas X, Marolleau JP, Braun T, Adès L, Chantepie S, Lemasle E, Berthon C, Malfuson JV, Pautas C, Lambert J, Boissel N, Celli-Lebras K, Caillot D, Turlure P, Vey N, Pigneux A, Recher C, Terré C, Gardin C, Itzykson R, Preudhomme C, Dombret H, de Botton S. Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study. Blood. 2021 May 20;137(20):2827-2837. doi: 10.1182/blood.2020010165. PMID: 33881523.
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Blood. 2021 May 20;137(20):2827-2837. doi: 10.1182/blood.2020010165.

Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study.

Blood

Matthieu Duchmann, Jean-Baptiste Micol, Nicolas Duployez, Emmanuel Raffoux, Xavier Thomas, Jean-Pierre Marolleau, Thorsten Braun, Lionel Adès, Sylvain Chantepie, Emilie Lemasle, Céline Berthon, Jean-Valère Malfuson, Cécile Pautas, Juliette Lambert, Nicolas Boissel, Karine Celli-Lebras, Denis Caillot, Pascal Turlure, Norbert Vey, Arnaud Pigneux, Christian Recher, Christine Terré, Claude Gardin, Raphaël Itzykson, Claude Preudhomme, Hervé Dombret, Stéphane de Botton

Affiliations

  1. Hematology Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
  2. Université de Paris, Génomes, Biologie Cellulaire et Thérapeutique Unité (U)944, INSERM, Centre National de la Recherche Scientifique (CNRS), Paris, France.
  3. Département d'Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
  4. Laboratory of Hematology, U1277-Cancer Heterogeneity Plasticity and Resistance to Therapies (CANTHER), Centre Hospitalier Universitaire (CHU) Université de Lille INSERM, Lille, France.
  5. Research Unit EA-3518, Institut de Recherche Saint-Louis, Université de Paris, Paris, France.
  6. Service Hématologie Adultes, Hôpital Saint-Louis, AP-HP, Paris, France.
  7. Hematology Department, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre Bénite, France.
  8. Hematology Department, CHU Amiens, Amiens, France.
  9. Department of Hematology, Université Paris Nord, Hôpital Avicenne, AP-HP, Bobigny, France.
  10. Senior Hematology Unit, Department of Hematology, Hôpital Saint-Louis, AP-HP, Université de Paris, Paris, France.
  11. Hematology Department, CHU Caen, Caen, France.
  12. Hematology Department, Henri Becquerel Center, Rouen, France.
  13. Hematology Department, CHU Lille, Lille, France.
  14. Hematology Department, Hôpital d'Instruction des Armées (HIA) Percy, Clamart, France.
  15. Hematology Department, Henri Mondor Hospital, AP-HP, Créteil, France.
  16. Hematology Department, Versailles Hospital, Le Chesnay, France.
  17. Adolescent and Young Adult Unit Unit, Department of Hematology, Saint-Louis Hospital, AP-HP, Paris, France.
  18. Acute Leukemia French Association Coordination, Saint-Louis Hospital, Paris, France.
  19. Hematology Department, CHU Dijon, Dijon, France.
  20. Hematology Department, Centre Hospitalier Régional Universitaire (CHRU) Limoges, Limoges, France.
  21. Hematology Department, Paoli Calmettes Institute, Marseille, France.
  22. Hematology Department, Hôpital Haut-Lévèque, CHU de Bordeaux, Bordeaux, France.
  23. Institut Universitaire du Cancer de Toulouse Oncopole, CHU de Toulouse, Université de Toulouse 3 Paul Sabatier, Toulouse, France; and.
  24. Cytogenetic Laboratory, Versailles Hospital, Le Chesnay, France.

PMID: 33881523 DOI: 10.1182/blood.2020010165

Abstract

In patients with isocitrate dehydrogenase (IDH)-mutated acute myeloid leukemia (AML) treated by intensive chemotherapy (IC), prognostic significance of co-occurring genetic alterations and allogeneic hematopoietic stem cell transplantation (HSCT) are of particular interest with the advent of IDH1/2 mutant inhibitors. We retrospectively analyzed 319 patients with newly diagnosed AML (127 with IDH1, 135 with IDH2R140, and 57 with IDH2R172 mutations) treated with IC in 3 Acute Leukemia French Association prospective trials. In each IDH subgroup, we analyzed the prognostic impact of clinical and genetic covariates, and the role of HSCT. In patients with IDH1 mutations, the presence of NPM1 mutations was the only variable predicting improved overall survival (OS) in multivariate analysis (P < .0001). In IDH2R140-mutated AML, normal karyotype (P = .008) and NPM1 mutations (P = .01) predicted better OS. NPM1 mutations were associated with better disease-free survival (DFS; P = .0009), whereas the presence of DNMT3A mutations was associated with shorter DFS (P = .0006). In IDH2R172-mutated AML, platelet count was the only variable retained in the multivariate model for OS (P = .002). Among nonfavorable European LeukemiaNet 2010-eligible patients, 71 (36%) underwent HSCT in first complete remission (CR1) and had longer OS (P = .03) and DFS (P = .02) than nontransplanted patients. Future clinical trials testing frontline IDH inhibitors combined with IC may consider stratification on NPM1 mutational status, the primary prognostic factor in IDH1- or IDH2R140-mutated AML. HSCT improve OS of nonfavorable IDH1/2-mutated AML and should be fully integrated into the treatment strategy.

© 2021 by The American Society of Hematology.

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