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ACUTE MYELOID LEUKEMIA

Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO

Leukemia volume 37, pages 91–101 (2023)Cite this article

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Abstract

The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.

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Fig. 1: Overall survival curves.
Fig. 2: Kaplan–Meier survival curves.

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Data availability

Some de-identified data will be shared with other researchers upon reasonable request to the corresponding authors (pierre-yves.dumas@u-bordeaux.fr). The sharing will require a detailed proposal to the study investigators, and a data transfer agreement must be signed.

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Acknowledgements

We would like to thank Astellas for their financial support enabling e-CRF. Astellas was not involved in data collection, analysis, or in the writing of this article.

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Authors and Affiliations

  1. CHU Bordeaux, Service d’Hématologie Clinique et de Thérapie Cellulaire, F-33000, Bordeaux, France

    Pierre-Yves Dumas, Ariane Mineur & Arnaud Pigneux

  2. Hôpital Saint Louis, APHP, service d’hématologie adultes, Paris, France

    Emmanuel Raffoux & Hervé Dombret

  3. Centre Hospitalier Universitaire de Toulouse, Service d’Epidémiologie, CERPOP, Inserm, Université Toulouse III Paul Sabatier, Toulouse, France

    Emilie Bérard

  4. Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Université Toulouse III Paul Sabatier, Toulouse, France

    Sarah Bertoli & Christian Récher

  5. Institut Paoli Calmettes, Marseille, France

    Marie-Anne Hospital

  6. Hospices Civils de Lyon, Hôpital Lyon Sud, Service d’Hématologie clinique, Pierre Bénite, France

    Maël Heiblig

  7. CHRU Jean Minjoz, Service d’Hématologie, F-25000, Besançon, France

    Yohann Desbrosses

  8. Service d’Hématologie, CHU Nancy Brabois, 54500, Vandoeuvre les Nancy, France

    Caroline Bonmati

  9. CHU Henri-Mondor, Service d’Hématologie Clinique et de Thérapie Cellulaire; 1, rue Gustave Eiffel, 94010, Créteil, France

    Cécile Pautas

  10. Centre hospitalier de Versailles, Service Hématologie, Le Chesnay, France

    Juliette Lambert

  11. Service des maladies du sang, CHU d’Angers, France/Fédération hospitalo-universitaire « Grand Ouest against Leukemia »/Université d’Angers, Inserm UMR 1307, CNRS UMR 6075, Nantes Université, CRCI2NA, F-49000, Angers, France

    Corentin Orvain

  12. Service Hématologie, Centre Hospitalier de la Côte Basque, 64100, Bayonne, France

    Anne Banos

  13. Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France

    Florence Pasquier

  14. Hematology Department, Nantes University Hospital, Nantes, France

    Pierre Peterlin

  15. Service d’hématologie Clinique, CHU de Rennes, 35000, Rennes, France

    Tony Marchand

  16. Hôpital Pitié Salpetrière, Service d’hématologie, Paris, France

    Madalina Uzunov

  17. Hôpital de Meaux, Service d’Hématologie, Meaux, France

    Jamilé Frayfer

  18. CHU limoges, Service d’Hématologie Clinique et de Thérapie Cellulaire, F-87000, Limoges, France

    Pascal Turlure

  19. Université Cote d’Azur, CHU de Nice, Département d’hématologie clinique, Nice, France

    Thomas Cluzeau

  20. Department of Hematology, Nîmes University Hospital, Nîmes, France

    Eric Jourdan

  21. Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré, Reims, France

    Chantal Himberlin

  22. CHU Saint Etienne. Service d’hématologie clinique et thérapie cellulaire, 42 000, Saint Etienne, France

    Emmanuelle Tavernier

  23. Hématologie et thérapie cellulaire, CHRU de Tours, Tours, France

    Alban Villate

  24. Centre hospitalier Sud francilien, Service d’hématologie clinique, Corbeil-Essonnes, France

    Stephanie Haiat

  25. Service Hématologie clinique, CHU Dijon, Dijon, France

    Marie-Lorraine Chretien

  26. CHU Grenoble-Alpes, Grenoble, France

    Martin Carre

  27. CHU de Caen, IHBN, Service d’hématologie clinique, Caen, France

    Sylvain Chantepie

  28. Centre Hospitalier René Dubos, Service d’hématologie et thérapie cellulaire, Cergy-Pontoise, France

    Ioana Vaida

  29. CH Roubaix, service d’hématologie, F-59100, Roubaix, France

    Mathieu Wemeau

  30. CH Avignon, service d’onco-hématologie, Avignon, France

    Safia Chebrek

  31. CHU Brest, Hôpital Morvan, Service de cancérologie-hématologie, Brest, France

    Gaelle Guillerm

  32. Service d’hématologie clinique et de thérapie cellulaire, CHU de Clermont-Ferrand, Clermont-Ferrand, France; EA 7453 (CHELTER), Université Clermont Auvergne, Clermont-Ferrand, France

    Romain Guièze

  33. CHR Metz-Thionville, Hôpital Mercy, service d’hématologie, Metz, France

    Houria Debarri

  34. Hôpital Saint Eloi CHU Montpellier, Service d’Hématologie Clinique, 34295, Montpellier, France

    Eve Gehlkopf

  35. Department of Haematology, Centre hospitalier Le Mans, Le Mans, France

    Kamel Laribi

  36. Service Hématologie Adultes, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Université Paris Cité, Paris, France

    Ambroise Marcais

  37. CHT Troyes, Service d’Hématologie Clinique, 10000, Troyes, France

    Alberto Santagostino

  38. Hematology Biology, Nantes University Hospital, Nantes, France

    Marie-Christine Béné

Authors
  1. Pierre-Yves Dumas
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  2. Emmanuel Raffoux
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  3. Emilie Bérard
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  5. Marie-Anne Hospital
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  14. Pierre Peterlin
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Contributions

Conceptualization, P.Y.D.; Methodology, P.Y.D., E.B.; Patients care, P.Y.D., E.R., S.B., M.A.H., M.H., Y.D., C.B., C.P., J.L., C.O., A.B., F.P., P.P., T.M., M.U., J.F., P.T., T.C., E.J., C.H., E.T., A.V., S.H., M.L.C., M.C., S.C., I.V., M.W., S.C., G.G., R.G., H.D., E.G., K.L., A.M., A.S., A.P., H.D., C.R.; Collected the data, A.M., M.C.B.; Analyzed data, P.Y.D., E.B.; Writing—original draft, P.Y.D.; Revised the manuscript, C.R., J.L., P.P., M.H., C.O., R.G.; Review and editing, P.Y.D., E.B., C.R.; Funding acquisition, P.Y.D., A.M.

Corresponding author

Correspondence to Pierre-Yves Dumas.

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Competing interests

Pierre-Yves Dumas: Daiichi-Sankyo, Jazz Pharmaceutical, Astellas, Abbvie, Celgene, Janssen. Emmanuel Raffoux: Daiichi-Sankyo, Astellas, Abbvie, Celgene, Pfizer. Emilie Berard: no competing interest. Sarah Bertoli: Jazz Pharmaceuticals, Daiichi-Sankyo, Sanofi, Astellas and BMS. Marie-Anne Hospital: no competing interest. Maël Heiblig: Astellas, Pfizer, Abbvie, Jazz Pharmaceuticals, Servier. Yohann Desbrosses: Jazz Pharmaceuticals, Abbvie, Celgene, Novartis. Caroline Bonmati: no competing interest. Cécile Pautas: Abbvie, BMS. Juliette Lambert: Pfizer, Astellas, Abbvie. Corentin Orvain: Novartis. Anne Banos: no competing interest. Florence Pasquier: no competing interest. Pierre Peterlin: Daiichi-Sankyo, Jazz Pharmaceutical, Astellas, Abbvie, BMS. Tony Marchand: Jazz Pharmaceutical, Servier. Madalina Uzunov: no competing interest. Jamilé Frayfer: no competing interest. Pascal Turlure: Daiichi-Sankyo. Thomas Cluzeau: Astellas, Novartis and institution: Novartis, Astellas, Arog. Eric Jourdan: Novartis, Abbvie, BMS. Chantal Himberlin: no competing interest. Emmanuelle Tavernier: Abbvie, BMS. Alban Villate: no competing interest. Stephanie Haiat: no competing interest. Marie-Lorraine Chretien: no competing interest. Martin Carre: Astellas, BMS, Jazz pharmaceutical. Sylvain Chantepie: no competing interest. Ioana Vaida: no competing interest. Mathieu Wemeau: Abbvie, AOP Orphan, BMS, Gilead, Novartis. Safia Chebrek: no competing interest. Gaelle Guillerm: no competing interest. Romain Guièze: Abbvie, Janssen, Beigene, Astrazeneca, Roche, Amgen.. Houria Debarri: no competing interest. Eve Gehlkopf: no competing interest. Kamel Laribi: Outside this work, KL received Grants from Novartis, Takeda, Jansen, Abbvie, and personal fees from Novartis, Takeda, Abbvie, Iqone, Astra Zeneca, and Beigene.. Ambroise Marcais: no competing interest. Alberto Santagostino: no competing interest. Marie-Christine Béné: no competing interest. Ariane Mineur: no competing interest. Arnaud Pigneux: Grant/Research Support: Astellas, Roche; Speaker’s Bureau: Astellas, AbbVie, Gilead, Pfizer, Roche, Sanofi; Consultant: Jazz, AbbVie, Agios, BMS, Gilead, Novartis, Pfizer, Roche, Takeda. Hervé Dombret: Honoraria/consulting: Abbvie, Amgen, Astellas, Celgene-BMS, Daiichi Sankyo, Incyte,. Jazz Pharmaceuticals, Pfizer, Servier; research funding: Amgen, Astellas, Celgene-BMS, Incyte, Jazz Pharmaceuticals, Pfizer. Christian Récher: Research grants from AbbVie, Amgen, Novartis, BMS-Celgene, Jazz Pharmaceuticals, Agios, Chugai, MaaT Pharma, Astellas, Roche, Daiichi-Sankyo and Iqvia; an advisory role for AbbVie, Janssen, Jazz Pharmaceuticals, Novartis, Celgene, Otsuka, Astellas, Daiichi-Sankyo, Macrogenics, Pfizer. Roche, Servier and Takeda.

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Dumas, PY., Raffoux, E., Bérard, E. et al. Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO. Leukemia 37, 91–101 (2023). https://doi.org/10.1038/s41375-022-01742-7

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