Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

Anne Bouvier; Jean-Francois Hamel; Jacques Delaunay; Eric Delabesse; Pierre-Yves Dumas; Marie-Pierre Ledoux; Pierre Peterlin; Isabelle Luquet; Gabrielle Roth Guepin; Claude Eric Bulabois; Maria Pilar Gallego Hernanz; Gaelle Guillerm; Romain Guieze; Yosr Hicheri; Celestine Simand; Chantal Himberlin; Mathilde Hunault-Berger; Marc Bernard; Eric Jourdan; Denis Caillot; Veronique Dorvaux; Emmanuelle Tavernier; Etienne Daguindau; Anne Banos; Mario Ojeda-Uribe; Emmanuel Gyan; Magda Alexis; Jean-Pierre Marolleau; Pascal Turlure; Didier Bouscary; Catherine Humbrecht; Hacene Zerazhi; Marie-Christine Bene; Arnaud Pigneux; Martin Carre; Norbert Ifrah; Odile Blanchet; Norbert Vey; Christian Recher; Pascale Cornillet-Lefebvre

doi:10.1111/ejh.13626

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Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

Anne Bouvier ¹ Jean-Francois Hamel ^{2, 3} Jacques Delaunay ⁴ Eric Delabesse ^{5, 6} Pierre-Yves Dumas ^{7, 8} Marie-Pierre Ledoux ⁹ Pierre Peterlin ¹⁰ Isabelle Luquet ¹¹ Gabrielle Roth Guepin ¹² Claude Eric Bulabois ¹³ Maria Pilar Gallego Hernanz ¹⁴ Gaelle Guillerm ¹⁵ Romain Guieze ¹⁶ Yosr Hicheri ¹⁷ Celestine Simand ⁹ Chantal Himberlin ¹⁸ Mathilde Hunault-Berger ^{1, 19, 20} Marc Bernard ²¹ Eric Jourdan ²² Denis Caillot ²³ Veronique Dorvaux ²⁴ Emmanuelle Tavernier ²⁵ Etienne Daguindau ²⁶ Anne Banos ²⁷ Mario Ojeda-Uribe ²⁸ Emmanuel Gyan ^{29, 30, 31} Magda Alexis ³² Jean-Pierre Marolleau ^{33, 34} Pascal Turlure ³⁵ Didier Bouscary ^{36, 37} Catherine Humbrecht Hacene Zerazhi ³⁸ Marie-Christine Bene ¹⁰ Arnaud Pigneux ³⁹ Martin Carre ¹³ Norbert Ifrah ^{3, 40} Odile Blanchet ^{41, 3} Norbert Vey ⁴² Christian Recher ⁴³ Pascale Cornillet-Lefebvre ⁴⁴

1 CRCINA-ÉQUIPE 7 - Innate Immunity and Immunotherapy

CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers

2 Irset - Institut de recherche en santé, environnement et travail

3 CHU Angers - Centre Hospitalier Universitaire d'Angers

4 Hôpital privé du Confluent [Nantes]

5 CRCT - Centre de Recherches en Cancérologie de Toulouse

6 CHU Toulouse [Toulouse]

7 CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France.

8 BMGIC, U1035 INSERM, University of Bordeaux, Bordeaux, France

9 ICANS - Institut de Cancérologie de Strasbourg Europe

10 CHU Nantes - Centre hospitalier universitaire de Nantes

11 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole

12 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy

13 CHU - Centre Hospitalier Universitaire [Grenoble]

14 Service d'Hématologie [CHU Poitiers]

15 CHU - BREST - Hôpital Morvan - CHRU de Brest

16 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias

17 CHU Saint-Eloi

18 CHU Reims - Centre Hospitalier Universitaire de Reims

19 FHU GOAL - Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers]

20 Service des maladies du sang [Angers]

21 CHU Pontchaillou [Rennes]

22 Département d'Hématologie [CHU Nîmes]

23 CHU Dijon

24 CHR Metz-Thionville - Centre hospitalier régional Metz-Thionville

25 Institut de Cancérologie de la Loire Lucien Neuwirth

26 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon

27 Le CHCB, Centre Hospitalier de la Côte Basque

28 CH E.Muller Mulhouse - Centre Hospitalier Emile Muller [Mulhouse]

29 GICC EA 7501 - Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...]

30 LNOx - ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx)

GICC EA 7501 - Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...], CNRS - Centre National de la Recherche Scientifique : EMR7001 / ERL7001, CHRU Tours - Centre Hospitalier Régional Universitaire de Tours

31 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours

32 CHRO - Centre Hospitalier Régional d'Orléans

33 CHU Amiens-Picardie

34 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666

35 Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges]

36 Hôpital Cochin [AP-HP]

37 IC UM3 (UMR 8104 / U1016) - Institut Cochin

38 Centre Hospitalier Henri Duffaut (Avignon)

39 Biothérapies des maladies génétiques et cancers

40 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers

41 Centre de Ressources Biologiques [CHU Angers]

42 Institut Paoli-Calmettes

43 Service d'Hématologie [IUCT Toulouse]

44 Service d'Hématologie Biologique [Hôpital Robert Debré, Paris]

Abstract : In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem-cell transplantation. (P = .086; P = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1, IDH2, and ASXL1), six clusters of patients with significant different outcome were identified. Five clusters were based on FLT3-ITD, NPM1, and CEBPA mutations as well as epigenetic modifiers (DNMT3A, IDH1/2, ASXL1), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated FLT3-ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate-risk cytogenetic.

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https://hal-u-picardie.archives-ouvertes.fr/hal-03604930
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Soumis le : jeudi 10 mars 2022 - 16:47:08
Dernière modification le : mercredi 27 avril 2022 - 04:04:02

Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

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Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

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