Title :

A Randomised Phase II Study of Azacitidine (AZA) Alone or with Lenalidomide (LEN), Valproic Acid (VPA) or Idarubicin (IDA) in Higher-Risk MDS or Low Blast AML: GFM's "Pick a Winner" Trial, with the Impact of Somatic Mutations

Author(s) :

Adès, Lionel [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Université Paris Cité [UPCité]
Duployez, Nicolas [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Guerci-Bresler, Agnes [Auteur]
Centre Hospitalier Universitaire de Nancy [CHU Nancy]
Laribi, Kamel [Auteur]
Centre Hospitalier Le Mans (CH Le Mans)
Peterlin, Pierre [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Nantes Université [Nantes Univ]
Vey, Norbert [Auteur]
Institut Paoli-Calmettes [IPC]
Aix Marseille Université [AMU]
Centre de Recherche en Cancérologie de Marseille [CRCM]
Thepot, Sylvain [Auteur]
Stress Adaptation and Tumor Escape - SATE [CRCI2NA / Eq 7]
Wickenhauser, Stefan [Auteur]
Centre Hospitalier Universitaire de Nîmes [CHU Nîmes]
Zerazhi, Hacene [Auteur]
Centre Hospitalier Henri Duffaut (Avignon)
Stamatoullas, Aspassia [Auteur]
Wattel, Eric [Auteur]
Laboratoire de biologie et modélisation de la cellule [LBMC UMR 5239]
Récher, Christian [Auteur]
Service Hématologie - IUCT-Oncopole [CHU Toulouse]
Toma, Andréa [Auteur]
Hôpital Henri Mondor
Dimicoli-Salazar, Sophie [Auteur]
Biothérapies des maladies génétiques et cancers
Braun, Thorsten [Auteur]
Charité - UniversitätsMedizin = Berlin University Medicine
Beyne-Rauzy, Odile [Auteur]
Centre Hospitalier Universitaire de Toulouse [CHU Toulouse]
Marolleau, Jean-Pierre [Auteur]
CHU Amiens-Picardie
HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 [HEMATIM]
Cheze, Stéphane [Auteur]
CHU Caen
Park, Sophie [Auteur]
Centre Hospitalier Universitaire [CHU Grenoble] [CHUGA]
Cluzeau, Thomas [Auteur]
XLIM [XLIM]
Nimubona, Stanislas [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Bordessoule, Dominique [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Benramdane, Riad [Auteur]
Centre Hospitalier René Dubos [Pontoise]
Quesnel, Bruno [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Amé, Shanti [Auteur]
Département d'Oncologie et Hématologie [Strasbourg]
Botton, Stephane [Auteur]
Institut Gustave Roussy [IGR]
Département d'hématologie [Gustave Roussy]
Chermat, Fathia [Auteur]
Preudhomme, Claude [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Chevret, Sylvie [Auteur]
Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé [ECSTRRA [CRESS - U1153 / UMR_A 1125]]
Fenaux, Pierre [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]

Journal title :

British Journal of Haematology

Pages :

535--544

Publisher :

Wiley

Publication date :

2022

ISSN :

0007-1048

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie

English abstract : [en]

In order to improve the outcome observed with azacitidine (AZA) in higher-risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more ...
Show more >In order to improve the outcome observed with azacitidine (AZA) in higher-risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA-PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher-risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six\,cycles, 69 (21.4%) CR\,+\,PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7\,months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six\,cycles were higher in the AZA-LEN And AZA-IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy-related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Submission date :

2024-02-17T03:56:34Z