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 - Université de Picardie Jules Verne Accéder directement au contenu
Article Dans Une Revue British Journal of Haematology Année : 2022

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

1 AP-HP - Hopital Saint-Louis [AP-HP]
2 UPCité - Université Paris Cité
3 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
4 CHU Nancy - Centre Hospitalier Universitaire de Nancy
5 Centre Hospitalier Le Mans (CH Le Mans)
6 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
7 Nantes Univ - Nantes Université
8 IPC - Institut Paoli-Calmettes
9 AMU - Aix Marseille Université
10 CRCM - Centre de Recherche en Cancérologie de Marseille
11 CRCI2NA / Eq 7 - Stress Adaptation and Tumor Escape - SATE
12 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
13 Centre Hospitalier Henri Duffaut (Avignon)
14 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
15 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
16 Hôpital Henri Mondor
17 Biothérapies des maladies génétiques et cancers
18 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
19 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
20 CHU Amiens-Picardie
21 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
22 CHU Caen
23 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
24 XLIM - XLIM
25 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
26 CRIBL - Contrôle de la Réponse Immune B et des Lymphoproliférations
27 Centre Hospitalier René Dubos [Pontoise]
28 Département d'Oncologie et Hématologie [Strasbourg]
29 IGR - Institut Gustave Roussy
30 Département d'hématologie [Gustave Roussy]
31 ECSTRRA [CRESS - U1153 / UMR_A 1125] - Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé
Aspassia Stamatoullas
  • Fonction : Auteur
Stéphane Cheze
  • Fonction : Auteur
Thomas Cluzeau
Fathia Chermat
  • Fonction : Auteur

Résumé

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.
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Dates et versions

hal-03740498 , version 1 (29-07-2022)

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Citer

Lionel Adès, Nicolas Duployez, Agnes Guerci-Bresler, Kamel Laribi, Pierre Peterlin, et al.. 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. British Journal of Haematology, 2022, 198 (3), pp.535--544. ⟨10.1111/bjh.18193⟩. ⟨hal-03740498⟩
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