Bortezomib combined with low-dose cytarabine in Intermediate-2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM.
Fiche publication
Date publication
juillet 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GUERCI-BRESLER Agnès, Dr AME Shanti
Tous les auteurs :
Natarajan-Ame S, Park S, Ades L, Vey N, Guerci-Bresler A, Cahn JY, Etienne G, Bordessoule D, Ravoet C, Legros L, Cheze S, Stamatoullas A, Berger E, Schmidt A, Charbonnier A, Chaury MP, Braun T, Fenaux P, Dreyfus F
Lien Pubmed
Résumé
Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-kappaB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1.5 mg/m(2) , days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m(2) , then 20 mg/m(2) from days 1-14), every 28 d for four cycles. Median follow-up was 29.7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow-CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2.5% HI), compared to none in the 12 previously treated patients (P < 0.01). Responders had better overall survival (median 18.2 vs. 10 months). One CR and 3 marrow-CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.
Référence
Br J Haematol. 2012 Jul;158(2):232-7