TY - JOUR
T1 - 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
T2 - GFM's “pick a winner” trial, with the impact of somatic mutations
AU - Adès, Lionel
AU - Duployez, Nicolas
AU - Guerci-Bresler, Agnes
AU - Laribi, Kamel
AU - Peterlin, Pierre
AU - Vey, Norbert
AU - Thepot, Sylvain
AU - Wickenhauser, Stefan
AU - Zerazhi, Hacene
AU - Stamatoullas, Aspassia
AU - Wattel, Eric
AU - Recher, Christian
AU - Toma, Andrea
AU - Dimicoli-Salazar, Sophie
AU - Braun, Thorsten
AU - Beyne-Rauzy, Odile
AU - Marolleau, Jean Pierre
AU - Cheze, Stéphane
AU - Park, Sophie
AU - Cluzeau, Thomas
AU - Nimubona, Stanislas
AU - Bordessoule, Dominique
AU - Benramdane, Riad
AU - Quesnel, Bruno
AU - Amé, Shanti
AU - de Botton, Stéphane
AU - Chermat, Fathia
AU - Preudhomme, Claude
AU - Chevret, Sylvie
AU - Fenaux, Pierre
N1 - Publisher Copyright:
© 2022 British Society for Haematology and John Wiley & Sons Ltd.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
AB - 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.
KW - MDS
KW - clinical trials
KW - molecular biology
UR - http://www.scopus.com/inward/record.url?scp=85128324162&partnerID=8YFLogxK
U2 - 10.1111/bjh.18193
DO - 10.1111/bjh.18193
M3 - Article
C2 - 35438802
AN - SCOPUS:85128324162
SN - 0007-1048
VL - 198
SP - 535
EP - 544
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -