Treatment of AML with Azacytidine (AZA): Current Results of the French ATU Program.
Authors: Fabre Claire , Gardin Claude , Mbida Rose-Marie , Quesnel Bruno , Dreyfus François , Isnard Françoise , Mannone Lionel , Legros Laurence , Prebet Thomas , Vey Norbert , Beyne-Rauzy Odile , Dalbies Florence , Cheze Stéphane , Delaunay Jacques , Fruchart Christophe , Marfaing-Koka Anne , Stamatoullas Aspasia , Bordessoule Dominique , Cambier Nathalie , Cornillon Jérôme , Dartigeas Caroline , Delmas-Marsalet Béatrice , Fenaux Pierre 
Published: April 2020

Abstract
Background: AZA is an approved drug for MDS by FDA, currently being investigated in AML. ATUs are patient named programs launched by French health authorities for yet unapproved but promising drugs, and one is ongoing for AZA in MDS and AML.
Patients: 108 AML pts from 29 centres included from Sept 2004 to June 2007 in this program, and who had completed at least one course of AZA, are analyzed. They received AZA 75 mg/m2/d (d 1–7) (SC) every 4 weeks, planned for a minimum of 4 courses.
Results: Median age was 75 y [range 43–91], M/F was 66/42. 51 pts had AML without and 57 pts with preceding MDS, p-AML and s-AML, respectively (resp). Pts had M0, 1, 2, 3, 4, 5, 6, and 7, in 8, 16, 30, 0, 21, 15, 6 and 4% of cases, resp. 42, 17 and 12 pts were resistant, in first or second relapse, resp, to previous cytotoxic chemotherapy (CT), including intensive anthr-AraC CT in 64 pts and LD AraC in 7, while 37 pts (all with s-AML) were untreated. Karyotype was normal, fav (t(8;21), inv 16), unfav (−7/7q- or complex), int (all others) and NA in 38, 0, 45, 18 pts and 7 pts, resp. Pts received a median of 4 cycles [range 2–16]. Response was assessed only after 4 cycles, unless pts progressed before. Thus, 15 pts were not yet evaluable. Of the remaining 93 pts, 12 (13%) achieved CR, 34 (36%) PR, (OR=49%) and 43 (46%) were considered failure. 4 pts died before end of cycle 2, without evidence of progression. 35 of the 46 responders received maintenance therapy after response was achieved. Allogeneic SCT was performed in 5 responders (2 CR+3 PR). Myelosuppression lead to dose reduction in 16% pts and hospitalization in 17% pts but no toxic death was seen. Other side effects included local reactions (reversible with local NSAID) (19%), grade I-II GI disorders (52%). OR was 34% (11% CR+23% PR) in p-AML and 60% in s-AML pts (12% CR+48% PR) (p&lt;0.05). In p-AML, OR was 75%, 17%, 11% for normal, int and unfav karyotype (p&lt;0.001), while in s-AML, OR was 73%, 57%, 48% for normal, int and unfav karyotype (p=NS). Considering previous treatments, OR in p-AML was 63% and 24% for pts in 1st relapse and &gt; 1 relapse/refractory, resp (p&lt;0.05). In s-AML, OR was 61% and 46%, in previously treated or not pts, resp (p=NS). Median actuarial response duration was 6 months (m) (range 1–22+) in s-AML, and 3 m (1–28+) in p-AML. Median actuarial survival was 9 m [3–30] and 5 m [2–31+[in s- and p-AML, resp.
Conclusion: In this very high risk population (in relapse, refractory or post MDS), AZA gave 49% CR and PR, which were higher in s-AML. A prognostic value of cytogenetics and of prior treatment for response was seen in p-AML, but was only marginal in s-AML. An update will be presented.