A Prognostic Score for Overall Survival (OS) with Azacitidine (AZA) In Higher Risk MDS Based on 282 Patients (pts), and Validated In 175 Pts From the AZA 001 Trial

• Published in: Blood 2010-11, Vol.116 (21), p.3996-3996
• Main Authors: Itzykson, Raphael, Thepot, Sylvain, Quesnel, Bruno, Dreyfus, Francois, Beyne-Rauzy, Odile, Turlure, Pascal, Recher, Christian, Dartigeas, Caroline, Vey, Norbert, Legros, Laurence, Delaunay, Jacques, Salanoubat, Celia, Visanica, Sorin, Stamatoullas, Aspasia, Isnard, Françoise, Marfaing-Koka, Anne, Botton, Stephane De, Chelgoum, Youcef, Taksin, Anne-Laure, Plantier, Isabelle, Ame, Shanti, Boehrer, Simone, Gardin, Claude, Beach, CL, Ades, Lionel, Fenaux, Pierre
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V116.21.3996.3996

Abstract 3996 AZA significantly improves OS in higher-risk MDS (including RAEB-t/AML) compared to conventional treatments (AZA 001 trial, Lancet Onc, 2009), but prognostic factors of response and OS to AZA remain largely unknown. We designed a prognostic score for OS in a cohort of AZA treated higher-risk MDS in a patient-named compassionate program (French ATU), and validated it in patients from the AZA 001 trial. Between Sept 2004 and Jan 2009, prior to AZA approval in Europe, IPSS int-2/high risk MDS (including RAEB-t) not previously treated with intensive chemotherapy (IC), allo SCT, or a hypomethylating agent were included in a compassionate program (ATU), and received AZA (planned schedule 75 mg/m2/d ×7 d every 28 d for ≥4 cycles). Independent prognostic factors of OS were individualized in a Cox model. A prognostic score was then developed based on those factors. After validation of the score as a continuous variable, pts were grouped in three distinct risk categories. We subsequently tried to validate this score in the 175 higher risk MDS pts treated with AZA at the same schedule in AZA 001 trial (4 of the 179 pts randomized to AZA in that trial did not start AZA). The ATU cohort included 282 pts with de novo (74%) or therapy related (t) (26%) higher-risk MDS (IPSS int-2 in 54% high in 43%, at least int-2 in 2%). ECOG PS ≥2, RBC transfusion dependence ≥4 units/8 weeks and circulating blasts were present in 21%, 46% and 46% of pts respectively (resp). Cytogenetic risk was good, int, and poor in 31%, 17% and 47% (unknown in 5%). 10% pts had previously been treated with LD araC for their MDS. Multivariate analysis of survival retained PS ≥2 (HR= 2.0 [95% CI: 1.4–2.9]), RBC transfusion dependence ≥4 units/8 weeks (HR=1.9 [1.4-2.6]), presence of circulating blasts (HR=2.0 [1.5-2.7]), and IPSS cytogenetic risk (intermediate: HR=1.4 [0.8-2.3], poor: HR=3.0 [2.0-4.3]) as independent prognostic factors (all p