A post-hoc analysis of outcomes of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) who received oral azacitidine (Oral-AZA) maintenance therapy in the QUAZAR AML-001 study.

person Maria Teresa Voso Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy info_outline Maria Teresa Voso, Stéphane De Botton, Michael Pfeilstöcker, Angela Figuera Alvarez, Kefeng Wang, Wendy L. See, Manuel Ugidos Guerrero, Daniel Lopes de Menezes, Erica Petrlik, Thomas Prebet, Gail J. Roboz

Authors person Maria Teresa Voso Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy info_outline Maria Teresa Voso, Stéphane De Botton, Michael Pfeilstöcker, Angela Figuera Alvarez, Kefeng Wang, Wendy L. See, Manuel Ugidos Guerrero, Daniel Lopes de Menezes, Erica Petrlik, Thomas Prebet, Gail J. Roboz Organizations Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy, Institut Gustave Roussy, Villejuif, France, Third Medical Department for Hematology and Oncology, Hanusch Hospital and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria, Hospital Universitario de La Princesa, Madrid, Spain, Bristol Myers Squibb, Princeton, NJ, Bristol Myers Squibb, San Francisco, CA, BMS Center for Innovation and Translational Research Europe (CITRE), Seville, Spain, Bristol Myers Squibb, Summit, NJ, Weill Cornell Medicine, New York, NY Abstract Disclosures Research Funding Bristol Myers Squibb Background: AML-MRC represents 25%–34% of all AML cases, and patients with this AML subtype generally have poor outcomes. In this subanalysis of the QUAZAR AML-001study, we report outcomes of patients with AML-MRC who received Oral-AZA vs placebo (PBO). Methods: QUAZAR AML-001 was a phase 3 study of Oral-AZA maintenance therapy in patients with AML in first remission after intensive chemotherapy who were not eligible for hematopoietic stem cell transplantation (HSCT). Patients ≥ 55 years of age with AML and intermediate- or poor-risk cytogenetics received Oral-AZA 300 mg or PBO QD for 14 d per 28-d cycles. In this analysis, WHO 2008 criteria were used to identify patients with secondary AML and/or patients with AML-MRC (both groups are referred to as AML-MRC in this analysis). Data on mutational profiles at diagnosis were not available. Overall survival (OS) from time of randomization to time of death from any cause after censoring for HSCT, and relapse-free survival (RFS) from time of randomization, were calculated using the Kaplan–Meier method. Duration of measurable residual disease (MRD) negativity achieved on treatment was calculated from the first MRD-negative assessment. Results: Overall, 101/472 patients had AML-MRC; 56/238 (23.5%) patients in the Oral-AZA arm and 45/234 (19.2%) patients in the PBO arm. Karyotype/cytogenetics data at diagnosis were available for 87/101 (86.1%) patients with AML-MRC and 331/371 (89.2%) patients with non-AML-MRC. A greater proportion of AML-MRC than non-AML-MRC patients had poor-risk cytogenetics (20/101 [19.8%] vs 46/371 [12.4%]), del(5q) (10/87 [11.5%] vs 9/331 [2.7%]), and monosomy 7/del(7q) (9/87 [10.3%] vs 14/331 [4.2%]). Median OS did not significantly differ in patients with AML-MRC vs non-AML-MRC in either treatment arm (Oral-AZA: 19.9 mo vs 25.1 mo, P = 0.2694; PBO: 14.8 mo vs 14.9 mo, P = 0.2099). In both treatment arms, the median RFS was inferior for patients with AML-MRC vs non-AML-MRC (Oral-AZA 7.5 mo vs 10.5 mo, P = 0.0430; PBO: 3.7 mo vs 4.9 mo, P = 0.0109). Oral-AZA significantly prolonged median OS and RFS, and the duration of MRD negativity for patients with AML-MRC compared with PBO (Table). Conclusions: Oral-AZA significantly improved OS and RFS compared with PBO for patients with AML-MRC indicating that Oral-AZA maintenance is an effective treatment option for these patients with particularly poor prognosis. Clinical trial information: NCT01757535. Summary of outcomes of patients with AML-MRC in each treatment arm. Outcome Oral-AZA (n = 56) PBO (n = 45) P value OS, median (95% CI), mo 19.9 (14.59–31.97) 14.8 (10.05–19.65) – HR (95% CI) 0.59 (0.36–0.94) 0.0261 RFS, median (95% CI), mo 7.5 (3.75–14.29) 3.7 (1.94–6.34) – HR (95% CI) 0.57 (0.36–0.88) 0.0111 Duration of MRD negativity, median, mo 8.1 0 0.0032 HR, hazard ratio.