Real World Management of Patients with Acute Myeloid Leukemia: Results from French Cancer Population-Based Registries
Authors: Mounier Morgane , Sobh Mohamad , Monnereau Alain , Troussard Xavier , Maynadie Marc , Michallet Mauricette 
Published: October 2019

Abstract
Introduction:
Cancer registries are required for the analysis of incidence and mortality rates and trends but are also useful as complement to clinical studies to support decision on individual patient management. Acute myeloid leukemia (AML) is more common in older people, with a continuous slow rise in young adulthood turning into rapidly increasing incidence by age from approximately 50 years. Clinical studies have criteria for inclusion and exclusion, which impose selection. This has less implication in younger patients because most of them receive intensive treatment, fewer have secondary AML, and few have severely impaired performance status. Many clinically relevant questions cannot be answered in randomized studies, because of limited patient numbers, problems with randomization, or resource availability.
Population-based registries provide a way to achieve new information through the study of geographic differences. Healthcare authorities are interested in geographic variation to ensure equal level of health care for the citizens and the general population to know where to go for the best of care.
The aim of this study was to describe the management and outcomes of adult AML patients diagnosed and reported to 3 different regional cancer population-based registries considered representative of the whole French population between years 2006 and 2012.
Patients and methods:
A total of 1106 patients were available in the 3 registries (446 in Gironde department, 472 in Basse-Normandie, and 188 in Côte d'Or department); 584 (53%) were males, age at diagnosis was comparable between the 3 departments with median of 66 years (range: 18-99), 431 (39%) were less than 65 years old and 437 (39%) were older than 75 years. Therapy-related AML was diagnosed in 126 (11%) patients, cytogenetic analysis was not homogeneously performed among the three departments, and also among those who had it done (N=815, 74%), 29% were normal, and from the remaining with abnormal cytogenetics, 69 (8%) were favorable prognosis, 121 (15%) intermediate, and 359 (44%) were unfavorable.
Results:
Two-third of patients (N=725, 66%) were followed in university hospitals, 7% in anti-cancer centers and the rest were followed in other hospitals. Among the total population, 915 (83%) were treated for their AML, most of them were <75 years old, and the rest of patients were not treated or received palliative care, only 67% of patients > 75 years were treated. There was no statistical difference in terms of overall survival (OS) between males and females (p=0.99). When stratifying according to age < 60, 60-65, 66-75 and > 75 years, OS probability at 5 years was 50% (95%CI: 44-56), 20% (95%CI: 12-27), 16% (95%CI: 11-21), 2% (95%CI: 1-4) respectively. OS was not different between the 3 departments. Information about inclusion in clinical trials was available for 50% of patients, among them 174 (19%) were included in clinical trials and 284 (31%) not. There was a clear significant survival advantage for patients included in clinical trial independently from age, p<0.001. OS was significantly better for patients treated in university hospitals and anti-cancer centers than those followed in other centers p<0.001. When evaluating the impact of period of treatment, survival outcome significantly improved during years 2010-2012 compared to years 2006-2009, p=0.04 only for patients aged less than 65 years, while patients older than 65 years did not have survival improvement over time, p=0.41. In addition patients who received allogeneic hematopoietic cells transplantation (allo-SCT) had a better OS, p=0.01. In multivariate analysis, age <65 years (HR=0.45, 95% CI: 0.38-0.54, p<0.001), favorable cytogenetics (HR=0.26, 95% CI: 0.15-0.45, p<0.001), unfavorable cytogenetics (HR=1.61, 95% CI: 1.32-1.97, p<0.001) and allo-SCT (HR=0.49, 95% CI: 0.38-0.64, p<0.001) significantly impacted OS.
Conclusion:
This analysis allowed to point out some disparities in the real world management of AML patients. Interestingly, the fact that survival outcome for patients treated in clinical trials is different from the rest of the population reflects an important point to consider by health authorities. In addition, we observed a lack of improvement over time for older patients that needs more attention. A prognostic evaluation is ongoing to verify patients deemed eligible for allo-SCT to find out among them the proportion of those really transplanted.

Disclosures
Troussard: Gilead: Other: scientific advisory board. Michallet:Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy; Novartis: Research Funding.