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Comparative Study
. 2016 Nov 1;7(44):72044-72056.
doi: 10.18632/oncotarget.12495.

Improved outcome in acute myeloid leukemia patients enrolled in clinical trials: A national population-based cohort study of Danish intensive chemotherapy patients

Lene Sofie Granfeldt Østgård  1   2 , Mette Nørgaard  2 , Henrik Sengeløv  3 , Bruno C Medeiros  4 , Lars Kjeldsen  3 , Ulrik Malthe Overgaard  5 , Marianne Tang Severinsen  6   7 , Claus Werenberg Marcher  8 , Morten Krogh Jensen  9 , Jan Maxwell Nørgaard  1
Affiliations
Comparative Study

Improved outcome in acute myeloid leukemia patients enrolled in clinical trials: A national population-based cohort study of Danish intensive chemotherapy patients

Lene Sofie Granfeldt Østgård et al. Oncotarget. .

Abstract

Clinical trials are critical to improve AML treatment. It remains, however, unclear if clinical trial participation per se affects prognosis and to what extent the patients selected for trials differ from those of patients receiving intensive therapy off-trial.We conducted a population-based cohort study of newly diagnosed Danish AML patients treated with intensive chemotherapy between 2000-2013. We estimated accrual rates and compared characteristics, complete remission (CR) rates, and relative risks (RRs) of death at 90-day, 1-year, and 3-years in clinical trial patients to patients treated off-trial.Of 867 patients, 58.3% (n = 504) were included in a clinical trial. Accrual rates were similar across age groups (p = 0.55). Patients with poor performance status, comorbidity, therapy-related and secondary AML were less likely to be enrolled in trials. CR rates were 80.2% in trial-patients versus 68.6% in patients treated off- trial. Also, trial-patients had superior survival at 1-year; 72%, vs. 54% (adjusted RR of death 1.28(CI = 1.06-1.54)), and at 3 years; 45% vs. 29% (adjusted RR 1.14(CI = 1.03-1.26)) compared to patients treated off-trial.Despite high accrual rates, patients enrolled in clinical trials had a favorable prognostic profile and a better survival than patients treated off-trial. In conclusion, all trial results should be extrapolated with caution and population-based studies of "real world patients" have a prominent role in examining the prognosis of AML.

Keywords: acute myeloid leukemia; chemotherapy; population-based; prognosis; trials.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that there are no conflicts of interest to report.

Figures

Figure 1
Figure 1. Flowchart of patient selection for the study
Patients diagnosed at a time where no age-appropriate trial was open were excluded from the study. All information was obtained from the Danish National Leukemia Registry (DNLR), the Danish National Registry of Patients, and clinical trial office registries. The DNLR contains detailed and valid clinical information on all AML patients (completeness 99.6%) diagnosed in Denmark since 2000. [9]
Figure 2
Figure 2. Accrual rates by age and over time
Trial inclusion by age groups (A), accrual rates per calendar year (B), and accrual rates by consecutive years since trial opening (C) The accrual rates did not differ between age groups (Cochran-Armitage Test for Trend, p = 0.55), but accrual rates increased both with time (B) and the longer a trial remained open (C), (Cochran-Armitage Test for Trend, p < 0.001).
Figure 3
Figure 3. Survival in AML patients by trial status
Kaplan Meier Plots with 95%CI bands for the study population overall (A), in patients younger than 60 years (B), and in patients 60 years or older (C).
See this image and copyright information in PMC

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