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

TY - JOUR

T1 - Improved outcome in acute myeloid leukemia patients enrolled in clinical trials

T2 - A national population-based cohort study of Danish intensive chemotherapy patients

AU - Østgård, Lene Sofie Granfeldt

AU - Nørgaard, Mette

AU - Sengeløv, Henrik

AU - Medeiros, Bruno C

AU - Kjeldsen, Lars

AU - Overgaard, Ulrik Malthe

AU - Severinsen, Marianne Tang

AU - Marcher, Claus Werenberg

AU - Jensen, Morten Krogh

AU - Nørgaard, Jan Maxwell

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.18632/oncotarget.12495

DO - 10.18632/oncotarget.12495

M3 - Journal article

C2 - 27732947

SN - 1949-2553

VL - 7

SP - 72044

EP - 72056

JO - Oncotarget

JF - Oncotarget

IS - 44

ER -