Acute Myeloid Leukemia (AML): Prospective Comparison of Different Treatments with a Common Standard Treatment - A Study by the German AML Intergroup

Abstract 2175

Eight years from the start of a cooperation among five multicenter study groups in Germany, and three years after entering the last patient we here present updated therapeutic results. A total of 3171 patients 16–60 years of age with AML including primary and secondary AML and high-risk MDS, and excluding APL with t(15;17), were treated in the five study groups cooperating by a general upfront randomization allocating 10% of their patients to a common standard treatment and 90% to the study group own regimens before any treatment had been started. The standard treatment consisted of remission induction by two courses of standard dose araC over seven days with daunorubicin 60mg/m²/d on three days. Patients in complete remission received three monthly courses of high-dose araC 3g/m²q 12 h on day 1,3 and 5. In the participating study groups a total of 2866 patients eligible by the inclusion criteria of the AML Intergroup study were treated according to the study group own regimens with 828 patients in study group A, 373 in B, 235 in C, 808 in D, 622 in E, and 305 patients were treated according to the common standard. In an attempt to conduct treatment optimization trials the study group own strategies relied on a risk-oriented stratification among treatment options (group A), a randomized stratification (group D), or combinations of randomization and risk-adaption (B, C, E). High-dose araC was used up to cumulative 54g/m² in groups A, E, and in the standard arm, and up to 36 to 40g/m² in groups B, C, D. Marked differences were also seen in the use of allogeneic stem cell transplantation with 27% allografts in 1^st CR in study group A, 33% in B, 19% in C, 23% in D, 25% in group E, and 21% in the common standard arm. Unlike the differences in the study groups strategies in the amounts of high-dose araC, and in the numbers of allografts in 1^st remission, the risk profiles regarding age, secondary AML, cytogenetic groups, mutations in NPM1/FLT3-ITD, levels of WBC and LDH were concordant between the common standard arm and the study group own populations, except for single differences in secondary leukemia (group B), cytogenetics (C), and WBC (D). The study group itself was not an independent prognostic factor for any outcome. Similar patient populations could thus be evaluated to compare the treatment strategy of each study group with that of the common standard arm. The outcome of the standard treatment was 66.7% (95% CI 61.0–72.0) complete remissions, an overall survival of 44.3% (95% CI 37.9–50.9), and a relapse free survival of 44.9% (95% CI 36.9–52.5) at 5 years. Adjusted for prognostic baseline variables no significant difference in the remission rate and overall survival between the standard arm and any of the study groups were observed. Comparable patterns were also found for relapse free survival where the long-term results of the standard treatment were not further improved in any of the five study groups. We conclude that in unselected patients with AML a prospective comparison shows very similar outcomes of any current treatment strategy when compared with that of the common standard treatment. Present reliable and unbiased analyses became possible by a strictly prospective approach and intent-to-treat evaluation. These representative results can form a solid basis for novel therapeutic approaches.