Prospective evaluation of residual disease in intensively treated patients with acute myeloid leukemia (AML) as surrogate endpoint for survival

点击翻译按钮获取中文摘要

Acute myeloid leukemia is a genetically and phenotypically heterogeneous disorder with an incidence of 3 to 4 per 100 000 men and warnen per year and a median age at diagnosis of about 70 years. Prognosis, especially in older patients, has remained very poor. In patients considered suitable for intensive chemotherapy, the combination of an anthracycline and cytarabine remains the standard of care. For patients achieving a complete remission (CR), postremission therapy (PRT) ranging from chemotherapy to allogeneic hematopoietic stem cell transplantation is required; intensive PRT is still under debate in older patients. Beyond pre-treatment geneticsbased risk stratification, measurement of residual disease (RD) during treatment and follow up emerges as an important prognostic factor in first CR. Furthermore, RD may provide a tool for a read-out of therapeutic efficacy. In this diagnostic study we intend to measure RD using multiparameter flow cytometry across 5 up-front randomized clinical trials which will accrue more than 1000 patients. According to the leukemia-associated phenotype at diagnosis, RD will be assessed early (after induction) and late (after consolidation) during treatment. The aim of the study is to show that levels of RD measured early during treatment are closely related to overall survival and thus may serve as an early surrogate. There is a growing public demand that new, promising drugs are approved for therapy as rapidly as possible. Therefore, it is of great interest to obtain these approvals based on early biomarker endpoints such as RD rather than on longterm survival endpoints.