Do gene mutations impact clinical outcome in elderly acute myeloid leukemia (AML) patients?

Victoria Prassek, MD, from Ludwig-Maximilians-University (LMU), Munich, Germany, discusses whether gene mutations impact clinical outcome in very old, intensively treated acute myeloid leukemia (AML) patients enrolled in AML Cooperative Group (AMLCG) 1999 and 2008 trials (NCT00266136, NCT01382147) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. She describes the aim of this study, which was to validate existing risk classifications and identify genetic markers associated with clinical outcome in this subset of patients. AML is a disease of the elderly, with a median age of diagnosis of 68 years, and the outcome of elderly patients is very poor, partly because patients may not be fit enough for intensive chemotherapy. Dr Prassek argues that there is a need to be able to predict positive outcomes of intensive chemotherapy in these patients. She summarizes results indicating that even in very old, intensively treated AML patients, molecular factors and adverse cytogenetics play an important role and can predict inferior survival. On the other hand, patients in the favorable and intermediate groups according to the ELN and MRC risk classifications may benefit from intensive chemotherapy, indicating that if there are no medical counterindications for such an intensive therapy, it may be beneficial to treat these patients with intensive induction therapy. Dr Prassek also highlights that IDH-1 mutated patients do not reach complete remission (CR) after intensive induction therapy, suggesting that IDH-1 may be a novel marker for inferior prognosis and chemorefractory disease in elderly AML patients. This raises the need to consider whether patients with IDH-1 mutations should be treated with intensive chemotherapy, or a less severe therapy with a greater focus on quality of life.

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