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A personalized approach for Acute Myeloid Leukemia: biologic, prognostic and therapeutic insights
Khaled et al. reviewed the diagnosis and treatment of Acute Myeloid Leukemia (AML) to provide insights into the emerging novel biomarkers, new molecular approaches and therapeutic agents that are anticipated to be useful for the implementation of personalized medicine in AML. This review has implications for the management of patients with the most unmet needs; older patients and patients with high-risk disease. Their findings were published in Oncology (Williston Park) in April 2016.1
Epigenetic modulators
Hypomethylating agents (HMAs), including 5-azacytidine or decitabine, may be an effective approach in older patients. The effectiveness of these agents was observed in two large randomized trials. Also of note are the results of a landmark 10-day regimen of decitabine, 20mg/m2, in previously untreated older AML patients which demonstrated a 47% complete remission (CR) rate and a 64% overall response (OR) rate.
NPM1 mutations
Nucleophosmin (NPM) is a nucleolar phosphoprotein that normally shuttles between the nucleus and the cytoplasm to maintain cellular processes. Frameshift mutations at the C-terminus of this protein are relatively common in cytogenic-normal (CN-AML) patients (occurring in 45% to 60% of this subset). In older CN-AML patients treated with intensive induction chemotherapy, NPM1 mutations predict for excellent disease response and better survival.
Immunotherapeutic agents
SGN-CD33A, a humanized CD33 antibody conjugated to a pyrrolobenzodiazepine (PBD), has shown promising results in AML patients. Early results from a phase I clinical trials have recently been presented. In one trial of SGN-CD33A monotherapy in patients who had CD33-positive AML in relapse or who had declined intensive induction chemotherapy, a dose of 40μg/kg led to a 60% OR rate in treatment-naïve patients.
Summary
In summary, in order to improve outcomes in AML patients, the challenge is how to match molecular and clinical information with emerging compounds in order to select the best treatment for individual patients. The success of personalized approaches in AML is likely to depend on the ability to readily attain molecular information and improve patient access to new drugs.
References