Acute Myeloid Leukemia (AML)

Dear Colleagues,

Precision medicine has opened the door to personalized therapy for specific Acute Myeloid Leukemia (AML) patient populations with promising results. Several targeted therapies have been approved or are being tested for specific mutations (i.e., FLT3, IDH, BCL-2, and TP53), obtaining improvements in clinical outcomes and less toxicity as compared with some intensive or non-intensive regimens, potentially allowing for combination therapy. Unfit patients, especially older patients, have higher disease progression and a lower tolerance than fit patients, and are treated with non-intensive schemes (i.e., low-dose cytarabine (LDAC) or hypomethylating agents (HMAs)). This subset of patients could potentially benefit from emerging therapies focused on specific poor prognosis features (FLT3, secondary AML). HMAs in combination with small molecule inhibitors (unspecific such as glasdegib or venetoclax or specific such as FLT3 or IDH inhibitors) could increase survival and quality of life in older/unfit patients, which represent the most difficult-to-treat AML population. Venetoclax is an oral selective inhibitor of broad-spectrum B-cell lymphoma 2 (BCL-2), and therefore is not considered to be a targeted therapy. The promising results of phase 1b trials exploring the combination of venetoclax plus HMAs or LDAC led to FDA approval and commercialization of this new drug for AML. The recent positive results of the phase 3 trial of azacitidine plus venetoclax could open the door to further indications of venetoclax in AML. Appropriate clinical development and use of non-approved combinations in the context of clinical trials should be recommended in order to avoid unexpected adverse events in AML patients.

This Special Issue will highlight the critical role of supportive care and appropriate management of new drugs and combinations to ensure therapeutic success in AML cases. In addition, we will critically assess epidemiological and real-life evidence of AML outcomes beyond the clinical trial setting.

Dr. Pau Montesinos
Guest Editor

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