Acute Myeloid Leukemia (AMl): Advances in Targeted Therapy

Acute myeloid leukemia, or AML, is an uncommon but serious form of cancer that starts in thebone marrow and quickly spreads to the blood. It’s a fast-moving condition that can becomelife-threatening without prompt treatment. While most often diagnosed in adults over 60, AMLcan also occur in children and younger adults. Advances in therapies are improving survival andquality of life for many patients.

Conventional Chemotherapy and Vyxeos (CPX-351)

CPX-351 (Vyxeos®) is a dual-drug liposomal chemotherapy combining daunorubicin and cytarabine in a fixed 1:5 ratio, approved for newly diagnosed therapy-related AML and AML with myelodysplasia-related changes (AML-MRC). Clinical trials have shown that CPX-351 leads to improved overall survival, remission rates, and post-transplant outcomes compared to standard 7+3 chemotherapy, with a similar safety profile. A post hoc analysis, referencing the 2017 European LeukemiaNet (ELN) classification, further evaluated long-term outcomes across risk groups.

As published in Frontiers in Oncology, read the full study here.

Targeted Therapies in AML

1. Menin Inhibitors: Revumenib
a. The FDA’s recent approval of revumenib (Revuforj®) marks a major advancement for patients with KMT2A (MLL) rearrangements or NPM1 mutations. These genetic changes disrupt transcriptional regulation, driving the development of leukemia. Revumenib works by blocking the interaction between menin and these mutations, helping to restore normal blood cell development. Data from the AUGMENT-101 trial showed promising results in relapsed or refractory AML patients, particularly in those with these high-risk genetic profiles.

2. BCL-2 Inhibitors: Venetoclax
a. Venetoclax (Venclexta®) is a targeted therapy that inhibits BCL-2, an anti-apoptotic protein that helps leukemia cells survive. By reactivating programmed cell death, venetoclax has become a transformative option for older or medically unfit AML patients. When combined with hypomethylating agents such as azacitidine or decitabine, or with low-dose cytarabine, it has demonstrated high remission rates—especially in patients with IDH or NPM1 mutations.

3. IDH Inhibitors: Ivosidenib and Olutasidenib
a. Mutations in IDH1 and IDH2 produce an abnormal metabolite that blocks normal cell differentiation. IDH inhibitors such as ivosidenib (Tibsovo®) and olutasidenib (Rezlidhia®) directly target this pathway, allowing leukemic cells to mature and die off naturally. Both agents are FDA-approved and have shown effectiveness in treating relapsed or refractory AML, with manageable side effects and encouraging response rates.

4. FLT3 Inhibitors: Midostaurin, Gilteritinib, and Quizartinib
a. FLT3 mutations—including FLT3-ITD and FLT3-TKD—are common in AML and linked to aggressive disease. Targeted therapies such as midostaurin (Rydapt®), gilteritinib (Xospata®), and quizartinib (Vanflyta®) have significantly improved outcomes for patients with FLT3-mutated AML. Midostaurin is used alongside chemotherapy in newly diagnosed cases, while gilteritinib and quizartinib are approved for relapsed or refractory disease and offer mutation-specific targeting to improve survival.

Future Directions in AML Therapy

The evolving treatment landscape for acute myeloid leukemia (AML) is shifting toward a more personalized approach, driven by the integration of targeted therapies such as venetoclax (Venclexta®), revumenib (Revuforj®), and FLT3 or IDH inhibitors. These advancements move beyond traditional chemotherapy, allowing for therapies tailored to the patient’s unique genetic and clinical characteristics.

Today, molecular profiling at diagnosis has become a cornerstone of AML management, helping guide the selection of appropriate targeted treatments. Ongoing clinical trials are expanding this approach, investigating combinations of targeted agents with immunotherapies, monoclonal antibodies, and even CAR T-cell therapies for AML. With these innovations, the future of AML treatment is becoming increasingly individualized—offering new hope for improved survival and reduced treatment-related toxicity in this historically difficult-to-treat disease.