Promising Advances in Acute Myeloid Leukemia Treatment for Older Patients
Understanding Acute Myeloid Leukemia
A recent study has revealed promising outcomes regarding the treatment of acute myeloid leukemia (AML) in older patients through the combination of targeted therapy and chemotherapy. AML is a type of blood cancer that originates in the bone marrow, which is responsible for blood cell formation. This cancer arises due to abnormal changes in myeloid cells, which typically develop into white blood cells. However, when these cells undergo abnormal transformations, they grow aggressively and without restraint.
Leukemias are classified based on the speed of cell growth, with AML being one form. It is generally diagnosed later in life, with a median age of diagnosis at 67 years.
Challenges of Treating AML in Older Patients
Treating AML in older patients poses distinct challenges. While chemotherapy can induce remission, many elderly patients may be too frail to endure the harsh effects of standard chemotherapy regimens. Consequently, pharmaceutical companies are focusing on developing gentler yet effective treatment options for older patients diagnosed with acute myeloid leukemia.
Successful Combination Therapy Results
A collaborative study led by researchers from Dana-Farber Cancer Institute in Boston and sponsored by Genentech and AbbVie reported significant findings regarding the treatment of AML. In this phase-1 multicenter clinical trial involving 145 patients, a combination of Venetoclax with either decitabine or azacitidine resulted in near-complete to complete remission in 70% of participants. The median age of the patients in this study was 74 years. The findings were published in the journal Blood.
Patients received Venetoclax orally at varying doses (400, 800, or 1200 mg), while decitabine or azacitidine was administered via injection at doses of 20 mg/m² and 75 mg/m². Notably, all participants had no prior treatment, and nearly half (49%) exhibited abnormal cellular characteristics that heightened their susceptibility to AML and diminished their response to treatments. Despite these challenges, the median overall survival reported was 17.5 months, although some side effects, including nausea, diarrhea, fatigue, and decreased white blood cell counts, were observed.
Regulatory Approval and Future Trials
Venetoclax is a targeted therapy designed to inactivate the BCl-2 protein, which typically prevents cancer cell death. Conversely, azacitidine works by reactivating tumor suppressor genes, which act as brakes on cell division, thus inhibiting uncontrolled cell growth. Azacitidine accomplishes this by inhibiting DNA methyltransferases, leading to the reactivation of these crucial brake proteins.
Given the encouraging results from the study, the U.S. Food and Drug Administration (FDA) has granted expedited regulatory approval for this treatment approach. A phase-3 clinical trial is currently underway, comparing azacitidine alone with its combination with Venetoclax.
Conclusion
The findings from this study signify a potential breakthrough in the treatment of AML among older patients, offering hope for improved outcomes with less aggressive therapies.
Written by Vinayak Khattar, Ph.D., M.B.A.
Reference: DiNardo, C. D., Pratz, K., Pullarkat, V., Jonas, B. A., Arellano, M., Becker, P. S., . . . Letai, A. (2018). Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. doi:10.1182/blood-2018-08-868752