Drug combo may overcome resistance in AML
Researchers at Oregon Health & Science University report that combining the leukemia drug venetoclax with the breast‑cancer drug palbociclib showed significantly stronger and more durable anti‑leukemia effects than venetoclax alone in lab tests on samples from more than 300 acute myeloid leukemia (AML) patients and in mouse models carrying human leukemia cells. The team found that AML cells adapt to venetoclax monotherapy by ramping up protein production, but adding palbociclib blocks this adaptation, extending mouse survival to 11–12 months in most cases and suggesting a way to overcome resistance that could move into clinical trials for a disease that affects over 20,000 Americans annually and still has only a 25%–40% five‑year survival rate.
📌 Key Facts
- OHSU scientists tested drug combinations on samples from more than 300 AML patients and identified venetoclax plus palbociclib as the most effective pairing.
- In mouse models with venetoclax‑resistant human AML, the combination led to most mice living 11–12 months, whereas venetoclax alone did not extend survival.
- The study shows AML cells adapt to venetoclax by increasing protein production, an escape route that palbociclib blocks, and the findings are being used to justify future clinical trials in patients.
📊 Relevant Data
Non-Hispanic White males have the highest age-adjusted incidence rate of acute myeloid leukemia (AML) at 5.5 per 100,000 population, compared to 4.6 for Non-Hispanic Black males, 4.1 for Hispanic males, 4.0 for Non-Hispanic Asian/Pacific Islander males, and 3.9 for Non-Hispanic American Indian/Alaska Native males.
Black patients with acute myeloid leukemia (AML) have significantly lower median overall survival and 5-year relative survival rates compared to White patients.
Effect of racial disparities on cancer survival in hematologic malignancies: a SEER database analysis — Taylor & Francis Online
African American ancestry is associated with shorter survival in AML patients receiving standard therapy, with distinct molecular and clinical factors identified through multiomic profiling.
Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia — Nature Genetics
Black patients with AML experience worse overall survival compared to White patients, even with similar FLT3 mutation rates, in the era of FLT3 inhibitors.
Persistent racial disparities in AML survival in the FLT3 inhibitor era — ASCO Publications