Combining menin inhibitors with intensive chemotherapy can decrease the risk of differentiation syndrome, a severe side effect. The chemotherapy debulks the tumor, reducing the number of malignant cells available to cause this inflammatory reaction when they differentiate, improving tolerability.
Combinations of menin inhibitors with standard chemotherapy are achieving impressively high remission rates (e.g., 89% composite remission) in newly diagnosed KMT2A-rearranged AML. This is a significant development, as this genetic subtype has historically been very challenging to treat effectively.
While adding a menin inhibitor to the azacitidine/venetoclax doublet for older/unfit AML patients increases response rates, it leaves little reserve for marrow function. This can lead to increased risk of early, fatal complications like infection or bleeding, requiring careful dose management.
The future standard of care for AML could move towards all-oral triplet therapies. Citing promising data from the SAVE trial, the speaker suggests these better-tolerated, outpatient regimens could replace harsh inpatient chemotherapy for many patients, improving quality of life.
When evaluating data for relapsed/refractory AML, clinicians must look beyond headline response rates. The number of prior therapies a patient has received dramatically impacts outcomes. A trial with a median of one prior treatment will have vastly different results than one with five.