Association between Targeted Therapy and Survival in Patients with AML
Authors: Russo Pierantonio , Nathan Ramaa , Pfeffer Daniel , Moore Alex 
Published: December 2024

Introduction
Acute Myeloid Leukemia (AML) is a hematologic malignancy with poor prognosis, particularly in high-risk patients. However, targeted therapy, even without achieving complete remission (CR), prolongs survival in patients with AML. This real-world study examines the association between targeted therapy and survival in patients with AML presenting with targetable mutations.
Methods
We analyzed genomic test data (July 2018 to December 2023), sourced from a leading genomics data provider and linked with Symphony administrative claims. We identified patients undergoing genetic biomarker tests (panel vs. single gene tests), turnaround time (TAT) from test order to result, and test results.
A cohort of 2,239 AML patients with at least 6 months of pre-diagnosis claims history and positive test results for IDH1, IDH2, or FLT3 mutations were identified. Targeted therapy was recorded if patients had claims for ivosidenib (IDH1), enasidenib (IDH2), or midostaurin/gilteritinib (FLT3). Confounding factors included age at diagnosis, sex, baseline Elixhauser Comorbidity Index (ECI), TAT and multiple positive mutation results. Mortality was tracked from diagnosis over 12-months , with patients censored if they left the database or if no event occurred the 12 months. Cox proportional hazards models were used to determine the impact of targeted therapies and non-targeted therapies on overall survival (OS).
Results
The cohort included 2,239 AML patients with a median age of 71 years (19-79) (55% males and 45% females), with medium to severe baseline ECI (score &gt;5) in 29.1%. Therapy for targetable mutations was recorded in 521 (23%); 1,718 (77%) with targetable mutations did not receive targeted therapy. A multivariate Cox proportional hazard model demonstrated a decreasing risk of death over time for those on targeted therapy. Across all mutations, the hazard model showed a time-varying reduced risk of death with use of target therapy by 94% (HR=0.066; p&lt;0.01) at 1 month to 27% (HR=0.73; p&lt;0.01) at 8 months. For individual mutations, the use of targeted therapy reduced risk of death within 12 months by 85.1% for IDH1 (HR=0.149; p&lt;0.01), 66.3% for IDH2 (HR=0.337; p&lt;0.01) and time-varying reduced risk for FLT3 by 96% (HR=0.041; p&lt;0.01) at 1 month to 28% (HR=0.72; p&lt;0.01) at 7 months.
Additional multivariate analyses were conducted across all mutations, separately for patients aged 65 years or older (N=1,510; 67%) and for patients aged less than 65 years (N=729; 33%). For patients 65 years or older, the hazard models showed a time-varying reduced risk of death with use of targeted therapy by 92% (HR=0.08; p&lt;0.01) at 1 month to 18% (HR=0.819; p&lt;0.01) at 9 months, beyond which there is no significant difference. For patients less than 65 years, the hazard models showed a time-varying reduced risk of death with use of targeted therapy by 95% (HR=0.049; p&lt;0.01) at 1 month to 31% (HR=0.689; p&lt;0.01) at 7 months, beyond which there is no significant difference.
Conclusion
Targeted therapies have an impact on survival in patients exhibiting targetable mutations. Our findings support the notion that incorporating targeted therapies for actionable mutations into treatment regimens can enhance survival outcomes for patients with AML. However, a significant number of biomarker-positive AML patients do not receive targeted therapies, highlighting challenges such as disparities in access to care and provider awareness. Addressing these issues is essential to ensure all eligible patients benefit from advancements in targeted therapies, ultimately improving survival and quality of life.