Real-World Outcomes of Acute Myeloid Leukemia Patients Undergoing Treatment With Tyrosine Kinase Inhibitor (TKI) Therapy Targeting FLT3, IDH1, or IDH2.

Abstract

Background and aims: Acute myeloid leukemia (AML) remains the most common cause of death in adults with acute leukemia. Tyrosine kinase inhibitors (TKIs) have shown significant clinical efficacy in defined patient subgroups. Real-world outcomes of AML patients undergoing TKI therapy have not been widely reported.

Methods: In this real-world retrospective study, we included 482 adult patients with AML treated with a TKI targeting FLT3, IDH1, or IDH2 from January 1, 2015, to December 31, 2023, in the countrywide Flatiron Health electronic health record-derived deidentified database. We utilized unadjusted Kaplan-Meier methods to calculate median real-world event-free survival (rwEFS) and overall survival (rwOS). We utilized a multivariable Cox regression model to evaluate characteristics associated with rwOS, modeling post-TKI stem cell transplant (SCT) as a time-varying covariate.

Results: Those who received treatment at 1L (first-line) and 2L+ (second-line and beyond) had similar length of TKI therapy (3.7 vs. 3.4 months), rwEFS (2.2 vs. 2.5 months), and rwOS (12.3 vs. 13.1 months), respectively. Among all patients, greater rwOS was associated with receiving pre-TKI SCT (p < 0.001), commercial insurance (vs. Medicaid; p = 0.035), younger age (p = 0.043), and favorable 2017 ELN risk classification (vs. adverse; p = 0.032). When restricted to patients treated with TKI at 2L+ without prior SCT, rwEFS were 1.4, 1.6, and 2.1 months by targetable mutation (IDH2, IDH1, and FLT3), and rwOS were 8.7, 15.4, and 9.5 months, respectively.

Conclusion: Patients treated with HMA plus TKI did not have significant differences compared to TKI alone. In this substantial, real-world cohort of AML patients receiving TKIs, clinical outcomes remained deficient irrespective of timing of TKI start, mutational target, and concurrent HMA.