BCR::ABL1 Mutational Profiling in US Patients With Chronic-phase Chronic Myeloid Leukemia on Tyrosine Kinase Inhibitors

Background/Aim: Widespread use of BCR::ABL1 tyrosine kinase inhibitors (TKIs) has transformed the clinical landscape of chronic myeloid leukemia (CML). However, BCR::ABL1 mutation-driven treatment resistance challenges optimal care and outcomes. The purpose of this study was to ascertain real-world practices concerning such mutational profiling in US hematology and oncology practices, which were mainly community-based. Materials and Methods: This is the first chart review of BCR::ABL1 kinase domain mutational profiling in the US. In this study of the Cardinal Health Oncology Provider Extended Network (OPEN), 13 hematologists and/or oncologists selected charts of adults with chronic-phase CML for approximately equal numbers of patients who underwent such testing (Cohort 1; n=26) or did not (Cohort 2; n=25). Results: Across most time points, failure and warning signs by molecular testing were not significantly more frequent in patients who did or did not undergo BCR::ABL1 mutational profiling. Conversely, similar frequencies of optimal milestones were observed in patients with or without testing. Patients who underwent BCR::ABL1 mutational profiling were more likely to have splenomegaly (p=0.0069) versus those who did not. Conclusion: There were few significant differences in failure and warning signs by molecular testing in patients who did or did not undergo mutational profiling. Patients who underwent BCR::ABL1 mutational profiling were significantly more likely to have splenomegaly, which is not included in consensus guidelines as a reason to conduct such testing. Taken together, these findings raise potential concerns about consensus guideline adherence as a means to optimize CML management for TKI resistance.