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.