Predicting Response to Therapy With TKIs in Patients With Chronic Myeloid Leukemia
Posted: Thursday, March 22, 2018
In patients with chronic myeloid leukemia in chronic phase (CML-CP), the use of a prediction model could be beneficial to determine who may qualify for treatment discontinuation, according to a study published in Cancer. Lead author Jorge E. Cortes, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues, created a model to identify the optimal BCR-ABL1 transcript level during the first 12 months of therapy with tyrosine kinase inhibitors (TKIs), which would predict the achievement of a deep molecular response for at least 2 years.
The study analyzed data for 603 newly diagnosed patients with CML-CP who were enrolled in several prospective clinical trials, which included administration of imatinib, high-dose imatinib, nilotinib, dasatinib, or ponatinib. A sustained molecular response was considered to be a BCR-ABL1 level ≤ 0.0032% on the international scale (MR4.5) in all consecutive assessments performed every 6 months for at least 2 years.
The investigators determined the best fit average levels, or typical transcript levels of patients who achieved the target response, were 0.051%, 0.019%, 0.007%, and 0.003% at 3, 6, 9, and 12 months, respectively. The minimum acceptable levels, which are levels achieved by 95% of patients who reached the target endpoint, were 1.561%, 0.592%, 0.225%, and 0.085%, respectively.
“The proper interpretation of transcript levels achieved early during the course of therapy may help to predict later responses and outcomes,” concluded Dr. Cortes and colleagues. “Models such as the one proposed here can be built to guide therapy for patients on a continuous basis.”