Selecting, Switching, and Discontinuing First-Line TKIs in CML

New York—During his presentation at the 2019 Lymphoma & Myeloma congress, Sangmin Lee, MD, Assistant Professor of Medicine, Weill Cornell Medical College, New York, told attendees about current approaches to optimizing the care of patients with chronic myeloid leukemia (CML) in the era of tyrosine kinase inhibitors (TKIs).

“In CML we have been very fortunate. There are a lot of options available that were not available 20 years ago,” said Dr Lee. There are currently several second-generation TKIs approved by the FDA for the first-line treatment of CML (eg, imatinib, dasatinib, ponatinib, nilotinib, and bosutinib), he said.

Choosing a First-Line TKI

Despite data existing on these drugs in the context of CML, their progression-free and overall survival benefits remain unclear. Thus, making considerations when selecting the right TKI for a patient with CML is crucial.

According to Dr Lee, TKIs are generally selected based on the side effect profile of the drug or the preference of the insurance provider.

“In practice, for older patients with significant comorbidities, it’s perfectly acceptable to use imatinib because imatinib seems to be better tolerated than the other TKIs. For other patients who are younger, we tend to use second-generation TKIs and among bosutinib, dasatinib, and nilotinib, generally speaking, there are different side-effect profiles and we may choose a TKI based on a patient’s baseline comorbidities,” he told attendees.

However, because none of these drugs have been compared head-to-head, insurance companies also tend to dictate which therapy a patient should receive.

Dr Lee also summarized certain data on the second-line and beyond to illustrate the side effects of TKIs. These side effects include pulmonary arterial hypertension, pleural effusions, QT prolongation, diarrhea, and cardiovascular events.

Switching and Discontinuing TKIs

One problem of note that Dr Lee shared vis-à-vis patients with CML not responding to TKIs or having adverse reactions was in deciding when the best time would be to switch or discontinue TKI therapy.

Although the optimum time point to switch TKIs is unknown, Dr Lee suggests consideration of switching if no complete cytogenetic response is observed at 12 months.

In addition, TKIs may be discontinued in compliant patients who have prolonged deep responses (MR4.0 –BCR-ABL ≤0.01% for 2 years). However, it is advised that patients be monitored monthly shortly after discontinuation, as the majority of molecular relapses occur within 6 months of stopping therapy.—Hina Porcelli