Dr Atluri on TKI Selection in Chronic Myeloid Leukemia

“In my personal practice, my preference tends to be starting with second-generation TKIs because when we look at our goals for therapy in CML, it should be about achieving a major molecular response and a deep molecular response.”

Himachandana Atluri, MD, an assistant professor of medicine (Hematology and Oncology) at the Feinberg School of Medicine at Northwestern University, detailed factors to consider before selecting a TKI for the treatment of chronic myeloid leukemia (CML).

The process of selecting optimal TKIs for patients with CML depends on comfort level with each therapy; however, starting with second-generation TKIs is Atluri’s approach, she began. The goal for managing CML is to achieve deep major molecular responses (MMR) where patients achieve remission and therefore stop treatment, she emphasized. Although treatment of second-generation TKIs tends to be more difficult to tolerate, patients can achieve deeper remission faster, she explained.

In October 2024, the FDA granted an accelerated approval to asciminib (Scemblix) for the treatment of patients with newly diagnosed, Philadelphia chromosome–positive CML in chronic phase. The regulatory decision was based on data from the phase 3 ASC4FIRST trial (NCT04971226), which revealed that patients with CML treated with asciminib (n = 201) achieved a 48-week MMR of 68% (95% CI, 61%-74%) vs 49% (95% CI, 42%-56%) in patients treated with investigator’s choice TKI (n = 204).

Of note, selecting treatment can also depend on patients’ comorbidities, Atluri continued. For example, if a patient has pulmonary hypertension, dasatinib (Sprycel) would not be the best option due to its known safety profile, with pulmonary hypertension as a common adverse effect, she explained. Furthermore, bosutinib (Bosulif) would not be a feasible option for a patient with irritable bowel syndrome, is prone to diarrhea, or has liver-related concerns, she said. Additionally, she also noted that those with high-risk cardiovascular disease may not be the best candidates to receive asciminib. Therefore, the selection of TKIs depends on the safety profiles of each therapy, which is discussed with patients as they choose what is best for them, Atluri concluded.