Dr Swoboda on the Role of TKIs in Chronic Myeloid Leukemia

David M. Swoboda, MD, hematologist/oncologist, Tampa General Hospital Cancer Institute, discussed the roles of available TKIs for the treatment of patients with chronic myeloid leukemia (CML).

Since the introduction of imatinib (Gleevec), which was the first TKI to earn FDA approval for the treatment of patients with CML, investigators have been working to develop improved TKIs, Swoboda began. These efforts led to the development of the second generation of TKIs in the space with the aim of achieving deeper and more durable responses, he continued. Three new TKIs subsequently received FDA approval: dasatinib (Sprycel), nilotinib (Tasigna), and bosutinib (Bosulif).

Following the development of the second-generation TKIs, the emergence of a resistance mutation in T315I led to the need for new TKIs that could overcome this mechanism, Swoboda explained. This led to the development and FDA approval of ponatinib (Iclusig), which targets this mutation, he continued.

The most significant recent shift in terms of TKIs for patients with CML came with the development ofasciminib (Scemblix), Swoboda said. In October 2024, the FDA granted accelerated approval to asciminib for the treatment of adult patients with newly diagnosed, Philadelphia chromosome–positive CML in chronic phase. The approval was supported by data from the phase 3 ASC4FIRST study (NCT04971226).

Findings from ASC4FIRST demonstrated that patients who received asciminib (n = 201) achieved a 48-week major molecular response rate of 68% (95% CI, 61%-74%) compared with 49% (95% CI, 42%-56%) among patients who were treated with investigator-selected TKIs (n = 204), for a difference of 19% (95% CI, 10%-28%; P < .001). In terms of safety, the most common adverse effects occurring in at least 20% of patients included musculoskeletal pain, rash, fatigue, upper respiratory tract infection, headache, abdominal pain, and diarrhea.

Asciminib differs from the other approved TKIs in the space because it is an allosteric inhibitor, Swoboda noted. Most patients with CML who are treated with TKIs are now receiving asciminib or second-generation TKIs, based on the safety profiles of these agents and patient comorbidities, he said. The treatment of patients with CML has moved towards a more targeted and individualized approach, he concluded.