Dr Jabbour on the Role of Bosutinib as a Therapeutic Option for TKI-Pretreated CML

Elias Jabbour, MD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the role of bosutinib (Bosulif) as a therapeutic alternative for patients with chronic myeloid leukemia (CML) who have developed resistance or intolerance to prior TKIs, as supported by confirmatory data from the phase 4 BYOND trial (NCT02228382).

The FDA approved bosutinib in 2012 for the treatment of patients with Philadelphia chromosome (Ph)–positive CML who are intolerant to or have become resistant to prior therapy. The recommended dose of bosutinib for this indication is 500 mg once daily. Although the 500 mg dose was found to be effective in an outpatient setting, it was later optimized at 400 mg for frontline therapy, where it demonstrated superior efficacy vs the standard of care, imatinib (Gleevec), Jabbour states.

The single-arm, open-label, non-randomized BYOND trial further assessed the agent in patients with TKI-pretreated CML, Jabbour details. Final results from BYOND were published in Leukemia in September 2024, and showed that bosutinib generated high response rates and a manageable safety profile in patients with TKI-pretreated CML. A complete cytogenic response (CCyR) was achieved or maintained with bosutinib by 81.1% (95% CI, 73.7%-87.2%) of evaluable patients at any time. Moreover, major molecular response (MMR), MR4, and MR4.5 was achieved or maintained by 71.8% (95% CI, 63.9%-78.9%), 59.7% (95% CI, 51.4%-67.7%), and 48.3% (95% CI, 40.1%-56.6%) of patients, respectively, at any time on treatment.

For those who did not achieve CCyR at baseline, a CCyR was achieved with bosutinib at any time during treatment in 63.5% (95% CI, 49.0%-76.4%) of patients. Patients without MMR, MR4, or MR4.5 at baseline achieved respective response rates of 59.5% (95% CI, 47.9%-70.4%), 52.7% (95% CI, 43.0%-62.2%), and 42.7% (95% CI, 34.1%-51.7%) at any time during treatment. Notably, most patients achieved deeper MRs during treatment with bosutinib vs baseline.

Although early use of bosutinib is associated with high rates of diarrhea, which may lead to high treatment dropout rates, the BYOND trial indicated that the agent could be optimized for long-term effectiveness by tailoring and escalating doses as needed, Jabbour explains. The agent’s manageable safety profile further supported its sustained efficacy, reinforcing bosutinib’s role as an important TKI for pretreated patients with CML. Overall, the phase 4 BEYOND trial has shown that bosutinib is clinically active, generates sustained responses, and has a manageable safety profile, reinforcing bosutinib’s role as an important TKI for pretreated patients with CML, Jabbour concludes.