# A lower initial dose of bosutinib for patients with chronic myeloid leukemia patients resistant and/or intolerant to prior therapy: a single-arm, multicenter, phase 2 trial (BOGI trial)

## TL;DR

A lower starting dose of bosutinib reduces treatment discontinuation in chronic myeloid leukemia patients without affecting effectiveness.

## Contribution

A lower initial dose of bosutinib reduces discontinuation due to drug-related toxicities while maintaining efficacy in CML patients.

## Key findings

- A lower initial dose of bosutinib reduced discontinuation due to drug-related toxicities by 11.4% compared to historical controls.
- The incidence of diarrhea was significantly lower at 3% compared to 25% in prior studies.
- Patients who achieved a major molecular response tended to have higher trough concentrations of bosutinib.

## Abstract

Although bosutinib is generally safe and effective, drug-related toxicities (DRTs) such as diarrhea or increased transaminase levels often lead to treatment discontinuation. To clarify whether a lower initial dose of bosutinib (i.e., starting at 200 mg) would reduce rates of discontinuation due to DRTs, we conducted a phase 2 study of BOsutinib Gradual Increase (BOGI trial, UMIN 000032282) as a second/third-line treatment for chronic myeloid leukemia (CML). Between February 4, 2019 and May 24, 2022, 35 patients were enrolled. The rate of bosutinib discontinuation at 12 months was 25.7% vs. 35.9% in a historical control study (Japanese phase 1/2 study) (p = 0.102). The rate of bosutinib discontinuation due to DRTs was significantly lower, at 11.4% vs. 28.2% (p = 0.015). The incidence of grade 3/4 transaminase elevation was 20% vs. 29% (p = 0.427), while the incidence of diarrhea was 3% vs. 25% (p = 0.009). The median dose intensity of bosutinib was higher (391.7 mg/day vs. 353.9 mg/day). Pharmacokinetic analysis of bosutinib showed that patients who achieved a major molecular response tended to have high trough concentrations. Thus, a low initial dose of bosutinib followed by dose escalation reduced discontinuation due to severe DRTs while maintaining high dose intensity and efficacy.

The online version contains supplementary material available at 10.1007/s12185-024-03830-z.