Efficacy and safety following bosutinib dose reduction in patients with Philadelphia chromosome‒positive leukemias

Vamsi Kota, Tim H. Brümmendorf, Carlo Gambacorti-Passerini, Jeff H. Lipton, Dong Wook Kim, Fiona An, Eric Leip, Rocco J. Crescenzo, Roxanne Ferdinand, Jorge E. Cortes

Research output: Contribution to journalArticlepeer-review

Abstract

The recommended starting dose of bosutinib is 500 mg/day for chronic-phase (CP) or accelerated-/blast-phase Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy. However, some patients may require dose reductions to manage the occurrences of adverse events (AEs). Bosutinib efficacy and safety were evaluated following dose reductions in a phase I/II study of Ph + patients with CP CML resistant/intolerant to imatinib or imatinib plus dasatinib and/or nilotinib, and those with accelerated-/blast-phase CML or acute lymphoblastic leukemia after at least imatinib treatment. In all, 570 patients with ≥4 years’ follow-up were included in this analysis. Among 144 patients who dose-reduced to bosutinib 400 mg/day (without reduction to 300 mg/day), 22 (15 %) had complete cytogenetic response (CCyR) before and after reduction, 40 (28 %) initially achieved CCyR after reduction, and 4 (3 %) only had CCyR before reduction. Among 95 patients who dose-reduced to bosutinib 300 mg/day, 23 (24 %) had CCyR before and after reduction, 13 (14 %) initially achieved CCyR after reduction, and 3 (3 %) only had CCyR before reduction. Results were similar to matched controls who remained on 500 mg/day, indicating dose reductions had not substantially affected efficacy. The incidence of treatment-emergent AEs was lower after dose reductions, particularly for gastrointestinal events. The incidence of hematologic toxicities generally was similar before and after dose reduction. The management of AEs with bosutinib through dose reduction can lead to improved/maintained efficacy and better tolerability; still, approximately half of patients on treatment at year 4, maintained a dose of ≥500 mg/day ClinicalTrials.gov: NCT00261846.

Original languageEnglish (US)
Article number106690
JournalLeukemia Research
Volume111
DOIs
StatePublished - Dec 2021

Keywords

  • Bosutinib
  • Chronic myeloid leukemia
  • Dose modification
  • Dose reduction

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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