Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors

Carlo Gambacorti-Passerini, Hagop M. Kantarjian, Dong Wook Kim, Hanna J. Khoury, Anna G. Turkina, Tim H. Brümmendorf, Ewa Matczak, Nathalie Bardy-Bouxin, Mark Shapiro, Kathleen Turnbull, Eric Leip, Jorge E. Cortes

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Long-term efficacy and safety of bosutinib (≥4 years follow-up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated-phase [AP, n = 79] chronic myeloid leukemia [CML], blast-phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1-88.6), 2.8 (0.03-55.9), 0.97 (0.3-89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan-Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib-related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge-to-transplant role in BP patients); toxicity was manageable.

Original languageEnglish (US)
Pages (from-to)755-768
Number of pages14
JournalAmerican Journal of Hematology
Volume90
Issue number9
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Hematology

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    Gambacorti-Passerini, C., Kantarjian, H. M., Kim, D. W., Khoury, H. J., Turkina, A. G., Brümmendorf, T. H., Matczak, E., Bardy-Bouxin, N., Shapiro, M., Turnbull, K., Leip, E., & Cortes, J. E. (2015). Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors. American Journal of Hematology, 90(9), 755-768. https://doi.org/10.1002/ajh.24034