Step-in dosing of bosutinib in pts with chronic phase chronic myeloid leukemia (CML) after second-generation tyrosine kinase inhibitor (TKI) therapy: results of the Bosutinib Dose Optimization (BODO) Study
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Step-in dosing of bosutinib in pts with chronic phase chronic myeloid leukemia (CML) after second-generation tyrosine kinase inhibitor (TKI) therapy: results of the Bosutinib Dose Optimization (BODO) Study. / Isfort, Susanne; Manz, Kirsi; Teichmann, Lino L; Crysandt, Martina; Burchert, Andreas; Hochhaus, Andreas; Saussele, Susanne; Kiani, Alexander; Göthert, Joachim R; Illmer, Thomas; Schafhausen, Philippe; Al-Ali, Haifa Kathrin; Stegelmann, Frank; Hänel, Mathias; Pfeiffer, Tim; Giagounidis, Aristoteles; Franke, Georg-Nikolaus; Koschmieder, Steffen; Fabarius, Alice; Ernst, Thomas; Warnken-Uhlich, Mareille; Wolber, Uta; Kohn, Denise; Pfirrmann, Markus; Wolf, Dominik; Brümmendorf, Tim H; German CML study group.
in: ANN HEMATOL, Jahrgang 102, Nr. 10, 10.2023, S. 2741-2752.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Step-in dosing of bosutinib in pts with chronic phase chronic myeloid leukemia (CML) after second-generation tyrosine kinase inhibitor (TKI) therapy: results of the Bosutinib Dose Optimization (BODO) Study
AU - Isfort, Susanne
AU - Manz, Kirsi
AU - Teichmann, Lino L
AU - Crysandt, Martina
AU - Burchert, Andreas
AU - Hochhaus, Andreas
AU - Saussele, Susanne
AU - Kiani, Alexander
AU - Göthert, Joachim R
AU - Illmer, Thomas
AU - Schafhausen, Philippe
AU - Al-Ali, Haifa Kathrin
AU - Stegelmann, Frank
AU - Hänel, Mathias
AU - Pfeiffer, Tim
AU - Giagounidis, Aristoteles
AU - Franke, Georg-Nikolaus
AU - Koschmieder, Steffen
AU - Fabarius, Alice
AU - Ernst, Thomas
AU - Warnken-Uhlich, Mareille
AU - Wolber, Uta
AU - Kohn, Denise
AU - Pfirrmann, Markus
AU - Wolf, Dominik
AU - Brümmendorf, Tim H
AU - German CML study group
N1 - © 2023. The Author(s).
PY - 2023/10
Y1 - 2023/10
N2 - The approved dose of bosutinib in chronic phase CML is 400 mg QD in first-line and 500 mg QD in later-line treatment. However, given that gastrointestinal (GI) toxicity typically occurs early after treatment initiation, physicians often tend to start therapy with lower doses although this has never been tested systematically in prospective trials in the Western world. The Bosutinib Dose Optimization (BODO) Study, a multicenter phase II study, investigated the tolerability and efficacy of a step-in dosing concept of bosutinib (starting at 300 mg QD) in chronic phase CML patients in 2nd or 3rd line who were intolerant and/or refractory to previous TKI treatment. Of 57 patients included until premature closure of the study due to slow recruitment, 34 (60%) reached the targeted dose level of 500 mg QD following the 2-weekly step-in dosing regimen. While the dosing-in concept failed to reduce GI toxicity (grade II-IV, primary study endpoint) to < 40% (overall rate of 60%; 95% CI: 45-74%), bosutinib treatment (mean dosage: 403 mg/day) showed remarkable efficacy with a cumulative major molecular remission (MMR) rate of 79% (95% CI: 66 to 88%) at month 24. Of thirty patients refractory to previous therapy and not in MMR at baseline, 19 (64%) achieved an MMR during treatment. GI toxicity did not significantly impact on patient-reported outcomes (PRO) and led to treatment discontinuation in only one patient. Overall, the results of our trial support the efficacy and safety of bosutinib after failure of second-generation TKI pre-treatment. Trial registration: NCT02577926.
AB - The approved dose of bosutinib in chronic phase CML is 400 mg QD in first-line and 500 mg QD in later-line treatment. However, given that gastrointestinal (GI) toxicity typically occurs early after treatment initiation, physicians often tend to start therapy with lower doses although this has never been tested systematically in prospective trials in the Western world. The Bosutinib Dose Optimization (BODO) Study, a multicenter phase II study, investigated the tolerability and efficacy of a step-in dosing concept of bosutinib (starting at 300 mg QD) in chronic phase CML patients in 2nd or 3rd line who were intolerant and/or refractory to previous TKI treatment. Of 57 patients included until premature closure of the study due to slow recruitment, 34 (60%) reached the targeted dose level of 500 mg QD following the 2-weekly step-in dosing regimen. While the dosing-in concept failed to reduce GI toxicity (grade II-IV, primary study endpoint) to < 40% (overall rate of 60%; 95% CI: 45-74%), bosutinib treatment (mean dosage: 403 mg/day) showed remarkable efficacy with a cumulative major molecular remission (MMR) rate of 79% (95% CI: 66 to 88%) at month 24. Of thirty patients refractory to previous therapy and not in MMR at baseline, 19 (64%) achieved an MMR during treatment. GI toxicity did not significantly impact on patient-reported outcomes (PRO) and led to treatment discontinuation in only one patient. Overall, the results of our trial support the efficacy and safety of bosutinib after failure of second-generation TKI pre-treatment. Trial registration: NCT02577926.
KW - Humans
KW - Tyrosine Kinase Inhibitors
KW - Prospective Studies
KW - Aniline Compounds/adverse effects
KW - Leukemia, Myeloid, Chronic-Phase/drug therapy
U2 - 10.1007/s00277-023-05394-0
DO - 10.1007/s00277-023-05394-0
M3 - SCORING: Journal article
C2 - 37592092
VL - 102
SP - 2741
EP - 2752
JO - ANN HEMATOL
JF - ANN HEMATOL
SN - 0939-5555
IS - 10
ER -