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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

Standard

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, Vol. 102, No. 10, 10.2023, p. 2741-2752.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Isfort, S, Manz, K, Teichmann, LL, Crysandt, M, Burchert, A, Hochhaus, A, Saussele, S, Kiani, A, Göthert, JR, Illmer, T, Schafhausen, P, Al-Ali, HK, Stegelmann, F, Hänel, M, Pfeiffer, T, Giagounidis, A, Franke, G-N, Koschmieder, S, Fabarius, A, Ernst, T, Warnken-Uhlich, M, Wolber, U, Kohn, D, Pfirrmann, M, Wolf, D, Brümmendorf, TH & German CML study group 2023, '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', ANN HEMATOL, vol. 102, no. 10, pp. 2741-2752. https://doi.org/10.1007/s00277-023-05394-0

APA

Isfort, S., Manz, K., Teichmann, L. L., Crysandt, M., Burchert, A., Hochhaus, A., Saussele, S., Kiani, A., Göthert, J. R., Illmer, T., Schafhausen, P., Al-Ali, H. K., Stegelmann, F., Hänel, M., Pfeiffer, T., Giagounidis, A., Franke, G-N., Koschmieder, S., Fabarius, A., ... German CML study group (2023). 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. ANN HEMATOL, 102(10), 2741-2752. https://doi.org/10.1007/s00277-023-05394-0

Vancouver

Isfort S, Manz K, Teichmann LL, Crysandt M, Burchert A, Hochhaus A et al. 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. ANN HEMATOL. 2023 Oct;102(10):2741-2752. https://doi.org/10.1007/s00277-023-05394-0

Bibtex

@article{aabee04c029c4619bde2f081d8ab8ffc,
title = "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",
abstract = "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.",
keywords = "Humans, Tyrosine Kinase Inhibitors, Prospective Studies, Aniline Compounds/adverse effects, Leukemia, Myeloid, Chronic-Phase/drug therapy",
author = "Susanne Isfort and Kirsi Manz and Teichmann, {Lino L} and Martina Crysandt and Andreas Burchert and Andreas Hochhaus and Susanne Saussele and Alexander Kiani and G{\"o}thert, {Joachim R} and Thomas Illmer and Philippe Schafhausen and Al-Ali, {Haifa Kathrin} and Frank Stegelmann and Mathias H{\"a}nel and Tim Pfeiffer and Aristoteles Giagounidis and Georg-Nikolaus Franke and Steffen Koschmieder and Alice Fabarius and Thomas Ernst and Mareille Warnken-Uhlich and Uta Wolber and Denise Kohn and Markus Pfirrmann and Dominik Wolf and Br{\"u}mmendorf, {Tim H} and {German CML study group}",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = oct,
doi = "10.1007/s00277-023-05394-0",
language = "English",
volume = "102",
pages = "2741--2752",
journal = "ANN HEMATOL",
issn = "0939-5555",
publisher = "Springer",
number = "10",

}

RIS

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 -