{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:20:29Z","timestamp":1772130029317,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014476","name":"Pfizer Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007210","name":"RWTH Aachen University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007210","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The approved dose of bosutinib in chronic phase CML is 400\u00a0mg QD in first-line and 500\u00a0mg 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 <jats:underline>Bo<\/jats:underline>sutinib <jats:underline>Do<\/jats:underline>se Optimization (BODO) Study, a multicenter phase II study, investigated the tolerability and efficacy of a step-in dosing concept of bosutinib (starting at 300\u00a0mg QD) in chronic phase CML patients in 2<jats:sup>nd<\/jats:sup> or 3<jats:sup>rd<\/jats:sup> 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\u00a0mg QD following the 2-weekly step-in dosing regimen. While the dosing-in concept failed to reduce GI toxicity (grade II\u2013IV, primary study endpoint) to\u2009&lt;\u200940% (overall rate of 60%; 95% CI: 45\u201374%), bosutinib treatment (mean dosage: 403\u00a0mg\/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.<\/jats:p>","DOI":"10.1007\/s00277-023-05394-0","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T03:21:32Z","timestamp":1692328892000},"page":"2741-2752","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"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"],"prefix":"10.1007","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2855-561X","authenticated-orcid":false,"given":"Susanne","family":"Isfort","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsi","family":"Manz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lino L.","family":"Teichmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Crysandt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Burchert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Hochhaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Saussele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Kiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim R.","family":"G\u00f6thert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Illmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Schafhausen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifa Kathrin","family":"Al-Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Stegelmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"H\u00e4nel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Pfeiffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aristoteles","family":"Giagounidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg-Nikolaus","family":"Franke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Koschmieder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Fabarius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Ernst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mareille","family":"Warnken-Uhlich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uta","family":"Wolber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Kohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Pfirrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim H.","family":"Br\u00fcmmendorf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the German CML study group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"issue":"3","key":"5394_CR1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1200\/JCO.2017.74.7162","volume":"36","author":"JE Cortes","year":"2018","unstructured":"Cortes JE, Gambacorti-Passerini C, Deininger MW et al (2018) Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol 36(3):231\u2013237. https:\/\/doi.org\/10.1200\/JCO.2017.74.7162","journal-title":"J Clin Oncol"},{"key":"5394_CR2","doi-asserted-by":"publisher","unstructured":"Brummendorf TH, Cortes JE, Milojkovic D, et al. (2022) Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial. Leukemia https:\/\/doi.org\/10.1038\/s41375-022-01589-y","DOI":"10.1038\/s41375-022-01589-y"},{"issue":"17","key":"5394_CR3","doi-asserted-by":"publisher","first-page":"4567","DOI":"10.1182\/blood-2011-05-355594","volume":"118","author":"JE Cortes","year":"2011","unstructured":"Cortes JE, Kantarjian HM, Brummendorf TH et al (2011) Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 118(17):4567\u20134576. https:\/\/doi.org\/10.1182\/blood-2011-05-355594","journal-title":"Blood"},{"issue":"8","key":"5394_CR4","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.3324\/haematol.2017.171249","volume":"103","author":"C Gambacorti-Passerini","year":"2018","unstructured":"Gambacorti-Passerini C, Cortes JE, Lipton JH et al (2018) Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I\/II study. Haematologica 103(8):1298\u20131307. https:\/\/doi.org\/10.3324\/haematol.2017.171249","journal-title":"Haematologica"},{"issue":"9","key":"5394_CR5","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1002\/ajh.24034","volume":"90","author":"C Gambacorti-Passerini","year":"2015","unstructured":"Gambacorti-Passerini C, Kantarjian HM, Kim DW et al (2015) Long-term efficacy and safety of bosutinib in patients with advanced leukemia following resistance\/intolerance to imatinib and other tyrosine kinase inhibitors. Am J Hematol 90(9):755\u2013768. https:\/\/doi.org\/10.1002\/ajh.24034","journal-title":"Am J Hematol"},{"issue":"1","key":"5394_CR6","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/bjh.13801","volume":"172","author":"TH Brummendorf","year":"2016","unstructured":"Brummendorf TH, Cortes JE, Khoury HJ et al (2016) Factors influencing long-term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib. Br J Haematol 172(1):97\u2013110. https:\/\/doi.org\/10.1111\/bjh.13801","journal-title":"Br J Haematol"},{"issue":"9","key":"5394_CR7","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1182\/blood-2013-07-513937","volume":"123","author":"HM Kantarjian","year":"2014","unstructured":"Kantarjian HM, Cortes JE, Kim DW et al (2014) Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood 123(9):1309\u20131318. https:\/\/doi.org\/10.1182\/blood-2013-07-513937","journal-title":"Blood"},{"issue":"15","key":"5394_CR8","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.1182\/blood-2011-11-390120","volume":"119","author":"HJ Khoury","year":"2012","unstructured":"Khoury HJ, Cortes JE, Kantarjian HM et al (2012) Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and\/or nilotinib therapy failure. Blood 119(15):3403\u20133412. https:\/\/doi.org\/10.1182\/blood-2011-11-390120","journal-title":"Blood"},{"issue":"6","key":"5394_CR9","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1111\/ejh.13608","volume":"106","author":"JE Cortes","year":"2021","unstructured":"Cortes JE, Kantarjian HM, Mauro MJ et al (2021) Long-term cardiac, vascular, hypertension, and effusion safety of bosutinib in patients with Philadelphia chromosome-positive leukemia resistant or intolerant to prior therapy. Eur J Haematol 106(6):808\u2013820. https:\/\/doi.org\/10.1111\/ejh.13608","journal-title":"Eur J Haematol"},{"issue":"8","key":"5394_CR10","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1038\/s41375-020-0915-9","volume":"34","author":"A Hochhaus","year":"2020","unstructured":"Hochhaus A, Gambacorti-Passerini C, Abboud C et al (2020) Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study. Leukemia 34(8):2125\u20132137. https:\/\/doi.org\/10.1038\/s41375-020-0915-9","journal-title":"Leukemia"},{"issue":"3","key":"5394_CR11","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1093\/annonc\/mdy019","volume":"29","author":"HJ Khoury","year":"2018","unstructured":"Khoury HJ, Gambacorti-Passerini C, Brummendorf TH (2018) Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia. Ann Oncol 29(3):578\u2013587. https:\/\/doi.org\/10.1093\/annonc\/mdy019","journal-title":"Ann Oncol"},{"key":"5394_CR12","doi-asserted-by":"publisher","first-page":"106690","DOI":"10.1016\/j.leukres.2021.106690","volume":"111","author":"V Kota","year":"2021","unstructured":"Kota V, Brummendorf TH, Gambacorti-Passerini C et al (2021) Efficacy and safety following bosutinib dose reduction in patients with Philadelphia chromosomepositive leukemias. Leuk Res 111:106690. https:\/\/doi.org\/10.1016\/j.leukres.2021.106690","journal-title":"Leuk Res"},{"issue":"Supplement 1","key":"5394_CR13","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1182\/blood-2018-99-110543","volume":"132","author":"THG-PC Brummendorf","year":"2018","unstructured":"Brummendorf THG-PC, Hochhaus A, Lipton JH, Kota V, Deininger MW, Leip E, Viqueira A, Ferdinand R, Cortes JE (2018) Efficacy and safety following dose reduction of bosutinib or imatinib in patients with newly diagnosed hronic myeloid leukemia: analysis of the phase 3 BFORE trial. Blood 132(Supplement 1):3005","journal-title":"Blood"},{"issue":"4","key":"5394_CR14","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","volume":"34","author":"A Hochhaus","year":"2020","unstructured":"Hochhaus A, Baccarani M, Silver RT et al (2020) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34(4):966\u2013984. https:\/\/doi.org\/10.1038\/s41375-020-0776-2","journal-title":"Leukemia"},{"issue":"21","key":"5394_CR15","first-page":"4918","volume":"58","author":"OE Bechter","year":"1998","unstructured":"Bechter OE, Eisterer W, Pall G, Hilbe W, Kuhr T, Thaler J (1998) Telomere length and telomerase activity predict survival in patients with B cell chronic lymphocytic leukemia. Cancer Res 58(21):4918\u20134922","journal-title":"Cancer Res"},{"issue":"4","key":"5394_CR16","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1081\/BIP-120024206","volume":"13","author":"H Wang","year":"2003","unstructured":"Wang H, Chen B, Chow SC (2003) Sample size determination based on rank tests in clinical trials. J Biopharm Stat 13(4):735\u2013751. https:\/\/doi.org\/10.1081\/BIP-120024206","journal-title":"J Biopharm Stat"},{"key":"5394_CR17","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1093\/biomet\/26.4.404","volume":"26","author":"CJAPES Clopper","year":"1934","unstructured":"Clopper CJAPES (1934) The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26:404\u2013413","journal-title":"Biometrika"},{"key":"5394_CR18","first-page":"141","volume":"5","author":"OOJS Aalen","year":"1978","unstructured":"Aalen OOJS (1978) An empirical transition matrix for non-homogeneous Markov chains based on censored observations. Scand J Stat 5:141\u2013150","journal-title":"Scand J Stat"},{"issue":"6","key":"5394_CR19","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/(sici)1097-0258(19990330)18:6<695::aid-sim60>3.0.co;2-o","volume":"18","author":"TA Gooley","year":"1999","unstructured":"Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18(6):695\u2013706. https:\/\/doi.org\/10.1002\/(sici)1097-0258(19990330)18:6%3c695::aid-sim60%3e3.0.co;2-o","journal-title":"Stat Med"},{"issue":"Supplement 1","key":"5394_CR20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1182\/blood-2020-137393","volume":"136","author":"T Br\u00fcmmendorf","year":"2020","unstructured":"Br\u00fcmmendorf T, Cortes J, Milojkovic D et al (2020) Bosutinib (BOS) versus imatinib for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML): final 5-year results from the Bfore trial. Blood 136(Supplement 1):41\u201342","journal-title":"Blood"},{"key":"5394_CR21","doi-asserted-by":"crossref","unstructured":"Gambacorti-Passerini C, Br\u00fcmmendorf T, Tee Goh Y, et al. (2021) Second-line bosutinib for patients with chronic phase chronic myeloid leukemia : final 10-year results of a phase 1\/2 study. presented at: EHA 2021","DOI":"10.1200\/JCO.2021.39.15_suppl.7009"},{"key":"5394_CR22","doi-asserted-by":"crossref","unstructured":"Br\u00fcmmendorf T, Cortes J, Busque L, et al. (2021) The effect of body mass index on efficacy and safety of bosutinib or imatinib in patients with newly diagnosed chronic myeloid leukemia. presented at: EHA Annual Meeting 2021; 2021; virtuell.","DOI":"10.1200\/JCO.2021.39.15_suppl.7037"},{"issue":"28","key":"5394_CR23","doi-asserted-by":"publisher","first-page":"3486","DOI":"10.1200\/JCO.2011.38.7522","volume":"30","author":"JE Cortes","year":"2012","unstructured":"Cortes JE, Kim DW, Kantarjian HM et al (2012) Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol 30(28):3486\u20133492. https:\/\/doi.org\/10.1200\/JCO.2011.38.7522","journal-title":"J Clin Oncol"},{"key":"5394_CR24","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s40164-018-0101-1","volume":"7","author":"A Mita","year":"2018","unstructured":"Mita A, Abumiya M, Miura M et al (2018) Correlation of plasma concentration and adverse effects of bosutinib: standard dose or dose-escalation regimens of bosutinib treatment for patients with chronic myeloid leukemia. Exp Hematol Oncol 7:9. https:\/\/doi.org\/10.1186\/s40164-018-0101-1","journal-title":"Exp Hematol Oncol"},{"issue":"6","key":"5394_CR25","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1007\/s12185-022-03314-y","volume":"115","author":"N Takahashi","year":"2022","unstructured":"Takahashi N, Cortes JE, Sakaida E et al (2022) Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis. Int J Hematol 115(6):838\u2013851. https:\/\/doi.org\/10.1007\/s12185-022-03314-y","journal-title":"Int J Hematol"},{"issue":"1","key":"5394_CR26","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s12185-021-03144-4","volume":"114","author":"C Chuah","year":"2021","unstructured":"Chuah C, Koh LP, Numbenjapon T et al (2021) Efficacy and safety of bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia in the Asian subpopulation of the phase 3 BFORE trial. Int J Hematol 114(1):65\u201378. https:\/\/doi.org\/10.1007\/s12185-021-03144-4","journal-title":"Int J Hematol"},{"key":"5394_CR27","doi-asserted-by":"crossref","unstructured":"Kota VB, TH, Gambacorti-Passerini C, Lipton JH, Kim D-W, An F, Leip E, Crescenzo RJ, Ferdinand R, Cortes JE (2021) Efficacy and safety following bosutinib dose reduction in patients with Philadelphia chromosome\u2012positive leukemias. Leukemia Res 2021;In Press, Journal Pre-proof, Available online 21","DOI":"10.1016\/j.leukres.2021.106690"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-023-05394-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-023-05394-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-023-05394-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T10:06:38Z","timestamp":1694253998000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-023-05394-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,18]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["5394"],"URL":"https:\/\/doi.org\/10.1007\/s00277-023-05394-0","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,18]]},"assertion":[{"value":"30 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by institutional review boards and independent ethics committees at each center (leading ethics committee: ethics committee at the medical faculty of the University of Bonn) and conducted in accordance with all local legal and regulatory requirements, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Pts, Guidelines for Good Clinical Practice and the Declaration of Helsinki. All pts provided written informed consent at study inclusion.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"SI reports advisory board honoraria from GSK, Pfizer, Incyte, and Novartis, honoraria from Novartis, BMS, Pfizer, Incyte, and AOP Orphan; and other financial support (e.g., travel support) from Alexion, Novartis, Pfizer, Mundipharma, Roche, Hexal, and AOP Orphan. LT reports advisory activity for Pfizer. MC reports honoraria from Pfizer, Incyte, Astra Zeneca, and Novartis. AB reports research funding from AOP health, honoraria from AOP Orphan, and membership on an entity\u00b4s board of directors or advisory committees from Gilead, Pfizer, and Incyte. AH reports research support from Novartis, Pfizer, BMS, and Incyte. SS reports research funding\u00a0from Novartis, BMS, and Incyte and honoraria\u00a0from Novartis, BMS, Incyte, Pfizer, and Roche. AK reports honoraria, advisory role, and travel support from Pfizer. JRG reports honoraria, advisory board membership, and consultancy roles for Pfizer. PS reports consulting\/advisory role\/honoraria\/travel and accommodation support from Alexion, AOP Orphan, Blueprint Medicines, BMS\/Celgene, Merck Serono, MSD, Novartis, Pfizer, Roche, and Sobi. FS reports honoraria from and consultancy for Abbvie, AOP Pharma, BMS\/Celgene, Incyte, Novartis, and Pfizer. MH reports advisory board honoraria from Novartis and Pfizer and honoraria from Novartis. GF reports honoraria\/advisory board honoraria from Novartis, Pfizer, and MSD and travel support from Gilead and Takeda. SK reports funding from Novartis and Bristol-Myers Squibb; advisory board honoraria from Pfizer, Incyte, Ariad, Novartis, and BMS; patent for BET inhibitor at RWTH Aachen University; honoraria from Novartis, BMS, Pfizer, Incyte, and Ariad; and other financial support (e.g., travel support) from Novartis, BMS, Incyte, Ariad, and Pfizer. DW reports advisory board honoraria, honoraria, and research support from Pfizer, BMS, Incyte, and Novartis. THB reports consultancy from Janssen, Merck, Novartis, and Pfizer, research funding from Novartis and Pfizer, honoraria from Pfizer and Novartis, and other expenses (travel, accommodation, expenses) from Janssen, Merck, Novartis, and Pfizer. KM, TI, AF, TE, HKA, AG, TP, MWU, UW, DK, and MP report no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}