{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:13:08Z","timestamp":1788513188710,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the overall second primary malignancy (SPM) burden in patients with B\u2010cell lymphomas treated with Bruton's tyrosine kinase (BTK) inhibitors and compare SPM risk versus non\u2010BTK inhibitor or placebo controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched major databases from inception to September 30, 2025. The primary outcome was SPM incidence. Consistent treatment backgrounds were defined as comparable baseline clinical and treatment characteristics, with BTK inhibitor exposure as the main between\u2010arm difference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty\u2010two studies involving 9337 patients were included, mainly CLL\/SLL; MCL was the largest non\u2010CLL\/SLL subtype. Pooled SPM incidence was 8% (95% CI: 6%\u201311%) with a median follow\u2010up of 31.5\u2009months. Multivariable meta\u2010regression identified follow\u2010up duration as the only independent predictor, whereas disease subtype, inhibitor generation, prior therapy lines, study design, and age were not significant. Furthermore, SPM patterns were comparable between CLL\/SLL and non\u2010CLL\/SLL cohorts. Compared with controls, BTK inhibitors did not significantly increase SPM risk (RR\u2009=\u20091.30, 95% CI: 0.95\u20131.78), a finding confirmed in analyses with consistent treatment backgrounds (RR\u2009=\u20091.03, 95% CI: 0.85\u20131.25).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SPMs occur across disease backgrounds and are mainly influenced by follow\u2010up duration. Current evidence does not establish a direct carcinogenic effect of BTK inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.70235","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T23:34:36Z","timestamp":1781480076000},"page":"1016-1025","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Second Primary Malignancies in Patients With B\u2010Cell Lymphomas Treated With Bruton's Tyrosine Kinase Inhibitors: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"117","author":[{"given":"Cuiping","family":"Ma","sequence":"first","affiliation":[{"name":"Oncology Department Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexia","family":"Lu","sequence":"additional","affiliation":[{"name":"Oncology Department Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahang","family":"Li","sequence":"additional","affiliation":[{"name":"Oncology Department Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Oncology Department Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6112-2947","authenticated-orcid":false,"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Oncology Department Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.06.006"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-025-01434-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2025.0048"},{"key":"e_1_2_10_5_1","volume-title":"Drugs@FDA","author":"U.S. Food and Drug Administration (FDA)","year":"2024"},{"key":"e_1_2_10_6_1","volume-title":"Drugs@FDA","author":"U.S. Food and Drug Administration (FDA)","year":"2024"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.10.034"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0987-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.29.1112"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17132093"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16213574"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-567388"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014960"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2201817"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00196-7"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2025.2525982"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(22)00289-7"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1445-2197.2003.02748.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2017.04.023"},{"key":"e_1_2_10_21_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions, Version 6.3 (Updated February 2022)","author":"Higgins J. P. T.","year":"2022"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18162"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.4765"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1620944"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003698"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.e20051"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024476"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30262-2"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-023-00784-z"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2017.06.028"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.5398"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-019-0237-1"},{"key":"e_1_2_10_33_1","volume-title":"Abstracts from the XXI Biennial Meeting of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL 2025)","author":"Bharathi V.","year":"2025"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-01072-6"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.114009"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-04-639203"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-281170"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.12.1085"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-08-870238"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024028205"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.70235","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ejh.70235","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.70235","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:21:44Z","timestamp":1788510104000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.70235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,14]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/ejh.70235"],"URL":"https:\/\/doi.org\/10.1111\/ejh.70235","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,14]]},"assertion":[{"value":"2026-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}