{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:38:32Z","timestamp":1777876712857,"version":"3.51.4"},"reference-count":62,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The emergence of new antileukemic drugs, including Bruton tyrosine kinase inhibitors (BTKis), phosphoinositide 3-kinase inhibitors (PI3Kis), and B-cell lymphoma 2 antagonists (BCL-2a), has significantly improved the outcomes for patients with relapsed\/refractory chronic lymphocytic leukemia (CLL). Despite advances in treatment efficacy, the comprehensive safety profile of these novel agents versus traditional chemotherapy and immunotherapy has not been adequately explored, and there have been few direct comparisons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>This study aimed to compare the safety profiles of novel therapeutic agents, chemotherapy, and immunotherapy in patients with relapsed\/refractory CLL using a Bayesian network meta-analysis (NMA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A systematic literature review was conducted to identify randomized clinical trials on relapsed\/refractory CLL. The search encompassed major medical databases (MEDLINE, Embase, and CENTRAL) and gray literature, with the aim to integrate the findings into a Bayesian NMA framework for safety outcome assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Systematic literature review with Bayesian NMA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The systematic search identified 14 randomized trials that formed networks for the comparison of safety outcomes. No differences were shown between therapies in terms of overall adverse events (AEs). However, bendamustine\u2009+\u2009rituximab had a more favorable safety profile for grade \u2a7e3 AEs when compared with ibrutinib (risk ratio 0.62 (95% credible interval 0.40\u20130.86)), acalabrutinib (0.69 (0.45\u20130.94)), zanubrutinib (0.64 (0.42\u20130.91)), and venetoclax\u2009+\u2009rituximab (0.87 (0.79\u20130.96)). The frequency of grade \u2a7e3 AEs, serious AEs, and treatment discontinuations and deaths due to AEs was comparable between acalabrutinib, zanubrutinib, and venetoclax\u2009+\u2009rituximab. There were no significant differences in the safety profiles regarding hematological events, events affecting the quality of life, and infections for most comparisons of venetoclax\u2009+\u2009rituximab with BTKis. Among BTKi-specific events, zanubrutinib was associated with a higher risk of hypertension (2.96 (1.74\u20135.16)) and bleeding (1.38 (1.06\u20131.81)) than acalabrutinib. No differences in the risk of atrial fibrillation were found between acalabrutinib and zanubrutinib (1.56 (0.74\u20133.34)).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our findings showed that venetoclax\u2009+\u2009rituximab, acalabrutinib, and zanubrutinib have acceptable safety profiles, which indicates that they may be the preferred therapeutic options in the setting of relapsed\/refractory CLL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>PROSPERO CRD42022304330.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359241285988","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T21:17:09Z","timestamp":1728508629000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative safety of novel targeted therapies in relapsed\/refractory chronic lymphocytic leukemia: a network meta-analysis"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5089-5349","authenticated-orcid":false,"given":"Magdalena","family":"Monica","sequence":"first","affiliation":[{"name":"Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, ul. \u0141azarza 16, Krak\u00f3w 31-530, Poland"},{"name":"Department of Nutrition and Drug Research, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krak\u00f3w 31-066, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Reczek","sequence":"additional","affiliation":[{"name":"HTA Consulting, Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Kawalec","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Drug Research, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"bibr1-17588359241285988","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.840616"},{"key":"bibr2-17588359241285988","unstructured":"Cancer Stat Facts: Leukemia\u2014chronic lymphocytic leukemia (CLL), https:\/\/seer.cancer.gov\/statfacts\/html\/clyl.html (accessed 16 December 2022)."},{"key":"bibr3-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01156-x"},{"key":"bibr4-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400376"},{"key":"bibr5-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.03355"},{"key":"bibr6-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713976"},{"key":"bibr7-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1054"},{"key":"bibr8-17588359241285988","volume":"372","author":"Page MJ","year":"2021","journal-title":"BMJ"},{"key":"bibr9-17588359241285988","doi-asserted-by":"publisher","DOI":"10.7326\/M14-2385"},{"key":"bibr10-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1177\/17588359241263710"},{"key":"bibr11-17588359241285988","unstructured":"Package \u201cgemtc,\u201d https:\/\/cran.r-project.org\/web\/packages\/gemtc\/gemtc.pdf (accessed 20 October 2023)"},{"key":"bibr12-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"bibr13-17588359241285988","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2019-0844"},{"key":"bibr14-17588359241285988","volume-title":"Paper presented at the International Workshop on CLL","author":"Hillmen P"},{"key":"bibr15-17588359241285988","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211582"},{"key":"bibr16-17588359241285988","unstructured":"European Medicines Agency. 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