{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:18:11Z","timestamp":1783012691207,"version":"3.54.6"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Immunoglobulin heavy chain variable region\u2010unmutated (\n                    <jats:italic>IGHV<\/jats:italic>\n                    \u2010U) chronic lymphocytic leukemia (CLL) represents a biologically aggressive subgroup with limited responsiveness to chemoimmunotherapy (CIT). To clarify the comparative effectiveness of available frontline options, we conducted a comprehensive Bayesian network meta\u2010analysis of randomized clinical trials including more than 4500\n                    <jats:italic>IGHV<\/jats:italic>\n                    \u2010U patients. Targeted therapies consistently outperformed CIT backbones, confirming the minimal benefit of cytotoxic approaches in this population. Acalabrutinib\u2010based regimens, either as monotherapy or combined with obinutuzumab, emerged as the most effective strategies for progression\u2010free survival, followed by other BTK inhibitors and venetoclax\u2010based combinations. Chlorambucil\u2010 and Fludarabine\u2010containing regimens ranked lowest. The fixed\u2010duration venetoclax\u2010obinutuzumab regimen also demonstrated strong efficacy, though estimates were less precise due to a smaller evidence base. Overall, heterogeneity was low, model fit was robust, and no statistical evidence was detected. These findings support targeted agents as the preferred first\u2010line treatment for\n                    <jats:italic>IGHV<\/jats:italic>\n                    \u2010U CLL and provide a quantitative framework to guide regimen selection while highlighting the need for head\u2010to\u2010head trials and long\u2010term follow\u2010up to optimize treatment sequencing.\n                  <\/jats:p>","DOI":"10.1111\/ejh.70191","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:15:47Z","timestamp":1776230147000},"page":"375-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First\u2010Line Treatment of\n                    <scp>IGHV<\/scp>\n                    \u2010Unmutated Chronic Lymphocytic Leukemia: A Network Meta\u2010Analysis of Targeted and Chemoimmunotherapy 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