{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:56:11Z","timestamp":1792036571697,"version":"4.4.0"},"reference-count":39,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: This study compared overall survival (OS) associated with common real-world treatment sequences in patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL) in the United States. Methods: Utilizing the nationwide Flatiron Health electronic health record-derived de-identified database, adult CLL\/SLL patients who initiated systemic therapy (JAN2016-NOV2023) and received at least two lines of therapy (LoTs) were analyzed. Treatment regimens were categorized based on drug class, and most frequent (n \u2265 50) sequences (first LoT followed by [\u2192] second LoT) were compared. OS from initiation of the first LoT was compared using multivariable Cox proportional hazard models, and adjusted hazard ratios with 95% CIs were reported. Results: Among 2354 eligible patients, n = 1711 (73%) received the 16 most frequent treatment sequences. Sequencing chemoimmunotherapy (CIT) \u2192 CIT (HR: 2.29 [1.23\u20134.28]), anti-CD20 monoclonal antibody (anti-CD20mab) monotherapy \u2192 CIT (1.95 [1.03\u20133.69]), and covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapy \u2192 anti-CD20mab monotherapy (2.00 [1.07\u20133.74]) were associated with worse OS compared to patients treated with cBTKi monotherapy \u2192 B-cell lymphoma 2 inhibitors (BCL2i) + anti-CD20mab (reference). Conclusions: OS associated with other sequences were not significantly different from the reference sequence in adjusted analyses, suggesting a lack of evidence for the optimal standard of care for sequencing the first two LoTs in real-world settings. Future research should reassess sequencing outcomes as novel treatments become adopted into clinical practice.<\/jats:p>","DOI":"10.3390\/cancers17152592","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T08:33:06Z","timestamp":1754555586000},"page":"2592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Overall Survival Associated with Real-World Treatment Sequences in Patients with CLL\/SLL in the United States"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-9040","authenticated-orcid":false,"given":"Joanna M.","family":"Rhodes","sequence":"first","affiliation":[{"name":"Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-8021","authenticated-orcid":false,"given":"Naleen Raj","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Khanal","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"He","sequence":"additional","affiliation":[{"name":"Syneos Health, Morrisville, NC 27560, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarang","family":"Abhyankar","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Pagel","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-3941","authenticated-orcid":false,"given":"Lisa M.","family":"Hess","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Z.","family":"Skarbnik","sequence":"additional","affiliation":[{"name":"Novant Health Cancer Institute, Charlotte, NC 28204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S0140-6736(24)00595-6","article-title":"Chronic lymphocytic leukaemia","volume":"404","author":"Jain","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bewarder, M., Stilgenbauer, S., Thurner, L., and Kaddu-Mulindwa, D. 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