{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:02:40Z","timestamp":1784782960103,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematol. Rep.","Hematology Reports"],"abstract":"<jats:p>Surrogate endpoints are increasingly used in chronic lymphocytic leukemia (CLL) to accelerate treatment evaluation, but their validity is context-dependent. This review examines key endpoints\u2014progression-free survival (PFS), time to next treatment (TTNT), measurable residual disease (MRD), and quality of life (QoL)\/patient-reported outcomes (PROs). PFS, while standard, is limited by competing risks and poor reflection of toxicity and patient experience. TTNT captures both efficacy and tolerability but is influenced by external factors. MRD is a strong predictor of outcomes in fixed-duration venetoclax-based regimens but less reliable in continuous therapies. QoL and PROs provide essential patient-centered insight often missed by traditional endpoints. We propose a practical framework in which endpoint selection depends on treatment type, patient characteristics, and intended use. MRD is most informative after fixed-duration therapy, TTNT in continuous treatment, and PROs in vulnerable populations. Overall, surrogate endpoints in CLL require setting-specific validation to ensure they reflect meaningful clinical benefit.<\/jats:p>","DOI":"10.3390\/hematolrep18040050","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:17:52Z","timestamp":1784647072000},"page":"50","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Surrogate Endpoints in CLL: From Promise and Pitfalls to a Context-Specific Validation Framework"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-6507","authenticated-orcid":false,"given":"Stefano","family":"Molica","sequence":"first","affiliation":[{"name":"Department Haematology, Castle Hill Hospital, Hull-York Medical School, Cottingham HU16 5JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41408-025-01434-2","article-title":"First-line treatment for CLL in the era of targeted therapy","volume":"16","author":"Davids","year":"2026","journal-title":"Blood Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.clml.2025.07.012","article-title":"Survival Outcomes in Patients with Chronic Lymphocytic Leukemia: A SEER Analysis","volume":"26","author":"Modi","year":"2026","journal-title":"Clin. 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