{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:10:33Z","timestamp":1772539833064,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>One of the main issues in the treatment of patients with chronic lymphocytic leukemia (CLL) deals with the choice between continuous or fixed-duration therapy. Continuous ibrutinib (IB), the first-in-class BTK inhibitor, and obinutuzumab-chlorambucil (G-CHL) are commonly used therapies for elderly and\/or comorbid patients. No head-to-head comparison has been carried out. Within the Italian campus CLL network, we performed a retrospective study on CLL patients without TP53 disruption treated with IB or G-CHL as first-line therapy. Patients in the G-CHL arm had a higher CIRS score and the worst renal function. The overall response rates between the G-CHL and IB arms were similar, but more complete remissions (CRs) were achieved with G-CHL (<jats:italic>p<\/jats:italic> = 0.0029). After a median follow-up of 30 months, the progression-free survival (PFS, <jats:italic>p<\/jats:italic> = 0.0061) and time to next treatment (TTNT, <jats:italic>p<\/jats:italic> = 0.0043), but not overall survival (OS, <jats:italic>p<\/jats:italic> = 0.6642), were better with IB than with G-CHL. Similar results were found after propensity score matching and multivariate analysis. While PFS and TTNT were longer with IB than with G-CHL in IGHV unmutated patients (<jats:italic>p<\/jats:italic> = 0.0190 and 0.0137), they were superimposable for IGHV mutated patients (<jats:italic>p<\/jats:italic> = 0.1900 and 0.1380). In the G-CHL arm, the depth of response (79% <jats:italic>vs<\/jats:italic>. 68% <jats:italic>vs<\/jats:italic>. 38% for CR, PR and SD\/PD; <jats:italic>p<\/jats:italic> &amp;lt; 0.0001) and measurable residual disease (MRD) influenced PFS (78% <jats:italic>vs<\/jats:italic>. 53% for undetectable MRD <jats:italic>vs<\/jats:italic>. detectable MRD, <jats:italic>p<\/jats:italic> = 0.0203). Hematological toxicities were common in the G-CHL arm, while IB was associated with higher costs. Although continuous IB provides better disease control in CLL, IGHV mutated patients and those achieving an undetectable MRD show a marked clinical and economic benefit from a fixed-duration obinutuzumab-based treatment.<\/jats:p>","DOI":"10.3389\/fonc.2022.1033413","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T04:44:15Z","timestamp":1669005855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Obinutuzumab plus chlorambucil versus ibrutinib in previously untreated chronic lymphocytic leukemia patients without TP53 disruptions: A real-life CLL campus study"],"prefix":"10.3389","volume":"12","author":[{"given":"Andrea","family":"Visentin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca 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