{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:36:37Z","timestamp":1780454197102,"version":"3.54.1"},"reference-count":147,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIRC (Associazione Italiana Ricerca sul Cancro)","award":["5 \u00d7 1000"],"award-info":[{"award-number":["5 \u00d7 1000"]}]},{"name":"AIRC (Associazione Italiana Ricerca sul Cancro)","award":["IG21352"],"award-info":[{"award-number":["IG21352"]}]},{"name":"AIRC (Associazione Italiana Ricerca sul Cancro)","award":["21198"],"award-info":[{"award-number":["21198"]}]},{"name":"Metastases Special Program","award":["5 \u00d7 1000"],"award-info":[{"award-number":["5 \u00d7 1000"]}]},{"name":"Metastases Special Program","award":["IG21352"],"award-info":[{"award-number":["IG21352"]}]},{"name":"Metastases Special Program","award":["21198"],"award-info":[{"award-number":["21198"]}]},{"name":"European Union\u2013FSE-REACT-EU","award":["5 \u00d7 1000"],"award-info":[{"award-number":["5 \u00d7 1000"]}]},{"name":"European Union\u2013FSE-REACT-EU","award":["IG21352"],"award-info":[{"award-number":["IG21352"]}]},{"name":"European Union\u2013FSE-REACT-EU","award":["21198"],"award-info":[{"award-number":["21198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The recent evolution in chronic lymphocytic leukemia (CLL) targeted therapies led to a progressive change in the way clinicians manage the goals of treatment and evaluate the response to treatment in respect to the paradigm of the chemoimmunotherapy era. Continuous therapies with BTK inhibitors achieve prolonged and sustained control of the disease. On the other hand, venetoclax and anti-CD20 monoclonal antibodies or, more recently, ibrutinib plus venetoclax combinations, given for a fixed duration, achieve undetectable measurable residual disease (uMRD) in the vast majority of patients. On these grounds, a time-limited MRD-driven strategy, a previously unexplored scenario in CLL, is being attempted. On the other side of the spectrum, novel genetic and non-genetic mechanisms of resistance to targeted treatments are emerging. Here we review the response assessment criteria, the evolution and clinical application of MRD analysis and the mechanisms of resistance according to the novel treatment strategies within clinical trials. The extent to which this novel evidence will translate in the real-life management of CLL patients remains an open issue to be addressed.<\/jats:p>","DOI":"10.3390\/cancers16112049","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T13:32:55Z","timestamp":1716903175000},"page":"2049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Monitoring Response and Resistance to Treatment in Chronic Lymphocytic Leukemia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-9533","authenticated-orcid":false,"given":"Ilaria","family":"Del Giudice","sequence":"first","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7909-8642","authenticated-orcid":false,"given":"Irene","family":"Della Starza","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00161 Rome, Italy"},{"name":"AIL Roma, ODV, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-2752","authenticated-orcid":false,"given":"Filomena","family":"De Falco","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Institute of Hematology and Center for Hemato-Oncological Research, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-9862","authenticated-orcid":false,"given":"Paolo","family":"Sportoletti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Institute of Hematology and Center for Hemato-Oncological Research, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL","volume":"131","author":"Hallek","year":"2018","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s41571-018-0037-8","article-title":"Evolution of CLL treatment\u2014From chemoimmunotherapy to targeted and individualized therapy","volume":"15","author":"Burger","year":"2018","journal-title":"Nat. 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