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Despite their proven, robust, and manifest efficacy, BTKis and BCL2is fail to provide long-term disease control in some categories of patients, and to date this is an unmet clinical need that is critical to recognize and address. Ongoing clinical trials are evaluating new treatment algorithms and new molecules to progressively thin this population. In this review for each category of patients we explicate the different possible patterns of treatment sequencing based on currently available evidence, starting from the frontline to currently ongoing trials, in order to optimize therapies as much as possible.<\/jats:p>","DOI":"10.3390\/cancers16112011","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T08:36:22Z","timestamp":1716798982000},"page":"2011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Treatment Sequencing in Chronic Lymphocytic Leukemia in 2024: Where We Are and Where We Are Headed"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-9009","authenticated-orcid":false,"given":"Alberto","family":"Fresa","sequence":"first","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idanna","family":"Innocenti","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Tomasso","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Stirparo","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Mosca","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Iadevaia","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Autore","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ghia","sequence":"additional","affiliation":[{"name":"Division of Experimental Oncology, Universit\u00e0 Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-1396","authenticated-orcid":false,"given":"Luca","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,25]]},"reference":[{"key":"ref_1","unstructured":"Howlader, N., Noone, A.M., Krapcho, M., Miller, D., Brest, A., Yu, M., Ruhl, J., Tatalovich, Z., Mariotto, A., and Lewis, D.R. 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