title: Front-line treatment of CLL in the era of novel agents.
abstract: Although chemoimmunotherapy prolongs survival and as such, is the standard of care for treatment-naïve patients, its effectiveness may be reduced by associated toxicity and dose reductions. In addition, it has been associated with the development of myelosuppression and secondary neoplasms; treatments are hence needed which offer greater survival and lowered toxicity. A range of new targeted agents, ibrutinib, idelalisib and venetoclax, have demonstrated such a balance in a second-line setting, offering CLL patients durable remissions and a modest toxicity profile. Ibrutinib has since been given first-line approval, and with news of second-generation targeted agents on the horizon, high-level discussions have taken place concerning their use in elderly or unfit patients; with potential use in younger patients in a first-line setting. This article reviews the potential first-line therapeutic options for treating CLL and their clinical potential and examines whether first-line chemotherapy has a place in the age of targeted agents.
authors.affiliation: Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, 93-510 Lodz, ul. Ciołkowskiego 2, Poland. Electronic address: robaktad@csk.umed.lodz.pl.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Department of Internal Medicine III, Ulm University, Albert-Einstein-Allee 23, Ulm 89081, Germany. Electronic address: Stephan.Stilgenbauer@uniklinik-ulm.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: Department of Hematology, Niguarda Cancer Center, Niguarda Hospital, Piazza Ospedale Maggiore 3, 20162 Milano, Italy. Electronic address: alessandra.tedeschi@ospedaleniguarda.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010809:Physical Fitness; D010880:Piperidines; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine
keywords: Bruton’s kinase inhibitor; Chronic lymphocytic leukaemia; Elderly; First-line; Ibrutinib; Idelalisib; PI3Kδ inhibitor; Venetoclax