title: Paving the way for new agents; is standard chemotherapy part of the treatment paradigm for chronic lymphocytic leukemia in the future?
abstract: BACKGROUND
  First and second generation tyrosine kinase inhibitors, represent a new, fully biologic and targeted approach to chronic lymphocytic leukemia and allowed to obtain high responses and acceptable tolerability even in elderly and high risk patients. On the other hand, prolonged experience with these agents has raised some questions on unexpected toxicities, response quality, treatment duration and onset of resistances.
  
  
  METHODS
  This review analyzes the main published studies with the aim to discuss whether, in future, new agents could become a part of standard treatments or even replace the chemo-immunotherapy in chronic lymphocytic leukemia. Expert commentary: Despite different trials has been already published and many are still ongoing, follow up times are, at present, too short. A chemo-free approach surely represents a desirable goal for chronic lymphocytic leukemia, nevertheless longer observation is warranted to better define the correct use of targeted therapies.
authors.affiliation: a Department of Hematology, Niguarda Cancer Center , Niguarda Hospital , Piazza Ospedale Maggiore 3, Milano , Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frustaci
authors.affiliation: a Department of Hematology, Niguarda Cancer Center , Niguarda Hospital , Piazza Ospedale Maggiore 3, Milano , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.affiliation: a Department of Hematology, Niguarda Cancer Center , Niguarda Hospital , Piazza Ospedale Maggiore 3, Milano , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Picardi
authors.affiliation: a Department of Hematology, Niguarda Cancer Center , Niguarda Hospital , Piazza Ospedale Maggiore 3, Milano , Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Mazzucchelli
authors.affiliation: a Department of Hematology, Niguarda Cancer Center , Niguarda Hospital , Piazza Ospedale Maggiore 3, Milano , Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cairoli
authors.affiliation: a Department of Hematology, Niguarda Cancer Center , Niguarda Hospital , Piazza Ospedale Maggiore 3, Milano , Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell
keywords: Chronic lymphocytic leukemia; acalabrutinib; chemoimmunotherapy; duvelisib; ibrutinib; idelalisib; new agents; targeted therapies; tyrosine kinase inhibitors; venetoclax