title: Advances in the treatment of relapsed/refractory chronic lymphocytic leukemia.
abstract: Treatment of chronic lymphocytic leukemia (CLL) has advanced with the introduction of chemoimmunotherapy (CIT) agents that have improved the outcomes of frontline therapy. However, most treated patients will relapse and require subsequent therapy. This review focuses on recent advances in the treatment of relapsed or refractory CLL. Until recently, treatment options for relapsed CLL were of limited efficacy. Retreatment with fludarabine, cyclophosphamide, and rituximab (FCR) was recommended for patients with a durable response to first-line FCR, although acquired genetic aberrations, impaired marrow reserve, and comorbidities often made this suboptimal therapy for many patients. New options include two agents targeting B cell receptor (BCR) signaling pathways (ibrutinib and idelalisib) and a B cell lymphoma-2 (BCL-2) inhibitor (venetoclax). Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative option for younger patients with a suitable donor.
authors.affiliation: McGill University Health Centre, Montreal, Quebec, Canada. chaim.shustik@mcgill.ca.
authors.forename: C
authors.initials: C
authors.lastname: Shustik
authors.affiliation: Department of Hematology, The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Bence-Bruckler
authors.affiliation: Department of Hematology, CHU de Québec-Université Laval, Quebec City, Quebec, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Delage
authors.affiliation: Division of Hematology and Hematological Malignancies, University of Calgary, Calgary, AB, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: Owen
authors.affiliation: Leukemia/BMT Program of BC, Division of Hematology, Vancouver General Hospital, BC Cancer Agency and The University of British Columbia, Vancouver, BC, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Toze
authors.affiliation: Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Coutre
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004358:Drug Therapy / Q000379:methods* / Q000639:trends; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D010880:Piperidines; D011687:Purines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D052999:Quinazolinones / Q000627:therapeutic use; D012008:Recurrence; D013449:Sulfonamides / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D010880:Piperidines; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; D052999:Quinazolinones; D013449:Sulfonamides; C551803:ibrutinib; D000225:Adenine; C579720:venetoclax; C552946:idelalisib
keywords: CLL; HSCT; Ibrutinib; Idelalisib; Venetoclax