title: Risk categories and refractory CLL in the era of chemoimmunotherapy.
abstract: Standardized criteria for diagnosis and response evaluation in chronic lymphocytic leukemia (CLL) are essential to achieve comparability of results and improvement of clinical care. With the increasing range of therapeutic options, the treatment context is important when defining refractory CLL. Refractory CLL has been defined as no response or response lasting ≤ 6 months from last therapy. This subgroup has a very poor outcome, and many trials use this group as an entry point for early drug development. With the intensification of first-line regimens, the proportion of patients with refractory CLL using these criteria decreases. This has immediate consequences for recruitment of patients into trials as well as salvage strategies. Conversely, patients who are not refractory according to the traditional definition but who have suboptimal or short response to intense therapy also have a very poor outcome. In this Perspective, we discuss recent results that may lead to a reassessment of risk categories in CLL focusing on fit patients who are eligible for all treatment options. We cover aspects of the history and biologic basis for refractory CLL and will focus on how emerging data on treatment failure from large trials using chemoimmunotherapy may help to define risk groups in CLL.
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 460, Heidelberg, Germany. thorsten.zenz@nct-heidelberg.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Zenz
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
mesh_terms: D000465:Algorithms; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000648:ultrastructure; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005544:Forecasting; D016158:Genes, p53; D006801:Humans; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008954:Models, Biological; D011379:Prognosis; D018570:Risk Assessment; D000069283:Rituximab; D009626:Terminology as Topic; D017211:Treatment Failure; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic; D000069283:Rituximab; D014740:Vidarabine; C024352:fludarabine