[Chronic lymphocytic leukemia: current standards and novel approaches].
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world and affects mainly elderly patients. In current phase III trials, standard treatment options were established that differ mainly based on the fitness and age of the patient. The combination of fludarabine, cyclophosphamide, and the CD20 antibody rituximab (FCR) is recommended for young patients without relevant comorbidity, while bendamustine and rituximab (BR) should be favored for elderly (ca. >65 years) fit individuals. Bendamustine plus ofatumumab is another option in this situation. Patients with major comorbidities should receive chlorambucil combined with CD20 antibody (obinutuzumab or ofatumumab). In 2014, several new compounds were approved for patients with ultrahigh risk genetic factors (17p-, TP53mut) and for relapsed/refractory CLL: both idelalisib and ibrutinib are orally bioavailable kinase inhibitors that block key regulators of central pathways. For both agents, very impressive data are available with regard to tolerability and efficacy that will change the treatment paradigm in CLL. With ABT-199, a direct apoptosis inducer is being developed that in early clinical trials produced high remission rates combined with good tolerability. Combinations and sequences of the "novel" compounds obinutuzumab, ofatumumab, idelalisib, ibrutinib, and ABT-199 will be studied in coming years in clinical trials in order to prolong remission duration and reduce side effects with the eventual aim of curing CLL.
Klinik für Innere Medizin III, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Deutschland.
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D005858:Germany; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology*; D008495:Medical Oncology / Q000379:methods*; D017410:Practice Guidelines as Topic; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013449:Sulfonamides; C579720:venetoclax