Advances in first-line treatment of chronic lymphocytic leukemia: current recommendations on management and first-line treatment by the German CLL Study Group (GCLLSG).
The management of patients with CLL is undergoing significant changes; during the last decade, the outcome of first-line therapies has been markedly improved with the addition of anti-CD20 antibodies to chemotherapy. Today, chemoimmunotherapy for physically fit patients ≤ 65 years should consist of fludarabine, cyclophosphamide, and rituximab (FCR). The combination of bendamustine and rituximab (BR) should be considered in physically fit patients > 65 years and in patients with a higher risk of infections. Patients with reduced fitness and/or relevant comorbidity should receive chlorambucil with a CD20 antibody, preferably obinutuzumab. Regardless of their fitness, patients with CLL carrying genetic aberrations such as del(17p) and/or TP53 mutation poorly respond to chemoimmunotherapy and therefore require different therapeutic approaches. An increasing understanding of the disease biology has led to the development of targeted drugs for the treatment of CLL, such as the BTK inhibitor ibrutinib and PI3K inhibitor idelalisib. These agents have shown efficacy in high-risk and relapsed/refractory patients and are currently being evaluated in clinical trials for first-line therapy. It is anticipated that these compounds and further other novel agents will profoundly change the therapy of CLL.
Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn and German CLL Study Group, University of Cologne, Cologne, Germany.
Paula
P
Cramer
Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn and German CLL Study Group, University of Cologne, Cologne, Germany.
Petra
P
Langerbeins
Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn and German CLL Study Group, University of Cologne, Cologne, Germany.
Barbara
B
Eichhorst
Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn and German CLL Study Group, University of Cologne, Cologne, Germany.|CECAD - Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases, University of Cologne, Cologne, Germany.
Michael
M
Hallek
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride / Q000627:therapeutic use; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005858:Germany; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D017410:Practice Guidelines as Topic; D000069283:Rituximab / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000069283:Rituximab; D003520:Cyclophosphamide; D000069461:Bendamustine Hydrochloride; D014740:Vidarabine; C024352:fludarabine
CLL; first-line treatment; high-risk