The randomized Haemato Oncology Foundation for Adults in The Netherlands 68 phase 3 trial compared front-line chemotherapy with chemotherapy plus the CD52 monoclonal antibody alemtuzumab for high-risk chronic lymphocytic leukemia, defined as at least 1 of the following: unmutated immunoglobulin heavy chain genes, deletion 17p or 11q, or trisomy 12. Fit patients were randomized to receive either 6 28-day cycles of oral FC chemotherapy (days 1 through 3: fludarabine 40 mg/m(2) per day and cyclophosphamide 250 mg/m(2) per day: n = 139) or FC plus subcutaneous alemtuzumab 30 mg day 1 (FCA, n = 133). FCA prolonged the primary end point, progression-free survival (3-year progression-free survival 53 vs 37%, P = .01), but not the secondary end point, overall survival (OS). However, a post hoc analysis showed that FCA increased OS in patients younger than 65 years (3-year OS 85% vs 76%, P = .035). FCA also increased the overall response rate (88 vs 78%, P = .036), and the bone marrow minimal residual disease-negative complete remission rate (64% vs 43%, P = .016). Opportunistic infections were more frequent following FCA, but without an increase in treatment related mortality (FCA: 3.8%, FC: 4.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529.

Department of Hematology Academisch Medisch Centrum Amsterdam The Netherlands

Department of Hematology Erasmus Medisch Centrum Daniel den Hoed Cancer Center Rotterdam The Netherlands;

Department of Hematology Hadassah University Hospital and Hebrew University Medical School Jerusalem Israel;

Department of Hematology Karolinska University Hospital Stockholm Sweden;

Department of Hematology Oslo University Hospital and Institute of Clinical Medicine University of Oslo Oslo Norway;

Department of Hematology Rigshospitalet Copenhagen Denmark;

Department of Hematology Turku University Central Hospital Finland;

Department of Hematology University Hospital Kralovske Vinohrady Prague Czech Republic;

Department of Hematology ZNA Stuivenberg Antwerp Belgium;

Department of Internal Medicine Meander Medical Center Amersfoort The Netherlands;

Maria Sklodowska Curie Memorial Institute and Oncology Centre Warsaw Poland on behalf of the Polish Lymphoma Research Group Centers;

The Haemato Oncology Foundation for Adults in The Netherlands Data Centre Erasmus Medisch Centrum Clinical Trial Center Rotterdam The Netherlands; and

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