Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL
Language English Country United States Media print-electronic
Document type Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
24735962
DOI
10.1182/blood-2014-01-547737
PII: S0006-4971(20)40172-7
Knihovny.cz E-resources
- MeSH
- Alemtuzumab MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell diagnosis drug therapy MeSH
- Cyclophosphamide administration & dosage adverse effects therapeutic use MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Disease-Free Survival MeSH
- Antineoplastic Agents administration & dosage adverse effects therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects therapeutic use MeSH
- Aged MeSH
- Vidarabine administration & dosage adverse effects analogs & derivatives therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Alemtuzumab MeSH
- Cyclophosphamide MeSH
- fludarabine MeSH Browser
- Antibodies, Monoclonal, Humanized MeSH
- Antineoplastic Agents MeSH
- Vidarabine MeSH
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 Karolinska University Hospital Stockholm Sweden;
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;
References provided by Crossref.org
Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology
Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia
The impact of SF3B1 mutations in CLL on the DNA-damage response
NTR
NTR529
