title: Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia.
abstract: Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) is associated with superior overall survival (OS) for patients with chronic lymphocytic leukemia (CLL). Alemtuzumab (A) was added to FCR (CFAR) in a phase 2 trial for high-risk untreated patients < 70 years with serum β-2 microglobulin (β2M) ≥ 4 mg/L. Sixty patients were enrolled; median age was 59 years (range, 42-69); 75% were male; median β2M was 5.1 mg/L (range, 4-11.6); and 51% were Rai III-IV. Complete remission (CR) was achieved in 70%, partial remission (PR) in 18%, nodular PR in 3%, for an overall response of 92%. Of 14 patients with 17p deletion, CR was achieved by 8 (57%). Of 57 BM samples evaluated by 3-color flow cytometry at the end of treatment, 41 (72%) were negative for residual disease. Grade 3-4 neutropenia and thrombocytopenia occurred with 33% and 13% courses, respectively. The median progression-free survival was 38 months and median OS was not reached. In conclusion, CFAR is an active frontline regimen for high-risk CLL. Response rates and survival are comparable with historic high-risk FCR-treated patients. CFAR may be a useful frontline regimen to achieve CR in patients with 17p deletion before allogeneic stem cell transplantation.
authors.affiliation: Departments of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Parikh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Xavier
authors.initials: X
authors.lastname: Badoux
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D012074:Remission Induction; D012307:Risk Factors; D000069283:Rituximab; D058496:Smith-Magenis Syndrome; D013921:Thrombocytopenia / Q000209:etiology; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine