title: Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia.
abstract: We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m(2) and cyclophosphamide 250 mg/m(2) days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete response (CR) rate as assessed by an independent review committee was 32% for the 500-mg and 50% for the 1000-mg cohort; the overall response (OR) rate was 77% and 73%, respectively. Based on univariable regression analyses, β2-microglobulin and the number of O-FC courses were significantly correlated (P < .05) with CR and OR rates and progression-free survival (PFS). The most frequent Common Terminology Criteria (CTC) grade 3-4 investigator-reported adverse events were neutropenia (48%), thrombocytopenia (15%), anemia (13%), and infection (8%). O-FC is active and safe in treatment-naive patients with CLL, including high-risk patients. This trial was registered at www.clinicaltrials.gov as NCT00410163.
authors.affiliation: The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. wwierda@mdanderson.org.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Laimonas
authors.initials: L
authors.lastname: Griskevicius
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Jirí
authors.initials: J
authors.lastname: Mayer
authors.forename: Lukás
authors.initials: L
authors.lastname: Smolej
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.forename: Rasa
authors.initials: R
authors.lastname: Griniute
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Hernandez-Ilizaliturri
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Michele
authors.initials: M
authors.lastname: Gorczyca
authors.forename: Chai-Ni
authors.initials: CN
authors.lastname: Chang
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chan
authors.forename: Ira
authors.initials: I
authors.lastname: Gupta
authors.forename: Tina G
authors.initials: TG
authors.lastname: Nielsen
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Russell
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D014740:Vidarabine; C527517:ofatumumab; C024352:fludarabine