title: Sequential ofatumumab and lenalidomide for the treatment of relapsed and refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.
abstract: Ofatumumab is a fully human anti-CD20 monoclonal antibody with enhanced antibody dependent and complement dependent cytotoxicity. Lenalidomide induces T cell and natural killer (NK) cell activation and in vitro enhances clearance of chronic lymphocytic leukemia (CLL) cells by monoclonal antibodies. We performed a multi-center, phase 2 trial of sequential treatment with ofatumumab and lenalidomide in patients with advanced, relapsed and refractory (R/R) CLL, consisting of ofatumumab 2000 mg intravenously on day 1 and lenalidomide 10 mg on days 8-28, for up to six cycles. Twenty-one subjects were included with median age of 63 years and two prior lines of therapy. The overall response rate was 47.6% and 23.8% had stable disease. Median overall survival was 21.5 months. Neutropenia and thrombocytopenia were the most frequent adverse events. Tumor flare reaction occurred in 43% of subjects. Intracycle sequential ofatumumab plus lenalidomide is active in high-risk R/R CLL and well tolerated except for frequent cytopenias.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Medical University of South Carolina , Charleston, SC , USA.
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Costa
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Fanning
authors.forename: Joe
authors.initials: J
authors.lastname: Stephenson
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Afrin
authors.forename: Emily
authors.initials: E
authors.lastname: Kistner-Griffin
authors.forename: Tricia A
authors.initials: TA
authors.lastname: Bentz
authors.forename: Robert K
authors.initials: RK
authors.lastname: Stuart
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide; C527517:ofatumumab
keywords: Ofatumumab; chronic lymphocytic leukemia; clinical trial; lenalidomide; small lymphocytic lymphoma