title: Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin's lymphoma.
abstract: Rituximab has significant activity as a single agent in the treatment of follicular non-Hodgkin's lymphoma (NHL). Interleukin 2 (IL-2) is a lymphokine that increases effector cell number. In an effort to augment antibody-dependent cell-mediated cytotoxicity (ADCC) associated with rituximab therapy, low-dose IL-2 was added to a standard rituximab regimen and patients were evaluated for safety and efficacy. Twenty patients with relapsed or refractory follicular NHL were treated with IL-2 (1.2 MIU/m(2)/d for 56 d subcutaneously) as outpatients. Rituximab (375 mg/m(2)) was given on d 15, 22, 29 and 36. The regimen was well tolerated and only three patients required dose adjustments in IL-2. Infusional toxicity associated with rituximab was not exacerbated by IL-2. Peripheral blood immunophenotyping demonstrated significant increases in circulating CD8+ and CD56+ lymphocytes in all evaluable patients (P = 0.0002). Increases in total eosinophil number were observed in all patients. Eleven patients responded to therapy, for an overall response rate of 55%. Four additional patients had stable disease. For these 15 patients, the median time to progression exceeded 13 months. We conclude concomitant cytokine therapy to enhance ADCC with monoclonal antibody therapy was well tolerated and did not exacerbate antibody-related infusional toxicity. Further studies of this rational combination are warranted and ongoing.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. jfriedberg@partners.org
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Christine
authors.initials: C
authors.lastname: Canning
authors.forename: Margaret
authors.initials: M
authors.lastname: Koval
authors.forename: Christine M
authors.initials: CM
authors.lastname: Poor
authors.forename: Luke M
authors.initials: LM
authors.lastname: Green
authors.forename: John
authors.initials: J
authors.lastname: Daley
authors.forename: Robert
authors.initials: R
authors.lastname: Soiffer
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Freedman
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D019002:CD56 Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019002:CD56 Antigen; D007376:Interleukin-2; D000069283:Rituximab