title: Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL.
  
  
  METHODS
  Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles.
  
  
  RESULTS
  Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient.
  
  
  CONCLUSIONS
  Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Department of Lymphoma/Myeloma, 1515 Holcombe Blvd, Box 429, Houston, TX 77030, USA. nhdang@mail.mdanderson.org
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Fredrick B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Barry
authors.initials: B
authors.lastname: Samuels
authors.forename: Felipe
authors.initials: F
authors.lastname: Samaniego
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Walker
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Arredondo
authors.forename: Ann T
authors.initials: AT
authors.lastname: Tong
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004167:Diphtheria Toxin / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000139:chemically induced; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D004167:Diphtheria Toxin; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox