Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

Abstract

PURPOSE:

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.

PATIENTS AND 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.

CONCLUSION:

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: Nam H Dang, Fredrick B Hagemeister, Barbara Pro, Peter McLaughlin, Jorge E Romaguera, Dan Jones, Barry Samuels, Felipe Samaniego, Anas Younes, Michael Wang, Andre Goy, Maria A Rodriguez, Pamela L Walker, Yolanda Arredondo, Ann T Tong, Luis Fayad
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 20 Pg. 4095-102 (Oct 15 2004) ISSN: 0732-183X [Print] United States
• PMID: 15353540 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CD4 Antigens
• CD8 Antigens
• Diphtheria Toxin
• Interleukin-2
• Receptors, Interleukin-2
• Recombinant Fusion Proteins
• denileukin diftitox

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, therapeutic use)
• CD4 Antigens (analysis)
• CD8 Antigens (analysis)
• Diphtheria Toxin (adverse effects, therapeutic use)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Humans
• Hypoalbuminemia (chemically induced)
• Interleukin-2 (adverse effects, therapeutic use)
• Lymphoma, B-Cell (drug therapy, mortality)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Receptors, Interleukin-2 (analysis)
• Recombinant Fusion Proteins (adverse effects, therapeutic use)
• Treatment Outcome