Originally published as JCO Early Release 10.1200/JCO.2004.03.071 on September 7 2004

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Phase II Study of Denileukin Diftitox for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

From the Departments of Lymphoma/Myeloma, Hematopathology, Diagnostic Radiology, and Cardiology, University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Nam H. Dang, MD, PhD, The University of Texas M.D. Anderson Cancer Center, Department of Lymphoma/Myeloma, 1515 Holcombe Blvd, Box 429, Houston, TX 77030; e-mail: nhdang{at}mail.mdanderson.org

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 µg/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.

Supported in part by the Medical Affairs Department of Ligand Pharmaceuticals Inc. The work of N.H. Dang is supported in part by a grant from The M.D. Anderson Physician-Scientist Program and the Gillson Longenbaugh Foundation.

The work reported is original, and interim results were presented previously at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003. Published in the Proceedings of the American Society of Clinical Oncology, 39th Annual Meeting, 2003, volume 2, page 570, abstract 2292; and at the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6-9, 2003. Published in the Journal of the American Society of Hematology, 2003, volume 102 (part 2), page 303b, abstract 4935.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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