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Annals of Oncology 15:1109-1114, 2004
© 2004 European Society for Medical Oncology

Depletion of normal B cells with rituximab as an adjunct to IL-2 therapy for renal cell carcinoma and melanoma

Background: We postulated that in patients with metastatic renal cell carcinoma (RCC) or melanoma, depletion of normal B cells using the anti-CD20 mAb rituximab before treatment with low-dose interleukin (IL)-2 would improve clinical outcome.

Patients and methods: Rituximab (375 mg/m2) weekly for 4 weeks. IL-2 [11 (million units) daily] s.c., 4 days a week for weeks 5–8, followed by a 2-week rest (weeks 9 and 10). Patients without disease progression continued on IL-2. Disease re-evaluation was performed after rituximab and after every course of IL-2.

Results: Fifteen patients with RCC and six with melanoma were enrolled. One patient had a partial response and seven patients had stable disease. Toxicities were similar to those expected with IL-2 alone, and there were no grade 4 events. Circulating B cells were depleted in all patients. The subsequent low-dose IL-2 increased absolute numbers of natural killer cells, activated CD4+ and activated CD8+ T cells. Expanded T cells produced interferon-{gamma}, but not IL-4. Proliferation of peripheral blood lymphocytes to phytohemagglutinin was diminished following rituximab treatment, suggesting that B cells participate in this response in vitro.

Conclusions: Our results suggest that depletion of circulating B cells with rituximab does not increase the response rate, alter the toxicity profile or change the biological activity in response to low-dose IL-2 in patients with RCC or melanoma.

M. Aklilu1, W. M. Stadler1,2,3, M. Markiewicz4, N. J. Vogelzang1,3, M. Mahowald4, M. Johnson4 and T. F. Gajewski1,3,4,*

1 Department of Medicine, Section of Hematology/Oncology; 2 Department of Surgery, Section of Urology; 3 University of Chicago Cancer Research Center; 4 Department of Pathology, University of Chicago, Chicago, IL, USA

*Correspondence to: Dr T. F. Gajewski, University of Chicago, 5841 South Maryland Ave, MC 2115, Chicago, IL 60637, USA. Tel: +1-773-702-4601; Fax: +1-773-702-3701; Email: tgajewsk{at}medicine.bsd.uchicago.edu

Key words: clinical trial, cytokines, immunoregulation, immunotherapy


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