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.


METHODS
Rituximab (375 mg/m(2)) 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.
Aklilu
M
M
Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
Stadler
W M
WM
Markiewicz
M
M
Vogelzang
N J
NJ
Mahowald
M
M
Johnson
M
M
Gajewski
T F
TF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000187:drug effects / Q000378:metabolism; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D000069283:Rituximab; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007136:Immunoglobulins; D007376:Interleukin-2; D000069283:Rituximab