Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms.
Increased interleukin-6 (IL-6) production and expression by malignant cells of the IL-6 receptor has been evidenced in a subgroup of non-Hodgkin's lymphomas, suggesting that this cytokine plays a role in lymphoma growth and in B clinical symptoms. In this study, the effect of the administration of an anti-IL-6 monoclonal antibody (MoAb) was analyzed in 11 patients seropositive for human immunodeficiency virus-1 and suffering from an immunoblastic or a polymorphic large-cell lymphoma. The antibody (BE-8, 10 to 40 mg/day) was administered for 21 days. Neutralization of in vivo IL-6 effect was assessed by monitoring C-reactive protein levels in the serum. In 5 patients, the lymphoma progressed during treatment. Among them were the 2 patients in whom endogenous IL-6 effect was not neutralized. Five patients experienced a stabilization, and 1 a partial remission. This effect on lymphoma growth lasted for 8 to 28 weeks. The anti-IL-6 MoAb had a clear effect on lymphoma-associated fever and cachexia. The mean body weight increase was 1.4 +/- 0.5 kg between day 1 and day 21, and reached 12 kg in 120 days in 1 patient who received three courses of treatment. Side effects were a consistent but moderate thrombocytopenia, and an occasional and moderate decrease of neutrophil counts. Immunization against the MoAb was observed in only 2 patients. These results indicate that in some cases of lymphomas growth of malignant cells may be partially IL-6-dependent and that neutralizing endogenous effect of IL-6 completely abrogates B clinical symptoms.
Emilie
D
D
INSERM U131, Hôpital Antoine Beclère, Clamart, France.
Wijdenes
J
J
Gisselbrecht
C
C
Jarrousse
B
B
Billaud
E
E
Blay
J Y
JY
Gabarre
J
J
Gaillard
J P
JP
Brochier
J
J
Raphael
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D007114:Immunization; D016219:Immunotherapy, Adoptive; D015850:Interleukin-6 / Q000276:immunology*; D016483:Lymphoma, AIDS-Related / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D051379:Mice; D012074:Remission Induction; D013736:Testicular Neoplasms / Q000628:therapy; D015430:Weight Gain
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015850:Interleukin-6