PURPOSE: To evaluate the safety and pharmacokinetics of siltuximab, an 
anti-interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell 
non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease.
EXPERIMENTAL DESIGN: In an open-label, dose-finding, 7 cohort, phase I study, 
patients with NHL, multiple myeloma, or symptomatic Castleman disease received 
siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. 
Response was assessed in all disease types. Clinical benefit response (CBR; 
composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest 
lymph node size) was also evaluated in Castleman disease.
RESULTS: Sixty-seven patients received a median of 16 siltuximab doses for a 
median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer. There was 
no dose-limiting toxicity, antibodies to siltuximab, or apparent dose-toxicity 
relationship. The most frequently reported possible drug-related adverse events 
were thrombocytopenia (25%), hypertriglyceridemia (19%), neutropenia (19%), 
leukopenia (18%), hypercholesterolemia (15%), and anemia (10%). None of these 
events led to dose delay/discontinuation except for neutropenia and 
thrombocytopenia (n = 1 each). No treatment-related deaths occurred. C-reactive 
protein (CRP) suppression was most pronounced at 12 mg/kg every 3 weeks. Mean 
terminal-phase half-life of siltuximab ranged 17.73 to 20.64 days. Thirty-two of 
37 (86%) patients with Castleman disease improved in 1 or more CBR component; 12 
of 36 evaluable Castleman disease patients had radiologic response [complete 
response (CR), n = 1; partial response (PR), n = 11], including 8 of 19 treated 
with 12 mg/kg; 2 of 14 (14%) evaluable NHL patients had PR; 2 of 13 (15%) 
patients with multiple myeloma had CR.
CONCLUSION: No dose-related or cumulative toxicity was apparent across all 
disease indications. A dose of 12 mg/kg every 3 weeks was recommended on the 
basis of the high response rates in Castleman disease and the sustained CRP 
suppression. Randomized studies are ongoing in Castleman disease and multiple 
myeloma.