FDA Approves Siltuximab for Rare Castleman’s Disease

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The U.S. Food and Drug Administration (FDA) has approved siltuximab (Sylvant injection) for the treatment of patients with multicentric Castleman’s disease who are human immunodeficiency virus (HIV)-negative and human herpes virus-8 (HHV-8)-negative.

Multicentric Castleman’s disease is a rare disorder similar to lymphoma that causes an abnormal overgrowth of immune cells in lymph nodes and related tissues in the body. The disease usually affects adults, who often suffer from fever, night sweats, weight loss, and weakness or fatigue. Siltuximab is the first FDA-approved drug to treat multcentric Castleman’s disease.

Durable Tumor Response With Siltuximab

The approval was based on an international, multicenter, randomized (2:1), phase II study comparing every-3-week intravenous infusions of siltuximab and best supportive care to placebo and best supportive care.  The trial enrolled 79 patients and randomly allocated 53 patients to the siltuximab arm plus best supportive care and 26 patients to the placebo arm plus best supportive care. Siltuximab was administered every 3 weeks as an intravenous infusion at a dose of 11 mg/kg.

The primary endpoint was durable tumor and symptomatic response, defined as a tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. The durable tumor and symptomatic response rates were 34% (18/53) vs 0% (0/26) for the siltuximab and placebo groups, respectively (95% confidence interval [CI] = 11.1–54.8, P = .0012).

Additional supportive prespecified endpoints included tumor response, time to treatment failure, and an increase in hemoglobin of at least 1.5 g/dL at week 13 in patients who were anemic at study entry. Tumor response rates were 38% vs 4% for the siltuximab and placebo groups, respectively (P < .05). 

The median time to treatment failure, with a median follow-up of 422 days, was not reached in the siltuximab arm and was 134 days in the placebo arm (hazard ratio [HR] = 0.418, 95% CI = 0.21–0.82, P < .05). An increase in the level of hemoglobin described above was observed in 19 patients on the siltuximab arm and no patients on the placebo arm (95%
CI = 28.3–85.1, P < .05). 

The common adverse reactions during treatment included pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection. ■