Scientific Publications by FDA Staff

Clin Cancer Res 2015 Mar 1;21(5):950-4

FDA Approval: Siltuximab for the Treatment of Patients with Multicentric Castleman Disease.

Deisseroth A, Ko CW, Nie L, Fourie Zirkelbach J, Zhao L, Bullock J, Mehrotra N, Del Valle P, Saber H, Sheth C, Gehrke B, Justice R, Farrell A, Pazdur R

On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for Injection, Janssen Biotech, Inc.), a chimeric human-mouse monoclonal antibody to interleukin-6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. The approval was primarily based on the results of a randomized, double-blind trial in which 79 symptomatic patients with MCD were allocated (2:1) to siltuximab plus best supportive care (BSC) or to placebo plus BSC. The primary efficacy endpoint was the proportion of patients in each arm achieving a durable tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. Tumor response was based on independent review of CT scans using the revised response criteria for malignant lymphoma, and symptomatic response was defined as complete resolution or stabilization of 34 MCD-related signs and symptoms as reported by the investigator. Thirty-four percent of patients in the siltuximab arm and no patients in the placebo arm met the primary endpoint (p=0.0012). The most common adverse reactions (>10% compared to placebo) during treatment with siltuximab were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.