First Randomized Study of Patients with Multicentric Castleman’s Disease

New Orleans—Patients with multicentric Castleman’s disease (MCD) who received siltuximab had a significantly better durable tumor and symptom response and time to treatment failure compared with a placebo group, according to the first multinational, randomized, double-blind, placebo-controlled study for MCD.

Raymond S. Wong, MD, the study’s lead author, presented the results during an oral abstract session at the ASH meeting. In September, Janssen Research & Development, LLC submitted a new drug application to the FDA for siltuximab to treat MCD in patients who are HIV-negative and HHV-8-negative.

The FDA granted siltuximab orphan drug status because it is intended to treat a condition affecting <200,000 people in the United States. MCD, a rare, lymphoproliferative disorder, is associated with high morbidity and is potentially fateful. Siltuximab is an anti-interleukin-6 monoclonal antibody undergoing trials for several cancers.

The phase 3 study included 79 treatment-naïve or pretreated patients with symptomatic MCD who were HIV-negative and HHV-8-negative. They enrolled at 38 sites in 19 countries and were randomized in a 1:2 ratio to receive placebo (n=26) or siltuximab (n=53) until treatment failure. They were allowed to take best supportive care and up to 1 mg/kg of prednisone per day. The median age was 48 years, 66% of patients were males, 48% were Asian, 39% were white, and 58% had received prior treatment.

The authors found that 34% of patients in the siltuximab group had a durable tumor and system response lasting at least 18 weeks compared with no patients in the placebo group (P=.0012). In addition, 37.7% of patients receiving siltuximab and 3.8% of patients taking placebo had a tumor response (P=.0022). The median time to treatment failure was 134 days in the placebo group but had not been met in the siltuximab group at a median follow up of 1.3 years (hazard ratio [HR], 0.418; P=.0084).

Further, 56% of patients in the siltuximab group and 19% of patients in the placebo group had a symptom response (P=.0018), while 25% and 0%, respectively, achieved a complete symptom response (P=.0037). The authors defined a symptom response as a durable reduction in the overall MCD symptom score by at least 15% for at least 18 weeks. A complete symptom response was achieved when patients had complete resolution of all MCD-related symptoms for at least 18 weeks. The median time to durable symptom response was 170 days in the siltuximab group but had not been reached in the placebo group (HR, 0.418; P=.0288).

Of the patients who had anemia at baseline, 61% treated with siltuximab and none treated with placebo had an increase of at least 1.5 mg/dL in their hemoglobin level at week 13 (P=.0002).

Dr. Wong noted that although patients received siltuximab for a longer time than placebo, there was no significant difference in adverse events. Grade 3 or higher adverse events were found in 54% of patients receiving placebo and 47% of patients receiving siltuximab, while grade 3 or higher serious adverse events were found in 15% and 19% of patients, respectively.

The most common grade 3 or higher adverse events in the siltuximab group were fatigue (9% of patients) and night sweats (8%). The most frequent adverse events regardless of grade in patients taking siltuximab were pruritus (42%), upper respiratory tract infection (36%), maculopapular rash and fatigue (34%), and peripheral edema (32%).