CHICAGO, IL—Siltuximab, a novel chimeric anti−interleukin-6 monoclonal antibody, is active in patients with multicentric Castleman’s disease (MCD) who have had insufficient response to or failed previous therapies, according to results of a prespecified subanalysis reported at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
Previously, siltuximab had shown significant improvement in durable tumor and symptomatic response (34.0% vs. 0.0% with placebo; P = 0.001) in patients with MCD, said Frits Van Rhee, MD, PhD, of the Myeloma Institute for Research and Therapy, Little Rock, AR.
“The study met its primary objective of demonstrating that siltuximab plus best supportive care is superior to placebo plus best supportive care in terms of durable tumor and symptomatic response in MCD,” he said. To date, this is the only multinational, randomized, double-blind, placebo-controlled study in MCD, a rare, lymphoproliferative disorder with high morbidity. Based on these results, the Food and Drug Administration recently approved siltuximab for the treatment of patients who are human immunodeficiency virus (HIV)-negative and human herpesvirus (HHV-8)-negative.
The study randomly assigned adults with confirmed symptomatic MCD who were HIV- and HHV-8-negative 2:1 to intravenous siltuximab 11 mg/kg (n=53) or placebo (n=26) every 3 weeks. All patients were stratified by corticosteroid use at randomization and all received best supportive care. Treatment was continued until treatment failure.
The majority of patients had received prior systemic treatment for MCD: 29 (54.7%) in the siltuximab arm and 17 (65.4%) in the placebo arm. The most frequently used agents were corticosteroids (94%), cyclophosphamide (50%), vincristine (26%), and rituximab (17%), Dr. Van Rhee reported.
Durable tumor and symptomatic responses were found to be similar for both pretreated (34.5% for siltuximab vs. 0% for placebo) and treatment-naïve subgroups (33.3% vs. 0%).
In both the pretreated and treatment-naïve patients with MCD, the secondary endpoints consistently favored siltuximab. Across both treatment groups, the median duration of follow-up was 422 days (range, 55-1,051 days). Median time to treatment failure was not reached in either siltuximab group compared with 184 days for placebo in the previously treated patients (hazard ratio [HR], 0.601, P = 0.2296) and 106 days in the treatment-naïve patients (HR, 0.189, P = 0.0051).
The frequencies of adverse events (AE) and serious AEs were similar across pretreated and treatment-naive patients. “Siltuximab appears to be well tolerated,” he concluded, adding that there was no increase in grade 3 AEs and serious AEs for the agent compared with placebo, despite longer treatment.
- Van Rhee F, Munshi NC, Wong R et al. Abstract 8514. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.