1. A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease
- Author
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van Rhee, Frits, Casper, Corey, Voorhees, Peter M, Fayad, Luis E, van de Velde, Helgi, Vermeulen, Jessica, Qin, Xiang, Qi, Ming, Tromp, Brenda, and Kurzrock, Razelle
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Hematology ,Rare Diseases ,Cardiovascular ,Cancer ,Clinical Research ,Patient Safety ,7.1 Individual care needs ,Management of diseases and conditions ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adolescent ,Adult ,Aged ,Antibodies ,Monoclonal ,Antineoplastic Agents ,Castleman Disease ,Disease-Free Survival ,Drug Administration Schedule ,Female ,Humans ,Infusions ,Intravenous ,Male ,Middle Aged ,Time Factors ,Treatment Outcome ,United States ,Young Adult ,multi-centric Castleman's disease ,interleukin-6 ,siltuximab ,clinical trial ,Oncology and Carcinogenesis ,Oncology and carcinogenesis - Abstract
BACKGROUND:Multicentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD. METHODS:This preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented. RESULTS:Median treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥ 3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥ 3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule. CONCLUSIONS:All MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab.
- Published
- 2015