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

Oncotarget
Frits van RheeRazelle Kurzrock

Abstract

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. 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. 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). Hypertr...Continue Reading

References

Jul 14, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frits van RheeRazelle Kurzrock
Jul 14, 2012·American Journal of Hematology·Angela DispenzieriThomas M Habermann
May 11, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Razelle KurzrockFrits van Rhee

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Citations

Dec 3, 2015·Expert Review of Clinical Immunology·Emma Mitchell, Graeme Jones
Jun 25, 2014·Drugs·Anthony Markham, Trina Patel
Dec 3, 2016·Therapeutic Advances in Hematology·Shayna SarosiekNikhil C Munshi
Dec 5, 2015·Immunotherapy·David C Fajgenbaum, Razelle Kurzrock
Sep 24, 2015·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Katherine A Lyseng-Williamson
Feb 1, 2017·Expert Opinion on Investigational Drugs·Andrea FerrarioFrancesco Passamonti
Jan 10, 2018·Nature Reviews. Clinical Oncology·Irene M GhobrialDavid P Steensma
Sep 8, 2020·American Journal of Hematology·David C FajgenbaumUNKNOWN Castleman Disease Collaborative Network Scientific Advisory Board diagnostic criteria international working group and treatm
Jun 20, 2020·Drugs in R&D·Paul C MacklisBenjamin H Kaffenberger
Aug 4, 2018·Hematological Oncology·Lorenzo TonialiniPier Luigi Zinzani
Apr 27, 2020·Infectious Disease Clinics of North America·Anne Y Liu
Aug 26, 2021·European Journal of Haematology·Aaron M GoodmanRazelle Kurzrock
Sep 19, 2021·The FEBS Journal·Kwun Wah WenBlossom Damania

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Methods Mentioned

BETA
biopsies

Clinical Trials Mentioned

NCT01400503
NCT00412321

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Castleman disease is a rare disorder that involves an overgrowth of cells in the lymph nodes. Unicentric Castleman disease affects one lymph node, usually in the chest or abdomen. Multicentric Castleman disease affects multiple lymph nodes, commonly located in the neck, collarbone, underarm and groin areas. Discover the latest research on Castleman disease here.

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Cellulitis (erysipelas) is a recurring and debilitating bacterial infection of the skin and underlying tissue. Discover the latest research on cellulitis here.

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