Tocilizumab in patients with symptomatic Kaposi sarcoma herpesvirus–associated multicentric Castleman disease
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Kaposi sarcoma (KS) herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent for KS and a plasmablastic form of multicentric Castleman disease (MCD; KSHV-MCD). 1 KSHV-MCD is a relapsing and remitting B-cell lymphoproliferative disorder that occurs primarily in people living with HIV. 2,3Patients present with anemia, thrombocytopenia, and inflammatory symptoms associated with elevated cytokines including interleukin-6 (IL-6) and IL-10, elevated levels of C-reactive protein (CRP), and elevated KSHV viral loads (KSHV-VLs).5][6] Treatment options include rituximab (a humanized monoclonal antibody against CD20), rituximab with liposomal doxorubicin or etoposide, or virus-activated cytotoxic therapy with high-dose zidovudine (AZT) and valganciclovir (VGC). 7-13However, some patients do not respond to rituximab, and, when used alone, it is associated with worsening or development of KS in 35% to 67%. 8,9
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Tocilizumab has minimal and short-lived effect in patients with HHV-8-associated multicentric Castleman's disease, most likely because of viral interleukin-6 signaling independent of the neutralized interleukin-6 receptor.
“A recent study showed that the effect of tocilizumab in patients with HHV-8–associated multicentric Castleman’s disease was minimal and short-lived, most likely because of viral interleukin-6 signaling that was independent of the neutralized interleukin-6 receptor.70”
From Cytokine storm (2020) · cites this paper as [70]
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KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways
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Fajgenbaum, D. C., & June, C. H. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2026131 · Cited by 3,196 · see citing works
- Authors
- Ramaswami, R., Lurain, K., Peer, C. J., Serquiña, A., Wang, V., Widell, A., Goncalves, P., Steinberg, S. M., Marshall, V., George, J., Figg, W. D., Whitby, D., Ziegelbauer, J., Uldrick, T. S., & Yarchoan, R.
- Affiliations
- HIV & AIDS Malignancy Branch,
- Clinical Pharmacology Program, and
- National Institutes of Health (US)
- Frederick National Laboratory for Cancer Research (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2020-06-18
- Volume
- 135
- Issue
- 25
- Pages
- 2316-2319
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC7316216
- OpenAlex
- W3015640978
- Cited by
- 51
- References
- 20
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 9 · 2021: 12 · 2020: 4
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (HHSN261200800001E), 75N91019D00024)
- Topics
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- tocilizumab, Kaposi's sarcoma-associated herpesvirus, interleukin-6, IL-10, rituximab resistance, B-cell lymphoproliferative disorders, cytokine inhibition
- MeSH terms
- Valganciclovir, Adult, Female, Castleman Disease, Herpesviridae Infections, Humans, Male, Middle Aged, Sarcoma, Kaposi, Zidovudine, HIV Infections, Interleukin-10, Treatment Outcome, Herpesvirus 8, Human, Anti-HIV Agents, Viral Load, Interleukin-1beta, Antibodies, Monoclonal, Humanized
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