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Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease

Research output: Contribution to journalArticlepeer-review

the Castleman Disease Collaborative Network Scientific Advisory Board diagnostic criteria international working group and treatment guidelines international working group

Original languageEnglish
Pages (from-to)1553-1561
Number of pages9
JournalAmerican Journal of Hematology
Volume95
Issue number12
DOIs
PublishedDec 2020

Bibliographical note

Funding Information: DCF receives research support from EUSA Pharma for the ACCELERATE study (formerly sponsored by Janssen Pharmaceuticals) and study drug from Pfizer for NCT03933904 without corresponding financial support. DCF has a provisional patent Methods of Treating Idiopathic Multicentric Castleman Disease with JAK1/2 inhibition (62/989437) pending. FvR receives research support from Janssen Pharmaceuticals and consultant fees from EUSA Pharma. AG receives consultant fees from EUSA Pharma. CH receives research support from Janssen Pharmaceuticals and consultant fees from EUSA Pharma. SF receives consulting fees, speaker honoraria, and serves an advisory board member for Janssen; receives speaker honoraria and is an advisory board member for EUSA Pharma; receives research funding from Gilead; serves on an advisory board for Sandoz; and receives speaker honoraria from Servier. RW has received research funding from Janssen Pharmaceuticals and served on advisory boards for Janssen Pharmaceuticals. PLZ has served on advisory boards and speaker's bureaus for Verastem, Celltrion, Gilead, Janssen, BMS, Servier, Immune Design, Celgene, Portola, Roche, Kyowa Kirin; and had consulting fees, speaker's bureaus, and advisory board membership for Veratem, MSD, and EUSA Pharma; advisory board membership with Sandoz; and consulting fees with Sanofi. NP receives consulting fees/honorarium from Celgene, Stemline, Incyte, Novartis, MustangBio, Roche Diagnostics, LFB, and Pacylex; and research funding/clinical trials support from Stemline, Novartis, Abbvie, Samus, Cellectis, Plexxikon, Daiichi‐Sankyo, Affymetrix, and SagerStrong Foundation. EO receives consulting fees and serves on an advisory board for EUSA Pharma. AD receives research support from Celgene, Takeda, Alnylam, and Pfizer; and serves in an advisory capacity for Janssen, Intellia, and Akcea. SM serves on Advisory Boards for BMS (formerly Celgene)/Acceleron and Novartis; receives honoraria from the Aplastic Anemia and MDS International Foundation, Bristol Myers Squib, McGraw Hill, Partnership for Health Analytic Research, and LLC (PHAR, LLC); receives consulting fees from BioPharm, BMS (formerly Celgene), Novartis; and research funding from BMS (formerly Celgene) and Novartis. DW, on behalf of the University of Washington, received research support from Janssen Pharmaceuticals for central pathology review for the 2014 van Rhee Lancet Oncology work. The remaining authors declare no relevant conflicts of interest. Publisher Copyright: © 2020 Wiley Periodicals LLC Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

  • the Castleman Disease Collaborative Network Scientific Advisory Board diagnostic criteria international working group and treatment guidelines international working group

Abstract

Idiopathic multicentric Castleman disease (iMCD) is a rare immunologic disorder characterized by systemic inflammation, multicentric lymphadenopathy, and organ dysfunction. Enlarged lymph nodes demonstrate a spectrum of characteristic but variable histopathologic features historically categorized into hyaline vascular (HV) (or hypervascular [HyperV] more recently), plasmacytic, or “mixed.” Though the etiology is unknown, a pro-inflammatory cytokine storm, often involving interleukin-6 (IL-6), contributes to pathogenesis. Anti-IL-6 therapy with siltuximab is the only FDA- or EMA-approved treatment based on efficacy and safety in multiple studies. Importantly, no patients considered to have HV histopathology achieved the primary endpoint in the Phase II study. NCCN currently recommends siltuximab first-line for iMCD, except for patients considered to have HV histopathology. We investigated whether histopathologic subtype should guide siltuximab treatment decisions. Secondary analyses of clinical trial and real-world data revealed similar clinical benefit across histopathologic subtypes. Notably, only 18 of 79 patients in the Phase II study were consistently classified into histopathologic subtype by three independent review panels, demonstrating limited reliability to guide treatment decisions. Real-world data further demonstrate siltuximab's effectiveness in patients considered to have HV (or HyperV). Though histopathology is a critical component for diagnosis, there is insufficient evidence to guide treatment based solely on lymph node histopathologic subtype.

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