TY - JOUR
T1 - Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease
AU - the Castleman Disease Collaborative Network Scientific Advisory Board diagnostic criteria international working group and treatment guidelines international working group
AU - Fajgenbaum, David C.
AU - Wu, David
AU - Goodman, Aaron
AU - Wong, Raymond
AU - Chadburn, Amy
AU - Nasta, Sunita
AU - Srkalovic, Gordan
AU - Mukherjee, Sudipto
AU - Leitch, Heather
AU - Jayanthan, Raj
AU - Ferrero, Simone
AU - Sato, Yasuharu
AU - Schey, Steve
AU - Dispenzieri, Angela
AU - Oksenhendler, Eric
AU - Zinzani, Pier Luigi
AU - Lechowicz, Mary Jo
AU - Hoffmann, Christian
AU - Pemmaraju, Naveen
AU - Bagg, Adam
AU - Fossa, Alexander
AU - Lim, Megan S.
AU - van Rhee, Frits
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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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U2 - 10.1002/ajh.25992
DO - 10.1002/ajh.25992
M3 - Article
C2 - 32894785
AN - SCOPUS:85091421976
SN - 0361-8609
VL - 95
SP - 1553
EP - 1561
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 12
ER -