Is tocilizumab a potential therapeutic option for refractory unicentric Castleman disease?

Abstract

Castleman disease is a rare lymphoproliferative disorder with 2 distinctly defined clinical forms. While multicentric Castleman disease (UCD) poses a potential therapeutic challenge, unicentric variant has historically been considered curable with surgical resection. Hence, little is known to guide management of patients with UCD, refractory to surgical resection and combination chemotherapy. We present a case of a patient, negative for HIV and HHV-8, who had an unsuccessful surgical intervention and no response to radiotherapy and chemotherapy. He had severe paraneoplastic pemphigus and was treated with tocilizumab, an anti-interleukin-6 receptor monoclonal antibody that has demonstrated good response rates in multicentric Castleman disease but demonstrated no clinical response despite 2 months of treatment. Our report is the first to describe a lack of response to tocilizumab in the rare setting of refractory UCD and discuss potential for distinct disease biology.

International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease

“…83 However, it should be pointed out that limited data exist regarding the effectiveness of this approach. 19,84 Any persisting lymphadenopathy should be surgically resected, if feasible. As with compression-related unresectable UCD, patients who continue to have unresectable UCD lymphadenopathy after treatment with anti-IL-6 monoclonal antibody therapy but have become otherwise asymptomatic can be observed.…”

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“…20 Pueden considerarse terapias alternativas para los pacientes que no son aptos a resección quirúrgica o radioterapia o, bien, que han fallado a estos tratamientos y estén sintomáticos, entre los que destacan anticuerpos monoclonales anti-CD-20 o anti-IL-6. 32,33 La enfermedad de Castleman es un proceso linfoproliferativo poco frecuente, con excelente pronóstico en la variedad unicéntrica y recaídas poco frecuentes; sin embargo, se cuenta con poca información acerca de estos pacientes y se requiere un alto grado de sospecha diagnóstica y, debido a que no existen datos clínicos y radiográficos específicos, es imprescindible el análisis histopatológico para establecer el diagnóstico de manera temprana y proporcionar un tratamiento oportuno, lo que mejora el pronóstico de estos pacientes. La divulgación y conocimiento de estas enfermedades son imprescindibles para establecer diagnósticos correctos, además de crear un acervo de información que permita estimar la incidencia en nuestro país, resaltando la importancia de la publicación de este tipo de casos.…”

Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?

“…Tocilizumab is a humanized monoclonal antibody that inhibits IL-6 binding to mIL-6R (membrane IL-6R) and sIL-6R and prevents its pro-inflammatory and fibrotic effects [ 108 ]. In addition to SS, this beneficial effect has been shown in a variety of conditions, such as rheumatoid arthritis, juvenile idiopathic arthritis, Takayasu’s arteritis, Still’s adult disease, giant cell arteritis, and Castleman’s disease [ 109 , 110 , 111 , 112 , 113 ].…”