International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease

Abstract

<jats:title>Abstract</jats:title> <jats:p>Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8–negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti–interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.</jats:p>

Castleman disease in pediatrics: Insights on presentation, treatment, and outcomes from a two‐site retrospective cohort study

“…Due to the lack of consensus in treatment of MCD at the institution and national levels until recently, 11…”

“…6 Although complete surgical resection is typically curative for patients with UCD, [6][7][8] patients with MCD or unresectable UCD disease have significantly worse prognosis due to lack of consistently effective therapies, with no consensus regarding first-line treatment until recently. [7][8][9][10][11] New consensus guidelines recommend use of antiinterleukin-6 (IL-6) monoclonal antibody (siltuximab or tocilizumab) with or without corticosteroids as first-line therapy for idiopathic MCD. 11 Use of rituximab in place of anti-IL-6 therapy, or the addition of conventional cytotoxic chemotherapy, should also be considered.…”

“…[7][8][9][10][11] New consensus guidelines recommend use of antiinterleukin-6 (IL-6) monoclonal antibody (siltuximab or tocilizumab) with or without corticosteroids as first-line therapy for idiopathic MCD. 11 Use of rituximab in place of anti-IL-6 therapy, or the addition of conventional cytotoxic chemotherapy, should also be considered. 9,10 Much of the CD literature is focused on an adult population, with pediatric CD described primarily in small case series, [12][13][14][15] and one review focusing on MCD in HHV8-endemic regions.…”

A case of Castleman disease that improved after kidney transplantation

“…Patients with severe iMCD who have marked organ dysfunction, poor performance status, and/or require critical care should be promptly started on a high-dose steroid regimen (e.g., methylprednisolone 500 mg daily) together with siltuximab or tocilizumab. However, POEMS-associated iMCD does not respond to IL-6 inhibitors; therefore, hematopoietic cell transplantation and radiation treatment can be considered [20]. The present patient was not treated with IL-6 inhibitors during KTP.…”

“…However, the indolent form, rather than the rapidly progressive form, does not seem to deteriorate with time. Disease severity should be assessed by determining the direction of iMCD treatment [20]. In non-severe diseases without life-threatening organ failure, an anti-IL-6 monoclonal antibody, siltuximab, or an anti-IL-6 receptor monoclonal antibody, tocilizumab, is the primary iMCD treatment.…”