Castleman Disease Treatment & Management

Updated: Jul 13, 2017
  • Author: Neetu Radhakrishnan, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment

Approach Considerations

Treatment varies depending on the type of Castleman disease: unicentric or multicentric. Surgical removal of the involved node is usually curative in unicentric disease, but is rarely curative in multicentric Castleman disease (MCD). Splenectomy can result in a transient symptomatic improvement in some patients.

There is no standard therapy for MCD, and clinical practice varies.

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Unicentric Castleman Disease

Surgery is usually curative. In patients whose lesions cannot be completely resected, outcomes remain favorable. Partially resected masses may remain stable and asymptomatic for many years.

Patients with unresectable diseases with compressive symptoms can be treated as described for HIV-negative MCD (below).

Systemic steroids can provide symptomatic relief but do not predictably reduce tumor size.

Radiation therapy with 30-45 Gy can result in complete and partial remission rates of 40% and 10%, respectively, but can cause radiation-induced fibrosis that makes subsequent surgical intervention more difficult. [10]

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Multicentric Castleman Disease

There is no standard therapy for MCD, and clinical practice varies. Patients with MCD should be encouraged to enroll in clinical trials, whenever available. If no clinical trial is available, therapy depends on HIV/HHV-8 status and then on the clinical aggressiveness of the disease. Treatment options are discussed below.

IL-6–directed therapy

Especially in HIV/HHV-8–negative patients with mild symptoms and no organ failure, immunotherapy with monoclonal antibodies directed at IL-6 (siltuximab) or the IL-6 receptor (tocilizumab) was reported to yield a 2-year overall survival rates and relapse-free rates of 94%-95% and 79%-85%, respectively. [11, 12]

Siltuximab is often preferred, based on its benefit in the only randomized trial. [13, 14] A case report by Patel et al describes an exceptional response to siltuximab in a patient whose pretreatment serum IL-6 levels were normal, but in whom next-generation sequencing demonstrated a missense mutation in the Janus Kinase 1 (JAK1) gene, which codes for a crucial signaling component of the IL-6/IL-6 receptor/gp130 machinery. Treatment with siltuximab in their patient resulted in a complete response lasting 7 years. [15]

Anti–IL-6–directed treatment is continued until progression of disease in order to maintain the response and prevent an early relapse.

Anti-CD20 monoclonal antibody therapy

If neither siltuximab nor tocilizumab is available, experts recommend the anti-CD20 monoclonal antibody rituximab, which affects IL-6 production..Rituximab may be administered or without steroids and/or chemotherapy and may be used regardless of HIV status and typically yields a good response, especially when used along with chemotherapy. However, rituximab therapy occasionally worsens Kaposi sarcoma, which must be carefully considered in HIV-positive patients with high viral load, low CD4 count, and active Kaposi sarcoma. [16, 17]

Cytotoxic chemotherapy

Cytotoxic chemotherapy has been used with agents such as vinblastine and etoposide, both as single agents, yielding symptomatic relief and a partial response in almost all patients. [18]

However, symptoms recur when treatment is stopped, necessitating intermittent maintenance therapy, often lifelong. Thus, combination chemotherapy is usually preferred to monotherapy when chemotherapy is given. Etoposide is often used with rituximab in HIV/HHV-8–positive patients with organ dysfunction and aggressive disease.

Treatment in HIV/HHV-8–positive patients

In most HIV/HHV-8–positive patients, experts often suggest a combination of ganciclovir plus rituximab, with etoposide added for symptomatic or aggressive disease. [19]

ART therapy is often included with the above combination regimen in patients with a low CD4 count, higher HIV load, and/or active Kaposi sarcoma.

Other therapies with limited efficacy data include the following:

  • Antiviral therapy (ganciclovir, cidofovir, interferon alpha)
  • Bortezomib: Shown to have activity in the plasma cell variant of Castleman disease [20]
  • Thalidomide plus rituximab: Has also been shown to induce some responses [21]
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Long-Term Monitoring

Disease response is assessed with imaging and laboratory data after about 4 cycles of therapy. A second round may be administered upon a partial response. IL-6–directed therapy should be given continuously.

Monitoring at periodic intervals (2-4 months) with a history and physical examination and serum biomarkers (including IL-6, CRP, serum free light chain assay, quantitative immunoglobulins) is often done. Generally, annual imaging can be discontinued after 5 years if the patient remains disease-free.

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