Castleman Disease Treatment & Management

Updated: Nov 24, 2021
  • Author: Geneva E Guarin, MD, MBA; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment

Approach Considerations

Treatment varies depending on the subtype of Castleman disease.

Unicentric Castleman disease

For unicentric Castleman disease (UCD), surgical removal of the enlarged lymph node is usually curative and is considered the gold standard for treatment. Systemic symptoms and laboratory abnormalities, if present, tend to resolve with complete resection of the enlarged lymph node or solitary region of lymph nodes. Recurrences of UCD have been rarely reported and are usually related to incomplete initial resection or missed lymph nodes at the initial evaluation, though not all UCD recurrences are in the same anatomical location. In rare cases, patients with UCD may have persistent inflammatory symptoms (but not laboratory markers) even after complete surgical resection.

Occasionally, a large UCD mass may be unresectable due to size or location. This is frequently encountered in the setting of a mediastinal mass that is very close to a main bronchus or major blood vessels. In these patients, initial debulking of the mass with systemic therapy, as described for human herpesvirus 8 (HHV-8)–negative/idiopathic multicentric Castleman disease (iMCD), followed by safer surgical intervention should be considered.

Human herpesvirus 8 (HHV-8)–associated multicentric Castleman disease (MCD)

In HHV-8–associated MCD, treatment with rituximab is highly effective. For patients with concomitant HIV infection and a low CD4 count and/or higher HIV load, antiretroviral therapy (ART) should be included with the rituximab. [17] For HIV-negative patients, there may also be a role for concomitant antiviral therapy with ganciclovir. Treatment with rituximab should be repeated upon relapse. Rituximab may be administered or without steroids and/or chemotherapy. However, rituximab therapy occasionally worsens Kaposi sarcoma, which must be carefully considered in HIV-positive patients with a high viral load, low CD4 count, and active Kaposi sarcoma. [18, 17] For HHV-8–associated MCD patients with evidence of life-threatening organ failure or poor performance status, liposomal doxorubicin or etoposide can be added.

HHV-8–negative MCD

Siltuximab (Sylvant) is the only drug approved by the US Food and Drug Administration (FDA) for HHV-8–negative MCD. Siltuximab is a monoclonal antibody that binds interleukin-6 (IL-6). Where available, siltuximab is the preferred therapy, based on its benefit in the only randomized trial [19] and its approval by the FDA; National Comprehensive Cancer Network (NCCN) guidelines recommend siltuximab as the preferred primary treatment. [20] If siltuximab is not available, tocilizumab (anti–IL-6 receptor therapy) may be used in its place. Anti–IL-6 treatment is continued until progression of disease in order to maintain the response and prevent an early relapse.

Of note, after siltuximab is administered, laboratory tests for IL-6 levels become uninterpretable, because the assays detect complexed IL-6 and drug. Therefore, IL-6 levels should not be used to guide or contribute to treatment decisions for at least 18-24 months after the last dose of siltuximab.

Also, 66% of patients in the clinical trial did not respond to siltuximab treatment, approximately half of whom did not have elevated IL-6 levels. Optimal treatment for siltuximab non-responders is not known, but the following agents have been used:

  • Other immunomodulatory therapies (eg, tocilizumab, sirolimus, corticosteroids, cyclosporine, anakinra, thalidomide, intravenous immunoglobulin [IVIg], bortezomib [21, 22] )
  • Targeted B cell depletion with rituximab
  • Cytotoxic chemotherapies (cyclophosphamide, etoposide, [23] adriamycin, vinblastine, or combinations such as rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] cyclophosphamide, vincristine, and prednisone [CVP]): Cytotoxic chemotherapy has been used as single agents or in combination, yielding symptomatic relief and a partial response in many patients. However, symptoms recur when treatment is stopped, necessitating intermittent maintenance therapy, often lifelong.
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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. [24]

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Multicentric Castleman Disease

The National Comprehensive Cancer Network (NCCN) recommends siltuximab as a preferred primary treatment for patients with HIV-negative HHV-8-negative/idiopathic multicentric Castleman disease (iMCD) with plasmacytic or mixed pathology. [20]

 

 

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Long-Term Monitoring

Disease response is assessed by evaluating lymph node size via imaging, as well as biochemical values. The following markers of inflammatory response and organ function can be evaluated33:

  • C-reactive protein
  • Hemoglobin
  • Albumin
  • Glomerular filtration rate

The frequency of monitoring depends on the severity of presentation, as follows [15] :

  • For severe presentation, initially monitoring should be daily
  • For less severe presentation, weekly assessment of clinical symptoms and laboratory values is necessary, then biweekly until maximum benefit has occurred

Radiological evaluation of lymph nodes with computed tomography is as follows [15] :

  • Begin at 6 weeks after treatment initiation
  • Repeat every 3 months until maximum response is achieved, then reduce to every 6 to 12 months
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