What are the treatment options for Castleman disease?

Treatment of Castleman Disease

Classification-Based Treatment Algorithm

Treatment of Castleman disease depends fundamentally on whether the disease is unicentric (UCD) or multicentric (MCD), with complete surgical resection being curative for UCD and systemic therapy required for MCD. 1, 2

Unicentric Castleman Disease (UCD)

Complete surgical excision is the definitive first-line treatment for UCD and is often curative. 1, 2

• Surgical resection should be performed whenever technically feasible, as it provides excellent prognosis with remission rates approaching 100% in resectable cases 2
• For unresectable UCD that is asymptomatic, observation alone is an acceptable management strategy 2
• When unresectable UCD causes symptoms from compression of vital structures, consider medical therapy (rituximab or corticosteroids), radiotherapy, or embolization to render the mass amenable to surgical resection 2
• For unresectable UCD patients with inflammatory syndrome, siltuximab (anti-IL-6 monoclonal antibody) should be considered as systemic therapy 2

Multicentric Castleman Disease (MCD)

MCD requires stratification into HHV-8-associated and idiopathic forms, as treatment differs significantly between these subtypes.

HHV-8-Associated MCD

Rituximab monotherapy is the recommended first-line treatment for HHV-8-associated MCD. 1

• For severe cases, add etoposide to rituximab therapy 1
• For patients with concomitant Kaposi sarcoma, use cytotoxic chemotherapy in combination with rituximab 1
• Antiretroviral therapy must always be administered in HIV-positive patients with HHV-8-associated MCD 1
• Clinical follow-up every 3-6 months is required to monitor for disease relapse, development of non-Hodgkin lymphoma, and reactivation or progression of Kaposi sarcoma 1

Idiopathic Multicentric Castleman Disease (iMCD)

Siltuximab (anti-IL-6 monoclonal antibody) with or without corticosteroids is the preferred first-line therapy for iMCD. 3

• If siltuximab is unavailable, tocilizumab (another anti-IL-6 agent) is an acceptable alternative 3
• For severe cases with marked inflammation or inadequate response to IL-6 blockade, use triple therapy with corticosteroids, rituximab, and cyclophosphamide 1, 4
• In the most severe presentations, adjuvant combination chemotherapy should be added to first-line therapy 3

Second-line and third-line therapies for treatment failures include:

• Rituximab monotherapy (if not used in first-line) 5, 3
• Immunomodulatory drugs, particularly thalidomide or lenalidomide, which show efficacy even in rituximab-resistant cases 6
• Combination chemotherapy regimens such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) 6
• Avoid bortezomib-based regimens as first-line due to induced neuropathy risk, despite high response rates 7

Special Clinical Scenarios

POEMS Syndrome with Castleman Disease

For localized disease with solitary or limited sclerotic bone lesions, radiation therapy is the definitive first-line treatment, achieving 97% 4-year overall survival. 7

• For disseminated POEMS-Castleman disease, use systemic chemotherapy followed by autologous stem cell transplantation 7
• Melphalan-dexamethasone achieves 81% hematologic response and 100% improvement in neuropathy 7
• Lenalidomide-dexamethasone is preferred in patients with pre-existing neuropathy due to lower neurotoxicity risk 7
• Do not use radiation alone for disseminated disease—systemic therapy is mandatory 7
• Neurologic improvement significantly lags behind hematologic response, with maximum neurologic response expected after 2-3 years; continue treatment even without immediate neurologic improvement 7

Renal Complications

• For patients with monoclonal immunoglobulin deposition disease (MIDD) components, bortezomib-based regimens may be considered despite neuropathy concerns, as they lead to deep and rapid responses 4
• Evaluate for kidney transplantation in severe renal impairment, but defer until disease is in complete remission 4

Refractory Cytopenias

• Splenectomy may be considered in cases with severe refractory anemia and thrombocytopenia 1

Pediatric Considerations

Interferon-based therapies and anakinra are recommended for pediatric Castleman disease, with 68% 5-year survival reported with modern therapies. 1

• Corticosteroid monotherapy has been successful in isolated pediatric cases 1
• Direct implementation of Langerhans cell histiocytosis protocols has been unsuccessful 1
• Treatment should be continued indefinitely if tolerated 1

Critical Monitoring Requirements

• HIV testing is recommended for all patients with Castleman disease 1
• Laboratory evaluation should include complete blood count with differential, inflammatory markers, and HHV-8 testing 1
• Rituximab treatment reduces but does not eliminate the risk of non-Hodgkin lymphoma—the risk remains high and requires ongoing surveillance 1
• For POEMS-Castleman disease, monitor serum VEGF levels as a marker of disease activity and treatment response 7