What are the treatment options for Castleman disease?

Treatment of Castleman Disease

Complete surgical resection is the definitive treatment for unicentric Castleman disease (UCD) and is often curative, while multicentric Castleman disease (MCD) requires systemic therapy with rituximab as first-line for HHV-8-associated disease and siltuximab for idiopathic MCD. 1, 2, 3

Classification-Based Treatment Algorithm

Unicentric Castleman Disease (UCD)

Resectable Disease:

• Surgical excision is the preferred first-line therapy and is often curative. 1, 3
• Complete resection should be pursued whenever technically feasible, as it provides excellent long-term outcomes with remission rates approaching 100% in successfully resected cases 3

Unresectable Disease:

• Asymptomatic unresectable UCD may be observed without immediate intervention. 3
• For symptomatic unresectable UCD with inflammatory syndrome (fever, elevated inflammatory markers), siltuximab 11 mg/kg IV every 3 weeks should be considered 2, 3
• For symptomatic disease due to mass effect on vital structures, consider medical therapy (rituximab or corticosteroids), radiotherapy, or embolization to render the lesion resectable 3
• Focal radiation therapy is an alternative for localized disease that cannot be surgically removed 1

Multicentric Castleman Disease (MCD)

HHV-8-Associated MCD:

• Rituximab monotherapy is the first-line treatment at standard dosing (375 mg/m² weekly × 4-8 doses) 1, 4
• For HIV-positive patients, antiretroviral therapy must always be administered concurrently 1
• For severe cases or inadequate response, add etoposide to rituximab 1
• For patients with concomitant Kaposi sarcoma, use cytotoxic chemotherapy in combination with rituximab 1

Idiopathic MCD (iMCD):

• Siltuximab is the preferred first-line therapy for HHV-8-negative, HIV-negative patients 2, 3

  • Dosing: 11 mg/kg IV over 1 hour every 3 weeks until treatment failure 2
  • Critical prerequisite: baseline serum albumin must be ≥3.2 g/dL to initiate treatment 2
  • Monitor for capillary leak syndrome (CLS), which can be life-threatening and typically occurs during the first cycle 2
  • Replace albumin if <3.5 g/dL or if reduction ≥0.5 g/dL from baseline 2
  • Premedicate with H1-antihistamine, acetaminophen, corticosteroid, and H2-antihistamine prior to each infusion 2

• For severe inflammation or inadequate response to siltuximab, consider triple therapy with corticosteroids, rituximab, and cyclophosphamide 1

Alternative Systemic Therapies:

• Immunomodulatory drugs (thalidomide, lenalidomide) have shown efficacy, particularly thalidomide for rituximab-resistant cases 5
• R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for aggressive disease 5
• Interferon-based therapies and anakinra for pediatric cases 1

Laboratory Monitoring Requirements

Before each siltuximab dose (first 12 months, then every 3 cycles): 2

• Absolute neutrophil count ≥1.0 × 10⁹/L
• Platelet count ≥50 × 10⁹/L (≥75 × 10⁹/L for first dose)
• Hemoglobin <17 g/dL
• Serum albumin monitoring for CLS risk

Special Considerations

POEMS Syndrome with Castleman Disease:

• For localized disease: radiation therapy achieves 97% 4-year overall survival 6
• For disseminated disease: systemic chemotherapy (melphalan-dexamethasone or lenalidomide-dexamethasone) followed by autologous stem cell transplantation 6
• Avoid bortezomib-based regimens as first-line due to neuropathy risk 6
• Neurologic improvement lags 2-3 years behind hematologic response—continue treatment despite delayed neurologic recovery 6

Refractory Disease Management:

• Splenectomy may be considered for severe refractory anemia and thrombocytopenia 1
• For low performance status or albumin <3.2 g/dL: consider low-intensity therapy with venetoclax-based regimens, steroids, or supportive care 1

Surveillance and Follow-Up

All patients require: 1

• Clinical follow-up every 3-6 months
• Monitor for disease relapse, development of non-Hodgkin lymphoma (risk remains elevated despite rituximab treatment), and Kaposi sarcoma progression in HHV-8-positive patients
• Treatment should be continued indefinitely if tolerated, with 68% 5-year survival reported with modern therapies 1

Critical Pitfalls to Avoid

• Do not use siltuximab in HIV-positive or HHV-8-positive patients—it does not bind virally produced IL-6 2
• Do not administer siltuximab during severe infections; wait until resolution 2
• Discontinue siltuximab permanently for severe infusion reactions, anaphylaxis, or cytokine release syndrome 2
• Do not use radiation alone for disseminated POEMS-associated disease—systemic therapy is mandatory 6