Treatment Approach for Castleman Disease
Initial Classification is Critical
Treatment of Castleman disease depends entirely on whether the disease is unicentric (UCD) or multicentric (MCD), and for MCD, whether it is HHV-8-associated, idiopathic, or POEMS-associated. 1, 2
Before initiating any therapy, you must:
- Classify as UCD vs MCD based on imaging showing single vs multiple lymph node regions 1, 2
- Test for HHV-8 and HIV in all MCD cases, as this fundamentally changes management 1, 2
- Obtain complete blood count, inflammatory markers, and consider POEMS workup (serum VEGF, monoclonal protein) if neuropathy or organomegaly present 1, 3
Unicentric Castleman Disease (UCD)
Surgical resection is the definitive and curative treatment for UCD. 1, 4, 5
- Complete excision of the involved lymph node provides excellent prognosis and is typically curative 1, 5
- No systemic therapy is required for localized disease 4
- Post-surgical follow-up should monitor for rare recurrence 5
HHV-8-Associated Multicentric Castleman Disease (HHV-8-MCD)
Rituximab monotherapy is the first-line treatment recommended by the American College of Oncology for HHV-8-associated MCD. 1, 2
Treatment Algorithm:
- Start rituximab monotherapy as standard first-line 1, 2
- Always add antiretroviral therapy if HIV-positive 2
- Add etoposide for severe cases or life-threatening presentations 2
- Add cytotoxic chemotherapy if concomitant Kaposi sarcoma is present 2
Critical Monitoring:
- Follow clinically every 3-6 months 1, 2
- Monitor for disease relapse, non-Hodgkin lymphoma development (risk remains elevated despite rituximab), and Kaposi sarcoma progression 1, 2
- Rituximab reduces but does not eliminate lymphoma risk 1, 2
Idiopathic Multicentric Castleman Disease (iMCD)
For HIV-negative, HHV-8-negative MCD, siltuximab (anti-IL-6 monoclonal antibody) is FDA-approved and represents the preferred first-line therapy. 6, 7
First-Line Therapy:
- Siltuximab 11 mg/kg IV every 3 weeks until treatment failure 6
- Tocilizumab is an alternative if siltuximab unavailable 7
- Corticosteroids can be added to IL-6 blockade 7
Pre-Treatment Requirements (per FDA label):
- Absolute neutrophil count ≥1.0 × 10⁹/L 6
- Platelet count ≥75 × 10⁹/L 6
- Hemoglobin <17 g/dL 6
- No active severe infections 6
Monitoring During Siltuximab:
- Check hematology labs before each dose for first 12 months, then every 3 cycles 6
- For retreatment: ANC ≥1.0 × 10⁹/L, platelets ≥50 × 10⁹/L, hemoglobin <17 g/dL 6
- Do not dose reduce—delay treatment if criteria not met 6
Second-Line for Severe or Refractory iMCD:
- Triple therapy with corticosteroids, rituximab, and cyclophosphamide for severe inflammation or inadequate IL-6 blockade response 2
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for aggressive disease 8
- Immunomodulatory drugs (thalidomide, lenalidomide) show efficacy in rituximab-resistant cases 8, 7
Critical Pitfall:
- Discontinue siltuximab permanently for severe infusion reactions, anaphylaxis, or cytokine release syndrome—do not rechallenge 6
POEMS-Associated Castleman Disease
For POEMS syndrome with Castleman disease, treatment stratification depends on whether disease is localized or disseminated. 3
Localized Disease (Solitary/Limited Sclerotic Bone Lesions):
- Radiation therapy is definitive first-line treatment 3
- Achieves 97% 4-year overall survival and 52% 4-year failure-free survival 3
- 50-70% of patients improve with radiation alone 3
Disseminated Disease:
- Systemic chemotherapy followed by autologous stem cell transplantation is recommended 1, 3
- Melphalan-dexamethasone achieves 81% hematologic response and 100% neuropathy improvement 3
- Lenalidomide-dexamethasone is preferred if significant neuropathy present (lower neurotoxicity) 3
- Autologous stem cell transplantation after induction achieves 100% clinical improvement in eligible patients 1, 3
Agents to AVOID:
- Do not use bortezomib-based regimens first-line despite high response rates—induces neuropathy 3
- Use thalidomide cautiously due to neurotoxicity, though it shows efficacy 3
- Do not use radiation alone for disseminated disease—systemic therapy is mandatory 3
Monitoring and Timeline:
- Monitor serum VEGF levels as disease activity marker 1, 3
- Neurologic improvement lags 2-3 years behind hematologic response—continue treatment even without immediate neurologic improvement 3
- Prognosis is 68% 5-year survival with modern therapies 1, 2
Special Considerations
Severe Cytopenias:
- Consider splenectomy for severe refractory anemia and thrombocytopenia 2