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 2
- Test for HHV-8 in all MCD cases 1, 2
- Test for HIV in all patients 1, 2
- Screen for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) 1, 3
- Obtain complete blood count with differential and inflammatory markers 1, 2
Unicentric Castleman Disease (UCD)
Surgical resection is the definitive treatment and is curative for UCD. 1, 4 Complete excision of the involved lymph node provides excellent prognosis with durable remissions. 4, 5
Multicentric Castleman Disease (MCD) - Treatment Algorithm by Subtype
HHV-8-Associated MCD
Rituximab monotherapy is the first-line treatment for HHV-8-associated MCD. 1, 2 The American College of Oncology specifically recommends this approach. 1, 2
- For severe cases, add etoposide to rituximab 2
- For patients with concomitant Kaposi sarcoma, use cytotoxic chemotherapy 2
- Always administer antiretroviral therapy in HIV-positive patients with HHV-8-MCD 2
- Rituximab reduces non-Hodgkin lymphoma incidence, though risk remains elevated 1, 2
Idiopathic MCD (iMCD)
Siltuximab (anti-IL-6 monoclonal antibody) at 11 mg/kg IV every 3 weeks is the preferred first-line therapy for idiopathic MCD. 6, 7 If siltuximab is unavailable, tocilizumab is an acceptable alternative. 7
Treatment criteria before each dose: 6
- Absolute neutrophil count ≥1.0 × 10⁹/L
- Platelet count ≥50 × 10⁹/L (≥75 × 10⁹/L for first dose)
- Hemoglobin <17 g/dL
- No severe active infections
For severe cases with inadequate response to IL-6 blockade:
- Add corticosteroids to siltuximab 2, 7
- Consider triple therapy with corticosteroids, rituximab, and cyclophosphamide 2
Do not reduce the siltuximab dose; delay treatment if criteria not met. 6
POEMS-Associated MCD
The treatment approach differs dramatically based on disease extent:
For localized disease (solitary or limited sclerotic bone lesions):
- Radiation therapy is the definitive first-line treatment, achieving 97% 4-year overall survival 3
- Improvement occurs in 50-70% of patients 3
For disseminated disease:
- Systemic chemotherapy followed by autologous stem cell transplantation is recommended 1, 3
- Melphalan-dexamethasone achieves 81% hematologic response and 100% improvement in neuropathy 3
- Lenalidomide-dexamethasone is preferred in patients with existing neuropathy due to lower neurotoxicity risk 3
- Autologous stem cell transplantation should be offered after induction chemotherapy, achieving 100% clinical improvement in eligible patients 1, 3
Critical pitfall: Do not use radiation alone for disseminated POEMS-MCD—systemic therapy is mandatory. 3
Avoid bortezomib-based regimens as first-line due to induced neuropathy risk, despite high response rates. 3
Monitoring and Follow-up
Clinical follow-up every 3-6 months is essential for all MCD patients, monitoring for: 1, 2
- Disease relapse
- Development of non-Hodgkin lymphoma (risk remains elevated even with treatment)
- Reactivation or progression of concomitant Kaposi sarcoma
For POEMS-associated disease:
- Monitor serum VEGF levels as a disease activity marker 1, 3
- Neurologic improvement significantly lags behind hematologic response—maximum neurologic response expected after 2-3 years of successful therapy 3
- Continue treatment even if immediate neurologic improvement is not apparent 3
- Perform hematology laboratory tests prior to each siltuximab dose for the first 12 months, then every 3 dosing cycles 6
Prognosis
- UCD: Excellent prognosis with surgical resection 4, 5
- POEMS-associated MCD: 68% 5-year survival with modern therapies, particularly interferon-based treatment 1, 2
- HHV-8-MCD: Improved outcomes with rituximab and antiretroviral therapy 8
- iMCD: Variable, but improved with anti-IL-6 therapies 7, 8