What are the treatment options for Castleman's Disease?

Treatment for Castleman's Disease

The treatment approach for Castleman's disease depends fundamentally on whether the disease is unicentric or multicentric, with surgical resection being curative for unicentric disease and systemic therapy required for multicentric disease. 1

Initial Classification and Workup

Before initiating treatment, classify the disease as unicentric (UCD) or multicentric (MCD), as this determines the entire treatment strategy. 1

Essential diagnostic steps include:

• Complete blood count with differential and inflammatory markers 1
• HHV-8 testing to distinguish HHV-8-associated from idiopathic MCD 1
• HIV testing, as HIV-positive status affects treatment selection 1
• Imaging to determine extent of lymph node involvement 2

Unicentric Castleman Disease (UCD)

Surgical resection is the definitive treatment for UCD and is often curative. 3, 4

• Complete excision of the affected lymph node(s) provides excellent outcomes with minimal recurrence 4
• The hyaline vascular variant comprises approximately 75% of UCD cases and responds particularly well to surgical management 5
• No systemic therapy is typically required after complete resection 2

Multicentric Castleman Disease (MCD)

Treatment for MCD differs significantly based on HHV-8 status:

HHV-8-Associated MCD

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

• Rituximab reduces the incidence of non-Hodgkin lymphoma, though risk remains elevated 1
• For severe cases, add etoposide to rituximab 1
• If concomitant Kaposi sarcoma is present, use cytotoxic chemotherapy in addition to rituximab 1
• HIV-positive patients must receive antiretroviral therapy concurrently 1

Idiopathic MCD (iMCD)

Siltuximab (anti-IL-6 monoclonal antibody) at 11 mg/kg IV every 3 weeks is the preferred first-line therapy for iMCD. 6, 7

The FDA-approved dosing regimen for siltuximab requires:

• Administration over 1 hour as IV infusion every 3 weeks until treatment failure 6
• Pre-treatment laboratory monitoring: absolute neutrophil count ≥1.0 × 10⁹/L, platelets ≥75 × 10⁹/L (≥50 × 10⁹/L for retreatment), hemoglobin <17 g/dL 6
• Hematology testing prior to each dose for the first 12 months, then every 3 cycles 6
• Do not administer during severe infections 6

Alternative first-line approach if siltuximab is unavailable:

• Tocilizumab (another anti-IL-6 agent) with or without corticosteroids 7

For severe iMCD with life-threatening symptoms or inadequate response to IL-6 blockade:

• Triple therapy with corticosteroids, rituximab, and cyclophosphamide 1, 8
• This combination addresses severe inflammation more aggressively 8

Second and Third-Line Therapies

When first-line therapy fails, the international consensus guidelines recommend tailoring treatment by disease severity, though specific agents should be selected based on individual response patterns and toxicity profiles. 7

Special Clinical Scenarios

Severe refractory cytopenias:

• Consider splenectomy for severe refractory anemia and thrombocytopenia 1

Monoclonal immunoglobulin deposition with renal failure:

• Bortezomib-based regimens may achieve rapid responses 8
• Defer kidney transplantation until complete disease remission 8

POEMS syndrome association:

• Requires specific diagnostic workup as management differs from isolated Castleman disease 1

Monitoring and Follow-Up

Clinical follow-up every 3-6 months is mandatory for all MCD patients. 1

Monitor specifically for:

• Disease relapse or progression 1
• Development of non-Hodgkin lymphoma (risk remains elevated despite rituximab) 1
• Reactivation or progression of Kaposi sarcoma in HHV-8-positive patients 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 and was not studied in these populations 6
• Do not reduce siltuximab dose; instead delay treatment if laboratory criteria are not met 6
• Discontinue siltuximab permanently for severe infusion reactions, anaphylaxis, or cytokine release syndrome 6
• Do not assume UCD based on imaging alone - histopathological confirmation with characteristic "onion skin" and "lollipop" appearances is essential 4