What is the preferred initial treatment for idiopathic multicentric Castleman disease when both rituximab (Rituxan) and tocilizumab (Actemra) are not affordable?

Management of Idiopathic Multicentric Castleman Disease When Rituximab and Tocilizumab Are Not Affordable

When both rituximab and tocilizumab are not affordable for a patient with idiopathic multicentric Castleman disease (iMCD), cyclophosphamide-based therapy is the recommended alternative treatment option. 1

First-line Treatment Options When Anti-IL6 Therapy is Not Available

Cyclophosphamide-Based Regimens

• Cyclophosphamide can be administered as part of combination chemotherapy regimens for iMCD patients 1
• In severe cases, etoposide can be added to cyclophosphamide to control the cytokine storm 1
• Cyclophosphamide has demonstrated efficacy in stabilizing or improving forced vital capacity (FVC) in various systemic autoimmune diseases, suggesting potential benefit in controlling the inflammatory component of iMCD 1

Corticosteroids

• Corticosteroids can be used as part of combination therapy with cyclophosphamide 1
• However, corticosteroid monotherapy has shown poor response rates (only 3% response) in iMCD and should not be used as the sole treatment 2
• Short-term corticosteroid use may help manage acute symptoms while initiating other therapies 1

Second-line Options

Azathioprine

• Azathioprine can be considered as an alternative immunosuppressive agent when other options are not available 1
• It has been supported as a first-line option for interstitial lung disease in various systemic autoimmune conditions, which shares some pathophysiologic features with iMCD 1

More Aggressive Chemotherapy

• CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen can be considered in refractory disease 1
• This approach should be reserved for patients who fail to respond to less intensive therapies 1

Combination Approaches for Severe Disease

Cyclophosphamide with Etoposide

• For patients with severe disease manifestations, combining cyclophosphamide with etoposide may provide more rapid disease control 1
• This combination can help manage the cytokine storm that characterizes severe iMCD 1

Bortezomib-Based Regimens

• Recent evidence suggests bortezomib-dexamethasone combinations may be effective in iMCD 3
• In a small study, rituximab-bortezomib-dexamethasone (RVD) showed promising results with all patients achieving at least partial response 3
• If bortezomib is available and affordable, it could be considered with dexamethasone alone when rituximab is not an option 3

Monitoring and Follow-up

• Clinical, virological, and biochemical responses should be regularly monitored during treatment 1
• Radiological evaluation using CT or PET-CT should be performed after completion of therapy 1
• Follow-up every 3-6 months is recommended to monitor for disease recurrence 1
• Patients should be educated about symptoms of relapse and instructed to seek immediate medical attention if these occur 1

Important Considerations and Pitfalls

• Anti-IL6 therapy (siltuximab or tocilizumab) remains the gold standard first-line treatment with significantly better outcomes than alternatives 2
• Consider exploring patient assistance programs or compassionate use programs to access rituximab or tocilizumab before resorting to alternative therapies 2
• Avoid corticosteroid monotherapy as it has shown extremely poor response rates (3%) compared to anti-IL6 therapy (52%) 2
• Be vigilant for development of secondary malignancies, particularly lymphomas, which remain a risk in iMCD patients 1
• Consider the patient's comorbidities when selecting cyclophosphamide, as it carries risks of infection, cytopenias, hemorrhagic cystitis, and infertility 1