Patients (n=79) were randomised to SYLVANT® (n=53) or placebo (n=26) and treated until treatment failure (disease progression based on increase in symptoms, radiologic progression or deterioration in performance status) or unacceptable toxicity (Figure 5).6, 7
For inclusion, patients had to:6-8
Patients could be newly diagnosed or previously treated, except those who had previously received IL-6 targeted treatment.
Patients were excluded if they:
The primary endpoint was the percentage of patients who achieved durable tumour and symptomatic response (as assessed by an independent radiology review) defined as either a complete response or a partial response for at least 18 weeks. There was no validated criteria to evaluate iMCD. As iMCD is lymphoproliferative, the modified Cheson criteria were used (as they can be used to evaluate lymph nodes), however the criteria were adjusted to include the assessment of cutaneous lesions caused by iMCD.
Symptoms were scored using the MCD-related overall symptom score, which is the sum of the severity grades of MCD-related signs and symptoms. The percentage change from baseline in MCD-related signs and symptoms and MCD-related overall symptom score at each cycle was calculated.6 A complete response was defined as a 100% reduction from baseline in the MCD-related overall symptoms score.
Key secondary endpoints included:7,8
Figure 5: Study design
6. SYLVANT® EU Summary of Product Characteristics (Sept 2019).
7. LLC Clinical Trial. A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman’s Disease 2018 [Available from: https://clinicaltrials.gov/ct2/show/NCT01024036?term=siltuximab&recrs=e&phase=1&draw=2&rank=3.
8. Van Rhee F, Wong RS, Munshi N, Rossi JF, Ke XY, Fossa A, et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966-74
9. Van Rhee F, Casper C, Voorhees PM, Fayad LE, Gibson D, Kanhai K, et al. Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials. Lancet Haematol. 2020;7(3):e209-e217.