SYLVANT® (siltuximab) is licensed for the treatment of adult patients with MCD who are HIV negative and HHV-8 negative.6
The efficacy and safety of SYLVANT® in symptomatic idiopathic Multicentric Castleman Disease (iMCD) was assessed in a Phase 2, multinational, randomised (2:1), double-blind, placebo-controlled study.6, 7 This pivotal trial compared the percentage of patients who achieved a durable tumour and symptomatic response (primary endpoint) in SYLVANT® (+ best supportive care [BSC]) and placebo (+ BSC) treatment groups.6, 7 Additional clinical and quality of life measures were included as secondary endpoints.
See Study Design
In general, patient baseline characteristics (including histological subtype) were well balanced between the treatment groups (Table 4).6 However the SYLVANT® group included a lower proportion of males than the placebo group.
Table 4: Baseline characteristics8
Significantly more iMCD patients receiving SYLVANT® (+ BSC) achieved a durable tumour and symptomatic response
(primary endpoint) than patients receiving placebo (+ BSC)8
The median duration of a durable tumour and symptomatic response with SYLVANT® (+BSC) was 383 days (range 232 – 676).8
Individual components of the primary endpoints were assessed as secondary endpoints. Significantly more patients receiving SYLVANT® (+BSC) vs those patients receiving placebo (+BSC) achieved a durable or complete symptomatic response (Figure 4). Individual components of the primary endpoints were assessed as secondary endpoints. More patients receiving SYLVANT® (+BSC) vs those patients receiving placebo (+BSC) achieved a durable or complete symptomatic response (Figure 4). For the 30 patients who achieved a durable symptomatic response with SYLVANT® (+BSC), the median time to response was 33 days.8 Time to durable symptomatic response was not evaluable for the placebo (+BSC) treatment arm. Time to durable symptomatic response was not evaluable for the placebo (+BSC) treatment arm.
In addition more patients receiving SYLVANT® (+BSC) achieved a partial or complete tumour response compared to those
receiving placebo (+BSC) (Figure 4).
Figure 4: Percentage of patients achieving primary and key secondary endpoints8
* p < 0.005.
† By independent review
An open label, non-randomised Phase 2 extension study assessed the long-term safety and efficacy of SYLVANT® in 60 patients with MCD (41 were recruited from the pivotal study; 19 from an additional phase 1 study).6,9 After a median of 6 years of follow-up, none of the 60 patients had died.
6. SYLVANT® Summary of Product Characteristics (2019).
7. Janssen Research & Development LLC. 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.