Long-term efficacy with SYLVANT® (siltuximab)1
Disease control was defined as “stability or improvement and no worsening in hemoglobin, fatigue, anorexia, fever, weight, and size of the largest lymph node.”
Durable Disease Control With SYLVANT (N=60)a
Disease control at last on-study assessmentb
Disease control for up to 6 yearsc
Over 6 years, patients may have missed or rescheduled a dose for multiple personal or physician directed reasons. Some patients may not have received the recommended dose (11 mg/kg, every 3 weeks).
Some of these patients discontinued before the 6-year data cutoff point while others were not dosed at 3 weeks.
Patients completed the trial up to the 6-year data cutoff point.
This study confirmed the proven efficacy and safety in patients with iMCD who started and stayed on SYLVANT.1
Patients should stay on SYLVANT until disease progression2
In a SYLVANT clinical trial, a durable response rate was defined as tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure.3
The CDCN established assessment criteria for evaluating response to treatment, taking into account all features of iMCD. These include2:
Complete response requires normalization of biochemical markers, lymph node response by CT scan, and improvements in clinical symptoms.2
In patients treated with anti-IL-6 treatments, lymph node response may take several months.2
Infusion-related reactions and hypersensitivity3
If your patient has a mild to moderate infusion reaction or an allergic reaction while receiving SYLVANT, you must stop the infusion and treat their reaction. If the reaction resolves, then treatment with SYLVANT can be restarted at a lower infusion rate
If your patient has a severe infusion or allergic reaction, you must stop the treatment with SYLVANT completely
Abbreviations: CDCN, Castleman Disease Collaborative Network; CRP, C-reactive protein; CT, computed tomography; GFR, glomerular filtration rate; IL-6, interleukin 6; iMCD, idiopathic multicentric Castleman disease.
Post hoc analysis: Assessing response to SYLVANT4
A post hoc analysis was conducted in patients who achieved the primary end point of durable tumor and symptomatic response in the pivotal phase 2 trial of siltuximab.
Following are the details about time to normalization of parameters in SYLVANT responders (n=18):
aNormalized defined as ≤ upper limit of normal.
b≥50% reduction in a 34-point symptom score from baseline.
cTimes to normalization were not significantly different between the 2 treatment arms.
dNormalized defined as ≥ lower limit of normal.
e≥50% decrease in the sum of the product of the diameters from baseline.
fMaintained for at least 18 weeks.
Abbreviation: IgG, immunoglobulin G.
Early indicators of response to SYLVANT included improved thrombocytosis and symptomatic responses, which occurred as early as 1 month after starting SYLVANT. Biochemical responses were also seen within 3 months of starting SYLVANT in the majority of responders.
Lymph node responses are slower to show improvements and should not be used to drive early treatment decisions after starting SYLVANT.
Limitations: Since the evidentiary value of post hoc analyses is less than that of primary or secondary analyses, cautious interpretation of these data is advised. Presentation of these data is not intended to represent additional treatment effects of the drug.
References: 1. van Rhee F, Casper C, Voorhees PM, 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. 2. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. 3. SYLVANT [package insert]. Hertfordshire, UK: EUSA Pharma (UK) Ltd; 2019. 4. van Rhee F, Rosenthal AL, Kanhai K, et al. Siltuximab is associated with improved progression-free survival in idiopathic multicentric Castleman disease. Blood Adv. Published ahead of print July 6, 2022. doi:10.1182/bloodadvances.2022007112