SILTUXIMAB INJ,LYPHL
Clinical Criteria Summary
Indication & Patient Selection
- • Diagnosis of Multicentric Castleman’s Disease (MCD)
- • ECOG Performance Status 0–2
- • Goals of care and role of palliative care consult have been discussed and documented
Exclusion Criteria / Contraindications
- • Care for the disease being treated not provided by VA or VA purchased care
- • HIV positive and/or HHV-8 positive
- • Chronic or unresolved infection
- • Hypersensitivity reaction to siltuximab or inactive ingredients (L-histidine, polysorbate 80, sucrose)
- • Severe hepatic impairment (Child-Pugh C)
- • Absolute Neutrophil Count (ANC) < 1.0 x 10^9/L prior to first dose
- • Platelet count < 75 x 10^9/L prior to first dose
- • Hemoglobin > 17 g/dL prior to first dose
Hematologic Treatment Criteria (Subsequent Doses)
- • ANC > 1.0 x 10^9/L
- • Platelet count > 50 x 10^9/L
- • Hemoglobin < 17 g/dL
- • If criteria are not met, consider delaying treatment; do not reduce dose
Monitoring & Safety Requirements
- • Perform hematologic lab tests prior to each siltuximab dose for the first 12 months and every 3 dosing cycles thereafter
- • Monitor therapeutic effect or drug concentration for concurrent CYP450 substrate therapies with narrow therapeutic indices (e.g., warfarin, cyclosporine, theophylline) upon initiation/discontinuation and as needed; adjust dose accordingly
- • Exercise caution when co-administered with CYP3A4 substrate drugs (e.g., oral contraceptives, lovastatin, atorvastatin) due to potential reduced efficacy
- • Inform patients to notify provider immediately if signs/symptoms suggestive of infection develop
- • Monitor for signs/symptoms of allergic reactions during infusion (difficulty breathing, chest tightness, wheezing, severe dizziness/light-headedness, swelling of lips or skin rash)
- • Monitor for signs/symptoms of infusion-related reactions (back pain, chest pain/discomfort, nausea/vomiting, flushing, erythema, palpitations)
- • Use cautiously in patients at risk of GI perforation; immediately evaluate if symptoms suggestive of GI perforation present
- • Assess disease response or progression via radiographic scan or symptomatology prior to each cycle and every 3 months
Discontinuation Recommendations
- • Patient develops signs of anaphylaxis during the infusion
- • Persistent, severe infusion-related reactions despite adequate premedication (antihistamines, acetaminophen, corticosteroids)
- • Non-compliance with therapy, laboratory, or follow-up requests
- • Decline in ECOG performance status to level unacceptable for patient to maintain quality of life
- • Persistent or recurring toxicity despite a 3-week delay in dosing
- • Evidence of progressive disease
Special Populations & Precautions
- • Women of childbearing potential: Exclude pregnancy prior to receiving siltuximab; provide contraceptive counseling on risks vs. benefits; utilize effective contraception during and for 3 months after treatment
- • Siltuximab may mask signs/symptoms of acute inflammation via suppression of fever and acute phase reactants (e.g., C-reactive protein); should not be given to patients with severe infections
- • Live vaccines should not be administered during therapy as IL-6 inhibition may interfere with normal immune response
- • Pharmacokinetic analysis shows no significant difference in clearance in mild-moderate hepatic impairment (Child-Pugh Classes A and B)