DENILEUKIN DIFTITOX-CXDL INJ,LYPHL
Clinical Criteria Summary
Indication & Patient Population
- Adults with relapsed or refractory (R/R) stage I–III cutaneous T-cell lymphoma (CTCL)
- Requires at least one prior systemic therapy
Disease Staging Criteria
- TNMB Staging System for CTCL characterized by 4 sites: skin (T), lymph nodes (N), blood (B), visceral organs (M)
- Early stage (IA–IIA):
- IA: patches/plaques < 10% BSA, no nodal, visceral or blood component
- IB: patches/plaques > 10% BSA, no extracutaneous disease
- IIA: patches/plaques + N1-2 lymph nodes
- Advanced stage (IIB–IV):
- IIB: tumors (> 1 cm) with/without N1-2 nodes
- IIIA: erythroderma (> 80% BSA) w/o blood involvement
- IIIB: erythroderma with low blood burden (B1)
- IVA1: high blood burden (B2) = Sezary Syndrome
- IVA2: N3 lymph node involvement
- IVB: visceral involvement, M1a (bone marrow only) or M1b (visceral organs)
Dosing & Administration Criteria
- 9 mcg/kg/day actual body weight IV over 60 minutes on Days 1 through 5 of a 21-day treatment cycle
- Continue administration until disease progression or unacceptable toxicity
- Premedications required for cycles 1–3: acetaminophen, diphenhydramine, antiemetic agents, and hydration about 30 minutes before each infusion; optional from cycle 4 onward
Safety Monitoring & Dose Modification Criteria
- Dosage modifications required for capillary leak syndrome (CLS), visual impairment, infusion-related reactions, hepatotoxicity, and other adverse reactions
- CLS defined as >2 of the following at any time during therapy: hypotension, edema, serum albumin < 3g/dL
- Regular assessment required for weight gain, new onset/worsening edema, dyspnea, hypotension
- Serum albumin must be monitored prior to each cycle and as clinically indicated
- Monitor for visual impairment, infusion-related reactions, hepatotoxicity (elevated ALT/AST/bilirubin), and embryofetal toxicity
Therapeutic Context & Place in Therapy
- Indicated for R/R CTCL after >1 line of therapy
- NCCN recommendations: useful for IB-IIA MF and III erythrodermic MF; preferred for IIB tumor MF
- Requires monitoring at baseline and throughout the course of therapy for capillary leak syndrome, ocular toxicity, infusion-related reactions, and hepatotoxicity
- Hematopoietic stem cell transplant noted as the only treatment with curative intent to date