Brand name: Lymphir™
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Introduction

Denileukin diftitox-cxdl, a recombinant DNA-derived fusion protein, is an IL2-receptor-directed cytotoxin.

Uses for Denileukin diftitox-cxdl

Denileukin has the following uses:

Denileukin diftitox-cxdl is indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

Denileukin diftitox-cxdl Dosage and Administration

General

Denileukin diftitox-cxdl is available in the following dosage form(s) and strength(s):

For injection: 300 mcg lyophilized cake in a single-dose vial for reconstitution and further dilution.

Dosage

Adults

Dosage and Administration

• Prior to starting each treatment cycle, assess hepatic and renal function. If serum albumin is less than 3 g/dL, delay administration until serum albumin is greater than or equal to 3 g/dL.

• The recommended dosage of denileukin diftitox-cxdl is 9 mcg/kg/day actual body weight administered as an IV infusion on Days 1 through 5 of a 21-day treatment cycle. Administer denileukin diftitox-cxdl until disease progression or unacceptable toxicity.

• Reconstitute and further dilute denileukin diftitox-cxdl prior to administration. Administer as an IV infusion over 60 minutes through an IV line using a syringe pump or IV infusion bag.

• Administer premedications as recommended.

• See full prescribing information for preparation and administration instructions, and dosage modification recommendations for adverse reactions.

Cautions for Denileukin diftitox-cxdl

Contraindications

None.

Warnings/Precautions

Warnings

Capillary Leak Syndrome

Denileukin diftitox-cxdl can cause capillary leak syndrome (CLS), including life-threatening or fatal reactions. CLS was defined in clinical trials as the occurrence of at least 2 of the following symptoms at any time during denileukin diftitox-cxdl therapy: hypotension, edema, and serum albumin <3 g/dL. These symptoms were not required to occur simultaneously to be characterized as CLS. As defined, CLS occurred in 27% of patients in the pooled population across 3 clinical trials, including 8% with Grade 3. There was one (0.8%) fatal occurrence of CLS. Of the patients with CLS, 22% had recurrence. The majority of CLS events (81%) occurred within the first 2 cycles of treatment. The median time to onset from Cycle 1, Day 1 was 6.5 days (range: 1 to 77), the median duration of CLS was 14 days (range: 2 to 40), and 75% of patients had resolution. The most common symptoms included edema, hypoalbuminemia, and hypotension. Pleural effusion, pericardial effusion, and dehydration also occurred. Regularly assess patients for weight gain, new onset or worsening of edema, dyspnea, and hypotension (including orthostatic changes). Monitor serum albumin levels prior to the initiation of each cycle of therapy and more often as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity. If denileukin is withheld, resume denileukin diftitox-cxdl following resolution of CLS and when serum albumin is greater than or equal to 3 g/dL.

Visual Impairment

Denileukin diftitox-cxdl can cause serious visual impairment, including changes in visual acuity and color vision. In the pooled population across 3 clinical trials, visual impairment occurred in 9%, with Grade 1 in 8% and Grade 2 in 1%. The most commonly reported symptom was blurred vision. Of the patients with visual impairment, 67% had resolution of their visual impairment. Perform baseline ophthalmic examination and monitor as clinically indicated. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, or blurred vision, refer for ophthalmologic evaluation. Withhold denileukin diftitox-cxdl until visual impairment resolves or permanently discontinue based on severity.

Infusion-related Reactions

Denileukin diftitox-cxdl can cause serious infusion-related reactions. Infusion-related reactions were reported in 69% of patients in the pooled population across 3 clinical trials of patients who received denileukin diftitox-cxdl, with Grade 3 infusion-related reactions in 3.4%. Eighty-three percent of infusion-related reactions occurred in Cycles 1 and 2. The most common symptoms included nausea, fatigue, chills, musculoskeletal pain, vomiting, fever, and arthralgia. Premedicate patients for the first three cycles prior to starting a denileukin diftitox-cxdl infusion. Monitor patients frequently during infusion. For Grade 2 or higher infusion reactions, premedicate at least 30 minutes prior to each subsequent infusion with a systemic steroid for at least 3 cycles. Interrupt or discontinue denileukin diftitox based on severity. Institute appropriate medical management.

Hepatotoxicity

Denileukin diftitox-cxdl can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 70% of patients, with Grade 3 ALT occurring in 22%; elevated AST occurred in 64% of patients, with Grade 3 AST elevation occurring in 9%. For Grade 3 events, median time to onset was 8 days (range: 1 to 15 days); median time to resolution was 15 days (range: 7 to 50 days). All cases of Grade 3 ALT or AST elevations resolved. Elevated total bilirubin occurred in 5% of patients, with Grade 3 occurring in 0.9%. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold, reduce dose, or permanently discontinue denileukin diftitox based on severity.

Embryo-Fetal Toxicity

Based on its mechanism of action, denileukin diftitox-cxdl can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiation of therapy. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 days following the last dose of denileukin diftitox-cxdl.

Specific Populations

Pregnancy

Based on its mechanism of action, denileukin diftitox-cxdl can cause fetal harm when administered to a pregnant woman. There are no available data on the use of denileukin diftitox-cxdl in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with the drug. Denileukin diftitox-cxdl causes depletion of regulatory T lymphocytes (Treg), immune activation, and capillary leak syndrome, compromising pregnancy maintenance. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Lactation

No data are available regarding the presence of denileukin diftitox-cxdl in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with denileukin diftitox-cxdl and for 7 days after the last dose.

Females and Males of Reproductive Potential

Based on its mechanism of action, denileukin diftitox-cxdl can cause fetal harm when administered to a pregnant woman. Based on findings in rats, male fertility may be compromised by treatment with denileukin diftitox-cxdl. The reversibility of the effect on fertility is unknown.

Pediatric Use

Safety and effectiveness of denileukin diftitox-cxdl in pediatric patients have not been established.

Geriatric Use

Of the 69 patients with Stage I-III relapsed or refractory CTCL who received denileukin diftitox-cxdl, 34 patients (49%) were 65 years of age and older and 10 patients (14%) were 75 years of age and older. Clinical studies of denileukin diftitox-cxdl did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

Common Adverse Effects

The most common adverse reactions (≥20%), including laboratory abnormalities, are increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments.

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Denileukin diftitox-cxdl is a fusion protein designed to direct the cytocidal action of diphtheria toxin (DT) to cells which express the IL-2 receptor. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors.

Advice to Patients

• Inform patients of the signs and symptoms of capillary leak syndrome. Advise patients to contact their healthcare provider immediately if any signs or symptoms of capillary leak syndrome occur, including edema or change in blood pressure. Instruct patients to weigh themselves daily and report weight gain.

• Inform patients that if they experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, or blurred vision, they should report it promptly.

• Inform patients of the signs and symptoms of infusion-related reactions. Advise patients to contact their healthcare provider immediately if any signs or symptoms of infusion-related reaction occur, including fever, chills, breathing problems, chest pain, or hives.

• Advise patients that liver enzyme elevations can occur and that they should report symptoms that may indicate liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.

• Advise pregnant women and female patients of reproductive potential of the potential risk to a fetus. Advise female patients of reproductive potential to inform their healthcare provider of a known or suspected pregnancy and to use effective contraception for 7 days after the last dose.

• Advise women not to breastfeed during treatment with denileukin diftitox-cxdl and for 7 days after the last dose.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Denileukin diftitox Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There are 2 for denileukin diftitox.

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