Brand Name
Lymphir
Generic Name
Denileukin Diftitox-Cxdl
View Brand Information FDA approval date: January 23, 2025
Classification: CD25-directed Cytotoxin
Form: Injection
What is Lymphir (Denileukin Diftitox-Cxdl)?
LYMPHIR is indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma after at least one prior systemic therapy. LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma after at least one prior systemic therapy.
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Brand Information
LYMPHIR (denileukin diftitox-cxdl)
WARNING: CAPILLARY LEAK SYNDROME
Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity
1INDICATIONS AND USAGE
LYMPHIR 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.
2DOSAGE FORMS AND STRENGTHS
For injection: 300 mcg/vial, sterile, white lyophilized cake in a single-dose vial for reconstitution and further dilution.
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
- Capillary Leak Syndrome
- Visual Impairment
- Infusion-Related Reactions
- Hepatotoxicity
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to LYMPHIR as a single agent in 119 patients with CTCL across 3 clinical trials. Patients received treatment with LYMPHIR as an intravenous infusion at 9 mcg/kg daily from Day 1 through Day 5 of each 21-day cycle until disease progression or unacceptable toxicity. Among 119 patients who received LYMPHIR the median number of cycles received was 5 (range: 1 to 42), with 13% exposed for 6 months or longer.
In this pooled safety population, the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were increased transaminases (70%), albumin decreased (53%), nausea (40%), edema (35%), hemoglobin decreased (34%), fatigue (30%), musculoskeletal pain (26%), rash (23%), chills (22%), constipation (22%), pyrexia (21%), and capillary leak syndrome (20%).
Relapsed or Refractory Stage I-III CTCL
Study 302
The safety of LYMPHIR was evaluated in Study 302, an open-label, single-arm, multicenter trial that included 69 patients with relapsed or refractory Stage I-III CTCL
The median age of patients was 64 years (range: 28 to 87 years), 49% were 65 years of age or older, 65% were men, 72% were White, 19% were Black or African American, 1.4% were Asian, and 14% were Hispanic or Latino.
Serious adverse reactions occurred in 38% of patients who received LYMPHIR. Serious adverse reactions in > 2% of patients included capillary leak syndrome (10%), infusion-related reaction (9%), sepsis (7%), skin infection (2.9%), pyrexia (2.9%), and rash (2.9%).
Permanent discontinuation of LYMPHIR due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of LYMPHIR included capillary leak syndrome, infusion-related reaction, renal insufficiency, respiratory failure, and sepsis.
Dosage interruptions of LYMPHIR due to an adverse reaction occurred in 38% of patients. Adverse reactions requiring dosage interruption of LYMPHIR included capillary leak syndrome, infusion-related reaction, weight increase, nausea, and tachycardia.
Table 3 summarizes the adverse reactions in Study 302.
#Only Grade 3 adverse reaction occurred
aIncludes fatigue, asthenia, and lethargy
bIncludes edema, edema peripheral, generalized edema, face edema, swelling face, peripheral swelling
cIncludes musculoskeletal pain, back pain, neck pain, pain in extremity, myalgia, bone pain
dIncludes headache, migraine
eIncludes amnesia, confusional state, delirium, memory impairment, disturbance in attention, somnolence, cognitive disorder
fIncludes rash, drug eruption, erythema, rash maculo-papular, rash papular, rash pustular, rash pruritic, dermatitis exfoliative generalized, acute generalized exanthematous pustulosis
gIncludes skin infection, skin bacterial infection, staphylococcal skin infection, impetigo
hIncludes acute kidney injury, blood creatinine increased
aIncludes fatigue, asthenia, and lethargy
bIncludes edema, edema peripheral, generalized edema, face edema, swelling face, peripheral swelling
cIncludes musculoskeletal pain, back pain, neck pain, pain in extremity, myalgia, bone pain
dIncludes headache, migraine
eIncludes amnesia, confusional state, delirium, memory impairment, disturbance in attention, somnolence, cognitive disorder
fIncludes rash, drug eruption, erythema, rash maculo-papular, rash papular, rash pustular, rash pruritic, dermatitis exfoliative generalized, acute generalized exanthematous pustulosis
gIncludes skin infection, skin bacterial infection, staphylococcal skin infection, impetigo
hIncludes acute kidney injury, blood creatinine increased
Clinically relevant adverse reactions in < 10% of patients who received LYMPHIR included sepsis and peripheral neuropathy.
Table 4 summarizes select laboratory abnormalities in Study 302.
aGraded according to NCI CTCAE version 5.0
bThe denominator used to calculate the rate was 67 based on the number of patients with a baseline value and at least one post-treatment value
cPercentage of patients with an increase of at least 1 CTCAE grade from baseline to the worst post-baseline value of any grade, or to the worst post-baseline value that is Grade 3 or 4
dThe denominator used to calculate the rate was based on 36 patients with a baseline value and at least one post-treatment value.
bThe denominator used to calculate the rate was 67 based on the number of patients with a baseline value and at least one post-treatment value
cPercentage of patients with an increase of at least 1 CTCAE grade from baseline to the worst post-baseline value of any grade, or to the worst post-baseline value that is Grade 3 or 4
dThe denominator used to calculate the rate was based on 36 patients with a baseline value and at least one post-treatment value.
4.2Postmarketing Experience
The following adverse reactions have been identified during post-approval use of denileukin diftitox. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Thyroid conditions: hyperthyroidism, thyroiditis, thyrotoxicosis, and hypothyroidism.
5DESCRIPTION
Denileukin diftitox-cxdl, an IL2-receptor-directed cytotoxin, is a recombinant DNA-derived fusion protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met
LYMPHIR (denileukin diftitox-cxdl) for injection is supplied as a sterile, white, lyophilized cake in a single-dose vial for intravenous use after reconstitution and dilution. Each vial of LYMPHIR contains 300 mcg of denileukin diftitox-cxdl, citric acid monohydrate (4.2 mg), edetate disodium (0.04 mg), methionine (3 mg), polysorbate 20 (1.2 mg), and trehalose (100.4 mg). Sodium hydroxide is used to adjust the pH of the formulation buffer. Following reconstitution with 2.1 mL of Sterile Water for Injection, USP, the resulting concentration of denileukin diftitox-cxdl is 150 mcg/mL at pH approximately 7.
6CLINICAL STUDIES
Relapsed or Refractory CTCL
The efficacy of LYMPHIR was evaluated in Study 302 (NCT01871727), an open-label, single-arm, multicenter trial in patients with relapsed or refractory Stage I to IV CTCL. Eligible patients were required to have expression of CD25 on ≥ 20% of biopsied malignant cells by immunohistochemistry
The efficacy population includes 69 patients with relapsed or refractory Stage I to III CTCL. Of the 69 patients, the median age was 64 years (range: 28 to 87 years), 65% were male, 73% were White, 19% Black or African American, 1% Asian, and 14% Hispanic or Latino. The CTCL disease stage was IA in 7%, IB in 23%, IIA in 13%, IIB in 35%, IIIA in 12%, and IIIB in 10%. The median number of prior therapies was 4 (range: 1 to 18), including both skin-directed and systemic therapies. Prior therapies included photodynamic therapy (56%), total skin electron beam therapy (42%), systemic retinoids (49%), methotrexate/pralatrexate (49%), histone deacetylase inhibitor (35%), brentuximab vedotin (26%) and mogamulizumab (12%).
Efficacy was established based on objective response rate (ORR), according to ISCL/EORTC Global Response Score (GRS) per Independent Review Committee (Olsen 2011). Efficacy results are shown in Table 5.
aORR, objective response rate per Olsen, et al (2011) Global Response Score (GRS), by Independent Review Committee (IRC).
bCI, confidence interval
cThe median (95% CI) DOR using Kaplan-Meier (KM) estimate was not estimable (NE) among the 25 subjects due to censoring.
bCI, confidence interval
cThe median (95% CI) DOR using Kaplan-Meier (KM) estimate was not estimable (NE) among the 25 subjects due to censoring.
Median time to response was 1.4 months (range: 0.7 to 5.6 months).
Among responders, the median follow-up for duration of response was 6.5 months (range: 3.5+, 23.5+ months).
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
LYMPHIR (denileukin diftitox-cxdl) for injection is supplied as a sterile, white, lyophilized cake for reconstitution in a single-dose vial containing 300 mcg denileukin diftitox-cxdl. Each carton contains one vial:
NDC 52658-7777-1
Storage and Handling
Store LYMPHIR in a refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze.
8PATIENT COUNSELING INFORMATION
Discuss the following with patients prior to and during treatment with LYMPHIR.
Capillary Leak Syndrome
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
Visual Impairment
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
Infusion-Related Reactions
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
Hepatotoxicity
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
Embryo-Fetal Toxicity
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
Lactation
Advise women not to breastfeed during treatment with LYMPHIR and for 7 days after the last dose
Manufactured by:
LYMPHIR™ is the trademark of Citius Oncology, Inc.
© 2024 Citius Oncology, Inc.
9PRINCIPAL DISPLAY PANEL
NDC 52658-7777-1
LYMPHIR™
(denileukin diftitox-cxdl)
For Injection
300 mcg/vial
(denileukin diftitox-cxdl)
For Injection
300 mcg/vial
For Intravenous Infusion
1 Vial Rx Only
