Denileukin Diftitox-cxdl (Lymphir)

Number: 1070

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses denileukin diftitox-cxdl (Lymphir) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of denileukin diftitox-cxdl (Lymphir) is required of all Aetna participating providers and members in applicable plan designs. For precertification of denileukin diftitox-cxdl (Lymphir), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   Cutaneous T-cell lymphoma

   Aetna considers denileukin diftitox-cxdl (Lymphir) medically necessary for treatment of stage I-III cutaneous T-cell lymphoma.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of denileukin diftitox-cxdl (Lymphir) therapy medically necessary in members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Denileukin diftitox-cxdl is available as Lymphir 300 mcg lyophilized cake in a single-dose vial for injection.

The recommended dosage and administration of Lymphir for the treatment of relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) is as follows:

• Delay start of treatment cycle if serum albumin level is below 3 g/dL.
• Administer Lymphir 9 mcg/kg/day actual body weight as an intravenous infusion on Days 1 through 5 of a 21-day cycle.
• Administer premedication as recommended.
• Refer to full prescribing information for preparation and administration instructions.

Source: Citius Pharmaceuticals, 2024

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96365 – 96368	Intravenous infusion administration
96413 - 96417	Intravenous chemotherapy administration
HCPCS codes covered for indications listed in the CPB:
J9161	Injection, denileukin diftitox-cxdl, 1 mcg
ICD-10 codes covered for indications listed in the CPB (not all-inclusive):
C84.A0 – C84.A9, C84.AA	Cutaneous T-cell lymphoma [Stage I-III]
C86.30 - C86.31	Subcutaneous panniculitis-like T-cell lymphoma [Stage I-III]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications

• Adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

Compendial Uses 

• Mycosis fungoides (MF) – primary treatment

Denileukin diftitox-cxdl is available as Lymphir (Citius Pharmaceuticals, Inc., 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 (Met₁-Thr₃₈₇)-His and the sequence for human interleukin-2 (IL-2; Ala₁-Thr₁₃₃). It is designed to direct the cytocidal action of diphtheria toxin (DT) to cells which express the IL-2 receptor. Following uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Lymphir has shown the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors (Citius Pharmaceuticals, 2024).

According to the prescribing information, Lymphir carries the following boxed warning of capillary leak syndrome (CLS), including life-threatening or fatal reactions. Monitor patients for signs and symptoms of CLS during treatment. Withhold Lymphir until CLS resolves or permanently discontinue based on severity.

Lymphir carries the following warnings and precautions:

• Visual impairment: Monitor and evaluate for visual impairment throughout treatment. Withhold Lymphir until visual impairment resolves or permanently discontinue based on severity.
• Infusion-related reactions: Monitor patients closely during infusions. Interrupt or discontinue for infusion-related reactions based on severity.
• Hepatotoxicity: Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.
• Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

Additionally, 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.

According to information on the Drugs.com website, on August 8, 2024, the U.S. Food and Drug Administration (FDA) approved Lymphir (denileukin diftitox-cxdl) for the treatment of of patients with relapsed or refractory (r/r) cutaneous T-cell lymphoma (CTCL) after at least 1 prior therapy. The FDA approval was based on supporting data from Study 302.

In Study 302, an open-label, single-arm, multicenter trial, investigators evaluated Lymphir (denileukin diftitox-cxdl) in patients with relapsed or refractory Stage I to IV CTCL. The study patients received a median number of 4 prior therapies (range: 1 to 18), including both skin-directed and systemic therapies. Patients received an intravenous infusion of Lymphir 9 mcg/kg daily from Day 1 through Day 5 of each 21-day cycle. Patients continued Lymphir treatment until disease progression or unacceptable toxicity. The primary efficacy population included 69 patients with relapsed or refractory Stage I to III CTCL and the primary efficacy outcome measure was objective response rate (ORR). The ORR was 36% (95% confidence interval [CI]: 25, 49), with 9% achieving a complete response (CR). The median time to response was 1.4 months (range: 0.7 to 5.6 months) and among responders, the median follow-up for duration of response was 6.5 months (range 3.5+, 23.5+ months). The duration of response was at least 6 months for 52% of patients and at least 12 months for 20% of patients.

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References