CurrentAnthemPolicy CC-0175

Proleukin (aldesleukin) — Clinical Coverage Criteria

Clinical coverage criteria for use of Proleukin (aldesleukin) under the medical benefit, specifying eligible indications, performance status requirements, pediatric combination use, and conditions that make therapy non‑approvable. Applies to Anthem members and their providers.

Policy Summary

PayerAnthem

PolicyProleukin (aldesleukin) — Clinical Coverage Criteria

Policy CodePolicy CC-0175

Change TypeNo material change

Effective Date07/01/2025

Next Review Date

Key ActionObtain prior authorization and document diagnosis and ECOG performance status 0-1 for eligible indications.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2FDA indications

0-1Required ECOG

J9015HCPCS

C43, C64, C74.90ICD-10 refs

2ANCCN citation

Coverage Criteria for Proleukin (aldesleukin)

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Approved indications

Requests for Proleukin (aldesleukin) may be approved if the following criteria are met:

Metastatic malignant melanoma

Performance status: ECOG (Eastern Cooperative Oncology Group) performance status 0-1

Metastatic renal cell cancer

Performance status: ECOG (Eastern Cooperative Oncology Group) performance status 0-1

High-risk pediatric neuroblastoma (post-induction and transplant): Individual is receiving therapy for high-risk neuroblastoma after response to induction therapy and stem cell transplantation

Must be used in combination with isotretinoin, dinutuximab, and sargramostim

Requests for Proleukin (aldesleukin) are subject to specific clinical and safety exclusions. Proleukin will not be approved for individuals with an abnormal thallium stress test or an abnormal pulmonary function test, for patients with organ allografts, or for those with active systemic infections. Requests that do not meet the listed approval criteria for covered indications (metastatic malignant melanoma, metastatic renal cell cancer with ECOG 0-1, or specified pediatric high‑risk neuroblastoma regimens) are also not approvable.

Proleukin carries black box warnings that restrict its use to administration in a hospital setting under the supervision of a qualified physician and to patients with normal cardiac and pulmonary function as defined by thallium stress testing and formal pulmonary function testing. Serious adverse effects, including capillary leak syndrome, cardiac complications, and impaired neutrophil function with increased risk of disseminated infection, require institution capability for high‑dose IL‑2 administration and close monitoring; therapy should be withheld for patients who develop moderate or severe lethargy or somnolence because of risk of progression to coma.

High‑dose interleukin‑2 (IL‑2, Proleukin) has a defined but limited role in metastatic cutaneous melanoma. The NCCN guidelines provide a category 2A recommendation permitting high‑dose IL‑2 as a second‑line or subsequent single‑agent option, but emphasize it is associated with significant toxicity and requires careful patient selection and institutional capability for administration and monitoring. Because of lower response rates and higher toxicity compared with immune checkpoint inhibitors and BRAF‑targeted therapies, IL‑2 is not a preferred second‑line therapy for most patients with metastatic melanoma.

When IL‑2 is considered for melanoma, ensure the patient meets performance requirements (ECOG performance status 0–1) and that the treating center can manage the drug’s serious adverse effects. Use should be reserved for selected patients after discussion of risks, alternative systemic options (checkpoint inhibitors, targeted therapy when appropriate), and when institutional resources for high‑dose IL‑2 care are available.

Regimen	Indication / Timing	Required combination agents	Key supporting evidence / notes
Proleukin (aldesleukin) high‑dose regimen	High‑risk pediatric neuroblastoma after response to induction therapy and following autologous stem cell transplantation	Must be used in combination with isotretinoin, dinutuximab (anti‑GD2), and sargramostim	Supported by the HR‑NBL1/SIOPEN randomized phase 3 trial (Ladenstein 2018) showing use of IL‑2 with anti‑GD2 antibody in this population; Unituxin guidance and trial literature referenced in policy
Administration setting and monitoring	Post‑induction and post‑stem cell transplant pediatric setting as specified above	Administration within institutions capable of managing cytokine‑related toxicities and pediatric transplant care	Policy requires documentation of treatment timing (after induction and stem cell transplant) and concurrent use of listed agents

Relevant Billing and Diagnosis Codes

HCPCSHCPCS

J9015

Injection, aldesleukin, per single use vial

ICD-10 DiagnosisICD-10

C43.0-C43.9	Malignant melanoma of skin
C64.1-C64.9	Malignant neoplasm of kidney
C74.90	Malignant neoplasm of unspecified part of unspecified adrenal gland

Provider Requirements and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Approval is limited to the specific indications and conditions described below; requests that do not meet all listed criteria may be denied.

HCPCS: J9015
ICD-10: C43.0-C43.9, C64.1-C64.9, C74.90

Note

Place in Therapy Considerations

Place in therapy considerations: NCCN provides a category 2A recommendation for high‑dose IL-2 (Proleukin) as a single‑agent option for metastatic or unresectable cutaneous melanoma as second‑line or subsequent therapy, but notes high toxicity and the need for careful patient selection and administration in specialized centers. IL-2 is generally not a preferred second‑line option because immune checkpoint inhibitors and BRAF‑targeted therapies are considered more effective and safer. NCCN also gives a category 2A recommendation for use in steroid‑refractory chronic GVHD after HSCT in select settings, but recommends participation in clinical trials and current evidence is insufficient to add this indication to covered criteria.

Documentation Required

Required Clinical Documentation

Required clinical documentation must support the diagnosis, ECOG performance status, and indication-specific eligibility. For metastatic melanoma or renal cell carcinoma include relevant pathology/imaging confirming metastatic disease and documentation of ECOG 0-1. For pediatric high‑risk neuroblastoma include documentation of response to induction therapy, stem cell transplantation, and that Proleukin will be given in combination with isotretinoin, dinutuximab, and sargramostim per regimen.

Denial Risk

Non-Approvable Conditions / Denial Risks

Non-approvable conditions — therapy may be denied if any of the following are present: abnormal thallium stress test, abnormal pulmonary function tests, organ allograft, active systemic infection, development of moderate or severe lethargy or somnolence, or when the criteria above are not met. Proleukin use is restricted to administration in a hospital setting under supervision of a qualified physician per boxed warnings.

Approved Regimens and Combinations

Component	Agent / Dose example (per source)	Role in regimen	Coverage status
Interleukin‑2	Proleukin (aldesleukin) — high‑dose IL‑2 as used in combination regimens (per trial protocols)	Immune‑stimulatory cytokine used to augment anti‑GD2 antibody activity	covered
Anti‑GD2 monoclonal antibody	Dinutuximab (ch14.18) or dinutuximab beta as used in HR‑NBL1/SIOPEN	Targeted antibody directed at GD2 on neuroblastoma cells	covered
Isotretinoin	Oral isotretinoin used as differentiation therapy in maintenance	Differentiation agent used as part of post‑consolidation/maintenance therapy	covered
Sargramostim	GM‑CSF (sargramostim) as used to stimulate myeloid recovery and enhance immunotherapy	Adjunct to enhance immune response and support hematopoiesis	covered

Line of Therapy Considerations

Second-line therapy

Second-line or subsequent therapy for metastatic/unresectable cutaneous melanoma: NCCN permits high-dose IL-2 (Proleukin) as second-line or subsequent single-agent therapy for metastatic or unresectable cutaneous melanoma (Category 2A), but it is not a preferred option due to significant toxicities and lower response rates compared with immune checkpoint inhibitors or BRAF-targeted therapies

Requires careful patient selection and institutional capability for high-dose IL-2 administration

Definitions

Melanoma

DefinitionMelanoma: A type of cancer that begins in the melanocytes; also referred to as malignant melanoma or cutaneous melanoma.

Primary cell typeOriginates in melanocytes (pigment-producing skin cells)

Alternate namesMalignant melanoma; cutaneous melanoma

Metastasis

DefinitionMetastasis: The spread of cancer from one part of the body to another; a metastatic tumor contains cells similar to the original (primary) tumor.

ImplicationIndicates cancer has spread beyond the primary site to distant organs or tissues

Tumor compositionMetastatic tumors contain cells that are like those in the primary tumor

Background

Proleukin (aldesleukin) is a recombinant interleukin‑2 (IL‑2) cytokine that exerts antitumor effects by interacting with IL‑2 receptors to induce proliferation and differentiation of immune cells, including B and T lymphocytes. The FDA‑approved indications are metastatic renal cell cancer and metastatic melanoma. Administration is limited to the hospital setting under physician supervision because of serious toxicities; the product’s boxed warnings require use only in patients with normal cardiac and pulmonary function as defined by thallium stress testing and formal pulmonary function testing, and identify risks such as capillary leak syndrome and impaired neutrophil function.