Commercial

Medical Policy

Notification

Leuprolide (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

Notification Issue Date:

This version of the policy will become effective 03/08/2021.

This policy has been updated to communicate the coverage position of leuprolide acetate (Fensolvi), represented by HCPCS J1950. Additionally, the medical necessity criteria have been revised to reflect the updated coverage position from the National Comprehensive Cancer Network (NCCN) for endometriosis, head and neck cancers, ovarian cancer, and prostate cancer.

Title:

Leuprolide (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

Policy #:

08.01.33l

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

COMPANY-DESIGNATED PREFERRED PRODUCTS

Although there are many leuprolide products on the market (e.g., Camcevi, Eligard, Lupron Depot), there is no reliable evidence of the superiority of any one product of leuprolide compared with other products. Although Lupron Depot (leuprolide acetate) and Camcevi (leuprolide mesylate) have been approved by the US Food and Drug Administration (FDA) for prostate cancer, and Company-recognized drug compendia support the use of these for certain cancers, leuprolide acetate (Eligard and Lupron Depot 7.5 mg, represented by Healthcare Common Procedure Coding System [HCPCS] J9217) are considered to be the lower cost alternative. The Company has designated leuprolide acetate (Eligard and Lupron Depot 7.5 mg, represented by HCPCS J9217) as its preferred products for the following indications:

Prostate cancer
Salivary gland tumors

These products are less costly and at least as likely to produce equivalent therapeutic results as the nonpreferred leuprolide products, which include but are not limited to Camcevi (represented by HCPCS J1952), Lupron Depot (represented by HCPCS J1950), and any other nonpreferred leuprolide products.

The company is managing the following leuprolide acetate products only: Camcevi™, Eligard®, Fensolvi®, Lupron Depot®.

NOTE: All other uses described in this policy as Medically Necessary are eligible for coverage and are not subject to the Company-designated Preferred Product requirement.

NONPREFERRED PRODUCTS

Use of the nonpreferred leuprolide products, which include, but are not limited to, Camcevi (represented by HCPCS J1952), Lupron Depot (represented by HCPCS J1950), and any other nonpreferred leuprolide product is considered medically necessary and, therefore, covered only for individuals who are currently receiving or have previously received a nonpreferred product for the specified leuprolide indication.

If the individual has not previously received leuprolide to treat the specified indication, these nonpreferred products are only eligible for coverage when the individual has contraindication(s) or intolerance(s) to the Company-designated preferred product, leuprolide acetate (Eligard and Lupron Depot 7.5 mg, represented by HCPCS J9217).

MEDICALLY NECESSARY INDICATIONS

Leuprolide acetate/mesylate for injection is considered medically necessary and, therefore, covered when the following criteria are met:

Breast Cancer
Leuprolide acetate for injection is considered medically necessary and, therefore, covered for:

Invasive or inflammatory breast cancer treatment in premenopausal females* with hormone receptor–positive breast cancer in combination with any of the following:
- Adjuvant endocrine therapy
- Endocrine therapy for recurrent unresectable (local or regional) or stage IV (M1) disease

Central Precocious Puberty

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for children with a clinical diagnosis of central precocious puberty confirmed by all of the following criteria:

An increased pubertal luteinizing hormone response to a GnRH stimulation test
A bone age greater than at least 1 year compared to chronological age

Endometriosis

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for a maximum of 6 months for initial treatment and a maximum of 6 months for retreatment (total 12 months) for the following:

Management of endometriosis, including pain relief and reduction of endometriotic lesions
Initial management of endometriosis and for management of recurrence of symptoms with norethindrone acetate, 5 mg daily

Head and Neck Cancers

Salivary Gland Tumors
Leuprolide acetate for injection is considered medically necessary and, therefore, covered as a single agent or in combination with abiraterone + prednisone for the treatment of androgen receptor–positive recurrent disease with either of the following:

Distant metastases in individuals with a performance status (PS) of 0–3
Unresectable locoregional recurrence or second primary with prior radiation therapy

Gender Dysphoria: Male-to-female

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for puberty suppression when all of the following criteria are met:

The adolescent has met the definition of gender nonconformity, gender incongruence, gender dysphoria, or is gender diverse.

If an individual has a diagnosis of gender dysphoria, the gender dysphoria has emerged or worsened with the onset of puberty.

The individual has reached at least Tanner stage 2 of development.

Note: Subject to the terms, conditions, and limitations of the member’s contract, oral and self-administered hormones are not covered under the medical benefit.

Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for hormone therapy as a single agent for persistent disease or recurrence of ovarian cancer/fallopian tube cancer/primary peritoneal cancer (endometrioid, serous), carcinosarcoma (malignant mixed Müllerian tumors), clear cell carcinoma of the ovary, grade 1 endometrioid carcinoma, mucinous carcinoma of the ovary when one of the following criteria are met:

For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)

For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)

For complete remission and relapse less than 6 months after completing chemotherapy (platinum-resistant disease)

For radiographic and/or clinical relapse in individuals with previous complete remission and relapse 6 months or longer after completing prior chemotherapy (platinum-sensitive disease)
As a single agent for clinical relapse in individuals with stage II–IV granulosa-cell tumors
Hormone therapy for low-grade serous carcinoma (serous, borderline epithelial), as a single agent for platinum-sensitive or platinum-resistant recurrence (if an aromatase inhibitor was given previously)

Prostate Cancer

Leuprolide acetate/mesylate for injection is considered medically necessary and, therefore, covered for:

Treatment (including palliative treatment) for individuals with advanced prostate cancer
Adjuvant ADT as a single agent or in combination with a first-generation antiandrogen, with external beam radiation therapy (EBRT) if adverse features (i.e., positive margins, seminal vesicle invasion, extracapsular extension, or detectable prostate-specific antigen [PSA]) noted after radical prostatectomy (RP) for individuals:

In the low-risk group^† and ≥10-year expected survival
With or without pelvic lymph node dissection (PLND) and no lymph node metastases in the favorable or unfavorable intermediate-risk group^† and >10-year expected survival
With PLND and no lymph node metastases in the high- or very-high-risk group^† or regional risk group (any T, N1, M0) and >5-year expected survival or symptomatic

Adjuvant ADT as a single agent or in combination with a first-generation antiandrogen, without EBRT if lymph node metastasis found during PLND for individuals:

In the favorable or unfavorable intermediate-risk group^† and >10-year expected survival
In the high or very-high-risk groups^† and >5-year expected survival or symptomatic
In the regional-risk group (any T, N1, M0) and >5-year expected survival or symptomatic

ADT as one of the following:

A single agent if life expectancy ≤5 years and symptomatic, may be considered in selected patients with very-low-, low-, and intermediate-risk disease
A single agent if life expectancy ≤5 years and asymptomatic, may be considered as initial therapy in selected patients with high- or very-high-risk disease where complications such as hydronephrosis or metastasis can be expected within 5 years
Initial therapy as a single agent (with or without EBRT), in combination with first-generation antiandrogen (with or without EBRT), or in combination with either abiraterone (preferred with EBRT) (excluding fine-particle formulation) with concurrent steroids (prednisone or methylprednisolone) in patients with regional-risk disease (Any T, N1, M0) and life expectancy > 5 years or symptomatic
Initial therapy as a single agent for patients in the regional risk group (Any T, N1, M0) and life expectancy ≤5 years and asymptomatic

ADT for individuals with life expectancy >5 years or symptomatic and one of the following:

In combination with radiation therapy (RT) as a single agent or in combination with a first-generation antiandrogen for 4-6 months for patients in the unfavorable intermediate-risk group
In combination with RT as a single agent or in combination with a first-generation antiandrogen for patients in the high- or very-high-risk group
In combination with RT and either abiraterone excluding fine particle formulation with concurrent steroids (prednisone or methylprednisolone) for patients in the very-high-risk group only
In combination with EBRT as a single agent, in combination with a first generation antiandrogen, or in combination with either abiraterone (preferred) or fine-particle abiraterone with concurrent steroid (prednisone or methylprednisolone) for patients in the regional risk group (Any T, N1, M0)

ADT as a single agent or in combination with a first-generation antiandrogen for one of the following:

M0 PSA persistence/recurrence after radical prostatectomy in combination with EBRT if studies negative for pelvic nodal recurrence and distant metastases ± positive fossa recurrence or imaging not performed and life expectancy >5 years (NCCN preferred)
M0 PSA persistence/recurrence after radical prostatectomy in combination with EBRT with or without abiraterone (excluding fine-particle formulation) with concurrent steroids (prednisone or methylprednisolone) if studies are positive for pelvic nodal recurrence and life expectancy >5 years
M0 PSA recurrence or positive digital rectal examination (DRE) after RT if studies negative for regional lymph nodes and distant metastases and life expectancy >5 years
Given with or without abiraterone (excluding fine-particle formulation) with concurrent steroids (prednisone or methylprednisolone) for M0 PSA recurrence or positive DRE after RT if studies positive for regional lymph nodes and life expectancy >5 years

Initial ADT with EBRT as a single agent or in combination with a first-generation antiandrogen if life expectancy >5 years or symptomatic and one of the following:
- For 4–6 months with or without brachytherapy for individuals in the unfavorable intermediate-risk group^†
- For 1.5–3 years for individuals in the high or very-high-risk group^†
- For 2 years of ADT in combination with abiraterone for individuals in the very-high-risk group^† only
- For 1–3 years with brachytherapy for individuals in the high or very-high-risk group^†
- For individuals in the regional risk group (any T, N1, M0) as a single agent, in combination with a first-generation antiandrogen, or in combination with abiraterone with concurrent steroid (prednisone or methylprednisolone) (NCCN-preferred regimen)
Single-agent treatment for individuals who progressed on observation of localized disease
For M1 castration-sensitive disease and one of the following:

As a single agent as ADT monotherapy if clear contraindications to combination therapy
In combination with docetaxel plus either abiraterone (NCCN preferred) (excluding fine-particle formulation) with concurrent steroids (prednisone or methylprednisolone) or darolutamide (NCCN preferred) for high-volume synchronous or metachronous metastases
In combination with either apalutamide or enzalutamide (Xtandi) (both NCCN preferred) for high-volume synchronous or metachronous metastases, or low-volume synchronous or metachronous metastases
In combination with abiraterone (and prednisone) for high-volume synchronous or metachronous metastases, or low-volume synchronous or metachronous metastases (NCCN preferred)
With EBRT to the primary tumor as a single agent or in combination with a first-generation antiandrogen alone
With EBRT to the primary tumor in combination with either abiraterone or fine particle abiraterone with concurrent steroids (prednisone or methylprednisolone) for low-volume synchronous metastases with low metastatic burden

For progressive M0 castration-sensitive prostate cancer (CSPC) after maximal pelvic therapy and one of the following:
- As a single agent
- In combination with a first-generation antiandrogen
- In combination with enzalutamide (Xtandi)
For M0 or M1 castration-resistant disease as ADT to maintain castrate levels of serum testosterone (<50 ng/dL)
For N0M0 second biochemical recurrence (BCR2) CSPC for any of the following:
- as a single agent
- in combination with a first-generation antiandrogen
- in combination with enzalutamide (high-risk* BCR2 only)
As ADT (with or without a first generation antiandrogen) in combination with metastasis-directed therapy (MDT) for BCR2 if N1M0 or metachronous oligometastatic CSPC
For M1 CSPC as a single agent (if clear contraindications to combination therapy) or in combination with a first-generation antiandrogen

*Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis.

^†According to NCCN guidelines:

Very low risk refers to individuals with clinical stage T1c, Grade Group 1, PSA <10 ng/mL, fewer than three prostate biopsy fragments/cores positive with 50% or less cancer in each fragment/core, and PSA density <0.15 mg/mL/g.
Low risk refers to individuals with clinical stage T1 to T2a, Grade Group 1, and PSA <10 ng/mL.
Intermediate risk refers to individuals
- Who have no high- or very-high-risk features and one or more intermediate-risk factors (IRF):
  - Clinical stage T2b to T2c
  - Grade Group 2 or 3
  - PSA 10 ng/mL to 20 ng/mL
- Favorable intermediate risk refers to individuals with 1 IRF, Grade Group 1 or 2, and <50% biopsy cores positive.
- Unfavorable intermediate risk refers to individuals with two or three IRFs, and/or Grade Group 3, and/or ≥50% biopsy cores positive
High risk refers to individuals who have no very-high-risk features and have at least one high-risk feature:

Clinical stage T3a, Grade Group 4 or 5, or PSA greater than 20 ng/mL

Very-high-risk refers to individuals with clinical stage T3b to T4 , or primary Gleason pattern 5, or two to three high-risk features, or more than four biopsy cores with grade Group 4 or 5

Uterine Leiomyomata (Uterine Fibroids)

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for the preoperative hematologic improvement of individuals with anemia caused by uterine leiomyomata concomitantly with iron therapy. According to the FDA-approved label, duration of therapy should be limited to up to 3 months.

Uterine Neoplasms

Leuprolide acetate for depot injection is considered medically necessary in combination with anastrozole, letrozole or exemestane in individuals who are premenopausal and not suitable for surgery (BSO) preferably with small tumor volume or an indolent growth pace and, therefore, covered for the treatment of any of the following:

low-grade endometrial stromal sarcoma (ESS) (NCCN - preferred)
adenosarcoma without sarcomatous overgrowth (NCCN - preferred)
estrogen receptor/progesterone receptor positive (ER/PR+) uterine sarcomas

As additional therapy following total hysterectomy with bilateral salpingo-oophorectomy (TH + BSO) for stage II-IV low-grade ESS or adenosarcoma without sarcomatous overgrowth.

NOT MEDICALLY NECESSARY 

The Company's products contain a definition of medical necessity that includes a requirement that a service not be more costly than an alternative service that is at least as likely to produce equivalent therapeutic or diagnostic results for the treatment of an individual's illness.

Although Lupron Depot (leuprolide acetate) has been approved by the FDA for prostate cancer and Compendia support the use of lupron Depot for multiple types of cancers, Eligard (leuprolide acetate) is considered to be the lower cost alternative.

For individuals receiving their first course of leuprolide for the following indications, use of Lupron Depot (represented by HCPCS J1950) is considered not medically necessary and, therefore, not covered for the following indications because it is more costly than the preferred product that is at least as likely to produce equivalent therapeutic results for that individual's condition.

Prostate cancer
Salivary gland tumors

For individuals receiving their first course of leuprolide for the following indications, use of leuprolide acetate (Fensolvi, represented by HCPCS J1951) is considered not medically necessary and, therefore, not covered for the following indications because it is more costly than the preferred products and at least as likely to produce equivalent therapeutic results for that individual's condition.

Breast cancer

Endometriosis

Gender dysphoria

Ovarian cancer/fallopian tube cancer/primary peritoneal cancer

Prostate cancer

Salivary gland tumors

Uterine leiomyomata (uterine fibroids)

Uterine Neoplasms

For individuals receiving their first course of leuprolide for the following indications, use of leuprolide mesylate (Camcevi, represented by HCPCS J1952) is considered not medically necessary and, therefore, not covered for the following indications because it is more costly than the preferred products and at least as likely to produce equivalent therapeutic results for that individual's condition.

Breast cancer

Central precocious puberty

Endometriosis

Gender dysphoria

Ovarian cancer/fallopian tube cancer/primary peritoneal cancer

Prostate cancer

Salivary gland tumors

Uterine leiomyomata (uterine fibroids)

Uterine Neoplasms

EXPERIMENTAL/INVESTIGATIONAL

All other uses for gonadotropin-releasing hormone agonist (Camcevi, Eligard, Fensolvi, Lupron Depot) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

MANDATES

PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

GLEASON SCORE

The Gleason score is a grading system for prostate cancer tissue. This score is determined by characterizing the prostate cancer cells on a grade scale of 1 (most differentiated) to 5 (least differentiated) based on the appearance under a microscope. The two most prevalent grades are added up to equal the Gleason score. Generally, prostate cancer with a Gleason score of 2–4 is considered well-differentiated or low grade; Gleason score 5–7 is considered moderately differentiated; Gleason score 8–10 is considered poorly differentiated or high grade.

GRADE GROUP

A revised grading system for prostate cancer tissue was created at the 2014 International Society of Urological Pathology Consensus Conference, which further assigns Grade Groups, derived from the Gleason Score.

Grade Group	Gleason Score	Gleason Pattern
1	≤ 6	≤ 3 + 3
2	7	3 + 4
3	7	4 + 3
4	8	4 + 4, 3 + 5, 5 + 3
5	9 or 10	4 + 5, 5 + 4, 5 + 5

TANNER SCALE

Tanner score is a scale of progression through puberty. Male individuals are rated for genital development and pubic hair growth. Female individuals are rated for breast development and pubic hair growth. Male and female individuals are categorized into one of five stages: Stage 1 (preadolescent) to Stage 5 (adult).

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, gonadotropin-releasing hormone agonist (Camcevi, Eligard, Fensolvi, Lupron Depot) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

However, drugs that are identified in this policy with uses that are considered not medically necessary are not eligible for coverage or reimbursement by the Company.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Leuprolide acetate (Eligard) for injection, 7.5 mg for 1-month administration, 22.5 mg for a 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration was approved by the FDA in January 2002 for palliative treatment of advanced prostate cancer. In July 2023, the prescribing information was revised from "palliative treatment" to "treatment" of advanced prostatic cancer. The safety and effectiveness of leuprolide acetate (Eligard) for injection in pediatric individuals have not been established.

Leuprolide acetate (Fensolvi) for injection, 45 mg for 6-month administration, was approved by the FDA on May 1, 2020, for treatment of children with central precocious puberty. The safety and effectiveness in pediatric individuals below the age of 2 years have not been established; therefore, its use in children under 2 years is not recommended.

Leuprolide acetate (Lupron Depot) for injection, 7.5 mg for 1-month administration, 22.5 mg for a 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration was approved by the FDA in January 1989 for palliative treatment of advanced prostate cancer. In 2022, the prescribing information for was revised from "palliative treatment" to "treatment" of advanced prostatic cancer.

Leuprolide acetate (Lupron Depot) for injection, 3.75 mg for 1-month administration and 11.25 mg for 3-month administration, was approved by the FDA in October 1990 for:

Management of endometriosis, including pain relief and reduction of endometriotic lesions
Preoperative hematologic improvement of individuals with anemia caused by uterine leiomyomata

Leuprolide acetate (Lupron Depot-PED) for injection was approved by the FDA in April 1993 for treatment of children with central precocious puberty. The safety and effectiveness in pediatric individuals below the age of 1 year have not been established; therefore, its use in children under 1 year is not recommended.

Leuprolide mesylate injectable emulsion, for subcutaneous (SC) use (Camcevi), 42 mg for a 6-month administration, was approved by the FDA on May 25, 2021, for treatment of adults with advanced prostate cancer. Leuprolide mesylate long-acting injectable (LAI) emulsion, in a prefilled syringe (Camcevi ETM) for SC use, was approved by the FDA on August 28, 2025. The recommended dosage is 21 mg administered every 3 months, as a treatment for advanced prostate cancer. The safety and effectiveness in pediatric individuals has not been established.

Description

Gonadotropin-releasing hormone (GnRH) analogue is a 10-amino-acid peptide that stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH directly increases its own receptor number by pulsatile secretion. GnRH analogues have a greater potency than the natural hormone and have a longer half-life. Initially, GnRH analogues stimulate the secretion of FSH and LH. With a continued secretion of GnRH analogues there is a decrease in the GnRH receptors leading to a decrease in FSH and LH secretion.

LEUPROLIDE ACETATE/MESYLATE

Leuprolide acetate (Lupron Depot) is a synthetic

nonapeptide analogue of the naturally occurring GnRH. Leuprolide binds to

gonadotropin (GnRH) receptors in the anterior pituitary gland. This initially causes a surge in LH and FSH — known as the “flare effect.” The continuous administration results in suppression of ovarian and testicular steroidogenesis. This induces a

hypogonadal state, which is therapeutically beneficial in hormone-sensitive conditions like prostate cancer, endometriosis, and central precocious puberty. Leuprolide acetate is available in multiple depot formulations (SC or IM) with various dosing intervals. Leuprolide

mesylate (

Camcevi) is a leuprolide injectable emulsion for subcutaneous use.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Services (AHFS) Drug Information 2023. Leuprolide Acetate. [Lexi-Comp website]. 01/11/2021. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed October 28, 2024.

American Association of Gynecologic Laparoscopists (AAGL): Advancing minimally invasive gynecology worldwide. AAGL Practice Report: Practice guidelines for the diagnosis and management of submucous leiomyomas. J Minim Invasive Gynecol. 2012;19(2):152-171.

Burstein H, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline update on ovarian suppression. J Clin Oncol. 2016;34(14):1689-1701.

Camcevi (leuprolide) injectable emulsion, for subcutaneous use. Accord BioPharma Inc.; Durham, NC. 05/2021. Available at: https://www.camcevi.com/. Accessed October 28, 2024.

Clowse M, Behera M, Anders C, et. al. Ovarian preservation of GnRH agonists during chemotherapy: a meta-analysis. J Womens Health. 2009;18(3):311-319.

ECRI Institute. Hormonal treatment with GnRH analogues to suppress puberty in transgender children and adolescents. Plymouth Meeting (PA): ECRI Institute; 2016 Jun 20. (Custom Rapid Responses).

Eligard (Leuprolide acetate for injectable suspension). Tolmar Pharmaceuticals, Inc. 07/2023. Available at: http://eligard.com/. Accessed October 28, 2024.

Elsevier's Clinical Pharmacology Compendium. Leuprolide. [ClinicalKey Web site]. 07/27/2023. Available at: https://www.clinicalkey.com/pharmacology/. [via subscription only]. Accessed October 28, 2024.

Fensolvi. (Leuprolide acetate for injectable suspension). Tolmar Pharmaceuticals, Inc; Fort Collins, CO. 11/2022. Available at: https://fensolvi.com/. Accessed October 28, 2024.

Guss C, Shumer D, Katz-Wise S. Transgender and gender nonconforming adolescent care: Psychosocial and medical considerations. Curr Opin Pediatr. 2015;26(4):421-426.

Hembree W, Cohen-Kettenis P, Delemarre-van de Waal H, et al. Endocrine treatment of transsexual persons: An Endocrine Society clinical practice guidelines. J Clin Endocrinol Metab.2009;94(9):3132-3154.

Lexi-Drugs Compendium. Leuprolide. [Lexicomp Online Web site]. 08/23/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed October 28, 2024.

Lexi-Drugs Compendium: Pediatric and Neonatal. Leuprolide. [Lexicomp Online Web site]. 08/23/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed October 28, 2024.

Lupron Depot® (Leuprolide acetate for depot suspension). AbbVie Inc. Prostate Cancer Indications: Updated 04/2022. Endometriosis and Fibroid Indications: 11.25 mg updated 03/2020; 3.75 mg updated 01/2023. Available at: http://www.lupron.com/. Accessed October 28, 2024.

Lupron Depot-PED® (Leuprolide acetate for depot suspension). AbbVie Inc. 04/2023. Available at: http://www.lupron.com/. Accessed October 28, 2024.

Micromedex® Healthcare Series. Leuprolide Acetate. [Micromedex Web site]. Last modified 08/12/2023. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed October 28, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Leuprolide acetate, Leuprolide acetate for depot suspension, Leuprolide mesylate. [NCCN Web site]. 2024. Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed October 28, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Breast Cancer V5.2024. 10/15/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf [via subscription only]. Accessed October 28, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Head and Neck Cancers V5.2024. 10/24/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf [via subscription only]. Accessed October 28, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Ovarian Cancer V3.2024. 07/15/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf [via subscription only]. Accessed October 28, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Prostate Cancer V4.2024. 05/17/2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf [via subscription only]. Accessed October 28, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Uterine Neoplasms. V3.2025. 03/07/2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf [via subscription only]. Accessed October 13, 2025.

Rugo H, Rumble B,

Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline. J Clin Oncol. 2016;34(25):3069-3103.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT 3.75 mg) prescribing information. [FDA Web site]. 01/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed October 16, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT 7.5, 22.5, 30, 45 mg) prescribing information. [FDA Web site]. 03/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed October 16, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT 11.25 mg) prescribing information. [FDA Web site]. 03/2020. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed October 16, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT-PED) prescribing information. [FDA Web site]. 04/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed October 16, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for injectable suspension, subcutaneous (Fensolvi) prescribing information. [FDA Web site]. 11/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed October 16, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate (ELIGARD) prescribing information. [FDA Web site]. Revised 05/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed October 16, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide injectable emulsion, for subcutaneous use (Camcevi) prescribing information. [FDA Web site]. 03/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed October 16, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide injectable emulsion, for subcutaneous use (Camcevi ETM) prescribing information. [FDA Web site]. 08/2025. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219745s000lbl.pdf. Accessed October 14, 2025.

World Professional Association for Transgender Health (WPATH). Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. 09/15/2022. Available at: https://www.wpath.org/publications/soc. Accessed October 28, 2024.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

See Attachments A, B, C, and D.

HCPCS Level II Code Number(s)

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT LUPRON DEPOT

J1950 Injection, leuprolide acetate (for depot suspension), per 3.75mg

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT FENSOLVI

J1951 Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT CAMCEVI

J1952 Leuprolide injectable, camcevi, 1 mg

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT ELIGARD AND LUPRON DEPOT

J9217 Leuprolide acetate (for depot suspension), 7.5 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.01.33l:

12/29/2025

This version of the policy will become effective 12/29/2025.

The following policy criteria have been revised in accordance with National Comprehensive Cancer Network (NCCN) guidelines:

Head and Neck Cancers
Prostate Cancer

The following policy criterion has been added in accordance with NCCN:

Uterine Neoplasms

The title of the policy was changed as follows:

FROM: Leuprolide Acetate (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

TO: Leuprolide (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

Camcevi™ ETM 21 mg, a newly FDA-approved 3-month formulation for advanced prostate cancer, has been added to the policy.

The following ICD-10 CM codes have been removed from this policy, due to laterality/specificity of codes:

C50.A0 Malignant inflammatory neoplasm of unspecified breast

The following ICD-10 CM codes have been added to this policy as medically necessary for LEUPROLIDE ACETATE 3.75 mg (J1950) and Leuprolide acetate (for depot suspension), 7.5 mg (J9217) and NOT medically necessary for Fensolvi (J1951) and Camcevi (J1952) :

C50.A1 Malignant inflammatory neoplasm of right breast
C50.A2 Malignant inflammatory neoplasm of left breast
C54.0 Malignant neoplasm of isthmus uteri
C54.3 Malignant neoplasm of fundus uteri
C54.8 Malignant neoplasm of overlapping sites of corpus uteri
C54.9 Malignant neoplasm of corpus uteri, unspecified
C55 Malignant neoplasm of uterus, part unspecified

Revisions From 08.01.33k:

10/01/2025

This version of the policy will become effective 10/01/2025.

The following ICD-10 CM codes have been added to this policy as medically necessary for LEUPROLIDE ACETATE 3.75 mg (J1950) and Leuprolide acetate (for depot suspension), 7.5 mg (J9217) and NOT medically necessary for Fensolvi (J1951) and Camcevi (J1952):

C50.A0 Malignant inflammatory neoplasm of unspecified breast
C50.A1 Malignant inflammatory neoplasm of right breast
C50.A2 Malignant inflammatory neoplasm of left breast

Revisions From 08.01.33j:

01/06/2025

This version of the policy will become effective 01/06/2025.

This policy was updated to communicate the Company's coverage position for leuprolide products (Camcevi, Eligard, Fensolvi, Lupron Depot), in accordance with US Food and Drug Administration (FDA), National Comprehensive Cancer Network (NCCN), and other Company-recognized Drug Compendia.

Policy criteria revisions were made to prostate cancer per NCCN and gender dysphoria to align with the gender-affirming interventions medical policy.

The title of the policy was changed as follows:

FROM: Gonadotropin-Releasing Hormone Agonist (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

TO: Leuprolide Acetate (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

The following ICD-10 CM codes have been removed from this policy, due to laterality/specificity of codes:

C50.19 C50.029, C50.119, C50.129, C50.229, C50.319, C50.329, C50.419, C50.429, C50.519, C50.529, C50.619, C50.629, C50.819, C50.829, C50.919, C50.929, C56.9, C57.00, C57.10, C57.20, N80.A49, N80.A59, and N80.A69

Revisions From 08.01.33i:

10/23/2023

This version of the policy will become effective 10/23/2023.

This policy was updated to communicate the Company's coverage position for gonadotropin-releasing hormone agonist (Camcevi, Eligard, Fensolvi, Lupron Depot), in accordance with US Food and Drug Administration (FDA), National Comprehensive Cancer Network (NCCN), and other Company-recognized Drug Compendia.

Policy criteria revisions were made to ovarian cancer and prostate cancer per National Comprehensive Cancer Network (NCCN).

Revisions From 08.01.33h:

01/02/2023

This version of the policy will become effective 01/02/2023.

This policy was updated to communicate the Company's coverage position for Gonadotropin-Releasing Hormone Agonist (Camcevi, Eligard, Fensolvi, Lupron Depot), in accordance with US Food and Drug Administration (FDA), National Comprehensive Cancer Network (NCCN), and other Company-recognized Drug Compendia.

Policy criteria revisions were made to inflammatory breast cancer, ovarian cancer, and prostate cancer, per US Food and Drug Administration (FDA) labeling or National Comprehensive Cancer Network (NCCN).

The coverage positions were added/revised for the following HCPCS codes:

J1950 Lupron Depot: Coverage changed from NOT Medically Necessary to Medically Necessary for Breast cancer and Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancers. Added NOT Medically Necessary coverage for prostate cancer.
J1951 Fensolvi: Coverage changed from Medically Necessary to NOT Medically Necessary for Endometriosis, uterine fibroids, gender dysphoria, since not clinically appropriate per Drug Compendia. Added NOT Medically Necessary coverage for prostate cancer.
J1952 Camcevi: Added NOT Medically Necessary coverage for all indications listed in the policy, due to the Company's Benefit language definition for Medical Necessity.

The following HCPCS code has been added to this policy:

J1952 Leuprolide injectable, camcevi, 1 mg

The following ICD-10 CM codes have been added to this policy as Medically Necessary for LEUPROLIDE ACETATE 3.75 mg (J1950):

C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.021, C50.022, C50.029, C50.111,

C50.112, C50.119, C50.121, C50.122, C50.129, C50.211, C50.212, C50.219, C50.221,

C50.222, C50.229, C50.311, C50.312, C50.319, C50.321, C50.322, C50.329, C50.411 ,

C50.412, C50.419, C50.421, C50.422, C50.429, C50.511, C50.512, C50.519,

C50.521, C50.522, C50.529, C50.611, C50.612, C50.619, C50.621, C50.622, C50.629,

C50.811, C50.812, C50.819, C50.821, C50.822, C50.829, C50.911, C50.912, C50.919,

C50.921, C50.922, C50.929, C56.1, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02,

C57.10, C57.11, C57.12, C57.20, C57.21, C57.22, C57.3, C57.4, C79.81, C79.82

The following ICD-10 codes have been added to this policy as Not Medically Necessary for LEUPROLIDE ACETATE 3.75 mg (J1950):

C07 Malignant neoplasm of parotid gland
C08.0 Malignant neoplasm of submandibular gland
C08.1 Malignant neoplasm of sublingual gland
C08.9 Malignant neoplasm of major salivary gland, unspecified
C61 Malignant neoplasm of prostate

The following ICD-10 CM code coverage has revised in this policy From Medically Necessary TO NOT Medically Necessary for LEUPROLIDE ACETATE 0.25 mg (J1951) Fensolvi:

D25.0, D25.1, D25.2, D25.9, E22.8, F64.0, F64.1, F64.2, F64.8, F64.9, N80.0, N80.6, N80.8, N80.9, N80.101, N80.102, N80.103, N80.111, N80.112, N80.113, N80.121, N80.122, N80.123, N80.201, N80.202, N80.203, N80.211, N80.212, N80.213, N80.221, N80.222, N80.223, N80.30 , N80.311, N80.312, N80.319, N80.321, N80.322, N80.329, N80.331, N80.332, N80.333, N80.341, N80.342, N80.343, N80.351, N80.352, N80.353, N80.361, N80.362, N80.363, N80.371, N80.372, N80.373, N80.381, N80.382, N80.383, N80.391, N80.392, N80.399, N80.3A1, N80.3A2, N80.3A3, N80.3B1, N80.3B2, N80.3B3, N80.3C1, N80.3C2, N80.3C3, N80.40 , N80.41 , N80.42 , N80.50 , N80.511, N80.512, N80.519, N80.521, N80.522, N80.529, N80.531, N80.532, N80.539, N80.541, N80.542, N80.549, N80.551, N80.552, N80.559, N80.561, N80.562, N80.569, N80.A0 , N80.A1 , N80.A2 , N80.A41, N80.A42, N80.A43, N80.A49, N80.A51, N80.A52, N80.A53, N80.A59, N80.A61, N80.A62, N80.A63, N80.A69, N80.B1 , N80.B2 , N80.B31, N80.B32, N80.B39, N80.B4 , N80.B5 , N80.B6 , N80.C0 , N80.C10, N80.C11, N80.C19, N80.C2 , N80.C3, N80.C4 , N80.C9, N80.D0, N80.D1, N80.D2, N80.D3, N80.D4, N80.D5, N80.D6, N80.D9.

The following ICD-10 codes have been added to this policy as Not Medically Necessary for LEUPROLIDE ACETATE 0.25 mg (J1951) Fensolvi:
C07, C08.0, C08.1, C08.9, C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.021, C50.022, C50.029, C50.111, C50.112, C50.119, C50.121, C50.122, C50.129, C50.211, C50.212, C50.219, C50.221, C50.222, C50.229, C50.311, C50.312, C50.319, C50.321, C50.322, C50.329, C50.411, C50.412, C50.419, C50.421, C50.422, C50.429, C50.511, C50.512, C50.519, C50.521, C50.522, C50.529, C50.611, C50.612, C50.619, C50.621, C50.622, C50.629, C50.811, C50.812, C50.819, C50.821, C50.822, C50.829, C50.911, C50.912, C50.919, C50.921, C50.922, C50.929, C56.1, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02, C57.10, C57.11, C57.12, C57.20, C57.21, C57.22, C57.3, C57.4, C61, C79.81, C79.82.

The following ICD-10 codes have been added to this policy as Not Medically Necessary for J1952 Camcevi:

C07, C08.0, C08.1, C08.9, C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.021, C50.022, C50.029, C50.111, C50.112, C50.119, C50.121, C50.122, C50.129, C50.211, C50.212, C50.219, C50.221, C50.222, C50.229, C50.311, C50.312, C50.319, C50.321, C50.322, C50.329, C50.411, C50.412, C50.419, C50.421, C50.422, C50.429, C50.511, C50.512, C50.519, C50.521, C50.522, C50.529, C50.611, C50.612, C50.619, C50.621, C50.622, C50.629, C50.811, C50.812, C50.819, C50.821, C50.822, C50.829, C50.911, C50.912, C50.919, C50.921, C50.922, C50.929, C56.1, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02, C57.10, C57.11, C57.12, C57.20, C57.21, C57.22, C57.3, C57.4, C61, C79.81, C79.82, D25.0, D25.1, D25.2, D25.9, E22.8, E30.1, F64.0, F64.1, F64.2, F64.8, F64.9, N80.0, N80.6, N80.8, N80.9, N80.101, N80.102, N80.103, N80.111, N80.112, N80.113, N80.121, N80.122, N80.123, N80.201, N80.202, N80.203, N80.211, N80.212, N80.213, N80.221, N80.222, N80.223, N80.30 , N80.311, N80.312, N80.319, N80.321, N80.322, N80.329, N80.331, N80.332, N80.333, N80.341, N80.342, N80.343, N80.351, N80.352, N80.353, N80.361, N80.362, N80.363, N80.371, N80.372, N80.373, N80.381, N80.382, N80.383, N80.391, N80.392, N80.399, N80.3A1, N80.3A2, N80.3A3, N80.3B1, N80.3B2, N80.3B3, N80.3C1, N80.3C2, N80.3C3, N80.40 , N80.41 , N80.42 , N80.50 , N80.511, N80.512, N80.519, N80.521, N80.522, N80.529, N80.531, N80.532, N80.539, N80.541, N80.542, N80.549, N80.551, N80.552, N80.559, N80.561, N80.562, N80.569, N80.A0 , N80.A1 , N80.A2 , N80.A41, N80.A42, N80.A43, N80.A49, N80.A51, N80.A52, N80.A53, N80.A59, N80.A61, N80.A62, N80.A63, N80.A69, N80.B1 , N80.B2 , N80.B31, N80.B32, N80.B39, N80.B4 , N80.B5 , N80.B6 , N80.C0 , N80.C10, N80.C11, N80.C19, N80.C2 , N80.C3 , N80.C4 , N80.C9 , N80.D0 , N80.D1 , N80.D2 , N80.D3 , N80.D4 , N80.D5 , N80.D6 , N80.D9.

Revisions From 08.01.33g:

10/01/2022

This version of the policy will become effective 10/01/2022.

The following ICD-10 CM codes have been termed (no longer valid codes) and removed from this policy:

N80.1 Endometriosis of ovary, N80.2 Endometriosis of fallopian tube, N80.3 Endometriosis of pelvic peritoneum, N80.4 Endometriosis of rectovaginal septum and vagina, N80.5 Endometriosis of intestine

The following ICD-10 CM codes have been added to this policy: N80.101, N80.102, N80.103, N80.111, N80.112, N80.113, N80.121, N80.122, N80.123, N80.201, N80.202, N80.203, N80.211, N80.212, N80.213, N80.221, N80.222, N80.223, N80.30, N80.311, N80.312, N80.319, N80.321, N80.322, N80.329, N80.331, N80.332, N80.333, N80.341, N80.342, N80.343, N80.351, N80.352, N80.353, N80.361, N80.362, N80.363, N80.371, N80.372, N80.373, N80.381, N80.382, N80.383, N80.391, N80.392, N80.399, N80.3A1, N80.3A2, N80.3A3, N80.3B1, N80.3B2, N80.3B3, N80.3C1, N80.3C2, N80.3C3, N80.40, N80.41, N80.42, N80.50, N80.511, N80.512, N80.519, N80.521, N80.522, N80.529, N80.531, N80.532, N80.539, N80.541, N80.542, N80.549, N80.551, N80.552, N80.559, N80.561, N80.562, N80.569, N80.A0, N80.A1, N80.A2, N80.A41, N80.A42, N80.A43, N80.A49, N80.A51, N80.A52, N80.A53, N80.A59, N80.A61, N80.A62, N80.A63, N80.A69, N80.B1, N80.B2, N80.B31, N80.B32, N80.B39, N80.B4, N80.B5, N80.B6, N80.C0, N80.C10, N80.C11, N80.C19, N80.C2, N80.C3, N80.C4, N80.C9, N80.D0, N80.D1, N80.D2, N80.D3, N80.D4, N80.D5, N80.D6, N80.D9.

Revisions From 08.01.33f:

10/25/2021

This version of the policy will become effective 10/25/2021.

This policy was updated to communicate the Company's coverage position for Gonadotropin-Releasing Hormone Agonist (Eligard®, Fensolvi®, Lupron Depot®), in accordance with US Food and Drug Administration (FDA) and National Comprehensive Cancer Network (NCCN).

The following criteria have been added to this policy:

Inflammatory breast cancer

The following policy criteria have been revised:

Revisions made to Ovarian cancer, per NCCN.

Extensive revisions made to Prostate cancer, per NCCN.

Revisions From 08.01.33e:

10/01/2021

This policy has been identified for the ICD-10 CM code update, effective 10/01/2021.

The following ICD-10 CM code has been added to this policy for HCPCS J9217:

C56.3 Malignant neoplasm of bilateral ovaries

Revisions From 08.01.33d:

07/01/2021

This policy has been updated to communicate the HCPCS code change for leuprolide acetate (Fensolvi).

The following HCPCS code has been removed from this policy for leuprolide acetate (Fensolvi) and is replaced by the following HCPCS code:

FROM: J1950 Injection, leuprolide acetate (for depot suspension), per 3.75 mg
TO: J1951 Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg

Note: J1950 will continue to represent Lupron Depot 3.75 mg

Revisions From 08.01.33c:

03/08/2021

This policy has been updated to communicate the coverage position of leuprolide acetate (Fensolvi), represented by HCPCS J1950. Additionally, the medical necessity criteria have been revised to reflect the updated coverage position from the National Comprehensive Cancer Network (NCCN) for endometriosis, head and neck cancers, ovarian cancer, and prostate cancer.

Revisions From 08.01.33b:

12/02/2019

This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the updated coverage position from the National Comprehensive Cancer Network (NCCN) for head and neck cancers, breast cancer, ovarian cancer, and prostate cancer. Criteria changes have been made for the coverage of gender dysphoria.

Revisions From 08.01.33a:

02/19/2018

This policy has undergone a routine review, and the medical necessity criteria have been revised for the indication of Prostate Cancer.

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

12/29/2025

Version Issued Date:

12/29/2025

Version Reissued Date: