Subject: Lupron Depot Endometriosis-Fibroid 1970-A SGM P2023

Drug

LUPRON DEPOT 3.75 mg  (leuprolide acetate for depot suspension)

LUPRON DEPOT-3 Month 11.25 mg  (leuprolide acetate for depot suspension)

Policy:

      I.  INDICATIONS

          The indications below including FDA-approved indications and
          compendial uses are considered a covered benefit provided that
          all the approval criteria are met and the member has no
          exclusions to the prescribed therapy.

          A.  FDA-Approved Indications
               1.  Endometriosis
               Lupron Depot 3.75 mg and Lupron Depot-3 Month 11.25 mg
               are indicated for management of endometriosis, including
               pain relief and reduction of endometriotic lesions. Lupron
               Depot 3.75 mg monthly and Lupron Depot-3 Month 11.25
               mg with norethindrone acetate 5 mg daily are also indicated
               for initial management of the painful symptoms of
               endometriosis and for management of recurrence of
               symptoms.

               Use of norethindrone acetate in combination with Lupron
               Depot 3.75 mg and Lupron Depot 11.25 mg is referred to as
               add-back therapy, and is intended to reduce the loss of bone
               mineral density (BMD) and reduce vasomotor symptoms
               associated with use of Lupron Depot 3.75 mg and Lupron
               Depot 11.25 mg.

               2.  Uterine Leiomyomata (Fibroids)
               When used concomitantly with iron therapy, Lupron Depot
               3.75 mg and Lupron Depot-3 Month 11.25 mg are indicated
               for preoperative hematologic improvement of women with
               anemia caused by fibroids for whom three months of
               hormonal suppression is deemed necessary. The clinician
               may wish to consider a one-month trial period on iron alone,
               as some women will respond to iron alone. Lupron Depot
               may be added if the response to iron alone is considered
               inadequate.

               Limitations of Use:
               For endometriosis: The total duration of therapy with Lupron
               Depot 3.75 mg and 11.25 mg plus add-back therapy should
               not exceed 12 months due to concerns about adverse impact
               on bone mineral density.

               For uterine leiomyomata: Lupron Depot 3.75 mg and 11.25
               mg are not indicated for combination use with norethindrone
               acetate add-back therapy for the preoperative hematologic
               improvement of women with anemia caused by heavy
               menstrual bleeding due to fibroids.

          B.  Compendial Uses
               1.  Breast cancer
               2.  Ovarian cancer – Epithelial ovarian cancer/fallopian tube
                    cancer/primary peritoneal cancer, and less common
                    ovarian cancers (grade 1 endometrioid carcinoma, low-
                    grade serous carcinoma, carcinosarcoma [malignant
                    mixed Müllerian tumors], mucinous carcinoma of the
                    ovary, or clear cell carcinoma of the ovary)
               3.  Recurrent androgen receptor positive salivary gland
                    tumors
               4.  Gender dysphoria (also known as gender non-conforming
                    or transgender persons)
               5.  Preservation of ovarian function in patients with cancer
               6.  Prevention of recurrent menstrual related attacks in acute
                    porphyria

          All other indications are considered experimental/investigational
          and not medically necessary.


    II.  PRESCRIBER SPECIALTIES

          For gender dysphoria, the medication must be prescribed by or
          in consultation with a provider specialized in the care of
          transgender youth (e.g., pediatric endocrinologist, family or
          internal medicine physician, obstetrician-gynecologist) that has
          collaborated care with a mental health provider for patients less
          than 18 years of age.


  III.  CRITERIA FOR INITIAL APPROVAL

          A.  Endometriosis
               Authorization of up to 6 months (one treatment course) may
               be granted to members for initial treatment of endometriosis.

          B.  Uterine leiomyomata (fibroids)
               Authorization of up to 3 months may be granted for initial
               treatment of uterine leiomyomata (fibroids) when either of
               the following criteria is met:
               1.  Member has anemia due to uterine leiomyomata, or
               2.  Lupron Depot will be used prior to surgery for uterine
                    leiomyomata.

          C.  Breast cancer
               Authorization of 12 months may be granted for treatment of
               hormone receptor-positive breast cancer.

          D.  Ovarian cancer
               Authorization of 12 months may be granted for treatment of
               persistent disease or recurrence of any of the following types
               of ovarian cancer when used as a single agent:
               1.  Epithelial ovarian cancer
               2.  Fallopian tube cancer
               3.  Primary peritoneal cancer
               4.  Grade 1 endometrioid carcinoma
               5.  Low-grade serous carcinoma
               6.  Carcinosarcoma (malignant mixed Müllerian tumors)
               7.  Mucinous carcinoma of the ovary
               8.  Clear cell carcinoma of the ovary

          E.  Salivary gland tumors
               Authorization of 12 months may be granted for treatment of
               recurrent salivary gland tumors when the tumor is androgen
               receptor positive.  

          F.  Gender dysphoria
               1.  Authorization of 12 months may be granted for pubertal
                    hormonal suppression in an adolescent member when all
                    of the following criteria are met:
                    i.     The member has a diagnosis of gender dysphoria.
                    ii.    The member has reached Tanner stage 2 of puberty
                           or greater.
                    iii.   The member’s comorbid conditions are reasonably
                           controlled.
                    iv.   The member has been educated on any
                           contraindications and side effects to therapy.
                    v.    The member has been informed of fertility
                           preservation options.
               2.  Authorization of 12 months may be granted for gender
                    transition when all of the following criteria are met:
                    i.     The member has a diagnosis of gender dysphoria.
                    ii.    The member will receive Lupron Depot concomitantly
                           with gender-affirming hormones.
                    iii.   The member’s comorbid conditions are reasonably
                           controlled.
                    iv.   The member has been educated on any
                          contraindications and side effects to therapy.
                    v.    The member has been informed of fertility
                           preservation options.

          G.  Preservation of ovarian function in patients with
               cancer
               Authorization of 3 months may be granted for preservation of
               ovarian function when the member is premenopausal and
               undergoing chemotherapy.

          H.  Prevention of recurrent menstrual related attacks in
               acute porphyria
               Authorization of 12 months may be granted for prevention of
               recurrent menstrual related attacks in members with acute
               porphyria when the requested medication is prescribed by or
               in consultation with a physician experienced in the
               management of porphyrias. 


    IV.  CONTINUATION OF THERAPY

          All members (including new members) requesting authorization
          for continuation of therapy must meet all initial authorization
          criteria in addition to the following diagnosis-specific criteria (if
          applicable).  

          A.  Endometriosis
               Authorization of up to 6 months (for a lifetime maximum of
               12 months total) may be granted for retreatment of
               endometriosis when all of the following criteria are met:
               1.  The member has had a recurrence of symptoms.
               2.  The member has a bone mineral density within normal
                    limits.

          B.  Uterine leiomyomata (fibroids)
               Authorization of up to 3 months (for a lifetime maximum of 6
               months total) may be granted when either of the following
               criteria is met:
               1.  Member has anemia due to uterine leiomyomata, or
               2.  Lupron Depot will be used prior to surgery for uterine
                    leiomyomata.

          C.  Breast cancer, ovarian cancer, and salivary gland
               tumors
               Authorization of 12 months may be granted for continued
               treatment of breast cancer, ovarian cancer, and salivary
               gland tumors in members requesting reauthorization when
               there is no evidence of unacceptable toxicity or disease
               progression while on the current regimen.

          D.  Gender dysphoria
               1.  Authorization of 12 months may be granted for continued
                    treatment for pubertal hormonal suppression in
                    adolescent members requesting reauthorization when all
                    of the following criteria are met:
                    i.     The member has a diagnosis of gender dysphoria.
                    ii.    The member has previously reached Tanner stage 2
                           of puberty or greater.
                    iii.   The member’s comorbid conditions are reasonably
                           controlled.
                    iv.   The member has been educated on any
                           contraindications and side effects to therapy.
                    v.    Before the start of therapy, the member has been
                           informed of fertility preservation options.
               2.  Authorization of 12 months may be granted for continued
                    treatment for gender transition in members requesting
                    reauthorization when all of the following criteria are met:
                    i.     The member has a diagnosis of gender dysphoria.
                    ii.    The member will receive Lupron Depot concomitantly
                           with gender-affirming hormones.
                    iii.   The member’s comorbid conditions are reasonably
                           controlled.
                    iv.   The member has been educated on any
                           contraindications and side effects to therapy.
                    v.    Before the start of therapy, the member has been
                           informed of fertility preservation options.

          E.  All members (including new members) requesting
               authorization for continuation of therapy for the
               specified indications below must meet all initial
               authorization criteria:
               1.  Preservation of ovarian function in patients with cancer
               2.  Prevention of recurrent menstrual related attacks in acute
                    porphyria

Place of Service:

Outpatient

The above policy is based on the following references:

1. Lupron Depot 3.75 mg [package insert]. North Chicago, IL: AbbVie Inc.; July 2022.
2. Lupron Depot-3 Month 11.25 mg [package insert.]. North Chicago, IL: AbbVie Inc.; March 2020.
3. The NCCN Drugs & Biologics Compendium® © 2022 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed December 11, 2022.
4. Management of symptomatic uterine leiomyomas: ACOG Practice Bulletin No. 228. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2021 June 1;137(6):e100-e115.
5. Marret H, Fritel X, Ouldamer L, et al. Therapeutic management of uterine fibroid tumors: updated French guidelines. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2012;165:156-164.
6. Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017:102(11):3869–3903.
7. Gender Identity Research and Education Society. Guidance for GPs and other clinicians on the treatment of gender variant people. UK Department of Health. Published March 10, 2008.
8. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, 7th version. ©2012 World Professional Association for Transgender Health. Available at http://www.wpath.org.
9. Fertility preservation in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018 Jul 1;36(19):1994-2001.
10. Clowse MEB, Behera MA, Anders CK, et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health (Larchmt). 2009 Mar; 18(3): 311–319. doi:10.1089/jwh.2008.0857
11. Stein P, Badminton M, Barth J, Rees D, Stewart MF; British and Irish Porphyria Network. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013 May;50(Pt 3):217-23.
12. Innala, E, Bäckström, T, Bixo, M, Andersson, C. Evaluation of gonadotrophin-releasing hormone agonist treatment for prevention of menstrual-related attacks in acute porphyria. Acta Obstet Gynecol2010;89:95–100.
13. Mahfouda S, Moore JK, Siafarikas A, et al. Puberty Suppression in Transgender Children and Adolescents. Lancet Diabetes Endocrinol. 2017; 5: 816-26.
14. Health Care for Transgender and Gender Diverse Individuals. ©2021 The American College of Obstetricians and Gynecologists. Available at: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2021/03/health-care-for-transgender-and-gender-diverse-individuals.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

June 11, 2023