Subject: Leukine 1929-A SGM P2021
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
A. Acute Myeloid Leukemia Following Induction Chemotherapy
Leukine is indicated to shorten time to neutrophil recovery and to reduce the incidence of severe, life-threatening, or fatal infections following induction chemotherapy
in adult patients 55 years and older with acute myeloid leukemia (AML).
B. Autologous Peripheral Blood Progenitor Cells Mobilization and Collection
Leukine is indicated in adult patients with cancer undergoing autologous hematopoietic stem cell transplantation for the mobilization of hematopoietic progenitor cells
into peripheral blood for collection by leukapheresis.
C. Autologous Peripheral Blood Progenitor Cell and Bone Marrow Transplantation
Leukine is indicated for acceleration of myeloid reconstitution following autologous peripheral blood progenitor cell (PBPC) or bone marrow transplantation in adult
and pediatric patients 2 years of age and older with non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukemia (ALL) and Hodgkin's lymphoma (HL).
D. Allogeneic Bone Marrow Transplantation (BMT)
Leukine is indicated for acceleration of myeloid reconstitution in adult and pediatric patients 2 years of age and older undergoing allogeneic BMT from human
leukocyte antigens (HLA)-matched related donors.
E. Allogenic or Autologous Bone Marrow Transplantation: Treatment of Delayed Neutrophil Recovery or Graft Failure
Leukine is indicated for the treatment of adult and pediatric patients 2 years and older who have undergone allogeneic or autologous BMT in whom
neutrophil recovery is delayed or failed.
F. Acute Exposure to Myelosuppressive Doses of Radiation (H-ARS)
Leukine is indicated to increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation
(Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).
B. Compendial Uses
1. Prophylaxis and treatment of chemotherapy-induced febrile neutropenia in non-myeloid malignancies
2. Treatment of neutropenia and anemia in patients with myelodysplastic syndromes (MDS)
3. Acute myeloid leukemia
4. Agranulocytosis (non-chemotherapy drug induced)
5. Aplastic anemia
6. Neutropenia related to HIV/AIDS
7. Stem cell transplantation-related indications
8. Neuroblastoma
9. Severe chronic neutropenia (congenital, cyclic, or idiopathic)
All other indications are considered experimental/investigational and not medically necessary.
II. REQUIRED DOCUMENTATION
Primary Prophylaxis of Febrile Neutropenia
A. Documentation must be provided of the member’s diagnosis and chemotherapeutic regimen.
B. If chemotherapeutic regimen has an intermediate risk of febrile neutropenia (10-19% [See Appendix B]), documentation must be provided outlining the
member’s risk factors that confirm the member is at high risk for febrile neutropenia.
III. CRITERIA FOR INITIAL APPROVAL
A. Neutropenia in cancer patients receiving myelosuppressive chemotherapy
Authorization of 6 months may be granted for prevention or treatment of febrile neutropenia when all of the following criteria are met (1, 2, and 3):
1. The requested medication will not be used in combination with other colony stimulating factors within any chemotherapy cycle.
2. The member will not be receiving concurrent chemotherapy and radiation therapy.
3. One of the following criteria is met (i, ii, or iii):
i. The requested medication will be used for primary prophylaxis in members with solid tumors or non-myeloid malignancies who have received, are
currently receiving, or will be receiving myelosuppressive anti-cancer therapy that is expected to result in 20% or higher incidence of febrile neutropenia (FN)
(See Appendix A) OR 10 – 19% risk of FN (See Appendix B) and who are considered to be at high risk of FN because of bone marrow compromise or co-morbidity,
including any of the following (not an all-inclusive list):
a. Active infections, open wounds, or recent surgery
b. Age greater than or equal to 65 years
c. Bone marrow involvement by tumor producing cytopenias
d. Previous chemotherapy or radiation therapy
e. Poor nutritional status
f. Poor performance status
g. Previous episodes of FN
h. Other serious co-morbidities, including renal dysfunction, liver dysfunction, HIV infection, cardiovascular disease
i. Persistent neutropenia
ii. The requested medication will be used for secondary prophylaxis in members with solid tumors or non-myeloid malignancies who experienced a febrile neutropenic
complication or a dose-limiting neutropenic event (a nadir or day of treatment count impacting the planned dose of chemotherapy) from a prior cycle of similar
chemotherapy, with the same dose and schedule planned for the current cycle (for which primary prophylaxis was not received).
iii. The requested medication will be used for treatment of high risk febrile neutropenia (FN) in deterioration members who have any of the following prognostic factors
that are predictive of clinical:
a. Age greater than 65 years
b. Being hospitalized at the time of the development of fever
c. Sepsis syndrome
d. Invasive fungal infection
e. Pneumonia or other clinically documented infection
f. Prolonged (neutropenia expected to last greater than 10 days) or profound (absolute neutrophil count less than 0.1 x 109/L) neutropenia
g. Prior episodes of febrile neutropenia
B. Neuroblastoma
Authorization of 6 months may be granted for treatment of high-risk neuroblastoma when used with either of the following:
1. Dinutuxin (Unituxin), interleukin-2 (aldesleukin (Proleukin)), and isotretinoin (13-cis-retinoic acid (RA))
2. Naxitamab-gqgk (Danyelza)
C. Other indications
Authorization of 6 months may be granted for members with any of the following indications:
1. Myelodysplastic syndrome (anemia or neutropenia)
2. Acute myeloid leukemia
3. Agranulocytosis (non-chemotherapy drug induced)
4. Aplastic anemia
5. Neutropenia related to HIV/AIDS
6. Stem cell transplantation-related indications
7. Severe chronic neutropenia (congenital, cyclic, or idiopathic)
8. Hematopoietic Syndrome of Acute Radiation Syndrome
Treatment for radiation-induced myelosuppression following a radiological/nuclear incident
IV. CONTINUATION OF THERAPY
All members (including new members) requesting authorization for continuation of therapy must meet all initial authorization criteria.
Special Notes:
APPENDIX
A. APPENDIX A: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 20% or Higher*
1. Acute Lymphoblastic Leukemia:
Select ALL regimens as directed by treatment protocol (see NCCN guidelines ALL)
2. Bladder Cancer:
i. Dose dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)
ii. CBDCa/Pac (carboplatin, paclitaxel)
3. Bone Cancer:
i. VAI (vincristine, doxorubicin or dactinomycin, ifosfamide)
ii. VDC-IE (vincristine, doxorubicin or dactinomycin, and cyclophosphamide alternating with
ifosfamide and etoposide)
iii. Cisplatin/doxorubicin
iv. VDC (cyclophosphamide, vincristine, doxorubicin or dactinomycin)
v. VIDE (vincristine, ifosfamide, doxorubicin or dactinomycin, etoposide)
4. Breast Cancer:
i. Docetaxel + trastuzumab
ii. Dose-dense AC (doxorubicin, cyclophosphamide) + paclitaxel (or dose dense paclitaxel)
iii. TAC (docetaxel, doxorubicin, cyclophosphamide)
iv. AT (doxorubicin, docetaxel)
v. Doc (docetaxel)
vi. TC (docetaxel, cyclophosphamide)
vii. TCH (docetaxel, carboplatin, trastuzumab)
5. Colorectal Cancer:
FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan)
6. Esophageal and Gastric Cancers:
Docetaxel/cisplatin/fluorouracil
7. Head and Neck Squamous Cell Carcinoma
TPF (docetaxel, cisplatin, 5-fluorouracil)
8. Hodgkin Lymphoma:
i. Brentuximab vedotin + AVD (doxorubicin, vinblastine, dacarbazine)
ii. Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)
9. Kidney Cancer:
Doxorubicin/gemcitabine
10. Non-Hodgkin's Lymphoma:
i. CHP (cyclophosphamide, doxorubicin, prednisone) + brentuximab vedotin
ii. Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)
iii. ICE (ifosfamide, carboplatin, etoposide)
iv. Dose-dense CHOP-14 (cyclophosphamide, doxorubicin, vincristine, prednisone) ± rituximab
v. MINE (mesna, ifosfamide, mitoxantrone, etoposide)
vi. DHAP (dexamethasone, cisplatin, cytarabine)
vii. ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine (Ara-C))
viii. HyperCVAD ± rituximab (cyclophosphamide, vincristine, doxorubicin, dexamethasone ± rituximab)
ix. VAPEC-B (vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide, bleomycin)
11. Melanoma:
Dacarbazine-based combination with IL-2, interferon alpha (dacarbazine, cisplatin, vinblastine, IL-2, interferon alfa)
12. Multiple myeloma:
i. VTD-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide + bortezomib)
ii. DT-PACE (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide)
13. Ovarian Cancer:
i. Topotecan
ii. Docetaxel
14. Pancreatic Cancer:
FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin)
15. Soft Tissue Sarcoma:
i. MAID (mesna, doxorubicin, ifosfamide, dacarbazine)
ii. Doxorubicin
iii. Ifosfamide/doxorubicin
16. Small Cell Lung Cancer:
i. Top (topotecan)
ii. CAV (cyclophosphamide, doxorubicin, vincristine)
17. Testicular cancer:
i. VelP (vinblastine, ifosfamide, cisplatin)
ii. VIP (etoposide, ifosfamide, cisplatin)
iii. TIP (paclitaxel, ifosfamide, cisplatin)
*Applies to chemotherapy regimens with or without monoclonal antibodies (e.g., trastuzumab, rituximab)
B. APPENDIX B: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 10% to 19%*
1. Occult primary – adenocarcinoma:
Gemcitabine/docetaxel
2. Breast cancer:
i. Docetaxel
ii. CMF classic (cyclophosphamide, methotrexate, fluorouracil)
iii. CA (doxorubicin, cyclophosphamide) (60 mg/m2) (hospitalized)
iv. AC (doxorubicin, cyclophosphamide) + sequential docetaxel (taxane portion only)
v. AC + sequential docetaxel + trastuzumab
vi. A (doxorubicin) (75 mg/m2)
vii. AC (doxorubicin, cyclophosphamide)
viii. CapDoc (capecitabine, docetaxel)
ix. Paclitaxel every 21 days
3. Cervical Cancer:
i. Irinotecan
ii. Cisplatin/topotecan
iii. Paclitaxel/cisplatin
iv. Topotecan
4. Colorectal Cancer:
i. FL (fluorouracil, leucovorin)
ii. CPT-11 (irinotecan) (350 mg/m2 q 3 wk)
iii. FOLFOX (fluorouracil, leucovorin, oxaliplatin)
5. Esophageal and Gastric Cancers:
i. Irinotecan/cisplatin
ii. Epirubicin/cisplatin/5-fluorouracil
iii. Epirubicin/cisplatin/capecitabine
6. Non-Hodgkin's lymphomas:
i. EPOCH-IT chemotherapy
ii. GDP (gemcitabine, dexamethasone, cisplatin/carboplatin)
iii. GDP (gemcitabine, dexamethasone, cisplatin/carboplatin) + rituximab
iv. FMR (fludarabine, mitoxantrone, rituximab)
v. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) including regimens with pegylated liposomal doxorubicin
vi. CHOP + rituximab (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) including regimens with pegylated liposomal doxorubicin
vii. Bendamustine
7. Non-Small Cell Lung Cancer:
i. Cisplatin/paclitaxel
ii. Cisplatin/vinorelbine
iii. Cisplatin/docetaxel
iv. Cisplatin/etoposide
v. Carboplatin/paclitaxel
vi. Docetaxel
8. Ovarian cancer:
Carboplatin/docetaxel
9. Prostate cancer:
Cabazitaxel
10. Small Cell Lung Cancer:
Etoposide/carboplatin
11. Testicular Cancer:
i. BEP (bleomycin, etoposide, cisplatin)
ii. Etoposide/cisplatin
12. Uterine sarcoma:
Docetaxel
*Applies to chemotherapy regimens with or without monoclonal antibodies (e.g., trastuzumab, rituximab)
This list is not comprehensive; there are other agents/regimens that have an intermediate/high risk for development of febrile neutropenia.
Place of Service:
Outpatient
The above policy is based on the following references:
- Leukine [package insert]. Lexington, MA: Partner Therapeutics, Inc.; May 2018.
- The NCCN Drugs & Biologics Compendium® © 2021 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed June 03, 2021.
- IBM Micromedex® DRUGDEX ® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at https://www.micromedexsolutions.com. (Accessed: June 03, 2021).
- Lexicomp Online, AHFS DI (Adult and Pediatric) [database online]. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc.; Accessed June 03, 2021.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Growth Factors. Version 4.2021. https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf Accessed June 03, 2021.
- Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of white blood cell growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(28):3199-3212.
- Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24(19):3187-3205.
- Danyelza [package insert]. New York, NY: Y-mAbs Therapeutics, Inc.; November 2020.
- Unituxin [package insert]. Research Triangle Park, NC: United Therapeutics Corp.; September 2020.
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.
November 23, 2021
