Neulasta (peg-filgrastim; G-CSF) Neupogen (filgrastim; G-CSF) Neulasta Onpro (peg-filgrastim; G-CSF) Leukine (sargramostim; GM-CSF) General Authorization Criteria for ALL Agents and Indications: Prescribed by, or in consultation with, a hematologist or oncologist Medical records, including labs and weight or body surface area (BSA), to support diagnosis and dosing is submitted with request RequestedagentisdosedandadministeredwithinFood and Drug Administration (FDA)labeledrecommendations o Will not be used concomitantly with radiation AND chemotherapy o Will be administered at the appropriate time after chemotherapy OR radiation Member does not have any contraindications or hypersensitivity to the requested agent Will not be used in combination with other myeloid growth factors Additional Criteria Based on Indication: Chemotherapy-Induced Febrile Neutropenia: (Neupogen, Neulasta, a n d Leukine) Memberisreceiving chemotherapy for a NON-myeloid cancer (i.e., solid tumor, lymphoma) o For PRIMARY prophylaxis: Member meets one of the following: Chemotherapy regimen isgiven after bone marrow transplant; OR Chemotherapy regimen has >20% risk of febrile neutropenia; OR Chemotherapy regimen has 10%-20% risk of febrile neutropenia AND member has ANY of the following risk factors for febrile neutropenia: o age > 65 years o priorchemotherapyorradiationtherapy o persistent neutropenia o bonemarrowinvolvementbytumor o Recent surgery and or open wounds o Liver dysfunction (bilirubin > 2.0) o Renal dysfunction (creatinine clearance (CRCL) <50) o o For SECONDARYprophylaxis (Neupogen, Neulasta, andleukine):memberpreviouslyexperiencedfebrile neutropeniafromthesame chemotherapyregimenandreducingordelayingchemotherapydosemay compromisetreatment outcome For TREATMENT of febrile neutropenia (Leukine and Neupogen) in members who did NOT receive colony stimulating factor (CSFs) prophylaxis: Member has risk factors for poor outcomes resulting from febrile Effective: 2/1/2018 Page 1
neutropenia (e.g., age > 65, sepsis, severe neutropenia (absolute neutrophil count (ANC)< 100/mcL), current infection, hospitalized at onset of fever, prior episode of febrile neutropenia) Severe chronic congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia: (Neupogen) o Member has one of the following: Evidence ofinadequate bone marrow reserve (e.g.,recurrentfevers,splenomegaly,mucosal ulcers, abdominal pain) Highriskfordeveloping serious bacterialinfection (e.g., primarilysevere neutropenia,indwelling venous catheters, prior serious infections) Current bacterial infection NeutropeniarelatedtoHuman Immunodeficiency Virus(HIV) or drug therapy; ganciclovir or zidovudine induced:(neupogen and Leukine) o Prescribed by, or in consultation with an Infectious Disease Specialist, Hematologist, or Human Immunodeficiency Virus(HIV)Specialist Neupogen may also be approved if medically necessary for the following indications: o AcuteMyeloidLeukemiainmembersreceivinginductionorconsolidationchemotherapy o Mobilizationofhematopoieticprogenitorcellsbefore autologousstemcelltransplant o Mobilization of hematopoietic progenitor cells in the donor before allogenicstem cell transplant o Treatment of acute radiation exposure in members who receive myelosuppressive doses of radiation at a dose of 2 gray (Gy) o Myelodysplastic Syndrome (MDS) or aplastic anemia in a member with an absolute neutrophil count (ANC) <500 Leukine may also be approved if medically necessary for the following indications: o Acute Myeloid Leukemia after induction chemotherapy for members age 55 years or older o Bone marrowtransplantfailure orengraftmentdelay o Myeloid reconstitution after allogenic bone marrow transplant o Myeloidreconstitutionafter autologousbone marrowtransplantinmemberswithhodgkin sdisease,non- Hodgkin's lymphoma, or acute lymphocytic leukemia o Before andafter autologous peripheralblood stem celltransplantation Initial Approval: Chemotherapy-induced neutropenia (primary or secondary prophylaxis): o Approveper cycle ofchemotherapy: Up to a 14 day supply for Neupogen, and Leukine One (1) 6 mg dose of Neulasta no less than every 14 days Include refills if number of cycles is provided o Treatment of neutropenia (e.g., congenital, cyclic, or idiopathic, Human Immunodeficiency Virus (HIV), or after chemo + bone marrowtransplant(bmt)): Approve for 3 months Effective: 2/1/2018 Page 2
Forotherindications o Up to six months or less Renewal: Pharmacy Prior Authorization Chemotherapy-induced neutropenia (primary or secondary prophylaxis): o Recent absolute neutrophil count (ANC) showing a response to therapy o Approveper cycle ofchemotherapy: Up to a 14 day supply for Neupogen, and Leukine One (1) 6 mg dose of Neulasta no less than every 14 days Include refills if number of cycles is provided, or up to 12 months All other indications: o Recentabsolute neutrophil count (ANC), complete bloodcount (CBC), and/orplateletcounts o Approve up to one year Additional Information: Note: Neutropenia is defined as an absolute neutrophil count (ANC) of < 500 neutrophils/mcl or an absolute neutrophil count (ANC) of < 1000 neutrophils/mcl and a predicted decline to < than or equal to 500 neutrophils/mcl over the next 48 hours. Determining the riskof febrile neutropenia: A member s risk for developing neutropenic fever may be assessed prior to the use of colony stimulating factors. This may be achieved by evaluating the degree of myelosuppression of the member s chemotherapy regimen in addition to the presence of other member-relatedrisk factors. Both Infectious Diseases Society of America (IDSA)and National Comprehensive Cancer Network (NCCN)recommend thatcolony stimulating factors be consideredwhen the risk of febrileneutropeniais>20%. Dosing Table: Medication Dosing Available Dosage forms Effective: 2/1/2018 Page 3
Neupogen Febrile Neutropenia (FN) or acute myeloid leukemia (AML): 5 mcg/kg/day (Not given 24 hours before chemotherapy and 24 hours after) Bone marrow transplant (BMT): 10 mcg/kg/day (given 24 hrs after bone marrow transplant (BMT) and given for at least 24 hours) Vials: 300 mcg/ml, single-dose vial 480 mcg/1.6 ml, single-dose vial Prefilled Syringe 300 mcg/0.5 ml per syringe 480 mcg/0.8 ml per syringe Neulasta Leukine Peripheral Blood Progenitor Cell (PBPC): 10 mcg/kg/day; at least 4 days before and up to 7 days Severe Chronic Neutropenia: o Idiopathic neutropenia:1.2 mcg/kg/day o Cyclic neutropenia: 2.1 mcg/kg/day o Congenitalneutropenia: 6mcg/kg/day divided 2times per day Febrile Neutropenia- 5mcg/kg/day Not given 24 hours before chemotherapy and 24 hours after chemotherapy Given once per chemotherapy cycle Acute myeloid leukemia (AML): 250 mcg/m 2 /day subcutaneous (SQ) or intravenous (IV) on day 11 or 4 days following the completion of induction chemotherapy 6 mg/0.6 ml, single-dose prefilled syringe 6 mg/0.6 ml, single-dose prefilled syringe co-packaged with the Onbody Injector (Neulasta Onpro kit). 500 mcg/ml vial 250 mcg powder for injection References: 1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Myeloid Growth 2. Factors V.1.2015. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloid_growth.pdf. Accessed August 16, 2017 3. 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 24:3187-3205. Available at: http://jco.ascopubs.org/cgi/reprint/24/19/3187. Accessed August 16, 2017 4. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Prevention and Treatment of Cancer- Related Infection. V.2.2015. Available at: http://www.nccn.org/professionals/physician_gls/pdf/infections.pdf Accessed Oct 5, 2015. Effective: 2/1/2018 Page 4
5. InfectiousDiseaseSociety ofamerica:clinicalpracticeguidelinefortheuseof AntimicrobialAgents in NeutropenicMembers with Cancer: 2010 Update by the Infectious Diseases Society of America. Available at: http://news.idsociety.org/idsa/issues/2011-01-01/17.html Accessed August 16, 2017 6. Zarxio (filgrastim-sndz) [package insert]. Princeton, NJ: Sandoz Inc. December 2014 7. Granix(tbo-filgrastim)[packageinsert].NorthWales,PA:Cephalon,Inc.July2015 8. Neupogen [package insert]. Thousand Oaks,CA:Amgen, IncJune 2016 9. Levine JD, Allan JD, Tessitore JH, Falcone N, Galasso F, Israel RJ, Groopman JE. Recombinant human granulocyte-macrophage colony-stimulating factor ameliorates zidovudine-induced neutropenia in members with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex. Blood. 1991;78:3148 3154. 10. Hermans P, Rozenbaum W, Jou A, et al. Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group. AIDS. 1996;10(14):1627-1633. 11. Hermans P, Rozenbaum W, Jou A, et al. Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group. AIDS. 1996;10(14):1627-1633. Table: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 20% or Higher Cancer Histology Treatment Setting Regimen Acute Lymphoblastic Leukemia (ALL) Bladder Cancer Induction Neoadjuvant, adjuvant, metastatic Prior adjuvant allowed ALL induction regimens (see NCCN guidelines) MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) CBDCa/Pac (carboplatin, paclitaxel) Breast Cancer Metastatic or relapsed Docetaxel + trastuzumab Adjuvant Adjuvant Metastatic (1st line) Metastatic (2nd line) Dose-dense AC followed by T (doxorubicin, cyclophosphamide, paclitaxel) TAC (docetaxel, doxorubicin, cyclophosphamide) AT (doxorubicin, docetaxel) Doc (docetaxel) Esophageal and Gastric Cancers Docetaxel/cisplatin/fluorouracil Effective: 2/1/2018 Page 5
Hodgkin Lymphoma Kidney Cancer Non-Hodgkin's Lymphoma Melanoma Diffuse large B-cell lymphoma {DLBCL], peripheral T-cell lymphomas (PTCL], 2nd line DLBCL, 2nd line, refractory PTCL, DLBCL, 2nd line DLBCL, PTCL, 2nd line, recurrent Relapsed Advanced, metastatic, or recurrent Advanced, metastatic, or recurrent BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) Doxorubicin/gemcitabine ICE (ifosfamide, carboplatin, etoposide) RICE (rituximab, ifosfamide, carboplatin, etoposide) CHOP-14 (cyclophosphamide, doxorubicin, vincristine, prednisone) + rituximab MINE (mesna, ifosfamide, novantrone, etoposide) DHAP (dexamethasone, cisplatin, cytarabine) ESHAP (etoposide, methylprednisolone, cisplatin, cytarabine (Ara-C)) HyperCVAD + rituximab (cyclophosphamide, vincristine, doxorubicin, dexamethasone + rituximab) VAPEC-B (vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide, bleomycin) Dacarbazine-based combination (dacarbazine, cisplatin, vinblastine) Dacarbazine-based combination with IL-2, interferon alpha (dacarbazine, cisplatin, vinblastine, IL-2, interferon alpha) Effective: 2/1/2018 Page 6
Ovarian Cancer Topotecan Pancreatic Cancer Soft Tissue Sarcoma Small Cell Lung Cancer Advanced or metastatic Recurrent Paclitaxel Docetaxel FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) MAID (mesna, doxorubicin, ifosfammide, dacarbazine) Doxorubicin Ifosfamide/doxorubicin Top (topotecan) CAV (cyclophosphamide, doxorubicin, vincristine) Testicular cancer Relapsed VelP (vinblastine, ifosfamide, cisplatin) VIP (etoposide, ifosfamide, cisplatin) BEP (bleomycin, etoposide, cisplatin) TIP (paclitaxel, ifosfamide, cisplatin) Source: Smith, et al., 2006; NCCN, 2016. Table: Selected Chemotherapy Regimens with an Incidence of Febrile Neutropenia of 10% to 19% Cancer Histolog y Occult primary - adenocarcinom a Treatment Setting Regimen Gemcitabine/docetaxel Effective: 2/1/2018 Page 7
Breast cancer Docetaxel every 21 days Adjuvant Adjuvant Adjuvant (taxane portion only) Adjuvant Metastatic (1st line) Metastatic (1st line) Metastatic (2nd line) CMF classic (cyclophosphamide, methotrexate, fluorouracil) CA (doxorubicin, cyclophosphamide) (60 mg/m2) (hospitalized) AC (doxorubicin, cyclophosphamide) + sequential docetaxel AC + sequential docetaxel + trastuzumab A (doxorubicin) (75) AC (doxorubicin, cyclophosphamide) CapDoc (capecitabine, docetaxel) FEC (fluorouracil, epirubicin, cyclophosphamide) + sequential docetaxel Metastatic or relapsed Paclitaxel every 21 days TC (docetaxel, cyclophosphamide) Cervical Cancer FOLFOX (fluorouracil, leucovorin, oxaliplatin) Colorectal Advanced FL (fluorouracil, leucovorin) Advanced (one prior chemo allowed) CPT-11 (irinotecan) (350 mg/m2 q 3 wk) Esophageal and Gastric Cancers Irinotecan/cisplatin Epirubicin/cisplatin/5-fluorouracil Epirubicin/cisplatin/capecitabine Head and Neck Induction Cis/Doc/5-FU (cisplatin, docetaxel, 5-fluorouracil) Multiple DT-PACE Effective: 2/1/2018 Page 8
myeloma (dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophoaphamide/eto poside) Non-Hodgkin's lymphomas Non-Small Cell Lung Cancer AIDS-related NHL, Burkitt lymphoma, recurrent, otehr NHL subtypes AIDS-related NHL, DLBCL, recurrent DLBCL, PTCL, 2nd line DLBCL, 2nd line, Burkitt lymphoma, other NHL subtypes Advanced/metasta tic Adjuvant, advanced/metastat ic Adjuvant, advanced/metastat ic Adjuvant, advanced/metastat ic DT-PACE + bortezomib (VTD-PACE) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) EPOCH-IT chemotherapy GDP (gemcitabine, dexamethasone, cisplatin) GDP (gemcitabine, dexamethasone, cisplatin) + rituximab FMR (fludarabine, mitoxantrone, rituximab) CHOP + rituximab (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) including regimens with pegylated liposomal doxorubicin or mitoxantrone substituted for doxorubicin Cisplatin/paclitaxel Cisplatin/vinorelbine Cisplatin/docetaxel Cisplatin/etoposide Effective: 2/1/2018 Page 9
Adjuvant, advanced/metastat ic Advanced/metasta tic Carboplatin/paclitaxel Docetaxel Ovarian Cancer Pancreatic Cancer Prostate Cancer Small Cell Lung Cancer Testicular Cancer Uterine Sarcoma Advanced or metastatic Carboplatin/docetaxel FOLFIRINOX Cabazitaxel Etoposide/carboplatin Etoposide/carboplatin Docetaxel Effective: 2/1/2018 Page 10