June MPU WV FINAL 2017.Docx

June 2017

In This Issue

Revised Criteria for Eculizumab ...... 6 Coverage for the Quadrivalent (RIV4) Influenza Virus Vaccine ...... 12 Revised Criteria for Bone Morphogenetic Protein ...... 15

Contents...... 24

Policy

The use of leuprolide acetate Lupron may be considered medically necessary for the following conditions:

• Prostate Cancer o As adjuvant androgen deprivation therapy as a single agent or in combination with an antiandrogen, with or without external beam radiation therapy (EBRT) if positive lymph nodes were found during pelvic lymph node dissection; or o Initial androgen deprivation therapy as a single agent or in combination with an antiandrogen for; . 4-6 months in combination with external beam radiation therapy (EBRT) with or without brachytherapy for patients in the intermediate risk group; or . 2-3 years in combination with EBRT with or without brachytherapy for patients in the high or very high risk group; or . 2-3 years in combination with EBRT and docetaxel for patients in the high or very high risk group; or . 2-3 years in combination with EBRT for regional disease (any T, N1, M0); or . Patients in the very high risk group who are not candidates for definitive therapy; or Highmark Blue Cross Blue Shield West Virginia is an independent licensee of the Blue Cross and Blue Shield Association. NaviNet is a registered trademark of NaviNet, Inc., which is an independent company that provides a secure, web-based portal between providers and health care insurance companies. Medical Policy Update June 2017

. Regional or metastatic disease. o Androgen deprivation therapy as a single agent or in combination with an antiandrogen for biochemical failure; . As a single agent; or . In combination with an antiandrogen; or . In combination with docetaxel with or without prednisone for M1 disease. o Used for castration-recurrent disease to maintain castrate levels of serum testosterone as a single agent or in combination with an antiandrogen; or o The palliative treatment of advanced prostatic cancer; or • The management of endometriosis, including pain relief and reduction of endometriotic lesions; o Duration of initial treatment or retreatment should be limited to 6 months; or • For the preoperative treatment of anemia due to uterine leiomyomata (fibroids) in combination with iron supplementation when iron therapy alone fails to correct the anemia; o The recommended duration of therapy is 3 months or less. • The treatment of children with central precocious puberty.

The use of leuprolide acetate for depot suspension (Lupron Depot) may be considered medically necessary for the following conditions:

• Breast Cancer - Invasive o For the treatment of premenopausal women* with hormone receptor-positive disease in combination with: . Adjuvant endocrine therapy; or . Endocrine therapy for recurrent or metastatic disease; or . *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. • Ovarian Cancer - Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer o For hormonal therapy as a single agent for persistent disease or recurrence. • Ovarian Cancer - Grade 1 (Low-Grade) Serous/Endometrioid Epithelial Carcinoma o As adjuvant hormone therapy as a single agent for stage IC-IV low-grade disease. • Ovarian Cancer - Malignant Sex Cord-Stromal Tumors o For hormonal therapy for clinical relapse in patients with stage II-IV granulosa cell tumors. • For the management of endometriosis including pain relief and reduction of endometriotic lesions o Duration of initial treatment or retreatment should be limited to 6 months; or • For the preoperative treatment of anemia due to uterine leiomyomata (fibroids) in combination with iron supplementation when iron therapy alone fails to correct the anemia; o The recommended duration of therapy is 3 months or less. • The palliative treatment of advanced prostatic cancer. • The treatment of children with central precocious puberty.

The use of leuprolide/leuprolide acetate (Lupron, Lupron Depot) in the treatment of conditions other than the above is considered not medically necessary.

2 Medical Policy Update June 2017

Highmark West Virginia has established coverage criteria for Lupron Depot Ped, Lupaneta Pack and Eligard.

The use of leuprolide acetate for depot suspension (Lupron Depot Ped) may be considered medically necessary for the treatment of children with central precocious puberty.

The use of leuprolide acetate for depot suspension (Lupron Depot Ped) for any other indication is considered not medically necessary.

Leuprolide and norethindrone (Lupaneta Pack) may be considered medically necessary for women 18 years of age and older for:

• The initial management of the painful symptoms of endometriosis; or • The management of recurrence of symptoms.

Initial treatment course is limited to 6 months and use is not recommended longer than a total of 12 months due to concerns about adverse impact on bone mineral density.

The use of Leuprolide and norethindrone (Lupaneta Pack) for any other indication is considered not medically necessary.

The use of leuprolide acetate (Eligard) may be considered medically necessary for the following conditions:

• Prostate Cancer o As adjuvant androgen deprivation therapy as a single agent or in combination with an antiandrogen, with or without external beam radiation therapy (EBRT) if positive lymph nodes were found during pelvic lymph node dissection; or o Initial androgen deprivation therapy as a single agent or in combination with an antiandrogen for: . 4-6 months in combination with external beam radiation therapy (EBRT) with or without brachytherapy for patients in the intermediate risk group; or . 2-3 years in combination with EBRT with or without brachytherapy for patients in the high or very high risk group; or . 2-3 years in combination with EBRT and docetaxel for patients in the high or very high risk group; or . 2-3 years in combination with EBRT for regional disease (any T, N1, M0); or . For patients in the very high risk group who are not candidates for definitive therapy; or . Regional or metastatic disease. o Androgen deprivation therapy as a single agent or in combination with an antiandrogen for biochemical failure: . Following radical prostatectomy in combination with external beam radiation therapy (EBRT) for disease without distant metastases; or . Following radical prostatectomy in combination with or without EBRT for distant metastatic disease; or . Or positive digital rectal examination (DRE) following radiation therapy if biopsy negative and no distant metastases; or 3 Medical Policy Update June 2017

. Or positive DRE following radiation therapy in patients who are not candidates for local therapy (especially if bone scan positive). o Used for progressive castration-naive disease: . As a single agent; or . In combination with an antiandrogen; or . In combination with docetaxel with or without prednisone for M1 disease. o Used for castration-recurrent disease to maintain castrate levels of serum testosterone as a single agent or in combination with an antiandrogen; or o The palliative treatment of advanced prostate cancer.

The use of leuprolide acetate (Eligard) for any other indication is considered not medically necessary.

This new criteria will apply to both professional provider and facility claims. The effective date is August 28, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-16, Leuprolide/Leuprolide Acetate (Lupron, Lupron Depot, Lupron Depot-Ped, Lupaneta Pack, Eligard) for additional information.

Revised Criteria for Treatment of Hereditary Angioedema (HAE) Effective August 28, 2017, Treatment of Hereditary Angioedema (HAE) clinical criteria has been revised.

The following clinical criteria have been removed from the Type III HAE policy criteria: • Prior treatment with 17 alpha-alkylated androgens (e.g., danazol and stanozolol) or anti-fibrinolytic agents (e.g., tranexamic acid (Lysteda), aminocaproic acid (Amikar), tranexamic acid (Cyklokapron)) for HAE prophylaxis has been ineffective, not tolerated, or ALL are contraindicated. The following has been added to policy Type III HAE criteria: • Trial and failure of second generation antihistamines (e.g. cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine). The following has been added to Hereditary Angioedema Type I and Type II for acute attacks: • Patient not self-administering two acute medications on the same day.

Additionally, the age criteria for C-1 esterase inhibitor [human] (Berinert) now includes all age groups per the most recent FDA indications.

Please see Medical Policy I-122, Treatment of Hereditary Angioedema (HAE) for more information.

4 Medical Policy Update June 2017

Revised Criteria for Alpha 1 Proteinase Inhibitor Infusions Highmark West Virginia considers the following criteria medically necessary for the administration of Alpha 1 Proteinase Inhibitor Infusions.

The effective date is August 28, 2017.

Place of Service: Outpatient

The following criteria has been changed in the policy: • There is a documented high risk phenotype** resulting in a low serum concentration of Alpha 1 antitrypsin (AAT), as evidenced by less than 80 mg per deciliter (mg/dL) (0.8 g/L) by radial immundiffusion (or less than 50 mg/dL (0.5 g/L) if measured by nephelometry) or less than 11 uM/L (35 % of normal).

Please refer to Medical Policy I-126, Alpha 1 Proteinase Inhibitor Infusions for more information.

Revised Criteria for Decitabine (Dacogen) Effective August 28, 2017, Decitabine (Dacogen®), Medical Policy I-128 clinical criteria has been revised.

The following clinical criteria have been updated:

Myelodysplastic Syndromes (MDS): Treatment of lower risk disease associated with symptomatic anemia and serum erythropoietin levels less than or equal to 500 mU/mL with no response to erythropoietin’s alone and in combination with lenalidomide and no response or intolerance to immunosuppressive therapy.

Acute Myeloid Leukemia (AML): • Used as a single agent in patients age greater than or equal to 60 years as: o Lower intensity induction therapy: . For intensive remission induction therapy in patients with unfavorable cytogenetic or molecular markers/antecedent hematologic disorder/therapy-related AML; or . When the patient is not a candidate for intensive remission induction therapy; or declines intensive therapy; or o Post-remission therapy: . Following a response to prior lower intensive therapy; or . Maintenance therapy following complete response to prior intensive therapy if the patient received hypomethylating agents (e.g. azacitidine, decitabine) during induction.

The following new indication has been added to the policy criteria per the National Comprehensive Cancer Network (NCCN):

Myeloproliferative Neoplasms - Primary Myelofibrosis and Post PV Myelofibrosis or Post ET MF: • For treatment of myelofibrosis (MF) accelerated phase; or 5 Medical Policy Update June 2017

• MF blast phase acute myeloid leukemia.

Revised Criteria for Eculizumab Highmark West Virginia considers the following criteria medically necessary for the administration of Eculizumab.

The effective date is August 28, 2017.

Place of Service: Outpatient

The following criteria have been added to the policy: • Change in the perimeter for Flow Cytometry results have been changed from greater than or equal to 10% of glycosylphosphatidylinositol-anchored proteins (GPI-AP)-deficient polymorphonuclear cells (PMNs) to 50% of glycosylphosphatidylinositol-anchored proteins (GPI-AP)-deficient polymorphonuclear cells (PMNs). • Qualifications for specific MAVE events are now listed. • Member clinical criteria for Hemoglobin that is less than or equal to 7 g/dL, or the individual has symptoms of anemia and the hemoglobin is less than equal to 9 g/dL; or Evidence of clinically elevated hemolysis lactate dehydrogenase (LDH) greater than or equal to 1.5 times the upper limit of normal (ULN) has been added to the policy.

Please refer to Medical Policy I-130, Eculizumab for more information.

Criteria Revised for Pertuzumab for Treatment of Malignancies Highmark West Virginia has revised clinical criteria for Pertuzumab (Perjeta). Additional coverage criteria have been added based upon National Comprehensive Cancer Network (NCCN) guidelines. Pertuzumab (Perjeta) may be considered medically necessary for the treatment of breast cancer for ANY ONE of the following indications: • Preoperative systemic therapy for patients HER2-positive stage IIA (T2, N0, M0), stage IIB (T2, N1, M0 or T3, N0, M0), or stage IIIA (T3, N1, M0) disease who desire breast preservation and fulfill criteria for breast-conserving surgery except for tumor size or for locally advanced disease (stage IIIA (any T, N2, M0), IIIB, or IIIC): o In combination with trastuzumab and paclitaxel (preferred regimen) or trastuzumab and docetaxel following AC (doxorubicin and cyclophosphamide) regimen; or o In combination with TCH (docetaxel, carboplatin, and trastuzumab) regimen (preferred regimen); or o In combination with trastuzumab and paclitaxel or trastuzumab and docetaxel prior to or following FEC (fluorouracil, epirubicin, and cyclophosphamide) regimen; or • Adjuvant systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive greater than or equal to T2 or greater than or equal to N1 early stage or locally advanced breast cancer if a pertuzumab-containing regimen was not used as neoadjuvant therapy: 6 Medical Policy Update June 2017

o In combination with trastuzumab and paclitaxel (preferred regimen) or trastuzumab and docetaxel following AC (doxorubicin and cyclophosphamide) regimen; or o In combination with TCH (docetaxel, carboplatin, and trastuzumab) regimen (preferred regimen); or o In combination with trastuzumab and paclitaxel or trastuzumab and docetaxel prior to or following FEC (fluorouracil, epirubicin, and cyclophosphamide) regimen; or • Used for recurrent or metastatic human epidermal growth factor receptor 2 (HER2)-positive disease that is either hormone receptor- negative, hormone receptor-positive and endocrine therapy refractory, for symptomatic visceral disease, or visceral crisis: o As preferred first-line therapy in combination with trastuzumab with docetaxel or paclitaxel; or o May be considered in combination with trastuzumab with or without cytotoxic therapy (e.g., vinorelbine or taxane) for one line of therapy beyond first-line therapy in patients previously treated with chemotherapy and trastuzumab in the absence of pertuzumab.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-40, Pertuzumab for Treatment of Malignancies for additional information.

Coverage Criteria Revised for talimogene laherparepvec (Imlygic) Highmark West Virginia has revised the coverage criteria for talimogene laherparepvec (Imlygic).

In addition to the FDA approved indication, talimogene laherparepvec (Imlygic) may be considered medically necessary when ANY ONE of the following criteria is met: • Primary and/or second-line treatment of unresectable stage III melanoma with clinical satellite or in-transit metastases; or • Unresectable distant metastatic melanoma; or • Primary and/or second-line treatment of unresectable local, satellite and/or in- transit recurrence; or • Unresectable or incomplete resection of nodal recurrence.

This will apply to both professional provider and facility claims. The effective date is August 28, 2017.

Please refer to Medical Policy I-147, talimogene laherparepvec (Imlygic) for additional information.

7 Medical Policy Update June 2017

Coverage Criteria Established for Pegaspargase (Oncaspar) Highmark West Virginia has established clinical criteria for Pegaspargase (Oncaspar®) for the treatment of Acute Lymphoblastic Leukemia (ALL): • As a component of a multiagent chemotherapeutic regimen for the first-line treatment of patients with ALL; or • As a component of a multiagent chemotherapeutic regimen for the treatment of patients with ALL and hypersensitivity to native forms of L-asparaginase; or • For patients with Philadelphia chromosome-positive ALL aged 15-39 years as a component of COG AALL-0031: o Vincristine, prednisone or dexamethasone, and pegaspargase, with or without daunorubicin; or o Prednisone or dexamethasone and pegaspargase with or without daunorubicin regimen with . Imatinib added during consolidation blocks as induction/consolidation therapy, or . With a second-generation kinase inhibitor for relapsed/refractory disease (if not used for induction); or • As preferred induction/consolidation therapy for Philadelphia chromosome- negative ALL for patients aged 15-39 years as a component of: o CALGB 10403 (daunorubicin, vincristine, prednisone, and pegaspargase) regimen; or o COG AALL0232 (daunorubicin, vincristine, prednisone, and pegaspargase) regimen for patients aged less than or equal to 21 years COG; or o AALL0434 (daunorubicin, vincristine, prednisone, and pegaspargase) regimen with nelarabine added to consolidation for T-cell ALL; or o DFCI ALL (doxorubicin, vincristine, prednisone, high-dose methotrexate, and pegaspargase) regimen; or o USC ALL (daunorubicin, vincristine, prednisone, and methotrexate with augmented pegaspargase) regimen for patients aged greater than or equal to 18 years; or o GRAALL-2003 (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) regimen; or o PETHEMA ALL-96 (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) regimen for patients aged less than 30 years; or • Induction/consolidation therapy for Philadelphia chromosome-negative ALL for patients aged greater than or equal to 40 years as a component of: o CALGB 8811 Larson (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) regimen for patients aged less than 60 years; or o CALGB 8811 Larson (reduced-dose daunorubicin, vincristine, reduced- dose prednisone, pegaspargase, and reduced-dose cyclophosphamide) regimen for patients aged greater than or equal to 60 years; or o Linker 4-drug (daunorubicin, vincristine, prednisone, and pegaspargase) regimen; or o MRC UKALLXII/ECOG2993 induction phase I (daunorubicin, vincristine, prednisone, and pegaspargase) regimen; or • Therapy for relapsed/refractory Philadelphia chromosome-negative ALL or for Philadelphia chromosome-positive ALL refractory to tyrosine kinase inhibitor therapy as a component of augmented Hyper-CVAD (cyclophosphamide, intensified vincristine, doxorubicin, intensified dexamethasone, and pegaspargase) regimen alternating with high-dose methotrexate and cytarabine.

8 Medical Policy Update June 2017

Pegaspargase (Oncaspar) may be considered medically necessary for the treatment of Non-Hodgkin’s Lymphoma - Extranodal NK/T-Cell Lymphoma, nasal type: • When used as a component of GELOX (gemcitabine, pegaspargase, and oxaliplatin) regimen as: o Induction therapy preceding and following radiation for stage I-II nasal disease in select patients who are fit for chemotherapy but are unable to tolerate intense chemotherapy; or o Additional therapy in patients with a positive biopsy following partial response to induction therapy or with refractory disease; or Additional therapy as a component of AspaMetDex (pegaspargase, methotrexate, and dexamethasone) regimen in patients with a positive biopsy following partial response to induction therapy or with refractory disease.

Pegaspargase (Oncaspar) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-158, Pegaspargase (Oncaspar®) for additional information.

Coverage Criteria Established for Bezlotoxumab (Zinplava) Highmark West Virginia has established clinical criteria for Bezlotoxumab (Zinplava) to reduce the recurrence of Clostridium difficile infection (CDI) in individuals who meet all of the following: • Individual is 18 years of age or older; and • Has a confirmed diagnosis of CDI, defined as: o Having passed 3 or more loose bowel movements in 24 or fewer hours; and o A positive stool test for toxigenic C. difficile from a stool sample collected no more than 10 days before treatment with Zinplava; and • Currently receiving the standard of care antibacterial drugs for CDI such as metronidazole, vancomycin, or fidaxomycin; and • Individual is at high risk of CDI recurrence when ANY ONE of the following is present: o Individual is 65 years of age or older; or o Has had one or more episodes of CDI within the six months prior to the episode under treatment; or o Are immunocompromised; or • Has clinically severe CDI (CDI with abdominal distension, hypoalbuminemia (serum albumin less than 3g /dl) and a white blood cell (WBC) count greater than or equal to 15,000 cells/ mm 3); and Zinplava will only be approved for one dose per active CDI. Zinplava will not be approved for any repeat doses for recurrence of the same active infection.

9 Medical Policy Update June 2017

This new criteria will apply to both professional provider and facility claims. The effective date is August 28, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-165, Bezlotoxumab (Zinplava) for additional information.

Coverage Criteria Established for Elotuzumab (Empliciti) Highmark West Virginia has established clinical criteria for Elotuzumab (Empliciti™) when all of the following are met: • Therapy for relapsed, progressive or refractory multiple myeloma; and • Patient has received one to three prior therapies; and • Elotuzumab is being used in combination with: o Lenalidomide and dexamethasone (preferred); or o Bortezomib and dexamethasone.

Elotuzumab (Empliciti) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-166, Elotuzumab (Empliciti™) for additional information.

Coverage Criteria Established for Necitumumab (Portrazza) Highmark West Virginia has established clinical criteria for Necitumumab (Portrazza™). Necitumumab (Portrazza) may be considered medically necessary in combination with gemcitabine and cisplatin as first-line treatment of adults 18 years of age and older with metastatic squamous non-small cell lung cancer (NSCLC).

Necitumumab (Portrazza) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-168, Necitumumab (Portrazza™) for additional information.

10 Medical Policy Update June 2017

Coverage Criteria Established for Siltuximab (Sylvant) Highmark West Virginia has established clinical criteria for Siltuximab (Sylvant). Siltuximab (Sylvant) may be considered medically necessary for the treatment of adults with Castleman disease (CD) when ALL of the following criteria are met: • Unicentric Castleman disease (UCD): o As a single-agent, second line therapy for relapsed or refractory UCD; and o Patient is human immunodeficiency virus-negative and human herpesvirus-8- negative. • Multicentric Castleman disease (MCD): o As a single-agent therapy for active MCD and when individual meets ANY ONE of the following . As primary treatment; or . For relapsed disease; or . If no response to primary treatment; and o Patient is human immunodeficiency virus-negative and human herpesvirus-8- negative; and o Patient does not have organ failure; and o No concurrent clinically significant infection (for example, Hepatitis B or C); and o No concurrent lymphoma; and . Members must have hematology laboratory tests prior to first siltuximab dose showing the following Absolute Neutrophil Count: greater than 1.0 x109/L; and . Platelet Count: greater than 75 x109/L; and . Hemoglobin less than 17g/dL.

Siltuximab (Sylvant) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-170, Siltuximab (Sylvant) for additional information.

11 Medical Policy Update June 2017

Coverage for the Quadrivalent (RIV4) Influenza Virus Vaccine Highmark West Virginia has changed its coverage position for the influenza virus vaccine, quadrivalent (RIV4), derived from recombinant DNA, Hemagglutinin (HA) protein only, preservative and antibiotic free, for intramuscular use.

Effective July 1, 2017, this immunization will no longer be considered experimental/investigational.

This change in coverage position applies to professional providers only.

Please refer to Medical Policy I-8, Immunizations, for additional information.

Correction: Medical Policy L-28, Tumor Markers Highmark West Virginia has corrected Medical Policy L-28, Tumor Markers. The statement listing the UroVysion® FISH Testing for Bladder Cancer as experimental/ investigational has been removed. As of February 6, 2017, this service has been considered medically necessary when specific criteria have been met. The corrected policy was published on June 12, 2017.

UroVysion testing may be considered medically necessary when the following criteria are met:

Previous Testing: • No repeat UroVysion testing on the same sample when a result was successfully obtained; and • Diagnosis o UroVysion is not indicated for the routine evaluation of hematuria or microhematuria and will not be reimbursed when billed with an ICD-10 code in the R31 Hematuria range. Exceptions may be made for uncertain or equivocal results on standard diagnostic assessments, such as cytology; or • Surveillance o UroVysion is indicated when the individual has a personal history of bladder cancer defined as an ICD-10 code in the C67 Malignant neoplasm of the bladder range; and o The member is being monitored for cancer recurrence; and . Member had been diagnosed with low grade bladder cancer and the results of cytology are equivocal; or . Member had been diagnosed with high grade bladder cancer and the results of cytology are negative or equivocal.

Please refer to Medical Policy L-28, Tumor Markers for additional information.

12 Medical Policy Update June 2017

Facility Criteria Applied to Intensity Modulated Radiation Therapy (IMRT) Highmark West Virginia has revised Medical Policy R-11, Intensity Modulated Radiation Therapy (IMRT), to apply the coverage criteria to facility. This policy will apply to both professional provider and facility claims. The effective date is August 28, 2017.

IMRT may be considered medically necessary when ALL the following criteria are met: • IMRT should not be used as a substitute for conventional radiation therapy methods; and • Sparing surrounding normal tissue is of added benefit; and • One or more of the following conditions are met: o The target volume is in close proximity to critical structures that must be protected; or o The volume of interest must be covered with narrow margins to adequately protect immediately adjacent structures; or o An immediately adjacent area has been previously irradiated and abutting portals must be established with high precision; or o Dose escalation is planned to deliver radiation doses in excess of those commonly utilized for similar tumors with conventional treatment. IMRT is considered not medically necessary for all other indications not listed in this medical policy.

Intensity modulated radiation therapy (IMRT) may be considered medically necessary in some clinical situations for the following conditions: • Primary bone and articular cartilage cancer of the skull and face, vertebral column, sacrum and coccyx as related to dose needed to be delivered; or • Primary, metastatic, or benign tumors of the central nervous system including the brain, brain stem, and spinal cord; or • Primary, metastatic, or benign tumors of the spine where the spinal cord tolerance may be exceeded with conventional treatment; or • Primary, metastatic, or benign lesions to the head and neck area including any of the following sites: lip; eye; thyroid; salivary glands; hypopharynx; oropharynx; nasopharynx; other parts of the pharynx not explicitly identified here; oral cavity; tongue; nasal cavities; middle ear; accessory sinuses; larynx; lymph nodes of the head, face and neck; pituitary gland, pineal gland, carotid body; and skin of lip, eyelid, ear and external auditory canal; or • Primary small cell and non-small cell lung cancer; or • Carcinoma of the prostate; or • Pelvic and retroperitoneal malignancies; or • Squamous cell cancer of the anus/anal canal; or • Locally advanced rectal adenocarcinoma when dosimetric planning predicts the risk of small intestine injury with standard 3D conformal treatment would be unacceptable; or • Gynecological cancer may be given consideration when one or more of the following conditions are met: o When the planned dose will be higher than the standard 45-50.4 Gy; or 13 Medical Policy Update June 2017

o A positive margin will be treated concomitantly; or o An extended field will be treated; or o There has been a history of adhesions or small bowel complications; or o Imaging confirms an excessive amount of small bowel in the treatment field; or • The use of IMRT for breast cancer will be reviewed on a case-by-case basis (e.g., IMRT may be indicated if the breast cancer cannot be adequately covered using 3D conformal therapy). The list of approved anatomic sites for IMRT is not all-inclusive. Therefore, requests for conditions other than those listed will be reviewed on a case-by-case basis as to medical necessity.

The rationale for using IMRT over other forms of radiation therapy should be documented in the patient’s medical record.

IMRT is considered not medically necessary for all other indications not listed in this policy.

Please refer to Medical Policy R-11, Intensity Modulated Radiation Therapy (IMRT) for additional information.

Coverage Criteria Revised for Radioimmunotherapy for the Evaluation and Treatment of Certain Non-Hodgkin’s Lymphoma Highmark West Virginia has revised the coverage criteria for radioimmunotherapy for the evaluation and treatment of certain Non-Hodgkin’s lymphoma. This policy will apply to professional provider claims. The effective date is August 28, 2017.

A single course of ibritumomab tiuxetan (Zevalin®) may be considered medically necessary for the treatment of individuals with relapsed or refractory CD20-positive, low- grade or follicular B-cell non-Hodgkin’s lymphoma.

The use of ibritumomab tiuxetan (Zevalin) for the initial treatment of follicular lymphoma may be considered medically necessary in individuals who are unable to tolerate standard chemotherapy, e.g., elderly or frail individuals.

The use of Ibritumomab tiuxetan (Zevalin) for consolidation after chemotherapy for CD20- positive follicular non-Hodgkin’s lymphoma may be considered medically necessary after at least partial response to chemotherapy.

Radioimmunotherapy with ibritumomab tiuxetan (Zevalin) for consolidation of a first remission following chemotherapy for de novo aggressive B-cell NHL is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer- reviewed literature.

The use of Ibritumomab tiuxetan (Zevalin) as part of a preparatory regimen before autologous or allogeneic hematopoietic stem-cell transplantation in patients with non- Hodgkin lymphoma is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the 14 Medical Policy Update June 2017

available published peer-reviewed literature.

Please refer to Medical Policy R-58, Radioimmunotherapy for the Evaluation and Treatment of Certain Non-Hodgkin’s Lymphoma for additional information.

New Coverage Criteria for Magnetic Esophageal Ring to Treat Gastroesophageal Reflux Disease (LINX) Highmark West Virginia has established coverage criteria for Magnetic Esophageal Ring to Treat Gastroesophageal Reflux Disease (LINX®). These criteria will apply to both professional provider and facility claims. The effective date is June 12, 2017.

A laparoscopically implantable magnetic esophageal ring (LINX™ Reflux Management System) may be considered medically necessary when ALL of the following conditions are met: • When used as an alternative treatment to surgical fundoplication; and • When the patient presents with gastroesophageal reflux disease (GERD) and is symptomatic two or more times per week; and • Who have GERD symptoms despite medical therapy or are intolerant to medical therapy.

Place of Service: Inpatient/Outpatient

Please refer to Medical Policy S-233, Magnetic Esophageal Ring to Treat Gastroesophageal Reflux Disease (LINX®) for additional information.

Revised Criteria for Bone Morphogenetic Protein Effective August 28, 2017, Medical Policy S-235, Bone Morphogenetic Protein clinical criteria has been revised. The revised policy clinical criteria apply to Professional and Facility claims.

Use of a recombinant human bone morphogenetic protein-2 (rhBMP-2; INFUSE) may be considered medically necessary in skeletally mature patients (greater than or equal to 18 years of age) when used in conjunction with an Infuse Bone Graft fusion device when the following criterion is met:

• For anterior lumbar interbody fusion (ALIF) or oblique lateral (OLIF) procedures when use of autograft, (i.e. gold standard) is unfeasible: and • Degenerative disc disease (DDD) at one level L2 - S1; and • No more than Grade I spondylolisthesis or Grade 1 retrolisthesis at the involved level; and • The disc degeneration is confirmed by history and x-ray studies; and • Non-responsive to at least six months of non-operative therapy that may include the following (not all inclusive): o Education/counseling o Physical Therapy o Non-steroidal, muscle relaxants, injections o Devices (e.g., brace, corset, orthopedic pillow, TENS, etc.).

Use of a recombinant human bone morphogenetic protein-2 (rhBMP-2; INFUSE) may be 15 Medical Policy Update June 2017

considered medically necessary in skeletally mature patients (greater than or equal to 18 years of age) when ALL the following criterion is met: • Treatment of acute, open fracture of the tibial shaft when use of autograft is unfeasible; and o Fracture has been stabilized with intramedullary nail (IM) fixation after appropriate wound management; and o Graft must be applied within 14 days after the initial fracture.

Note: Use of autograft [i.e., iliac crest bone graft (ICBG)] may be considered unfeasible due to situations that may include, but are not limited to: o Prior harvesting of ICBG; or o Concurrent medical conditions and co-morbidities (e.g. diabetes, tobacco use that increase risk of autograft use).

Repeat applications of INFUSE bone graft is considered not medically necessary as the safety and effectiveness has not been established.

Bone morphogenetic protein (rhBMP-2 INFUSE) is considered experimental/investigational for all other indications, and therefore, non-covered. The safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature including but not limited to: • Spinal fusion when use of autograft is feasible; or when used for spinal fusion procedures other than single-level anterior spinal fusion, or lateral oblique (e.g., posterior lumbar fusion, transforaminal lumbar fusion, more than single-level fusion). • As an alternative or adjunct treatment for sinus augmentation and/or localized alveolar ridge augmentation. • For the treatment of cervical spine conditions.

Recombinant human bone morphogenetic protein (rhBMP-7) also known as OP-1 is no longer marketed in the United States and therefore the clinical indications were removed from the policy bulletin.

16 Medical Policy Update June 2017

Medicare Advantage Policy

Criteria Revised for Pertuzumab for Treatment of Malignancies Highmark’s Medicare Advantage product has revised clinical criteria for Pertuzumab (Perjeta). Additional coverage criteria has been added based upon National Comprehensive Cancer Network (NCCN) guidelines. Pertuzumab (Perjeta) may be considered medically necessary for the treatment of breast cancer for ANY ONE of the following indications: • Preoperative systemic therapy for patients HER2-positive stage IIA (T2, N0, M0), stage IIB (T2, N1, M0 or T3, N0, M0), or stage IIIA (T3, N1, M0) disease who desire breast preservation and fulfill criteria for breast-conserving surgery except for tumor size or for locally advanced disease (stage IIIA (any T, N2, M0), IIIB, or IIIC): o In combination with trastuzumab and paclitaxel (preferred regimen) or trastuzumab and docetaxel following AC (doxorubicin and cyclophosphamide) regimen; or o In combination with TCH (docetaxel, carboplatin, and trastuzumab) regimen (preferred regimen); or o In combination with trastuzumab and paclitaxel or trastuzumab and docetaxel prior to or following FEC (fluorouracil, epirubicin, and cyclophosphamide) regimen; or • Adjuvant systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive greater than or equal to T2 or greater than or equal to N1 early stage or locally advanced breast cancer if a pertuzumab-containing regimen was not used as neoadjuvant therapy: o In combination with trastuzumab and paclitaxel (preferred regimen) or trastuzumab and docetaxel following AC (doxorubicin and cyclophosphamide) regimen; or o In combination with TCH (docetaxel, carboplatin, and trastuzumab) regimen (preferred regimen); or o In combination with trastuzumab and paclitaxel or trastuzumab and docetaxel prior to or following FEC (fluorouracil, epirubicin, and cyclophosphamide) regimen; or • Used for recurrent or metastatic human epidermal growth factor receptor 2 (HER2)-positive disease that is either hormone receptor- negative, hormone receptor-positive and endocrine therapy refractory, for symptomatic visceral disease, or visceral crisis: o As preferred first-line therapy in combination with trastuzumab with docetaxel or paclitaxel; or o May be considered in combination with trastuzumab with or without cytotoxic therapy (e.g., vinorelbine or taxane) for one line of therapy beyond first-line therapy in patients previously treated with chemotherapy and trastuzumab in the absence of pertuzumab.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

17 Medical Policy Update June 2017

Please refer to Medical Policy I-115, Pertuzumab for Treatment of Malignancies for additional information.

Coverage Criteria Revised for talimogene laherparepvec (Imlygic) Highmark’s Medicare Advantage product has revised the coverage criteria for talimogene laherparepvec (Imlygic).

This will apply to both professional provider and facility claims. The effective date is August 28, 2017.

Please refer to Medicare Advantage Medical Policy I-147, talimogene laherparepvec (Imlygic) for additional information.

Coverage Criteria Established for Pegaspargase (Oncaspar) Highmark’s Medicare Advantage product has established clinical criteria for Pegaspargase (Oncaspar®) for the treatment of Acute Lymphoblastic Leukemia (ALL): • As a component of a multiagent chemotherapeutic regimen for the first-line treatment of patients with ALL; or • As a component of a multiagent chemotherapeutic regimen for the treatment of patients with ALL and hypersensitivity to native forms of L-asparaginase; or • For patients with Philadelphia chromosome-positive ALL aged 15-39 years as a component of COG AALL-0031: o Vincristine, prednisone or dexamethasone, and pegaspargase, with or without daunorubicin; or o Prednisone or dexamethasone and pegaspargase with or without daunorubicin regimen with . Imatinib added during consolidation blocks as induction/consolidation therapy, or . With a second-generation kinase inhibitor for relapsed/refractory disease (if not used for induction); or • As preferred induction/consolidation therapy for Philadelphia chromosome- negative ALL for patients aged 15-39 years as a component of: o CALGB 10403 (daunorubicin, vincristine, prednisone, and pegaspargase) regimen; or o COG AALL0232 (daunorubicin, vincristine, prednisone, and pegaspargase) regimen for patients aged less than or equal to 21 years COG; or o AALL0434 (daunorubicin, vincristine, prednisone, and pegaspargase) regimen with nelarabine added to consolidation for T-cell ALL; or o DFCI ALL (doxorubicin, vincristine, prednisone, high-dose methotrexate, 18 Medical Policy Update June 2017

and pegaspargase) regimen; or o USC ALL (daunorubicin, vincristine, prednisone, and methotrexate with augmented pegaspargase) regimen for patients aged greater than or equal to 18 years; or o GRAALL-2003 (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) regimen; or o PETHEMA ALL-96 (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) regimen for patients aged less than 30 years; or • Induction/consolidation therapy for Philadelphia chromosome-negative ALL for patients aged greater than or equal to 40 years as a component of: o CALGB 8811 Larson (daunorubicin, vincristine, prednisone, pegaspargase, and cyclophosphamide) regimen for patients aged less than 60 years; or o CALGB 8811 Larson (reduced-dose daunorubicin, vincristine, reduced- dose prednisone, pegaspargase, and reduced-dose cyclophosphamide) regimen for patients aged greater than or equal to 60 years; or o Linker 4-drug (daunorubicin, vincristine, prednisone, and pegaspargase) regimen; or o MRC UKALLXII/ECOG2993 induction phase I (daunorubicin, vincristine, prednisone, and pegaspargase) regimen; or • Therapy for relapsed/refractory Philadelphia chromosome-negative ALL or for Philadelphia chromosome-positive ALL refractory to tyrosine kinase inhibitor therapy as a component of augmented Hyper-CVAD (cyclophosphamide, intensified vincristine, doxorubicin, intensified dexamethasone, and pegaspargase) regimen alternating with high-dose methotrexate and cytarabine.

Pegaspargase (Oncaspar) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-158, Pegaspargase (Oncaspar®) for additional information.

19 Medical Policy Update June 2017

Coverage Criteria Established for Bezlotoxumab (Zinplava) Highmark’s Medicare Advantage product has established clinical criteria for Bezlotoxumab (Zinplava) for the treatment of patients currently being treated for Clostridium difficile infection (CDI) who are at high risk of CDI recurrence.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-165, Bezlotoxumab (Zinplava) for additional information.

Coverage Criteria Established for Elotuzumab (Empliciti) Highmark’s Medicare Advantage product has established clinical criteria for Elotuzumab (Empliciti™) when all of the following are met: • Therapy for relapsed, progressive or refractory multiple myeloma; and • Patient has received one to three prior therapies; and • Elotuzumab is being used in combination with: o Lenalidomide and dexamethasone (preferred); or o Bortezomib and dexamethasone.

Elotuzumab (Empliciti) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-166, Elotuzumab (Empliciti™) for additional information.

Coverage Criteria Established for Necitumumab (Portrazza) Highmark’s Medicare Advantage product has established clinical criteria for Necitumumab (Portrazza™). Necitumumab (Portrazza) may be considered medically necessary in combination with gemcitabine and cisplatin as first-line treatment of adults 18 years of age and older with metastatic squamous non-small cell lung cancer (NSCLC).

Necitumumab (Portrazza) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient 20 Medical Policy Update June 2017

Please refer to Medical Policy I-168, Necitumumab (Portrazza™) for additional information.

Coverage Criteria Established for Siltuximab (Sylvant) Highmark’s Medicare Advantage product has established clinical criteria for Siltuximab (Sylvant). Siltuximab (Sylvant) may be considered medically necessary for the treatment of adults with Castleman disease (CD) when ALL of the following criteria are met: • Unicentric Castleman disease (UCD): o As a single-agent, second line therapy for relapsed or refractory UCD; and o Patient is human immunodeficiency virus-negative and human herpesvirus-8-negative. • Multicentric Castleman disease (MCD): o As a single-agent therapy for active MCD and when individual meets ANY ONE of the following . As primary treatment; or . For relapsed disease; or . If no response to primary treatment; and o Patient is human immunodeficiency virus-negative and human herpesvirus-8-negative; and o Patient does not have organ failure; and o No concurrent clinically significant infection (for example, Hepatitis B or C); and o No concurrent lymphoma; and . Members must have hematology laboratory tests prior to first siltuximab dose showing the following Absolute Neutrophil Count: greater than 1.0 x109/L; and . Platelet Count: greater than 75 x109/L; and . Hemoglobin less than 17g/dL.

Siltuximab (Sylvant) is considered experimental/investigational for any other indication and therefore non-covered. Scientific evidence does not support its use for any other indications.

This new criteria will apply to both professional provider and facility claims. The effective date is August 31, 2017.

Place of Service: Outpatient

Please refer to Medical Policy I-170, Siltuximab (Sylvant) for additional information.

21 Medical Policy Update June 2017

New Policy Established for MolDX: APC and MUTYH Gene Testing Highmark’s Medicare Advantage product has established new policy guidelines for MolDX: APC and MUTYH gene testing. This new policy will apply to both professional provider and facility claims. The effective date is March 13, 2017.

Please refer to Medical Policy L-165, MolDX: APC and MUTYH Gene Testing for more information.

22 Medical Policy Update June 2017

Comments on these new medical policies? We want to know what you think about our new medical policy changes. Send us an email with any questions or comments that you may have on the new medical policies in this edition of Medical Policy Update.

Write to us at [email protected].

Coverage Criteria Established for Leuprolide Acetate (Lupron Depot-Ped) and Leuprolide, norethindrone (Lupaneta Pack) Leuprolide acetate (Eligard) and Histrelin acetate (Vantas) ...... 1 Revised Criteria for Treatment of Hereditary Angioedema (HAE) ...... 4 Revised Criteria for Alpha 1 Proteinase Inhibitor Infusions...... 5 Revised Criteria for Decitabine (Dacogen) ...... 5 Revised Criteria for Eculizumab...... 6 Criteria Revised for Pertuzumab for Treatment of Malignancies ...... 6 Coverage Criteria Revised for talimogene laherparepvec (Imlygic)...... 7 Coverage Criteria Established for Pegaspargase (Oncaspar) ...... 8 Coverage Criteria Established for Bezlotoxumab (Zinplava) ...... 8 Coverage Criteria Established for Elotuzumab (Empliciti) ...... 10 Coverage Criteria Established for Necitumumab (Portrazza) ...... 10 Coverage Criteria Established for Siltuximab (Sylvant) ...... 11 Coverage for the Quadrivalent (RIV4) Influenza Virus Vaccine...... 12 Correction: Medical Policy L-28, Tumor Markers ...... 12 Facility Criteria Applied to Intensity Modulated Radiation Therapy (IMRT)...... 13 Coverage Criteria Revised for Radioimmunotherapy for the Evaluation and Treatment of Certain Non-Hodgkin’s Lymphoma ...... 14 New Coverage Criteria for Magnetic Esophageal Ring to Treat Gastroesophageal Reflux Disease (LINX)...... 15 Revised Criteria for Bone Morphogenetic Protein ...... 15 Criteria Revised for Pertuzumab for Treatment of Malignancies ...... 17 Coverage Criteria Revised for talimogene laherparepvec (Imlygic)...... 18 Coverage Criteria Established for Pegaspargase (Oncaspar) ...... 18 Coverage Criteria Established for Bezlotoxumab (Zinplava) ...... 20 Coverage Criteria Established for Elotuzumab (Empliciti) ...... 20 Coverage Criteria Established for Necitumumab (Portrazza) ...... 20 Coverage Criteria Established for Siltuximab (Sylvant) ...... 21 New Policy Established for MolDX: APC and MUTYH Gene Testing...... 22 Comments on these new medical policies?...... 23 Contents...... 23

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23 Medical Policy Update June 2017

About this newsletter

Medical Policy Update is the monthly newsletter for most health care professionals (and office staff) and facilities who participate in our networks and submit claims to Highmark using the 837P HIPAA transaction or the CMS 1500 form, or the 837I HIPAA transaction. Medical Policy Update focuses only on medical policy and claims administration updates, including coding guidelines and procedure code revisions, and is the sole source for this information. For all other news, information and updates, be sure to read Provider News, available on the Provider Resource Center at www.highmarkbcbswv.com.

Inquiries about Eligibility, Benefits, Claims Status or Authorizations For inquiries about eligibility, benefits, claim status or authorizations, Highmark encourages providers to use the electronic resources available to them - Navinet® and the applicable HIPAA transactions – prior to placing a telephone call to the Provider Service Center at 1-800-242-0514.

Acknowledgement

The five-digit numeric codes that appear in Medical Policy Update were obtained from the Current Procedural Terminology (CPT), as contained in CPT- 2017, Copyright 2016, by the American Medical Association. Medical Policy Update includes CPT descriptive terms and numeric procedure codes and modifiers that are copyrighted by the American Medical Association. These procedure codes and modifiers are used for reporting medical services and procedures.