MP/CG Update/Notice - January 2016 Form

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

January 28, 2016

Dear Provider: Anthem Blue Cross is pleased to provide you with our updated and new Medical Policies and Clinical UM Guidelines. The updated polices listed below are effective for service dates on and after May 1, 2016. The major new policies and changes are summarized below. Please refer to the specific policy for coding, language, and rationale updates and changes that are not summarized below. New Medical Policies and Clinical Guidelines effective May 1, 2016:

• DRUG.00079 Bendamustine Hydrochloride (TREANDA®): This document addresses the indications for the use of bendamustine hydrochloride (HCL), a cytotoxic, bifunctional mechlorethamine derivative with alkylator and antimetabolite activities used in the treatment of oncologic conditions. o Outlines the medically necessary, and investigational and not medically necessary criteria for bendamustine HCL

• DRUG.00080 Mepolizumab (Nucala®): This document addresses the use of mepolizumab (Nucala),
a humanized monoclonal antibody against interleukin-5 used for the treatment of individuals with severe eosinophilic asthma not well-controlled with inhaled corticosteroids and long-acting beta-agonists. o Outlines the medically necessary, and investigational and not medically necessary criteria for mepolizumab

• THER-RAD.00011 Image-guided Radiation Therapy (IGRT) with External Beam Radiation Therapy (EBRT): This document addresses image-guided radiation therapy (IGRT) when used in combination with conformal external beam radiation therapy (EBRT). o Outlines the medically necessary, and investigational and not medically necessary criteria for IGRT used in conjunction with EBRT

• CG-SURG-44 Coronary Angiography and Cardiac Catheterization in the Outpatient Setting:
This document addresses the diagnostic indications for outpatient cardiac catheterization and coronary angiography.
o Outlines the medically necessary and not medically necessary criteria for diagnostic cardiac catheterization and coronary angiography in the outpatient setting

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

• CG-SURG-48 Elective Percutaneous Coronary Interventions (PCI): This document addresses elective, non-emergent, primarily outpatient percutaneous coronary interventions (PCI), which refers to percutaneous transluminal coronary angioplasty (PTCA), performed with or without coronary stent implantation, and atherectomy for the treatment of coronary artery disease (CAD). o Outlines the medically necessary and not medically necessary clinical indications for elective percutaneous coronary interventions which may include the following procedures: • Percutaneous transluminal coronary angioplasty (PTCA) with or without stent implantation • Intracoronary atherectomy

• CG-SURG-49 Endovascular Techniques (Percutaneous or Open Exposure) for Arterial Revascularization of the Lower Extremities: This document addresses the use of peripheral vascular angioplasty, with and without stenting, and with or without atherectomy, for the treatment of occlusive peripheral arterial disease (PAD) of the lower extremities.
o Outlines the medically necessary and not medically necessary indications addressing endovascular techniques for arterial revascularization of the lower extremities Revised Medical Policies and Adopted Clinical UM Guidelines effective May 1, 2016:

• DME.00035 Electric Tumor Treatment Field (TTF): This document addresses electrical fields known as “tumor treatment fields (TTF)” that are created by low-intensity, intermediate frequency (100–200 kilohertz [kHz]) electric currents delivered to the malignant tumor site by insulated electrodes placed on the skin surface. TTF is felt to cause tumor cell death (apoptosis) by disrupting the assembly of microtubules during later stages of cell division. o No change to position statement o Updated Rationale, Background, Coding, Reference and Index sections

• DRUG.00039 Trastuzumab (Herceptin®): This document addresses the indications for trastuzumab, a humanized recombinant DNA monoclonal antibody that targets tumor cells overexpressing the human epidermal growth factor receptor 2 (HER2) protein and/or amplification of the HER2 gene. o Revised investigational and not medically necessary statement to include all other indications, including but not limited to: lung cancer, osteosarcoma and pancreatic cancer o Updated Description, Rationale, Definitions and Reference sections
o Removed ICD-9 codes from Coding section

• GENE.00029 Genetic Testing for Breast and/or Ovarian Cancer Syndrome: This document addresses genetic testing for individuals who are at higher than average risk for the development of breast and/or ovarian cancer. o Revised medically necessary criteria for BRCA 1 or BRCA 2 testing for individuals with a personal history of cancer and individuals with a family history of cancer o Clarified the meaning of multiple primary breast cancers
o Revised medically necessary criteria for individuals with a history of pancreatic cancer (or a first- or second-degree relative with a history of pancreatic cancer) to require a first-, second-, or third- degree relative with breast cancer (diagnosed at or prior to 50 years of age) and/or ovarian, fallopian tube, primary peritoneal or pancreatic cancer at any age. (Previous version of the policy required 2 or more relatives on the same side of the family but there was no requirement that breast cancer be diagnosed at or prior to 50 years of age) o Expanded medically necessary criteria addressing at risk populations to include racial background (African Americans) o Clarified criteria for individuals who are of Ashkenazi descent (or who have a first- or second- degree relative of Ashkenazi Jewish descent) who have a history of pancreatic cancer

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

o Revised medically necessary criteria for BRCA 1 or BRCA 2 testing for individuals with a family history of cancer by removing redundant criteria addressing individuals who have a first- or second-degree relative who has a history of ovarian cancer and 2 or more first-, second-, or third- degree relatives on the same side of the family with pancreatic cancer o Removed the DeCode BreastCancer™ test from investigational and not medically necessary statement o Updated Rationale, Background, Reference and Index sections o Removed ICD-9 codes from Coding section

• LAB.00031 Advanced Lipoprotein Testing: This document addresses the use of advanced testing of lipoproteins for cardiovascular disease (CVD) risk assessment and management and all other indications. o Title revised (old title was from Advanced Lipoprotein Testing in Cardiac Disease Risk Assessment and Management) o Expanded scope of policy o Revised position statement to state that advanced lipoprotein testing is investigational and not medically necessary for CVD risk assessment and management and for all other indications o Updated Description, Rationale, Coding and Reference sections

• MED.00103 Automated Evacuation of Meibomian Gland: This document addresses the use of devices which will automate the process of applying heat and intermittent pressure for the treatment of meibomian gland dysfunction, and associated imaging. o Revised scope of document to include imaging associated with the automated evacuation devices o Added tear film imaging as investigational and not medically necessary o Updated Description, Background, Coding and Reference sections

• MED.00113 Therapeutic Apheresis: This document addresses therapeutic apheresis, a procedure by which blood is removed from the body, separated into components, manipulated and returned to the individual. o Revised medically necessary indication for thrombotic microangiopathy clarifying that plasmapheresis (plasma exchange) is medically necessary for the treatment of thrombotic microangiopathy secondary to ticlopidine or malignancy o Added HLA incompatibility with haplo-type hematopoietic stem cell transplant as a medically necessary indication for plasmapheresis or plasma exchange
o Made a minor formatting change in medically necessary criteria for erythrocytapheresis or phlebotomy o Clarified that the treatment of thrombotic microangiopathy secondary to drugs other than ticlopidine (for example, clopidogrel, cyclosporine, gemcitabine, quinine, or tacrolimus) is investigational and not medically necessary o Removed hematopoietic stem cell transplant - ABO incompatible as investigational and not medically necessary indication for cytapheresis
o Made minor wording changes throughout position statement
o Updated Description, Rationale, Definitions, Coding and References sections

• SURG.00024 Bariatric Surgery and Other Treatments for Clinically Severe Obesity: This document addresses surgical and other treatments for clinically severe obesity.
o Title revised (old title was Surgery for Clinically Severe Obesity) o Expanded scope of document to include non-surgical treatments
o Added an investigational and not medically necessary statement for surgical procedures when criteria are not met

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

o Revised investigational and not medically necessary statement addressing other procedures and treatment modalities o Added balloon systems (such as the ReShape® Integrated Dual Balloon System) and vagus (or vagal) nerve blocking devices (such as the MAESTRO® Rechargeable System) as investigational and not medically necessary o Updated Description, Rationale, Background, Definitions, Coding, Reference and Index sections

• THER-RAD.00002 Proton Beam Radiation Therapy: This document addresses different applications of proton beam radiation therapy (PBRT) in the treatment of benign and malignant tumors and arteriovenous malformation. o Number revised (previous number was RAD.00015) o Reformatted medically necessary criteria
o Removed medically necessary, and investigational and not medically necessary position statements for localized prostate cancer
o Revised remaining investigational and not medically necessary statement to state PBRT is investigational and not medically necessary when criteria are not met and for all other indications, including but not limited to, the treatment of localized prostate cancer o Updated Description, Rationale, Background, Definitions, Coding and Reference sections o Removed Appendices

• THER-RAD.00008 Neutron Beam Radiotherapy: This document addresses neutron beam radiation therapy. o Re-categorized (previous category and number was RAD.00047) o Revised position statement to now consider neutron beam radiotherapy investigational and not medically necessary for all indications o Updated Rationale, Coding and Reference sections

• CG-DRUG-45 Octreotide acetate (Sandostatin®; Sandostatin® LAR Depot): This document addresses the clinical uses of octreotide acetate (Sandostatin, and Sandostatin LAR Depot), approved by the U.S. FDA to treat acromegaly, carcinoid tumors, vasoactive intestinal peptide tumors, and used as off-label treatment for other conditions.
o Removed medically necessary criteria for the treatment of adrenal gland tumors o Added the treatment of adrenal gland tumors as not medically necessary o Updated Discussion and Reference sections o Removed ICD-9 codes from Coding section

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

Anthem Blue Cross Medical Policies and Clinical UM Guidelines are developed by our Medical Policy and Technology Assessment Committee. The Committee, which includes Anthem medical directors and representatives from practicing physician groups, meets quarterly to review current scientific data and clinical developments. Medical Policies and Clinical UM Guidelines are subject to the approval of the Physician Relations Committee.

All coverage written or administered by Anthem Blue Cross excludes from coverage services or supplies that are investigational and/or not medically necessary. A member’s claim may not be eligible for payment if it was determined not to meet medical necessity criteria set forth in Anthem Blue Cross’ Medical Policies. Review procedures have been refined to facilitate claim investigation.

The complete list of our Medical Policies and Clinical UM Guidelines may be accessed on the Anthem Blue Cross Web site at www.anthem.com/ca, select “Provider”, and then select “Medical Policies and Clinical UM Guidelines” listed under “Learn More”. Recent changes to Medical Policies can be found under “Recent Updates". We thank you for your continued efforts on behalf of our members and your partnership toward improved access to quality health care for Californians.

Sincerely,

Jacob Asher, MD Vice President and Chief Medical Officer

Enclosure: Attachment A

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

Attachment A The revised medical policies listed below will become effective for services rendered
on or after May 1, 2016.

Medical Policy Number Medical Policy Title Medical Policy / Clinical Guideline Changes DRUG.00002 Tumor Necrosis Factor Antagonists • Added the treatment of hidradenitis suppurativa with adalimumab as medically necessary when criteria are met • Revised investigational and not medically necessary statement for adalimumab DRUG.00043 Tocilizumab (Actemra®) • Added the use of tocilizumab used as subsequent therapy for the treatment of an individual with relapsed/refractory or progressive multicentric Castleman disease (MCD) as medically necessary when criteria are met • Removed multicentric Castleman disease from investigational and not medically necessary position statement • Added unicentric Castleman disease as investigational and not medically necessary • Updated Description Rationale Background Definition DRUG.00046 Ipilimumab (Yervoy®) • Title revised - replaced trademark in brand name with registered mark • Revised ECOG performance status criterion to be 0-2 (previously 0-1) in medically necessary criteria addressing both first-line therapy and retreatment of individuals with melanoma • Added ipilimumab as medically necessary when used as a single agent or in combination with nivolumab as second-line or subsequent therapy for disease progression of an individual with metastatic or unresectable melanoma and a performance status of 0-2, if nivolumab not previously used • Added the adjuvant treatment of cutaneous melanoma in individuals with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete ti i l di l h d t di ll DRUG.00047 Brentuximab Vedotin (Adcetris®) • Clarified medically necessary criteria addressing Hodgkin lymphoma • Added the treatment of individuals with CD30+ positive T-cell lymphoma that is relapsed or refractory to first-line therapy as medically necessary

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

DRUG.00051 Ziv-aflibercept (Zaltrap®) • Added anal adenocarcinoma, appendiceal adenocarcinoma and small bowel adenocarcinoma as medically necessary when criteria are met • Updated Rationale, Background, Definition, Coding and DRUG.00053 Carfilzomib (Kyprolis®) • Title revised - replaced trademark in brand name with registered mark • Clarified and reformatted medically necessary criteria addressing the treatment of multiple myeloma • Added carfilzomib in combination with lenalidomide and dexamethasone as medically necessary when the individual has received one to three prior lines of therapy • Added the treatment of Waldenström's macroglobulinemia as medically necessary when criteria are met DRUG.00066 Antihemophilic Factors and Clotting Factors • Clarified medically necessary criteria addressing recombinant Factor VIIa (NovoSeven RT) by adding "for the treatment of bleeding episodes and peri-operative management" in individuals with Glanzmann’s thrombasthenia and a documented refractoriness to platelet transfusions with or without antibodies to platelets • Added the drug Nuwiq as medically necessary when the recombinant antihemophilic factor (Factor VIII) criteria are met • Added human plasma-derived coagulation Factor X, (Coagadex) as medically necessary when criteria are met • Added Coagadex as investigational and not medically necessary when the criteria are not met and for all other indications including, but not limited to perioperative management of bleeding in major surgery in individuals with moderate and severe hereditary Factor X deficiency • Clarified medically necessary criteria addressing human plasma- DRUG.00068

Vedolizumab (Entyvio®) • Title revised - replaced trademark in brand name with registered mark • Made minor wording changes in position statement DRUG.00071 Pembrolizumab (Keytruda®) • Revised ECOG performance status criterion to be 0-2 (previously 0-1) in medically necessary criteria addressing individuals with melanoma • Added the treatment of metastatic non-small cell lung cancer (NSCLC) as medically necessary when criteria are met • Clarified investigational and not medically necessary section • Updated Description, Rationale, Background, Definition,

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

DRUG.00075 Nivolumab (Opdivo®) • Revised medically necessary criteria addressing nivolumab used as second-line or subsequent therapy for individuals with melanoma with documented disease progression while receiving or since completing most recent therapy, to include in combination with ipilimumab, if PD-1 agent not previously used • Revised ECOG performance status criterion to be 0-2 (previously 0-1) in medically necessary criteria addressing individuals with melanoma and NSCLC • Expanded the use of nivolumab for the treatment of metastatic NSCLC to include all types (removed the word squamous) • Added the treatment of advanced or metastatic (clear cell) renal cell carcinoma (RCC) as medically necessary when criteria are met • Updated investigational and not medically necessary t t t GENE.00002 Preimplantation Genetic Diagnosis Testing • Added a history of trisomy in a previous pregnancy as a medically necessary indication for preimplantation genetic testing • Made minor wording changes in medically necessary section • Updated Description and Reference sections GENE.00011 Gene Expression Profiling for Managing Breast Cancer Treatment • Revised medically necessary criteria addressing tumor size to state: tumor greater than 1.0 cm and less than or equal to 5.0 cm (previously the upper limit was 4.0 cm) • Made minor wording changes in position statement U d d R i l R f d I d i GENE.00014 Analysis of KRAS Status • Removed the registered and trademark symbols from the position statement • Updated Description, Rationale, Background, Definition, GENE.00019 BRAF Mutation Analysis • Added BRAF V600E mutation analysis as medically necessary for individuals with non-small cell lung cancer (NSCLC) to select those who would benefit from treatment with vemurafenib (Zelboraf®)
• Added BRAF V600E mutation analysis as medically necessary for individuals with relapsed hairy-cell leukemia to select those who would benefit from treatment with vemurafenib (Zelboraf®)

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

RAD.00002 Positron Emission Tomography (PET) and PET/CT Fusion • Clarified language addressing standard imaging modalities in the Diagnosis or Staging sub-section of the medically necessary criteria U d t d C di d R f ti SURG.00007 Vagus Nerve Stimulation • Added the use of VNS for the treatment of Crohn's disease as investigational and not medically necessary • Clarified that VNS is investigational and not medically necessary for the treatment of obesity, including obesity- related food cravings • Added a cross-reference in the Description section to SURG.00024 Surgery for Clinically Severe Obesity which addresses the use of vagal nerve blocking therapy (VBLOC) for the treatment of morbid obesity SURG.00011 Allogeneic, Xenographic, Synthetic and Composite Products for Wound Healing and Soft Tissue Grafting • Added Perlane and Restlyane to list of products considered investigational and not medically necessary • Updated Description, Rationale, Coding and Reference sections SURG.00024 Bariatric Surgery and Other Treatments for Clinically Severe Obesity • Title revised (was Surgery for Clinically Severe Obesity) • Expanded scope of document to include non-surgical treatments
• Added an investigational and not medically necessary statement for surgical procedures when criteria are not met • Revised investigational and not medically necessary statement addressing other procedures and treatment modalities • Added balloon systems (such as the ReShape® Integrated Dual Balloon System) and vagus (or vagal) nerve blocking devices (such as the MAESTRO® Rechargeable System) as investigational and not medically necessary SURG.00033 Cardioverter Defibrillators • Title revised (was Implantable Cardioverter-Defibrillator [ICD]) • Added the use of a subcutaneous implantable cardioverter- defibrillator (S-ICD) as medically necessary when criteria are met • Updated investigational and not medically necessary statement

Anthem Blue Cross is the trade name of Blue Cross of California. Anthem Blue Cross and Anthem Blue Cross Life and Health Insurance Company are independent licensees of the Blue Cross Association. ANTHEM is a registered trademark of Anthem Insurance Companies, Inc. The Blue Cross name and symbol are registered marks of the Blue Cross Association.

SURG.00121 Transcatheter Heart Valve Procedures • Added the SAPIEN 3 transcatheter heart valve to medically necessary criteria addressing transcatheter aortic valve replacement (TAVR) • Made minor wording changes in position statement • Updated Rationale, Description, Background and Reference ti TRANS.00014
Mechanical Circulatory Assist Devices (Ventricular Assist Devices, Percutaneous Ventricular Assist Devices and Artificial Hearts) • Added the percutaneous ventricular assist device HeartMate PHP™ as investigational and not medically necessary
• Revised all sections of the position statement addressing the CardioWest temporary Total Artificial Heart (TAH-t) to reflect the new name of the device: SynCardia • Updated Description, Rationale, Background, Definitions, Reference and Index sections TRANS.00029 Hematopoietic Stem Cell Transplantation for Genetic Diseases and Aplastic Anemias • Added congenital amegakaryocytic thrombocytopenia (CAMT) as medically necessary when criteria are met • Added dyskeratosis congenita as medically necessary when criteria are met • Added immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome as medically