CLINICAL MEDICAL POLICY

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1 Policy Name: Policy Number: Responsible Department(s): CLINICAL MEDICAL POLICY Opdivo (nivolumab) MP-004-MC-PA Medical Management; Clinical Pharmacy Provider Notice Date: 09/01/2018; 06/15/2018; 04/01/2017 Issue Date: 07/15/2018 Effective Date: 07/15/2018; 05/01/2017 Annual Approval Date: 08/15/2019 Revision Date: 08/15/2018; 04/18/2018 Products: Application: Page Number(s): 1 of 15 Pennsylvania Medicare Assured All participating and nonparticipating hospitals and providers DISCLAIMER Gateway Health (Gateway) medical policy is intended to serve only as a general reference resource regarding coverage for the services described. This policy does not constitute medical advice and is not intended to govern or otherwise influence medical decisions. POLICY STATEMENT Gateway Health may provide coverage and reimbursement under the medical-surgical benefits of the Company s Medicare products for medically necessary intravenous infusions of Opdivo (nivolumab). This policy is designed to address medical necessity guidelines that are appropriate for the majority of individuals with a particular disease, illness or condition. Each person s unique clinical circumstances warrant individual consideration, based upon review of applicable medical records. DEFINITIONS Melanoma A form of cancer that begins in melanocytes (the cells that make the pigment melanin). Melanoma is frequently found on the trunk or the head and neck in men. For women, melanoma develops on the lower legs. Melanoma can also occur in the meninges, the digestive tract, lymph nodes, or other areas where melanocytes are found. Policy No. MP-004-MC-PA Page 1 of 15

2 Classical Hodgkin Lymphoma A neoplastic disorder of lymphoid tissue that accounts for approximately 95% of all cases of Hodgkin disease. The affected cells are usually an abnormal type of B lymphocytes. BRAF An oncogene that directs the production of a protein in the regulating MAP kinase/erks signaling pathway, which affects cell division, differentiation, and secretion. BRAF (V600E) A specific mutation in the BRAF gene. BRAF gene mutations can be found in several forms of cancer, including but not limited to melanoma and colorectal cancer. Confirming the presence of the BRAF mutation in tumor tissue may provide information needed to plan cancer treatments. Metastasis A cancer which has spread from one body part to another. When a metastatic tumor that contains cells like those cells in the original or primary tumor spreads beyond local lymph nodes, this is referred to as Stage IV cancer. Non-Small Cell Lung Cancer (NSCLC) This term describes a group of cancers of the lung which are named for the types of cells found in the tumor and the type of cells identified. There are three major types of NSCLC: squamous cell, large cell, and adenocarcinoma. PROCEDURES 1. The administration of Opdivo is provided for the following indications and criteria: A. Coverage may be provided when the diagnosis is unresectable or metastatic melanoma and the member meets the following criteria: 1) The member is 18 years of age or older; AND 2) Treatment is prescribed by an oncologist/hematologist; AND 3) The member has Stage III (unresectable) or IV (metastatic) disease; AND 4) Treatment will be used for BRAF V600 mutation positive or wild type, as a single agent; AND 5) Treatment will be used in combination with Yervoy (ipilimumab); AND 6) The dosing is within the following prescribing-supported parameters: a) Monotherapy: Does not exceed 3 mg/kg every two weeks; OR b) Opdivo is used in combination with Yervoy: Does not exceed 1 mg/kg (Opdivo), followed by 3 mg/kg (Yervoy) on the same day, every 3 weeks for 4 doses, then 240 mg (Opdivo) every 2 weeks B. Coverage may be provided when the diagnosis is metastatic squamous OR non-squamous non-small cell lung cancer and the member meets the following criteria: 1) The member is 18 years of age or older; AND 2) Treatment is prescribed by an oncologist/hematologist; AND 3) Treatment will be used for progression on or after platinum-based chemotherapy; members with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Opdivo; AND 4) The dosing is within the following prescribing-supported parameters: dose does not exceed 240 mg every 2 weeks C. Coverage may be provided when the diagnosis is classical Hodgkin Lymphoma (chl) and the member meets the following criteria: Policy No. MP-004-MC-PA Page 2 of 15

3 1) The member is aged 18 years or older; AND 2) Treatment is prescribed by an oncologist/hematologist; AND 3) The member has relapsed or has progressed disease after autologous hematopoietic stem cell transplant AND post-transplant brentuximab vedotin (Adcetris ); AND 4) The dosing is within the following prescribing-supported parameters: dose does not exceed 3 mg/kg every 2 weeks D. Coverage may be provided when the diagnosis is recurrent or metastatic squamous cell carcinoma of the head and neck and the member meets the following criteria: 1) The member is 18 years of age or older; AND 2) Treatment is prescribed by an oncologist/hematologist; AND 3) Treatment will be used for patients with disease progression on or after a platinum-based therapy, AND 4) The dosing is within the following prescribing-supported parameters: dose does not exceed 3 mg/kg every 2 weeks E. Coverage may be provided when the diagnosis is renal cell carcinoma (RCC) and the member meets the following criteria: 1) The member is 18 years of age or older; AND 2) Treatment is prescribed by an oncologist/hematologist; AND 4) The patient has experienced an relapse or Stage IV disease that is surgically unresectable; AND 6) The dosing is within the following prescribing-supported parameters: dose does not exceed 240 mg/kg every 2 weeks F. Coverage may be provided when the diagnosis is advanced or metastatic urothelial carcinoma, AND 1) The member is age 18 years or older; AND 2) Treatment is prescribed by an oncologist/hematologist; AND 3) Treatment will be used for members with disease progression during or following platinum-containing chemotherapy; OR 4) Treatment will be used for members with disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; AND 5) The dosing is within the following prescribing-supported parameters: a) Dose does not exceed 240 mg every 2 weeks G. Coverage may be provided when the diagnosis is microsatellite instability-high (MSI-H) or mismatch repair deficient (dmmr) metastatic colorectal cancer AND 1) The member is age 12 years or older, AND 2) Treatment is prescribed by an oncologist/hematologist, AND 3) Treatment will be used for members with disease progression following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan 4) The dosing is within the following prescribing-supported parameters: a) Does not exceed 240mg every 2 weeks Policy No. MP-004-MC-PA Page 3 of 15

4 H. Coverage is provided when the diagnosis is hepatocellular carcinoma; AND 1) The member is age 18 years of age or older; AND 2) The member has previously been treated with Sorafenib; AND 3) The dosing is within the following prescribing-supported parameters: a) Dose does not exceed 240 mg every 2 weeks 2. Warnings and Precautions Members with active autoimmune disease or medical conditions requiring systemic immunosuppression or with symptomatic interstitial lung disease 3. When OPDIVO is not covered OPDIVO will not be covered for any other condition above because the scientific evidence has not been established. Coverage may be provided for any non-fda labeled indication if it is determined that the use is a medically accepted indication supported by nationally recognized pharmacy compendia or peerreviewed medical literature for treatment of the diagnosis (es) for which it is prescribed. These requests will be reviewed on a case-by-case basis to determine medical necessity. When criteria are not met, the request will be forwarded to a Medical Director for review. The physician reviewer must override criteria when, in their professional judgment, the requested medication is medically necessary. 4. Post-payment Audit Statement The medical record must include documentation that reflects the medical necessity criteria and is subject to audit by Gateway Health at any time pursuant to the terms of your provider agreement. 5. Place of Service The place of service for the administration of OPDIVO is outpatient. Coverage Determination Gateway Health follows the coverage determinations made by CMS as outlined in either the national coverage determinations (NCD) or the state-specific local carrier determinations (LCD). There is no NCD located for this medication, and for Pennsylvania, Novitas Solutions, Inc. does not have a specific LCD for OPDIVO. There is an article, Article ID A53049, Approved Drugs and Biologicals: Includes Cancer Chemotherapeutic Agents that is to be applied to all drugs and biological CPT & HCPCS codes. Available at: 3d&. Policy No. MP-004-MC-PA Page 4 of 15

5 GOVERNING BODIES APPROVAL On December 22, 2014, OPDIVO was approved for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication was approved under the accelerated approval base on tumor response rate and durability of response. On March 4, 2015, the FDA granted approval for OPDIVO for the treatment of patients with metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy. On November 23, 2015, the FDA granted approval of OPDIVO for the treatment of patients with advanced (metastatic) renal cell carcinoma who have received a prior therapy. On May 16, 2016, the FDA granted accelerated approval to nivolumab (OPDIVO) for the treatment of patients with Classical Hodgkin Lymphoma (chl) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (ADCETRIS). On November 16, 2016, the FDA approved Opdivo (nivolumab) for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). The injection is indicated for patients with disease progression on or after platinum based therapy. On February 2, 2017, the FDA granted accelerated approval to Opdivo for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with a platinum-containing chemotherapy. On July 31, 2017, the FDA granted accelerated approval to Opdivo for the treatment of patients 12 years and older with mismatch repair deficient (dmmr) and microsatellite instability high (MSI-H) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. On September 22, 2017 the FDA approved Opdivo for the treatment of hepatocellular cancer in patients previously treated with sorafenib. CODING REQUIREMENTS Procedure Codes HCPCS Code Description J9299 Injection, nivolumab, 1 mg Diagnosis Codes ICD-10 Codes Description C00.0 Malignant neoplasm of external upper lip C00.1 Malignant neoplasm of external lower lip C00.2 Malignant neoplasm of external lip, unspecified Policy No. MP-004-MC-PA Page 5 of 15

6 C00.3 Malignant neoplasm of upper lip, inner aspect C00.4 Malignant neoplasm of lower lip, inner aspect C00.5 Malignant neoplasm of lip, unspecified, inner aspect C00.6 Malignant neoplasm of commissure of lip, unspecified C00.8 Malignant neoplasm of overlapping sites of lip C01 Malignant neoplasm of base of tongue C02.0 Malignant neoplasm of dorsal surface of tongue C02.1 Malignant neoplasm of border of tongue C02.2 Malignant neoplasm of ventral surface of tongue C02.3 Malignant neoplasm of anterior two-thirds of tongue, part unspecified C02.4 Malignant neoplasm of lingual tonsil C02.8 Malignant neoplasm of overlapping sites of tongue C02.9 Malignant neoplasm of tongue, unspecified C03.0 Malignant neoplasm of upper gum C03.1 Malignant neoplasm of lower gum C03.9 Malignant neoplasm of gum, unspecified C04.0 Malignant neoplasm of anterior floor of mouth C04.1 Malignant neoplasm of lateral floor of mouth C04.8 Malignant neoplasm of overlapping sites of floor of mouth C04.9 Malignant neoplasm of floor of mouth, unspecified C05.0 Malignant neoplasm of hard palate C05.1 Malignant neoplasm of soft palate C05.2 Malignant neoplasm of uvula C05.8 Malignant neoplasm of overlapping sites of palate C05.9 Malignant neoplasm of palate, unspecified C06.0 Malignant neoplasm of cheek mucosa C06.1 Malignant neoplasm of vestibule of mouth C06.2 Malignant neoplasm of retromolar area C06.80 Malignant neoplasm of overlapping sites of unspecified parts of mouth C06.89 Malignant neoplasm of overlapping sites of other parts of mouth C06.9 Malignant neoplasm of mouth, unspecified C08.0 Malignant neoplasm of submandibular gland C08.1 Malignant neoplasm of sublingual gland C08.9 Malignant neoplasm of major salivary gland, unspecified C09.0 Malignant neoplasm of tonsillar fossa C09.1 Malignant neoplasm of tonsillar pillar (anterior) (posterior) C09.8 Malignant neoplasm of overall sites of tonsil C09.9 Malignant neoplasm of tonsil, unspecified C10.0 Malignant neoplasm of vallecula C10.1 Malignant neoplasm of anterior surface of epiglottis C10.2 Malignant neoplasm of lateral wall of oropharynx C10.3 Malignant neoplasm of posterior wall of oropharynx Policy No. MP-004-MC-PA Page 6 of 15

7 C10.4 Malignant neoplasm of branchial cleft C10.8 Malignant neoplasm of overlapping sites of oropharynx C10.9 Malignant neoplasm of oropharynx, unspecified C11.0 Malignant neoplasm of superior wall of nasopharynx C11.1 Malignant neoplasm of posterior wall of nasopharynx C11.2 Malignant neoplasm of lateral wall of nasopharynx C11.3 Malignant neoplasm of anterior wall of nasopharynx C11.8 Malignant neoplasm of overlapping sites of nasopharynx C11.9 Malignant neoplasm of nasopharynx, unspecified C12 Malignant neoplasm of pyriform sinus C13.0 Malignant neoplasm of postcricoid region C13.1 Malignant neoplasm of aryepiglottic fold, hypopharyngeal aspect C13.2 Malignant neoplasm of posterior wall of hypopharynx C13.8 Malignant neoplasm of overlapping sites of hypopharynx C13.9 Malignant neoplasm of hypopharynx, unspecified C14.0 Malignant neoplasm of pharynx, unspecified C14.2 Malignant neoplasm of Waldeyer s ring C14.8 Malignant neoplasm of overlapping sites of lip, oral cavity and pharynx C15.3 Malignant neoplasm of upper third of esophagus C15.4 Malignant neoplasm of middle third esophagus C15.5 Malignant neoplasm of lower third of esophagus C15.8 Malignant neoplasm of overlapping sites of esophagus C15.9 Malignant neoplasm of esophagus, unspecified C18.0 Malignant neoplasm of cecum C18.1 Malignant neoplasm of appendix C18.2 Malignant neoplasm of ascending colon C18.3 Malignant neoplasm of hepatic flexure C18.4 Malignant neoplasm of transverse colon C18.5 Malignant neoplasm of splenic flexure C18.6 Malignant neoplasm of descending colon C18.7 Malignant neoplasm of sigmoid colon C18.8 Malignant neoplasm of overlapping sites of colon C18.9 Malignant neoplasm of colon, unspecified C19 Malignant neoplasm of rectosigmoid junction C20 Malignant neoplasm of rectum C21.0 Malignant neoplasm of anus, unspecified C21.1 Malignant neoplasm of anal canal C21.8 Malignant neoplasm of overlapping sites of rectum, anus and anal canal C22.0 Liver cell carcinoma C22.2 Hepatoblastoma C22.7 Other specified carcinoma of liver C22.8 Malignant neoplasm of liver, primary, unspecified as to type Policy No. MP-004-MC-PA Page 7 of 15

8 C22.9 Malignant neoplasm of liver, not specified as primary or secondary C30.0 Malignant neoplasm of nasal cavity C31.0 Malignant neoplasm of maxillary sinus C31.1 Malignant neoplasm of ethmoid sinus C31.2 Malignant neoplasm of frontal sinus C31.3 Malignant neoplasm of sphenoid sinus C31.8 Malignant neoplasm of overlapping sites of accessory sinuses C31.9 Malignant neoplasm of accessory sinus, unspecified C32.0 Malignant neoplasm of glottis C32.1 Malignant neoplasm of supraglottis C32.2 Malignant neoplasm of subglottis C32.3 Malignant neoplasm of laryngeal cartilage C32.8 Malignant neoplasm of overlapping sites of larynx C32.9 Malignant neoplasm of larynx, unspecified C33 Malignant neoplasm of trachea C34.00 Malignant neoplasm of unspecified main bronchus C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung C34.11 Malignant neoplasm of upper lobe, right bronchus or lung C34.12 Malignant neoplasm of upper lobe, left bronchus or lung C34.2 Malignant neoplasm of middle lobe, bronchus or lung C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung C34.31 Malignant neoplasm of lower lobe, right bronchus or lung C34.32 Malignant neoplasm of lower lobe, left bronchus or lung C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung C34.81 Malignant neoplasm of overlapping sites of right bronchus and lung C34.82 Malignant neoplasm of overlapping sites of left bronchus and lung C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung C34.91 Malignant neoplasm of unspecified part of right bronchus or lung C34.92 Malignant neoplasm of unspecified part of left bronchus or lung C43.0 Malignant melanoma of lip C43.10 Malignant melanoma of unspecified eyelid, including canthus C43.11 Malignant melanoma of right eyelid, including canthus C43.12 Malignant melanoma of left eyelid, including canthus C43.20 Malignant melanoma of unspecified ear and external auricular canal C43.21 Malignant melanoma of right ear and external auricular canal C43.22 Malignant melanoma of left ear and external auricular canal C43.30 Malignant melanoma of unspecified part of face C43.31 Malignant melanoma of nose C43.39 Malignant melanoma of other parts of face C43.4 Malignant melanoma of scalp and neck C43.51 Malignant melanoma of anal skin C43.52 Malignant melanoma of skin of breast C43.59 Malignant melanoma of other part of trunk Policy No. MP-004-MC-PA Page 8 of 15

9 C43.60 Malignant melanoma of unspecified upper limb, including shoulder C43.61 Malignant melanoma of right upper limb, including shoulder C43.62 Malignant melanoma of left upper limb, including shoulder C43.70 Malignant melanoma of unspecified lower limb, including hip C43.71 Malignant melanoma of right lower limb, including hip C43.72 Malignant melanoma of left lower limb, including hip C43.8 Malignant melanoma of overlapping sites of skin C43.9 Malignant melanoma of skin, unspecified C44.00 Unspecified malignant neoplasm of skin of lip C44.42 Squamous cell carcinoma of skin of scalp and neck C45.0 Mesothelioma of pleura C51.0 Malignant neoplasm of labium majus C51.1 Malignant neoplasm of labium minus C51.2 Malignant neoplasm of clitoris C51.8 Malignant neoplasm of overlapping sites of vulva C51.9 Malignant neoplasm of vulva, unspecified C52 Malignant neoplasm of vagina C57.7 Malignant neoplasm of other specified female genital organs C57.8 Malignant neoplasm of overlapping sites of female genital organs C57.9 Malignant neoplasm of female genital organ, unspecified C60.0 Malignant neoplasm of prepuce C60.1 Malignant neoplasm of glans penis C60.2 Malignant neoplasm of body of penis C60.8 Malignant neoplasm of overlapping sites of penis C60.9 Malignant neoplasm of penis, unspecified C61 Malignant neoplasm of prostate C63.00 Malignant neoplasm of unspecified epididymis C63.01 Malignant neoplasm of right epididymis C63.02 Malignant neoplasm of left epididymis C63.10 Malignant neoplasm of unspecified spermatic cord C63.11 Malignant neoplasm of right spermatic cord C63.12 Malignant neoplasm of left spermatic cord C63.2 Malignant neoplasm of scrotum C63.7 Malignant neoplasm of other specified male genital organs C63.8 Malignant neoplasm of overlapping sites of male genital organs C63.9 Malignant neoplasm of male genital organ, unspecified C64.1 Malignant neoplasm of right kidney, except renal pelvis C64.2 Malignant neoplasm of left kidney, expect renal pelvis C64.9 Malignant neoplasm of unspecified kidney, except renal pelvis C65.1 Malignant neoplasm of unspecified kidney, except renal pelvis C65.2 Malignant neoplasm of left renal pelvis C65.9 Malignant neoplasm of unspecified renal pelvis Policy No. MP-004-MC-PA Page 9 of 15

10 C66.1 Malignant neoplasm of right ureter C66.2 Malignant neoplasm of left ureter C66.9 Malignant neoplasm of unspecified ureter C67.0 Malignant neoplasm of trigone of bladder C67.1 Malignant neoplasm of dome of bladder C67.2 Malignant neoplasm of lateral wall of bladder C67.3 Malignant neoplasm of anterior wall of bladder C67.4 Malignant neoplasm of posterior wall of bladder C67.5 Malignant neoplasm of bladder neck C67.6 Malignant neoplasm of ureteric orifice C67.6 Malignant neoplasm of ureteric orifice C67.7 Malignant neoplasm of urachus C67.8 Malignant neoplasm of overlapping sites of bladder C67.9 Malignant neoplasm of bladder, unspecified C68.0 Malignant neoplasm of urethra C68.1 Malignant neoplasm of paraurethral glands C68.8 Malignant neoplasm of overlapping sites of urinary organs C68.9 Malignant neoplasm of urinary organ, unspecified C69.90 Malignant neoplasm of unspecified site of unspecified eye C69.91 Malignant neoplasm of unspecified site of right eye C69.92 Malignant neoplasm of unspecified site of left eye C76.0 Malignant neoplasm of head, face and neck C77.0 Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck C78.00 Secondary malignant neoplasm of unspecified lung C78.01 Secondary malignant neoplasm of right lung C78.02 Secondary malignant neoplasm left lung C78.1 Secondary malignant neoplasm of mediastinum C78.2 Secondary malignant neoplasm of pleura C78.30 Secondary malignant neoplasm of unspecified respiratory organ C78.39 Secondary malignant neoplasm of other respiratory organs C78.4 Secondary malignant neoplasm of small intestine C78.5 Secondary malignant neoplasm of large intestine and rectum C78.6 Secondary malignant neoplasm of retroperitoneum and peritoneum C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct C78.80 Secondary malignant neoplasm of unspecified digestive organ C78.89 Secondary malignant neoplasm of other digestive organs C79.31 Secondary malignant neoplasm of brain C81.00 Nodular lymphocyte predominate Hodgkin lymphoma, unspecified site C81.01 Nodular lymphocyte predominate Hodgkin lymphoma, lymph nodes of head, face and neck C81.02 Nodular lymphocyte predominate Hodgkin lymphoma, intrathoracic lymph nodes C81.03 Nodular lymphocyte predominate Hodgkin lymphoma, intra-abdominal lymph nodes Policy No. MP-004-MC-PA Page 10 of 15

11 C81.04 Nodular lymphocyte predominate Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.05 Nodular lymphocyte predominate Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.06 Nodular lymphocyte predominate Hodgkin lymphoma, intrapelvic lymph nodes C81.07 Nodular lymphocyte predominate Hodgkin lymphoma, spleen C81.08 Nodular lymphocyte predominate Hodgkin lymphoma, lymph nodes of multiple sites C81.09 Nodular lymphocyte predominate Hodgkin lymphoma, extranodal and solid organ sites C81.10 Nodular sclerosis classical Hodgkin lymphoma, unspecified site C81.11 Nodular sclerosis classical Hodgkin lymphoma, lymph nodes of head, face and neck C81.12 Nodular sclerosis classical Hodgkin lymphoma, intrathoracic lymph nodes C81.13 Nodular sclerosis classical Hodgkin lymphoma, intra-abdominal lymph nodes C81.14 Nodular sclerosis classical Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.15 Nodular sclerosis classical Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.16 Nodular sclerosis classical Hodgkin lymphoma, intrapelvic lymph nodes C81.17 Nodular sclerosis classical Hodgkin lymphoma, spleen C81.18 Nodular sclerosis classical Hodgkin lymphoma, lymph nodes of multiple sites C81.19 Nodular sclerosis classical Hodgkin lymphoma, extranodal and solid organ sites C81.20 Mixed cellularity classical Hodgkin lymphoma, unspecified site C81.21 Mixed cellularity classical Hodgkin lymphoma, lymph nodes of head, face and neck C81.22 Mixed cellularity classical Hodgkin lymphoma, intrathoracic lymph nodes C81.23 Mixed cellularity classical Hodgkin lymphoma, intra-abdominal lymph nodes C81.24 Mixed cellularity classical Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.25 Mixed cellularity classical Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.26 Mixed cellularity classical Hodgkin lymphoma, intrapelvic lymph nodes C81.27 Mixed cellularity classical Hodgkin lymphoma, spleen C81.28 Mixed cellularity classical Hodgkin lymphoma, lymph nodes of multiple sites C81.29 Mixed cellularity classical Hodgkin lymphoma, extranodal and solid organs C81.30 Lymphocyte depleted classical Hodgkin lymphoma, unspecified site C81.31 Lymphocyte depleted classical Hodgkin lymphoma, lymph nodes of head, face and neck C81.32 Lymphocyte depleted classical Hodgkin lymphoma, intrathoracic lymph nodes C81.33 Lymphocyte depleted classical Hodgkin lymphoma, intra-abdominal lymph nodes C81.34 Lymphocyte depleted classical Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.35 Lymphocyte depleted classical Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.36 Lymphocyte depleted classical Hodgkin lymphoma, intrapelvic lymph nodes C81.37 Lymphocyte depleted classical Hodgkin lymphoma, spleen C81.38 Lymphocyte depleted classical Hodgkin lymphoma, lymph nodes of multiple sites C81.39 Lymphocyte depleted classical Hodgkin lymphoma, extranodal and solid organ sites Policy No. MP-004-MC-PA Page 11 of 15

12 C81.40 Lymphocyte-rich classical Hodgkin lymphoma, unspecified site C81.41 Lymphocyte-rich classical Hodgkin lymphoma, lymph nodes of head, face and neck C81.42 Lymphocyte-rich classical Hodgkin lymphoma, intrathoracic lymph nodes C81.43 Lymphocyte-rich classical Hodgkin lymphoma, intra-abdominal lymph nodes C81.44 Lymphocyte-rich classical Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.45 Lymphocyte-rich classical Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.46 Lymphocyte-rich classical Hodgkin lymphoma, intrapelvic lymph nodes C81.47 Lymphocyte-rich classical Hodgkin lymphoma, spleen C81.48 Lymphocyte-rich classical Hodgkin lymphoma, lymph nodes of multiple sites C81.49 Lymphocyte-rich classical Hodgkin lymphoma, extranodal and solid organ sites C81.70 Other classical Hodgkin lymphoma, unspecified site C81.71 Other classical Hodgkin lymphoma, lymph nodes of head, face and neck C81.72 Other classical Hodgkin lymphoma, intrathoracic lymph nodes C81.73 Other classical Hodgkin lymphoma, intra-abdominal lymph nodes C81.74 Other classical Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.75 Other classical Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.76 Other classical Hodgkin lymphoma, intrapelvic lymph nodes C81.77 Other classical Hodgkin lymphoma, spleen C81.78 Other classical Hodgkin lymphoma, lymph nodes of multiple sites C81.79 Other classical Hodgkin lymphoma, extranodal and solid organ sites C81.90 Hodgkin lymphoma, unspecified, unspecified site C81.91 Hodgkin lymphoma, unspecified, lymph nodes of head, face, and neck C81.92 Hodgkin lymphoma, unspecified, intrathoracic lymph nodes C81.93 Hodgkin lymphoma, unspecified, intra-abdominal lymph nodes C81.94 Hodgkin lymphoma, unspecified, lymph nodes of axilla and upper limb C81.95 Hodgkin lymphoma, unspecified, lymph nodes of inguinal region and lower limb C81.96 Hodgkin lymphoma, unspecified, intrapelvic lymph nodes C81.97 Hodgkin lymphoma, unspecified, spleen C81.98 Hodgkin lymphoma, unspecified, lymph nodes of multiple sites C81.99 Hodgkin lymphoma, unspecified, extranodal and solid organ sites D03.0 Melanoma in situ of lip D03.10 Melanoma in situ of unspecified eyelid, including canthus D03.11 Melanoma in situ of right eyelid, including canthus D03.12 Melanoma in situ of left eyelid, including canthus D03.20 Melanoma in situ of unspecified ear and external auricular canal D03.21 Melanoma in situ of right ear and external auricular canal D03.22 Melanoma in situ of left ear and external auricular canal D03.30 Melanoma in situ of unspecified part of face D03.39 Melanoma in situ of other parts pf face D03.4 Melanoma in situ of scalp and neck D03.51 Melanoma in situ of anal skin D03.52 Melanoma in situ of breast (skin) (soft tissue) Policy No. MP-004-MC-PA Page 12 of 15

13 D03.59 Melanoma in situ of other parts of trunk D03.60 Melanoma in situ of unspecified upper limb, including shoulder D03.61 Melanoma in situ of right upper limb, including shoulder D03.62 Melanoma in situ of left upper limb, including shoulder D03.70 Melanoma in situ of unspecified lower limb, including hip D03.71 Melanoma in situ of right lower limb, including hip D03.72 Melanoma in situ of left lower limb, including hip D03.8 Melanoma in situ of other sites D03.9 Melanoma in situ, unspecified D37.01 Neoplasm of uncertain behavior of lip D37.02 Neoplasm of uncertain behavior of tongue D37.04 Neoplasm of uncertain behavior of the minor salivary glands D37.05 Neoplasm of uncertain behavior of pharynx D37.09 Neoplasm of uncertain behavior of other specified sites of the oral cavity D38.0 Neoplasm of uncertain behavior of larynx D38.5 Neoplasm of uncertain behavior of other respiratory organs D38.6 Neoplasm of uncertain behavior of respiratory organ, unspecified Z Personal history of other malignant neoplasm of bronchus and lung Z Personal history of other malignant neoplasm of kidney Z85.53 Personal history of malignant neoplasm of renal pelvis Z Personal history of malignant melanoma of skin REIMBURSEMENT Participating facilities will be reimbursed per their Gateway Health contract. The Eastern Cooperative Oncology Group (ECOG) Performance Status Grade ECOG Performance Status 0 Fully active, able to carry on all pre-disease performance without restriction Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50 percent of waking hours Capable of only limited self-care; confined to bed or chair more than 50 percent of waking hours 4 Completely disabled; cannot carry on any self-care; totally confined to bed or chair 5 Dead Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6): Policy No. MP-004-MC-PA Page 13 of 15

14 POLICY SOURCE(S) National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines ). Kidney Cancer, v [cited 2015 Nov 25]. Accessed on March 14, 2016 and available from: National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines ). Melanoma, v [cited 2015 Nov 10]. Accessed on March 14, 2016 and available from: NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2015 [cited 2015-Nov 25]. Accessed on March 14, 2016 and available from: OPDIVO (Nivolumab) injection [package insert]. Bristol-Myers Squibb Company. Princeton, NJ. September Accessed on March 14, 2016 and available at: OPDIVO (Nivolumab) injection [package insert]. Bristol-Myers Squibb Company. Princeton, NJ. May Accessed on July 27, 2016 and available at: Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): U.S. Food and Drug Administration. Accessed on March 14, 2016 and available from: Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. New Engl J Med. 2015; 372: Accessed on March 14, 2016 and available at: Motzer RJ, Escudier B, McDermott DF, et al. CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med Sep 25. [Epub ahead of print]. Accessed on March 14, 2016 and available at: Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015; 373(1): Accessed on March 16, 2016 and available at: Hodi FS, O Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363: Accessed on March 14, And available at: Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small cell lung cancer. N Engl J Med. 2015; 373: Accessed on March 14, 2016 and abstract available at: NCCN Guidelines Version : Head and Neck Cancers. Policy No. MP-004-MC-PA Page 14 of 15

15 NCCN Guidelines Version : Hodgkin Lymphoma. NCCN Guidelines Version : Kidney Cancer. NCCN Guidelines Version : Melanoma. NCCN Guidelines Version : Non-Small Cell Lung Cancer. Opdivo [package insert]. Bristol-Myers Squibb Company; Policy History Date Activity 10/01/2015 No LCD/NCD; Article ID A Approved Drugs and Biologicals 2/15/2017 QI/UM Committee Approval 05/01/2017 Provider effective date 04/18/2018 QI UM Committee Review Approval Annual Review Revisions: Issue Date added to opening policy box; New FDA approved conditions added; ICD-10 code update to coincide with newly FDA approved conditions: C08.0-C08.9, C10.0-C11.9, C14.0-C15.9, C18.0-C22.9, C44.00, C44.42, C45.0, C51.0-C52, C57.7-C57.9, C60.0-C61, C63.00-C63.9, C66.1-C68.9, C76.0-C78.89, and D Deleted C80.0 & C /15/2018 New Provider Effective Date 08/15/2018 Urgent Revision: Corrected error in section D #3 to current FDA indications. QI/UM Committee Review Approval 07/15/2018 Retro Provider effective date Policy No. MP-004-MC-PA Page 15 of 15