CLINICAL MEDICATION POLICY

Transcription

1 Policy Name: Policy Number: Approved By: CLINICAL MEDICATION POLICY Keytruda (pembrolizumab) MP-014-MD-DE Medical Management; Clinical Pharmacy Provider Notice Date: 01/15/2018; 08/01/2017; 06/01/2016 Issue Date: 02/15/2018 Original Effective Date: 02/15/2018; 09/01/2017; 07/01/2016 Annual Approval Date: 12/15/2018 Revision Date: 11/13/2017; 12/13/2016 Products: Application: Page Number(s): 1 of 14 Highmark Health Options Medicaid All participating hospitals and providers DISCLAIMER Highmark Health Options 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 Highmark Health Options provides coverage under the medical benefits of the Company s Medicaid products for medically necessary Keytruda (Pembrolizumab) administration. 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. The qualifications of the policy will meet the standards of the National Committee for Quality Assurance (NCQA) and the Delaware Department of Health and Social Services (DHSS) and all applicable state and federal regulations. Policy No. MP-014-MD-DE Page 1 of 14

2 DEFINITIONS Non-Small Cell Lung Cancer (NSCLC) A group of lung cancers which are named by the kinds of cells found in the cancer and the appearance of those cells under a microscope. There are three main types of non-small cell lung cancer: squamous cell carcinoma, large cell carcinoma and adenocarcinoma. The most common form of lung cancer is non-small cell. ALK Gene Rearrangements Anaplastic lymphoma kinase (ALK) function oncogene is a predictive biomarker that has been identified in a subset of patients with NSCLC. The presence of the ALK arrangement is predictive of treatment benefit with ALK targeted therapies. EGFR Mutation Epithelial growth factor receptor (EGFR) mutation is predictive of treatment benefit from EGFR tyrosine kinase inhibitor therapy. PD-L1 Cytotoxic T-cell inhibition occurs when binding of the programmed death 1 (PD-1) receptor to one of its ligands: ligand 1 (PD-L1) or 2 (PD-L2). Upregulation of the PD-L1 occurs in some tumors and it can inhibit active T-cell surveillance of tumors. Presence of the PD-L1 biomarker in tumor cells may be predictive of treatment benefit with PD-1 inhibitors. Melanoma A type of cancer that begins in the melanocytes. Melanoma is also referred to as malignant melanoma and cutaneous melanoma. PROCEDURES 1. Keytruda is considered medically necessary for the following: A. Keytruda is considered medically necessary as an intravenous infusion for the treatment of metastatic non-small cell lung cancer (NSCLC) when the member meets the following criteria: 1) The member must be 18 years of age or older; AND 2) Treatment with Keytruda is prescribed by an oncologist/hematologist; AND 3) Treatment will be used in members with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] 50%) as determined by an FDAapproved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC; OR 4) Treatment will be used in members with metastatic NSCLC whose tumors express PD- L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy; AND a) Members with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda; AND Treatment will be used in members with metastatic nonsquamous NSCLC in combination with pemetrexed and carboplatin as first-line therapy; AND 5) The medication dosing is within the following prescribing-supported parameter: dose does not exceed 200 mg every three weeks B. Keytruda is considered medically necessary for the treatment of unresectable or metastatic melanoma when the member meets the following criteria: 1) The member is 18 years of age or older; AND 2) Treatment with Keytruda is prescribed by an oncologist/hematologist; AND Policy No. MP-014-MD-DE Page 2 of 14

3 3) The member has Stage III (unresectable) or IV (metastatic) disease; AND 4) The medication dosing is within the following prescribing-supported parameter: dose does not exceed 200 mg/kg every three weeks C. Keytruda is considered medically necessary for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) when the member meets the following criteria: 1) The member is 18 years of age or older; AND 2) Treatment with Keytruda is prescribed by an oncologist/hematologist; AND 3) The member has had progression on or after platinum-containing chemotherapy; AND 4) The medication dosing is within the following prescribing-supported parameter: dose does not exceed 200 mg every 3 weeks D. Keytruda is considered medically necessary for the treatment of Classical Hodgkin Lymphoma (chl) when the member meets the following criteria: 1) Treatment with Keytruda is prescribed by an oncologist/hematologist; AND 2) The member has refractory disease or has relapsed after 3 or more prior lines of therapy. 3) The medication dosing is within the following prescribing-supported parameter: dose does not exceed 200mg every 3 weeks for adults and 2mg/kg (up to 200mg every 3 weeks for pediatrics). E. Keytruda is considered medically necessary for the treatment of urothelial carcinoma when the member meets the following criteria: 1) The member is 18 years of age or older; AND 2) Treatment with Keytruda is prescribed by an oncologist/hematologist; AND 3) The member has locally advanced or metastatic urothelial carcinoma and is not eligible for cisplatin-containing chemotherapy; OR 4) The member has locally advanced or metastatic urothelial carcinoma and had disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy 5) The medication dosing is within the following prescribing-supported parameter: dose does not exceed 200mg every 3 weeks. F. Keytruda is considered medically necessary for the treatment of Microsatellite Instability-High Cancer when the member meets the following criteria: 1) Treatment with Keytruda is prescribed by an oncologist/hematologist; AND 2) The member has unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options; OR 3) The member has colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan 4) Keytruda must not be used in pediatric patients with MSI-H central nervous system cancers. 5) The medication dosing is within the following prescribing-supported parameter: dose does not exceed 200mg every 3 weeks for adults and 2mg/kg (up to 200mg) every 3 weeks for pediatrics Policy No. MP-014-MD-DE Page 3 of 14

4 2. When Keytruda is not covered Keytruda is not covered for conditions other than those listed above because the scientific evidence has not been established. Coverage may be provided for any non-fda labeled indication or a medically accepted indication that is supported by nationally recognized pharmacy compendia or peer-reviewed medical literature for treatment of the diagnosis for which it is prescribed and will be reviewed on a case-by-case basis to determine medical necessity. When non-formulary 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. 3. Post-payment Audit Statement The medical record must include documentation that reflects the medical necessity criteria and is subject to audit by Highmark Health Options at any time pursuant to the terms of your provider agreement. 4. Place of Service The place of service for the administration of Keytruda is outpatient. GOVERNING BODIES APPROVAL The FDA approved Keytruda in September 2014 for the treatment of unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Keytruda was granted FDA approval in October 2015 for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors expressed programmed death ligand 1 )PD-L1) and who have disease progression on or after platinum-containing chemotherapy. The medication is also approved for patients with metastatic NSCLC epithelial growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) gene rearrangements who have disease progression on FDAapproved targeted therapy prior to receiving Keytruda. A companion laboratory test was approved to detect PD-L1 expression in non-small cell lung tumors. CODING REQUIREMENTS Procedure Codes HCPCS Code J9271 Description Injection, pembrolizumab, 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 C00.3 Malignant neoplasm of upper lip, inner aspect Policy No. MP-014-MD-DE Page 4 of 14

5 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 C00.9 Malignant neoplasm of lip, unspecified 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 C06.1 Malignant neoplasm of cheek mucosa 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 C07 Malignant neoplasm of parotid gland 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 tonsil C09.1 Malignant neoplasm of tonsillar pillar (anterior)(posterior) C09.8 Malignant neoplasm of overlapping sites of tonsil C09.9 Malignant neoplasm of tonsil, unspecified C10.0 Malignant neoplasm of vallecular 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 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 Policy No. MP-014-MD-DE Page 5 of 14

6 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 C16.0 Malignant neoplasm of cardia C16.1 Malignant neoplasm of fundus of stomach C16.2 Malignant neoplasm of body of stomach C16.3 Malignant neoplasm of pyloric antrum C16.4 Malignant neoplasm of pylorus C16.5 Malignant neoplasm of lesser curvature of stomach, unspecified C16.6 Malignant neoplasm of greater curvature of stomach, unspecified C16.8 Malignant neoplasm of overlapping sites of stomach C16.9 Malignant neoplasm of stomach, unspecified C30.0 Malignant neoplasm of nasal cavity C30.1 Malignant neoplasm of middle ear C31.0 Malignant neoplasm of maxillary sinus C31.1 Malignant neoplasm of ethmoidal 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 C34.01 Malignant neoplasm of right main bronchus C34.02 Malignant neoplasm of left 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 Policy No. MP-014-MD-DE Page 6 of 14

7 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 or lung C34.81 Malignant neoplasm of overlapping sites of right bronchus or lung C34.82 Malignant neoplasm of overlapping sites of left bronchus or lung C34.90 Malignant neoplasm of unspecified part of 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 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 C Squamous cell carcinoma of skin of unspecified eyelid, including canthus C Squamous cell carcinoma of skin of right eyelid, including canthus C Squamous cell carcinoma of skin of left eyelid, including canthus C Squamous cell carcinoma of skin of unspecified ear and external auricular canal C Squamous cell carcinoma of skin of right ear and external auricular canal C Squamous cell carcinoma of skin of left ear and external auricular canal C Squamous cell carcinoma of skin of unspecified parts of face C Squamous cell carcinoma of skin of nose C Squamous cell carcinoma of skin of other parts of face 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 Policy No. MP-014-MD-DE Page 7 of 14

8 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 unspecified male genital organs C63.8 Malignant neoplasm of overlapping sites of male genital organs C63.9 Malignant neoplasm of male genital organ, unspecified C65.1 Malignant neoplasm of right renal pelvis C65.2 Malignant neoplasm of left renal pelvis C65.9 Malignant neoplasm of unspecified renal pelvis 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 C67.7 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 C69.00 Malignant neoplasm of unspecified conjunctiva C69.01 Malignant neoplasm of right conjunctiva C69.02 Malignant neoplasm of left conjunctiva C69.10 Malignant neoplasm of unspecified cornea C69.11 Malignant neoplasm of right cornea C69.12 Malignant neoplasm of left cornea Policy No. MP-014-MD-DE Page 8 of 14

9 C69.20 Malignant neoplasm of unspecified retina C69.21 Malignant neoplasm of right retina C69.22 Malignant neoplasm of left retina C69.30 Malignant neoplasm of unspecified choroid C69.31 Malignant neoplasm of right choroid C69.32 Malignant neoplasm of left choroid C69.40 Malignant neoplasm of unspecified ciliary body C69.41 Malignant neoplasm of right ciliary body C69.42 Malignant neoplasm of left ciliary body C69.50 Malignant neoplasm of unspecified lacrimal gland and duct C69.51 Malignant neoplasm of right lacrimal gland and duct C69.52 Malignant neoplasm of left lacrimal gland and duct C69.60 Malignant neoplasm of unspecified orbit C69.61 Malignant neoplasm of right orbit C69.62 Malignant neoplasm of left orbit C69.80 Malignant neoplasm of overlapping sites of unspecified eye and adnexa C69.81 Malignant neoplasm of overlapping sites of right eye and adnexa C69.82 Malignant neoplasm of overlapping sites of left eye & adnexa 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 C77.0 Secondary and unspecified malignant neoplasm of lymph nodes of head, face, and neck C77.1 Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes C77.2 Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes C77.3 Secondary and unspecified malignant neoplasm of axilla and upper arm lymph nodes C77.4 Secondary and unspecified malignant neoplasm of inguinal and lower limb lymph nodes C77.5 Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes C77.8 Secondary and unspecified malignant neoplasm of lymph nodes of multiple regions C77.9 Secondary and unspecified malignant neoplasm of lymph node, unspecified C78.00 Secondary malignant neoplasm of unspecified lung C78.01 Secondary malignant neoplasm of right lung C78.02 Secondary malignant neoplasm of left lung C78.1 Secondary malignant neoplasm of mediastinum C78.2 Secondary malignant neoplasm of pleura C78.30 Secondary malignant neoplasm of unspecified respiratory organs 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 organs C78.89 Secondary malignant neoplasm of other digestive organs C79.00 Secondary malignant neoplasm of unspecified kidney and renal pelvis Policy No. MP-014-MD-DE Page 9 of 14

10 C79.01 Secondary malignant neoplasm of right kidney and renal pelvis C79.02 Secondary malignant neoplasm of left kidney and renal pelvis C79.10 Secondary malignant neoplasm of unspecified urinary organs C79.11 Secondary malignant neoplasm of bladder C79.19 Secondary malignant neoplasm of other urinary organs C79.2 Secondary malignant neoplasm of skin C79.31 Secondary malignant neoplasm of brain C79.32 Secondary malignant neoplasm of cerebral meninges C79.40 Secondary malignant neoplasm of unspecified part of nervous system C79.49 Secondary malignant neoplasm of other parts of nervous system C79.51 Secondary malignant neoplasm of bone C79.52 Secondary malignant neoplasm of bone marrow C79.60 Secondary malignant neoplasm of unspecified ovary C79.61 Secondary malignant neoplasm of right ovary C79.62 Secondary malignant neoplasm of left ovary C79.70 Secondary malignant neoplasm of unspecified adrenal gland C79.71 Secondary malignant neoplasm of right adrenal gland C79.72 Secondary malignant neoplasm of left adrenal gland C79.81 Secondary malignant neoplasm of breast C79.82 Secondary malignant neoplasm of genital organs C79.89 Secondary malignant neoplasm of other specified sites C79.9 Secondary malignant neoplasm of unspecified site C81.10 Nodular sclerosis Hodgkin lymphoma, unspecified site C81.11 Nodular sclerosis Hodgkin lymphoma, lymph nodes of head, face, and neck C81.12 Nodular sclerosis Hodgkin lymphoma, intrathoracic lymph nodes C81.13 Nodular sclerosis Hodgkin lymphoma, intra-abdominal lymph nodes C81.14 Nodular sclerosis Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.15 Nodular sclerosis Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.16 Nodular sclerosis Hodgkin lymphoma, intrapelvic lymph nodes C81.17 Nodular sclerosis Hodgkin lymphoma, spleen C81.18 Nodular sclerosis Hodgkin lymphoma, lymph nodes of multiple sites C81.19 Nodular sclerosis Hodgkin lymphoma, extranodal and solid organ sites C81.20 Mixed cellularity Hodgkin lymphoma, unspecified site C81.21 Mixed cellularity Hodgkin lymphoma, lymph nodes of head, face, and neck C81.22 Mixed cellularity Hodgkin lymphoma, intrathoracic lymph nodes C81.23 Mixed cellularity Hodgkin lymphoma, intra-abdominal lymph nodes C81.24 Mixed cellularity Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.25 Mixed cellularity Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.26 Mixed cellularity Hodgkin lymphoma, intrapelvic lymph nodes C81.27 Mixed cellularity Hodgkin lymphoma, spleen C81.28 Mixed cellularity Hodgkin lymphoma, lymph nodes of multiple sites C81.29 Mixed cellularity Hodgkin lymphoma, extranodal and solid organ sites C81.30 Lymphocyte depleted Hodgkin lymphoma, unspecified site C81.31 Lymphocyte depleted Hodgkin lymphoma, lymph nodes of head, face, and neck C81.32 Lymphocyte depleted Hodgkin lymphoma, intrathoracic lymph nodes Policy No. MP-014-MD-DE Page 10 of 14

11 C81.33 Lymphocyte depleted Hodgkin lymphoma, intra-abdominal lymph nodes C81.34 Lymphocyte depleted Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.35 Lymphocyte depleted Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.36 Lymphocyte depleted Hodgkin lymphoma, intrapelvic lymph nodes C81.37 Lymphocyte depleted Hodgkin lymphoma, spleen C81.38 Lymphocyte depleted Hodgkin lymphoma, lymph nodes of multiple sites C81.39 Lymphocyte depleted Hodgkin lymphoma, extranodal and solid organ sites C81.40 Lymphocyte-rich Hodgkin lymphoma, unspecified site C81.41 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of head, face, and neck C81.42 Lymphocyte-rich Hodgkin lymphoma, intrathoracic lymph nodes C81.43 Lymphocyte-rich Hodgkin lymphoma, intra-abdominal lymph nodes C81.44 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.45 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.46 Lymphocyte-rich Hodgkin lymphoma, intrapelvic lymph nodes C81.47 Lymphocyte-rich Hodgkin lymphoma, spleen C81.48 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of multiple sites C81.49 Lymphocyte-rich Hodgkin lymphoma, extranodal and solid organ sites C81.70 Other Hodgkin lymphoma, unspecified site C81.71 Other Hodgkin lymphoma, lymph nodes of head, face, and neck C81.72 Other Hodgkin lymphoma, intrathoracic lymph nodes C81.73 Other Hodgkin lymphoma, intra-abdominal lymph nodes C81.74 Other Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.75 Other Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.76 Other Hodgkin lymphoma, intrapelvic lymph nodes C81.77 Other Hodgkin lymphoma, spleen C81.78 Other Hodgkin lymphoma, lymph nodes of multiple sites C81.79 Other Hodgkin lymphoma, intrapelvic lymph nodes C76.0 Malignant neoplasm of head, face and neck C77.0 Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck C77.1 Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes C79.31 Secondary malignant neoplasm of brain 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 of face D03.4 Melanoma in situ of scalp and neck D03.51 Melanoma in situ of anal skin D06.52 Melanoma in situ of breast (skin) (soft tissue) Policy No. MP-014-MD-DE Page 11 of 14

12 D03.59 Melanoma in situ of other part of trunk D03.6 Melanoma in situ of upper limb, including shoulder 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 Z85.00 Personal history of malignant neoplasm of unspecified digestive organ Z Personal history of carcinoid tumor of stomach Z Personal history of malignant neoplasm of stomach Z Personal history of malignant carcinoid tumor of large intestine Z Personal history of malignant neoplasm of large intestine Z Personal history of malignant carcinoid tumor of rectum Z Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus Z85.05 Personal history of malignant neoplasm of liver Z Personal history of malignant carcinoid tumor of small intestine Z Personal history of malignant other malignant neoplasm of small intestine Z85.07 Personal history of malignant neoplasm of pancreas Z85.09 Personal history of malignant neoplasm of other digestive organs Z Personal history of malignant carcinoid tumor of bronchus and lung Z Personal history of malignant of other malignant neoplasm of bronchus and lung Z85.12 Personal history of malignant neoplasm of trachea Z85.20 Personal history of malignant neoplasm of unspecified respiratory organ Z85.21 Personal history of malignant neoplasm of larynx Z85.22 Personal history of malignant neoplasm of nasal cavities, middle ear, and accessory sinuses Z Personal history of malignant carcinoid tumor of thymus Z Personal history of other malignant neoplasm of thymus Z85.29 Personal history of malignant neoplasm of other respiratory and intrathoracic organs Z85.3 Personal history of malignant neoplasm of breast Z85.40 Personal history of malignant neoplasm of unspecified female genital organ Z85.41 Personal history of malignant neoplasm of cervix Z85.42 Personal history of malignant neoplasm of other parts of uterus Z85.43 Personal history of malignant neoplasm of ovary Z85.44 Personal history of malignant neoplasm of other female genital organs Z85.45 Personal history of malignant neoplasm of unspecified male genital organ Z85.46 Personal history of malignant neoplasm of prostate Z85.47 Personal history of malignant neoplasm of testes Z85.48 Personal history of malignant neoplasm of epididymis Z85.49 Personal history of malignant neoplasm of other male genital organs Z85.50 Personal history of malignant neoplasm of unspecified urinary tract organ Policy No. MP-014-MD-DE Page 12 of 14

13 Z85.51 Personal history of malignant neoplasm of bladder Z Personal history of malignant carcinoid tumor of kidney Z Personal history of other malignant neoplasm of kidney Z85.53 Personal history of malignant neoplasm of renal pelvis Z85.54 Personal history of malignant neoplasm of ureter Z85.59 Personal history of malignant neoplasm of other urinary tract organ Z85.71 Personal history of Hodgkin lymphoma Z Personal history of malignant neoplasm of tongue Z Personal history of malignant neoplasm of lip, oral cavity, and pharynx Z Personal history of malignant neoplasm of unspecified site of lip, oral cavity, and pharynx Z Personal history of malignant melanoma of skin REIMBURSEMENT Participating facilities will be reimbursed per their Highmark Health Options contract. POLICY SOURCE(S) Keytruda (pembrolizumab) Prescribing Information. Whitehouse Station, NJ: Merck; Dec Pembrolizumab In: Micromedex Solutions. US, Canada, UK: Truven Health Analytics Inc. Accessed on December 30, Ettinger DS, Wood DE, Akerley W et al. Non-small cell lung cancer. Version In National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines). Accessed on January 14, Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015; 372: National Cancer Institute. What you need to know about melanoma and other skin cancers. January 11, Available at: Accessed on April 27, National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology. For additional information visit the NCCN website: Accessed on April 27, Melanoma (V ) Revised November 25, 2015 Non-small Cell Lung Cancer (V ) Revised January 12, Policy No. MP-014-MD-DE Page 13 of 14

14 Policy History: Date Policy Information 04/27/2016 Initial policy developed 07/01/2016 Effective date 12/13/2016 Revisions: Annual Review, updated indications and dosage, and updated references: The disease/tumor criteria for NSCLC has been revised and updated - OLD CRITERIA The patient s disease has progressed on or after platinum-containing chemotherapy; AND If the patient has EGRF or ALK mutations, the patient has had disease progression on FDA-approved therapy (EGRF- or ALK-directed therapy) for these mutations prior to receiving Keytruda NEW CRITERIA Treatment will be used in members with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] 50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC; OR Treatment will be used in members with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy-- Members with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda; The ECOG criteria has been removed from the revised policy for all disease indications; The dosing for all disease indications has been revised to follow FDA indications; The treatment type has been updated for unresectable/metastatic melanoma - OLD CRITERIA The medication will be used as monotherapy for metastatic or unresectable disease as first-line therapy; OR The medication will be used as monotherapy for metastatic or unresectable disease as second-line or subsequent therapy for disease progression or following maximum clinical benefit from BRAF targeted therapy for patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 NEW CRITERIA The member has Stage III (unresectable) or IV (metastatic) disease; New indications were added to the revised policy for recurrent/ metastatic HNSCC ALL ICD 10 codes were updated and revised. The old policy version had ranges described, it was required to have each code documented individually; codes were added to include all pertinent coding for HNSCC; C44 codes added for squamous cell carcinoma; C76 and C77 codes added for HNSCC; D03 codes added for melanoma in situ; Z codes were added for personal history. NEW CODES HIGHLIGHTED IN RED IN ATTACHMENTS 06/27/2017 QI/UM Committee review approval 09/01/2017 Provider effective date 11/13/2017 Annual Review: Updated Indications and Dosage with Classic Hodgkin Lymphoma, urothelial carcinoma, microsatellite instability-high cancer, & gastric cancer; Added ICD- 10 codes for newly approved indications; Update References. 12/12/2017 QI/UM committee review approval 02/15/2018 New provider effective date Policy No. MP-014-MD-DE Page 14 of 14