Patient must be 18 years of age or older (unless otherwise specified); AND

Transcription

1 (Intravenus) Last Review Date: January 1, 2019 Number: MG.MM.PH.89 Medical Guideline Disclaimer C All rights reserved. The treating physician r primary care prvider must submit t EmblemHealth the clinical evidence that the patient meets the criteria fr the treatment r surgical prcedure. Withut this dcumentatin and infrmatin, EmblemHealth will nt be able t prperly review the request fr prir authrizatin. The clinical review criteria expressed belw reflects hw EmblemHealth determines whether certain services r supplies are medically necessary. EmblemHealth established the clinical review criteria based upn a review f currently available clinical infrmatin (including clinical utcme studies in the peer-reviewed published medical literature, regulatry status f the technlgy, evidence-based guidelines f public health and health research agencies, evidence-based guidelines and psitins f leading natinal health prfessinal rganizatins, views f physicians practicing in relevant clinical areas, and ther relevant factrs). EmblemHealth expressly reserves the right t revise these cnclusins as clinical infrmatin changes, and welcmes further relevant infrmatin. Each benefit prgram defines which services are cvered. The cnclusin that a particular service r supply is medically necessary des nt cnstitute a representatin r warranty that this service r supply is cvered and/r paid fr by EmblemHealth, as sme prgrams exclude cverage fr services r supplies that EmblemHealth cnsiders medically necessary. If there is a discrepancy between this guideline and a member's benefits prgram, the benefits prgram will gvern. In additin, cverage may be mandated by applicable legal requirements f a state, the Federal Gvernment r the Centers fr Medicare & Medicaid Services (CMS) fr Medicare and Medicaid members. All cding and web site links are accurate at time f publicatin. EmblemHealth Services Cmpany LLC, ( EmblemHealth ) has adpted the herein plicy in prviding management, administrative and ther services t HIP Health Plan f New Yrk, HIP Insurance Cmpany f New Yrk, Grup Health Incrprated and GHI HMO Select, related t health benefit plans ffered by these entities. All f the afrementined entities are affiliated cmpanies under cmmn cntrl f EmblemHealth Inc. Related Medical Guideline Off-Label Use f FDA-Apprved Drugs and Bilgicals LENGTH OF AUTHORIZATION SCCHN, chl, NSCLC, Urthelial Carcinma, MPM, MSI-H/dMMR, PMBCL, Cervical, Anal & Gastric Cancers can be authrized up t a maximum f 24 mnths f therapy. DOSING LIMITS Max Units (per dse and ver time) [Medical Benefit]: SCCHN, chl, NSCLC, Melanma, Urthelial, Gastric, CNS metastases, PMBCL, Anal, Cervical, & MSI-H/dMMR Cancer: 200 billable units every 21 days MPM & Uterine Cancer: 1150 billable units every 14 days Merkel Cell Carcinma & NK/T-Cell Lymphma: 250 billable units every 21 days Guideline I. INITIAL APPROVAL CRITERIA Cverage is prvided in the fllwing cnditins: Patient must be 18 years f age r lder (unless therwise specified); AND

2 Page 2 f 17 Patient has nt received previus therapy with a prgrammed death (PD-1/PD-L1)-directed therapy (e.g., avelumab, nivlumab, atezlizumab, durvalumab, etc.) unless therwise specified; AND Melanma Used as a single agent; AND Used as re-treatment therapy (see Sectin IV fr criteria); OR Patient has unresectable r metastatic disease; OR Patient has unresectable r metastatic Uveal Melanma Gastric Cancer Used as a single agent: AND Patient has gastric r gastr-esphageal junctin adencarcinma; AND Patient has recurrent lcally advanced r metastatic disease; AND Tumr expresses PD-L1 (CPS 1%) as determined by an FDA-apprved test; AND Patient prgressed n r after at least tw prir systemic treatments which must have included a flurpyrimidine and platinum-cntaining regimen; AND Patients with HER2 psitive disease must have previusly failed n HER2 directed therapy Merkel Cell Carcinma Used as a single agent; AND Patient has disseminated metastatic disease Nn-Small Cell Lung Cancer (NSCLC) Tumr has high PD-L1 expressin [(Tumr Prprtin Scre (TPS) 50%)] as determined by an FDA-apprved test; AND Used as a single agent fr metastatic r disseminated recurrent disease; AND Used as first-line therapy fr genmic tumr aberratin (e.g., EGFR, ALK, ROS1, and BRAF) negative r unknwn; OR Tumr expresses PD-L1 (TPS 1%) as determined by an FDA-apprved test; AND Used as a single agent fr metastatic disease; AND Disease must have prgressed during r fllwing cyttxic therapy; AND Patients with genmic tumr aberratins must have prgressed fllwing systemic therapy fr thse aberratins (e.g., EGFR, ALK, etc.); OR Used in cmbinatin with ne f the fllwing regimens fr metastatic r disseminated recurrent disease:

3 Page 3 f 17 In cmbinatin with pemetrexed and either carbplatin r cisplatin fr nnsquamus cell histlgy; OR In cmbinatin with carbplatin and paclitaxel fr squamus cell histlgy; AND Used as first-line therapy fr genmic tumr aberratin (e.g., EGFR, ALK, ROS1 and BRAF) negative r unknwn**, and PD-L1 expressin <50% r unknwn; OR Used as first-line therapy fr BRAF V600E-mutatin psitive tumrs; OR Used as subsequent therapy fr genmic tumr aberratin (e.g., EGFR, BRAF V600E, ALK, and ROS1) psitive and prir targeted therapy ; OR Used as subsequent therapy if PD-L1 expressin-psitive ( 50%) and genmic tumr aberratin (e.g., EGFR, ALK, ROS1 and BRAF) negative r unknwn**; OR Used as cntinuatin maintenance therapy; AND Patient has a perfrmance status f 0-2; AND Patient achieved tumr respnse r stable disease fllwing initial therapy; AND Used in cmbinatin with pemetrexed; AND Pembrlizumab was given first-line in cmbinatin with pemetrexed and either carbplatin r cisplatin fr disease f nn-squamus cell histlgy; OR Used as a single agent; AND Pembrlizumab was given first-line in cmbinatin with carbplatin and paclitaxel fr disease f squamus cell histlgy **Every effrt needs t be made t establish the genetic alteratin status. A bld assay may be used if a tissue assay is nt feasible. Squamus Cell Carcinma f the Head and Neck (SCCHN) Used as a single agent; AND Patient has unresectable, recurrent, persistent r metastatic disease; AND Patient has nn-naspharyngeal disease; AND Disease prgressed n r after platinum-cntaining chemtherapy Classical Hdgkin Lymphma (chl) Used as a single agent; AND Patient has relapsed r refractry disease; AND Patients must be at least 2 years ld; AND Used after three r mre prir lines f therapy OR as palliative therapy in patients ver 60 years ld

4 Page 4 f 17 Primary Mediastinal Large B-Cell Lymphma (PMBCL) Used as single agent; AND Patient has relapsed r refractry disease; AND Patient must be at least 2 years ld; AND Used after tw r mre prir lines f therapy Bladder Cancer/Urthelial Carcinma Must be used as a single agent; AND Patient has ne f the fllwing diagnses: Lcally advanced r metastatic Urthelial Carcinma Disease recurrence pst-cystectmy Recurrent r metastatic Primary Carcinma f the Urethra; AND Patient des nt have recurrent stage T3-4 disease r palpable inguinal lymph ndes Metastatic Upper GU Tract Tumrs Metastatic Urthelial Carcinma f the Prstate; AND Used as first-line therapy in cisplatin-ineligible patients; AND Patient is carbplatin-ineligible; OR Patient has a PD-L1 expressin f 10%; OR Used as subsequent therapy after previus platinum treatment* *If platinum treatment ccurred greater than 12 mnths ag, the patient shuld be re-treated with platinum-based therapy. Patients with cmrbidities (e.g., hearing lss, neurpathy, pr PS, renal insufficiency, etc.) may nt be eligible fr cisplatin. Carbplatin may be substituted fr cisplatin particularly in thse patients with a GFR <60 ml/min r a PS f 2. Cervical Cancer Used as a single agent: AND Patient has recurrent r metastatic disease; AND Tumr expresses PD-L1 (CPS 1%) as determined by an FDA-apprved test; AND Disease prgressed n r after chemtherapy Micrsatellite Instability-High (MSI-H) Cancer Patient must be at least 2 years ld; AND Used as a single agent; AND Patient s disease must be micrsatellite instability-high (MSI-H) r mismatch repair deficient (dmmr); AND Pediatric patients must nt have a diagnsis f MSI-H central nervus system cancer; AND Patient has ne f the fllwing cancers: Clrectal Cancer

5 Page 5 f 17 Initial therapy in patients with unresectable r metastatic disease wh are nt candidates fr intensive therapy; OR Used as primary treatment in patients with unresectable r metastatic disease wh failed adjuvant treatment with FOLFOX (flururacil, leucvrin and xaliplatin) r CapeOX (capecitabine-xaliplatin) in the previus 12 mnths; OR Used fr unresectable r metastatic disease that has prgressed fllwing treatment with a flurpyrimidine, xaliplatin, and irintecan Pancreatic Adencarcinma Secnd-line therapy fr lcally advanced, recurrent, r metastatic disease after prgressin fr patients with gd perfrmance status Bne Cancer (Ewing Sarcma, Mesenchymal Chndrsarcma, Ostesarcma, Dedifferentiated Chndrsarcma, r High-Grade Undifferentiated Plemrphic Sarcma) Used fr unresectable r metastatic disease after prgressin fllwing prir treatment and patient has n satisfactry alternative treatment ptins Gastric adencarcinma OR esphageal/esphaggastric junctin adencarcinma r squamus cell carcinma Subsequent therapy fr unresectable (r nt a candidate) lcally advanced, recurrent, r metastatic disease Ovarian Cancer (included epithelial varian, fallpian tube and primary peritneal cancers) Used fr patients with persistent r recurrent disease; AND Patient is nt experiencing an immediate bichemical relapse Uterine Cancer (Endmetrial Carcinma) Used fr patients with high risk tumrs, r recurrent r metastatic disease, that have prgressed fllwing prir cyttxic chemtherapy Penile Cancer Used as subsequent treatment f unresectable r metastatic disease that is prgressive and there are n ther satisfactry treatment ptins Testicular Cancer Used as third-line therapy r after prgressin with high-dse chemtherapy Hepatbiliary Cancer (Gall bladder cancer; intra-/extra-hepatic chlangicarcinma) Used as initial therapy fr unresectable r metastatic disease Cervical Cancer Used fr recurrent r metastatic disease Other Slid Tumr (e.g., adrenal gland tumrs, etc.) Used fr unresectable r metastatic disease that prgressed fllwing prir treatment and there are n satisfactry alternative treatment ptins Malignant Pleural Mesthelima Used as subsequent therapy as a single agent Central Nervus System Cancer Used fr newly diagnsed r recurrent disease as a single agent fr brain metastases; AND

6 Page 6 f 17 Pembrlizumab is active against the primary melanma r NSCLC tumr T-Cell Lymphma/Extrandal NK Patient has relapsed r refractry nasal type disease; AND Disease prgressed fllwing additinal treatment with asparaginase-based chemtherapy, clinical trials r ther best supprtive care Anal Carcinma Patient has metastatic squamus cell disease; AND Used as a single agent fr secnd-line therapy Hepatcellular Carcinma (HCC) Patient has previusly been treated with Nexavar (srafenib) As cnfirmed using an immuntherapy assay such as the PD-L1 IHC 22C3 pharmdx. FDA Apprved Indicatin(s); Cmpendia Apprved Indicatin(s) Genmic Aberratin Targeted Therapies (nt all inclusive) Sensitizing EGFR mutatin-psitive tumrs Erltinib Afatinib Gefitinib Osimertinib ALK rearrangement-psitive tumrs Criztinib Ceritinib Brigatinib Alectinib ROS1 rearrangement-psitive tumrs Criztinib Ceritinib BRAF V600E-mutatin psitive tumrs Dabrafenib/Trametinib PD-L1 expressin-psitive tumrs ( 50%) Pembrlizumab II. RENEWAL CRITERIA Cverage can be renewed based upn the fllwing criteria: Patient cntinues t meet criteria identified in sectin III; AND Tumr respnse with stabilizatin f disease r decrease in size f tumr r tumr spread; AND Absence f unacceptable txicity frm the drug. Examples f unacceptable txicity include severe infusin reactins, immune-mediated adverse reactins (e.g., pneumnitis, hepatitis, clitis, endcrinpathies, nephritis and renal dysfunctin, skin, etc), etc.).; AND

7 Page 7 f 17 Fr the fllw indicatins, patient has nt exceeded a maximum f twenty-fur (24) mnths f therapy: Squamus Cell Carcinma f the Head and Neck (SCCHN) Nn-Small Cell Lung Cancer (NSCLC) Classical Hdgkin Lymphma (chl) Primary Mediastinal Large B-Cell Lymphma (PMBCL) Urthelial Carcinma MSI-H Cancer (including the fllwing cancers: clrectal, pancreatic, bne, gastric/gastresphageal, varian, uterine, penile, testicular, hepatbiliary and ther slid tumrs) Anal Cancer Malignant Pleural Mesthelima Gastric/GEJ Adencarcinma Cervical Cancer Hepatcellular Carcinma (HCC) Melanma (metastatic r unresectable disease) Used fr re-treatment f patients wh experienced disease cntrl, but subsequently have disease prgressin/relapse > 3 mnths after treatment discntinuatin Limitatins/Exclusins Keytruda is nt cnsidered medically necessary fr indicatins ther than thse listed abve due t insufficient evidence f therapeutic value. Applicable Prcedure Cdes J9271 Injectin, pembrlizumab, 1 mg; 1 billable unit = 1 mg Applicable NDCs XX Keytruda 100 mg/4 ml single use vial Applicable Diagnsis Cdes C00.0 Malignant neplasm f external upper lip C00.1 Malignant neplasm f external lwer lip C00.2 Malignant neplasm f external lip, unspecified C00.3 Malignant neplasm f upper lip, inner aspect C00.4 Malignant neplasm f lwer lip, inner aspect C00.5 Malignant neplasm f lip, unspecified, inner aspect C00.6 Malignant neplasm f cmmissure f lip, unspecified C00.8 Malignant neplasm f verlapping sites f lip C01 Malignant neplasm f base f tngue C02.0 Malignant neplasm f drsal surface f tngue C02.1 Malignant neplasm f brder f tngue C02.2 Malignant neplasm f ventral surface f tngue C02.3 Malignant neplasm f anterir tw-thirds f tngue, part unspecified

8 Page 8 f 17 C02.4 Malignant neplasm f lingual tnsil C02.8 Malignant neplasm f verlapping sites f tngue C02.9 Malignant neplasm f tngue, unspecified C03.0 Malignant neplasm f upper gum C03.1 Malignant neplasm f lwer gum C03.9 Malignant neplasm f gum, unspecified C04.0 Malignant neplasm f anterir flr f muth C04.1 Malignant neplasm f lateral flr f muth C04.8 Malignant neplasm f verlapping sites f flr f muth C04.9 Malignant neplasm f flr f muth, unspecified C05.0 Malignant neplasm f hard palate C05.1 Malignant neplasm f sft palate C06.0 Malignant neplasm f cheek mucsa C06.2 Malignant neplasm f retrmlar area C06.80 Malignant neplasm f verlapping sites f unspecified parts f muth C06.89 Malignant neplasm f verlapping sites f ther parts f muth C06.9 Malignant neplasm f muth, unspecified C09.0 Malignant neplasm f tnsillar fssa C09.1 Malignant neplasm f tnsillar pillar (anterir) (psterir) C09.8 Malignant neplasm f verlapping sites f tnsil C09.9 Malignant neplasm f tnsil, unspecified C10.3 Malignant neplasm f psterir wall f rpharynx C11.0 Malignant neplasm f superir wall f naspharynx C11.1 Malignant neplasm f psterir wall f naspharynx C11.2 Malignant neplasm f lateral wall f naspharynx C11.3 Malignant neplasm f anterir wall f naspharynx C11.8 Malignant neplasm f verlapping sites f naspharynx C11.9 Malignant neplasm f naspharynx, unspecified C12 Malignant neplasm f pyrifrm sinus C13.0 Malignant neplasm f pstcricid regin C13.1 Malignant neplasm f aryepiglttic fld, hyppharyngeal aspect C13.2 Malignant neplasm f psterir wall f hyppharynx C13.8 Malignant neplasm f verlapping sites f hyppharynx C13.9 Malignant neplasm f hyppharynx, unspecified C14.0 Malignant neplasm f pharynx, unspecified C14.2 Malignant neplasm f Waldeyer's ring C14.8 Malignant neplasm f verlapping sites f lip, ral cavity and pharynx C15.3 Malignant neplasm f upper third f esphagus C15.4 Malignant neplasm f middle third f esphagus C15.5 Malignant neplasm f lwer third f esphagus C15.8 Malignant neplasm f verlapping sites f esphagus C15.9 Malignant neplasm f esphagus, unspecified C16.0 Malignant neplasm f cardia C16.1 Malignant neplasm f fundus f stmach C16.2 Malignant neplasm f bdy f stmach C16.3 Malignant neplasm f pylric antrum C16.4 Malignant neplasm f pylrus C16.5 Malignant neplasm f lesser curvature f stmach, unspecified C16.6 Malignant neplasm f greater curvature f stmach, unspecified C16.8 Malignant neplasm f verlapping sites f stmach C16.9 Malignant neplasm f stmach, unspecified C17.0 Malignant neplasm f dudenum C17.1 Malignant neplasm f jejunum C17.2 Malignant neplasm f ileum C17.8 Malignant neplasm f verlapping sites f small intestine

9 Page 9 f 17 C17.9 Malignant neplasm f small intestine, unspecified C18.0 Malignant neplasm f cecum C18.1 Malignant neplasm f appendix C18.2 Malignant neplasm f ascending cln C18.3 Malignant neplasm f hepatic flexure C18.4 Malignant neplasm f transverse cln C18.5 Malignant neplasm f splenic flexure C18.6 Malignant neplasm f descending cln C18.7 Malignant neplasm f sigmid cln C18.8 Malignant neplasm f verlapping sites f cln C18.9 Malignant neplasm f cln, unspecified C19 Malignant neplasm f rectsigmid junctin C20 Malignant neplasm f rectum C21.0 Malignant neplasm f anus, unspecified C21.1 Malignant neplasm f anal canal C21.2 Malignant neplasm f clacgenic zne C21.8 Malignant neplasm f verlapping sites f rectum, anus and anal canal C22.1 Intrahepatic bile duct carcinma C23 Malignant neplasm f gallbladder C24.0 Malignant neplasm f extrahepatic bile duct C24.1 Malignant neplasm f ampulla f Vater C24.8 Malignant neplasm f verlapping sites f biliary tract C24.9 Malignant neplasm f biliary tract, unspecified C25.0 Malignant neplasm f head f pancreas C25.1 Malignant neplasm f bdy f the pancreas C25.2 Malignant neplasm f tail f pancreas C25.3 Malignant neplasm f pancreatic duct C25.7 Malignant neplasm f ther parts f pancreas C25.8 Malignant neplasm f verlapping sites f pancreas C25.9 Malignant neplasm f pancreas, unspecified C31.0 Malignant neplasm f maxillary sinus C31.1 Malignant neplasm f ethmidal sinus C32.0 Malignant neplasm f glttis C32.1 Malignant neplasm f supraglttis C32.2 Malignant neplasm f subglttis C32.3 Malignant neplasm f laryngeal cartilage C32.8 Malignant neplasm f verlapping sites f larynx C32.9 Malignant neplasm f larynx, unspecified C33 Malignant neplasm f trachea C34.00 Malignant neplasm f unspecified main brnchus C34.01 Malignant neplasm f right main brnchus C34.02 Malignant neplasm f left main brnchus C34.10 Malignant neplasm f upper lbe, unspecified brnchus r lung C34.11 Malignant neplasm f upper lbe, right brnchus r lung C34.12 Malignant neplasm f upper lbe, left brnchus r lung C34.2 Malignant neplasm f middle lbe, brnchus r lung C34.30 Malignant neplasm f lwer lbe, unspecified brnchus r lung C34.31 Malignant neplasm f lwer lbe, right brnchus r lung C34.32 Malignant neplasm f lwer lbe, left brnchus r lung C34.80 Malignant neplasm f verlapping sites f unspecified brnchus and lung C34.81 Malignant neplasm f verlapping sites f right brnchus and lung C34.82 Malignant neplasm f verlapping sites f left brnchus and lung C34.90 Malignant neplasm f unspecified part f unspecified brnchus r lung C34.91 Malignant neplasm f unspecified part f right brnchus r lung C34.92 Malignant neplasm f unspecified part f left brnchus r lung

10 Page 10 f 17 C38.4 Malignant neplasm f pleura C40.00 Malignant neplasm f scapula and lng bnes f unspecified upper limb C40.01 Malignant neplasm f scapula and lng bnes f right upper limb C40.02 Malignant neplasm f scapula and lng bnes f left upper limb C40.10 Malignant neplasm f shrt bnes f unspecified upper limb C40.11 Malignant neplasm f shrt bnes f right upper limb C40.12 Malignant neplasm f shrt bnes f left upper limb C40.20 Malignant neplasm f lng bnes f unspecified lwer limb C40.21 Malignant neplasm f lng bnes f right lwer limb C40.22 Malignant neplasm f lng bnes f left lwer limb C40.30 Malignant neplasm f shrt bnes f unspecified lwer limb C40.31 Malignant neplasm f shrt bnes f right lwer limb C40.32 Malignant neplasm f shrt bnes f left lwer limb C40.80 Malignant neplasm f verlapping sites f bne and articular cartilage f unspecified limb C40.81 Malignant neplasm f verlapping sites f bne and articular cartilage f right limb C40.82 Malignant neplasm f verlapping sites f bne and articular cartilage f left limb C40.90 Malignant neplasm f unspecified bnes and articular cartilage f unspecified limb C40.91 Malignant neplasm f unspecified bnes and articular cartilage f right limb C40.92 Malignant neplasm f unspecified bnes and articular cartilage f left limb C41.0 Malignant neplasm f bnes f skull and face C41.1 Malignant neplasm f mandible C41.2 Malignant neplasm f vertebral clumn C41.3 Malignant neplasm f ribs, sternum and clavicle C41.4 Malignant neplasm f pelvic bnes, sacrum and cccyx C41.9 Malignant neplasm f bne and articular cartilage, unspecified C43.0 Malignant melanma f lip C43.10 Malignant melanma f unspecified eyelid, including canthus C43.11 Malignant melanma f right eyelid, including canthus C43.12 Malignant melanma f left eyelid, including canthus C43.20 Malignant melanma f unspecified ear and external auricular canal C43.21 Malignant melanma f right ear and external auricular canal C43.22 Malignant melanma f left ear and external auricular canal C43.30 Malignant melanma f unspecified part f face C43.31 Malignant melanma f nse C43.39 Malignant melanma f ther parts f face C43.4 Malignant melanma f scalp and neck C43.51 Malignant melanma f anal skin C43.52 Malignant melanma f skin f breast C43.59 Malignant melanma f ther part f trunk C43.60 Malignant melanma f unspecified upper limb, including shulder C43.61 Malignant melanma f right upper limb, including shulder C43.62 Malignant melanma f left upper limb, including shulder C43.70 Malignant melanma f unspecified lwer limb, including hip C43.71 Malignant melanma f right lwer limb, including hip C43.72 Malignant melanma f left lwer limb, including hip C43.8 Malignant melanma f verlapping sites f skin C43.9 Malignant melanma f skin, unspecified C44.00 Unspecified malignant neplasm f skin f lip C44.02 Squamus cell carcinma f skin f lip C44.09 Other specified malignant neplasm f skin f lip C45.0 Mesthelima f pleura C48.1 Malignant neplasm f specified parts f peritneum C48.2 Malignant neplasm f peritneum, unspecified C48.8 Malignant neplasm f verlapping sites f retrperitneum and peritneum C4A.0 Merkel cell carcinma f lip

11 Page 11 f 17 C4A.10 Merkel cell carcinma f eyelid, including canthus C4A.11 Merkel cell carcinma f right eyelid, including canthus C4A.12 Merkel cell carcinma f left eyelid, including canthus C4A.20 Merkel cell carcinma f unspecified ear and external auricular canal C4A.21 Merkel cell carcinma f right ear and external auricular canal C4A.22 Merkel cell carcinma f left ear and external auricular canal C4A.30 Merkel cell carcinma f unspecified part f face C4A.31 Merkel cell carcinma f nse C4A.39 Merkel cell carcinma f ther parts f face C4A.4 Merkel cell carcinma f scalp and neck C4A.51 Merkel cell carcinma f anal skin C4A.52 Merkel cell carcinma f skin f breast C4A.59 Merkel cell carcinma f ther part f trunk C4A.60 Merkel cell carcinma f unspecified upper limb, including shulder C4A.61 Merkel cell carcinma f right upper limb, including shulder C4A.62 Merkel cell carcinma f left upper limb, including shulder C4A.70 Merkel cell carcinma f unspecified lwer limb, including hip C4A.71 Merkel cell carcinma f right lwer limb, including hip C4A.72 Merkel cell carcinma f left lwer limb, including hip C4A.8 Merkel cell carcinma f verlapping sites C4A.9 Merkel cell carcinma, unspecified C53.0 Malignant neplasm f endcervix C53.1 Malignant neplasm f excervix C53.8 Malignant neplasm f verlapping sites f cervix uteri C53.9 Malignant neplasm f cervix uteri, unspecified C54.0 Malignant neplasm f isthmus uteri C54.1 Malignant neplasm f endmetrium C54.2 Malignant neplasm f mymetrium C54.3 Malignant neplasm f fundus uteri C54.8 Malignant neplasm f verlapping sites f crpus uteri C54.9 Malignant neplasm f crpus uteri, unspecified C55 Malignant neplasm f uterus, part unspecified C56.1 Malignant neplasm f right vary C56.2 Malignant neplasm f left vary C56.9 Malignant neplasm f unspecified vary C57.00 Malignant neplasm f unspecified fallpian tube C57.01 Malignant neplasm f right fallpian tube C57.02 Malignant neplasm f left fallpian tube C57.10 Malignant neplasm f unspecified brad ligament C57.11 Malignant neplasm f right brad ligament C57.12 Malignant neplasm f left brad ligament C57.20 Malignant neplasm f unspecified rund ligament C57.21 Malignant neplasm f right rund ligament C57.22 Malignant neplasm f left rund ligament C57.3 Malignant neplasm f parametrium C57.4 Malignant neplasm f uterine adnexa, unspecified C57.7 Malignant neplasm f ther specified female genital rgans C57.8 Malignant neplasm f verlapping sites f female genital rgans C57.9 Malignant neplasm f female genital rgan, unspecified

12 Page 12 f 17 C60.0 Malignant neplasm f prepuce C60.1 Malignant neplasm f glans penis C60.2 Malignant neplasm f bdy f penis C60.8 Malignant neplasm f verlapping sites f penis C60.9 Malignant neplasm f penis, unspecified C61 Malignant neplasm f prstate C62.00 Malignant neplasm f unspecified undescended testis C62.01 Malignant neplasm f undescended right testis C62.02 Malignant neplasm f undescended left testis C62.10 Malignant neplasm f unspecified descended testis C62.11 Malignant neplasm f descended right testis C62.12 Malignant neplasm f descended left testis C62.90 Malignant neplasm f unspecified testis, unspecified whether descended r undescended C62.91 Malignant neplasm f right testis, unspecified whether descended r undescended C62.92 Malignant neplasm f left testis, unspecified whether descended r undescended C63.7 Malignant neplasm f ther specified male genital rgans C63.8 Malignant neplasm f verlapping sites f male genital rgans C65.1 Malignant neplasm f right renal pelvis C65.2 Malignant neplasm f left renal pelvis C65.9 Malignant neplasm f unspecified renal pelvis C66.1 Malignant neplasm f right ureter C66.2 Malignant neplasm f left ureter C66.9 Malignant neplasm f unspecified ureter C67.0 Malignant neplasm f trigne f bladder C67.1 Malignant neplasm f dme f bladder C67.2 Malignant neplasm f lateral wall f bladder C67.3 Malignant neplasm f anterir wall f bladder C67.4 Malignant neplasm f psterir wall f bladder C67.5 Malignant neplasm f bladder neck C67.6 Malignant neplasm f ureteric rifice C67.7 Malignant neplasm f urachus C67.8 Malignant neplasm f verlapping sites f bladder C67.9 Malignant neplasm f bladder, unspecified C68.0 Malignant neplasm f urethra C69.30 Malignant neplasm f unspecified chrid C69.31 Malignant neplasm f right chrid C69.32 Malignant neplasm f left chrid C69.40 Malignant neplasm f unspecified ciliary bdy C69.41 Malignant neplasm f right ciliary bdy C69.42 Malignant neplasm f left ciliary bdy C69.60 Malignant neplasm f unspecified rbit C69.61 Malignant neplasm f right rbit C69.62 Malignant neplasm f left rbit C69.90 Malignant neplasm f unspecified site f unspecified eye C69.91 Malignant neplasm f unspecified site f right eye C69.92 Malignant neplasm f unspecified site f left eye C74.00 Malignant neplasm f crtex f unspecified adrenal gland C74.01 Malignant neplasm f crtex f right adrenal gland

13 Page 13 f 17 C74.02 Malignant neplasm f crtex f left adrenal gland C74.90 Malignant neplasm f unspecified part f unspecified adrenal gland C74.91 Malignant neplasm f unspecified part f right adrenal gland C74.92 Malignant neplasm f unspecified part f left adrenal gland C76.0 Malignant neplasm f head, face and neck C77.0 Secndary and unspecified malignant neplasm f lymph ndes f head, face and neck C78.00 Secndary malignant neplasm f unspecified lung C78.01 Secndary malignant neplasm f right lung C78.02 Secndary malignant neplasm f left lung C78.6 Secndary malignant neplasm f retrperitneum and peritneum C78.7 Secndary malignant neplasm f liver and intrahepatic bile duct C78.89 Secndary malignant neplasm f ther digestive rgans C79.31 Secndary malignant neplasm f brain C7B.00 Secndary carcinid tumrs unspecified site C7B.01 Secndary carcinid tumrs f distant lymph ndes C7B.02 Secndary carcinid tumrs f liver C7B.03 Secndary carcinid tumrs f bne C7B.04 Secndary carcinid tumrs f peritneum C7B.1 Secndary Merkel cell carcinma C7B.8 Other secndary neurendcrine tumrs C79.89 Secndary malignant neplasm f ther specified sites C79.9 Secndary malignant neplasm f unspecified site C80.0 Disseminated malignant neplasm, unspecified C80.1 Malignant (primary) neplasm, unspecified C81.10 Ndular sclersis Hdgkin lymphma, unspecified site C81.11 Ndular sclersis Hdgkin lymphma, lymph ndes f head, face, and neck C81.12 Ndular sclersis Hdgkin lymphma, intrathracic lymph ndes C81.13 Ndular sclersis Hdgkin lymphma, intra-abdminal lymph ndes C81.14 Ndular sclersis Hdgkin lymphma, lymph ndes f axilla and upper limb C81.15 Ndular sclersis Hdgkin lymphma, lymph ndes f inguinal regin and lwer limb C81.16 Ndular sclersis Hdgkin lymphma, intrapelvic lymph ndes C81.17 Ndular sclersis Hdgkin lymphma, spleen C81.18 Ndular sclersis Hdgkin lymphma, lymph ndes f multiple sites C81.19 Ndular sclersis Hdgkin lymphma, extrandal and slid rgan sites C81.20 Mixed cellularity Hdgkin lymphma, unspecified site C81.21 Mixed cellularity Hdgkin lymphma, lymph ndes f head, face, and neck C81.22 Mixed cellularity Hdgkin lymphma, intrathracic lymph ndes C81.23 Mixed cellularity Hdgkin lymphma, intra-abdminal lymph ndes C81.24 Mixed cellularity Hdgkin lymphma, lymph ndes f axilla and upper limb C81.25 Mixed cellularity Hdgkin lymphma, lymph ndes f inguinal regin and lwer limb C81.26 Mixed cellularity Hdgkin lymphma, intrapelvic lymph ndes C81.27 Mixed cellularity Hdgkin lymphma, spleen C81.28 Mixed cellularity Hdgkin lymphma, lymph ndes f multiple sites C81.29 Mixed cellularity Hdgkin lymphma, extrandal and slid rgan sites C81.30 Lymphcyte depleted Hdgkin lymphma, unspecified site C81.31 Lymphcyte depleted Hdgkin lymphma, lymph ndes f head, face, and neck C81.32 Lymphcyte depleted Hdgkin lymphma, intrathracic lymph ndes C81.33 Lymphcyte depleted Hdgkin lymphma, intra-abdminal lymph ndes C81.34 Lymphcyte depleted Hdgkin lymphma, lymph ndes f axilla and upper limb C81.35 Lymphcyte depleted Hdgkin lymphma, lymph ndes f inguinal regin and lwer limb C81.36 Lymphcyte depleted Hdgkin lymphma, intrapelvic lymph ndes C81.37 Lymphcyte depleted Hdgkin lymphma, spleen C81.38 Lymphcyte depleted Hdgkin lymphma, lymph ndes f multiple sites C81.39 Lymphcyte depleted Hdgkin lymphma, extrandal and slid rgan sites C81.40 Lymphcyte-rich Hdgkin lymphma, unspecified site

14 Page 14 f 17 C81.41 Lymphcyte-rich Hdgkin lymphma, lymph ndes f head, face, and neck C81.42 Lymphcyte-rich Hdgkin lymphma, intrathracic lymph ndes C81.43 Lymphcyte-rich Hdgkin lymphma, intra-abdminal lymph ndes C81.44 Lymphcyte-rich Hdgkin lymphma, lymph ndes f axilla and upper limb C81.45 Lymphcyte-rich Hdgkin lymphma, lymph ndes f inguinal regin and lwer limb C81.46 Lymphcyte-rich Hdgkin lymphma, intrapelvic lymph ndes C81.47 Lymphcyte-rich Hdgkin lymphma, spleen C81.48 Lymphcyte-rich Hdgkin lymphma, lymph ndes f multiple sites C81.49 Lymphcyte-rich Hdgkin lymphma, extrandal and slid rgan sites C81.70 Other Hdgkin lymphma unspecified site C81.71 Other Hdgkin lymphma lymph ndes f head, face, and neck C81.72 Other Hdgkin lymphma intrathracic lymph ndes C81.73 Other Hdgkin lymphma intra-abdminal lymph ndes C81.74 Other Hdgkin lymphma lymph ndes f axilla and upper limb C81.75 Other Hdgkin lymphma lymph ndes f inguinal regin and lwer limb C81.76 Other Hdgkin lymphma intrapelvic lymph ndes C81.77 Other Hdgkin lymphma spleen C81.78 Other Hdgkin lymphma lymph ndes f multiple sites C81.79 Other Hdgkin lymphma extrandal and slid rgan sites C81.90 Hdgkin lymphma, unspecified, unspecified site C81.91 Hdgkin lymphma, unspecified, lymph ndes f head, face, and neck C81.92 Hdgkin lymphma, unspecified, intrathracic lymph ndes C81.93 Hdgkin lymphma, unspecified, intra-abdminal lymph ndes C81.94 Hdgkin lymphma, unspecified, lymph ndes f axilla and upper limb C81.95 Hdgkin lymphma, unspecified, lymph ndes f inguinal regin and lwer limb C81.96 Hdgkin lymphma, unspecified, intrapelvic lymph ndes C81.97 Hdgkin lymphma, unspecified, spleen C81.98 Hdgkin lymphma, unspecified, lymph ndes f multiple sites C81.99 Hdgkin lymphma, unspecified, extrandal and slid rgan sites C84.90 Mature T/NK-cell lymphmas, unspecified site C84.91 Mature T/NK-cell lymphmas, lymph ndes f head, face, and neck C84.92 Mature T/NK-cell lymphmas, intrathracic lymph ndes C84.93 Mature T/NK-cell lymphmas, intra-abdminal lymph ndes C84.94 Mature T/NK-cell lymphmas, lymph ndes f axilla and upper limb C84.95 Mature T/NK-cell lymphmas, lymph ndes f inguinal regin and lwer limb C84.96 Mature T/NK-cell lymphmas, intrapelvic lymph ndes C84.97 Mature T/NK-cell lymphmas, spleen C84.98 Mature T/NK-cell lymphmas, lymph ndes f multiple sites C84.99 Mature T/NK-cell lymphmas, extrandal and slid rgan sites C84.Z0 C84.Z1 C84.Z2 C84.Z3 C84.Z4 C84.Z5 C84.Z6 C84.Z7 C84.Z8 C84.Z9 Other mature T/NK-cell lymphmas, Unspecified site Other mature T/NK-cell lymphmas, lymph ndes f head, face, and neck Other mature T/NK-cell lymphmas, intrathracic lymph ndes Other mature T/NK-cell lymphmas, intra-abdminal lymph ndes Other mature T/NK-cell lymphmas, lymph ndes f axilla and upper limb Other mature T/NK-cell lymphmas, lymph ndes f inguinal regin and lwer limb Other mature T/NK-cell lymphmas, intrapelvic lymph ndes Other mature T/NK-cell lymphmas, spleen Other mature T/NK-cell lymphmas, lymph ndes f multiple sites Other mature T/NK-cell lymphmas, extrandal and slid rgan sites C85.20 Mediastinal (thymic) large B-cell lymphma, unspecified site

15 Page 15 f 17 C85.21 Mediastinal (thymic) large B-cell lymphma, lymph ndes f head, face and neck C85.22 Mediastinal (thymic) large B-cell lymphma, intrathracic lymph ndes C85.23 Mediastinal (thymic) large B-cell lymphma, intra-abdminal lymph ndes C85.24 Mediastinal (thymic) large B-cell lymphma, lymph ndes f axilla and upper limb C85.25 Mediastinal (thymic) large B-cell lymphma, lymph ndes f inguinal regin and lwer limb C85.26 Mediastinal (thymic) large B-cell lymphma, intrapelvic lymph ndes C85.27 Mediastinal (thymic) large B-cell lymphma, spleen C85.28 Mediastinal (thymic) large B-cell lymphma, lymph ndes f multiple sites C85.29 Mediastinal (thymic) large B-cell lymphma, extrandal and slid rgan sites C86.0 Other specified types f T/NK-cell lymphma D09.0 Carcinma in situ f bladder D37.01 Neplasm f uncertain behavir f lip D37.02 Neplasm f uncertain behavir f tngue D37.05 Neplasm f uncertain behavir f pharynx D37.09 Neplasm f uncertain behavir f ther specified sites f the ral cavity D37.1 Neplasm f uncertain behavir f stmach D37.8 Neplasm f uncertain behavir f ther specified digestive rgans D37.9 Neplasm f uncertain behavir f digestive rgan, unspecified D38.0 Neplasm f uncertain behavir f larynx D38.5 Neplasm f uncertain behavir f ther respiratry rgans D38.6 Neplasm f uncertain behavir f respiratry rgan, unspecified Z80.49 Family histry f malignant neplasm f ther genital rgans Z85.00 Persnal histry f malignant neplasm f unspecified digestive rgan Z85.01 Persnal histry f malignant neplasm f esphagus Z Persnal histry f ther malignant neplasm f stmach Z Persnal histry f ther malignant neplasm f large intestine Z Persnal histry f ther malignant neplasm f small intestine Z85.07 Persnal histry f malignant neplasm f pancreas Z Persnal histry f ther malignant neplasm f brnchus and lung Z85.21 Persnal histry f malignant neplasm f larynx Z85.22 Persnal histry f malignant neplasm f nasal cavities, middle ear, and accessry sinuses Z85.43 Persnal histry f malignant neplasm f vary Z85.47 Persnal histry f malignant neplasm f testis Z85.49 Persnal histry f malignant neplasm f ther male genital rgans Z85.51 Persnal histry f malignant neplasm f bladder Z85.59 Persnal histry f malignant neplasm f ther urinary tract rgan Z85.71 Persnal histry f Hdgkin Lymphma Z Persnal histry f malignant neplasm f tngue Z Persnal histry f malignant neplasm f ther sites f lip, ral cavity and pharynx Z Persnal histry f malignant neplasm f unspecified site f lip, ral cavity and pharynx Z Persnal histry f malignant melanma f skin Z Persnal histry f Merkel cell carcinma Z Persnal histry f malignant neplasm f bne Z Persnal histry f malignant neplasm f ther endcrine glands Z85.59 Persnal histry f malignant neplasm f ther urinary tract rgan C22.0 Liver cell carcinma C22 Malignant neplasm f liver and intrahepatic bile ducts Z85.05 Persnal histry f malignant neplasm f liver

16 Page 16 f 17 Revisin Histry N/A References 1. Keytruda [package insert]. Whitehuse Statin, NJ; Merck & C, Inc; August Accessed August Referenced with permissin frm the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) pembrlizumab. Natinal Cmprehensive Cancer Netwrk, The NCCN Cmpendium is a derivative wrk f the NCCN Guidelines. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, and NCCN GUIDELINES are trademarks wned by the Natinal Cmprehensive Cancer Netwrk, Inc. T view the mst recent and cmplete versin f the Cmpendium, g nline t NCCN.rg. Accessed July Alley EW, Lpez J, Santr A, et al. Clinical safety and activity f pembrlizumab in patients with malignant pleural mesthelima (KEYNOTE-028): preliminary results frm a nn-randmised, pen-label, phase 1b trial. Lancet Oncl May;18(5): Ott PA, Bang YJ, Bertn-Rigaud D, et al. Safety and Antitumr Activity f Pembrlizumab in Advanced Prgrammed Death Ligand 1-Psitive Endmetrial Cancer: Results Frm the KEYNOTE- 028 Study. J Clin Oncl Aug 1;35(22): Ott PA, Piha-Paul SA, Munster P, et al. Safety and antitumr activity f the anti-pd-1 antibdy pembrlizumab in patients with recurrent carcinma f the anal canal. Ann Oncl May 1;28(5): di: /annnc/mdx Zinzani PL, Ribrag V, Mskwitz CH, et al. Safety and tlerability f pembrlizumab in patients with relapsed/refractry primary mediastinal large B-cell lymphma. Bld Jul 20;130(3): di: /bld Epub 2017 May U.S. Fd and Drug Administratins (FDA). Divisin f Drug Infrmatin. Health Alert. 1B9C490C37BFE6647&elq=3f e82421a8af346a664bedbfb&elqaid=3588&elqat=1. Accessed May Balar AV, Castellan D, O Dnnell PH, et al. First-line pembrlizumab in cisplatin-ineligible patients with lcally advanced and unresectable r metastatic urthelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncl 2017; 18: Referenced with permissin frm the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) Merkel Cell Carcinma. Versin Natinal Cmprehensive Cancer Netwrk, The NCCN Cmpendium is a derivative wrk f the NCCN Guidelines. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, and NCCN GUIDELINES are trademarks wned by the Natinal Cmprehensive Cancer Netwrk, Inc. T view the mst recent and cmplete versin f the Cmpendium, g nline t NCCN.rg. Accessed July Referenced with permissin frm the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) Bladder Cancer. Versin Natinal Cmprehensive Cancer Netwrk, 2018.

17 Page 17 f 17 The NCCN Cmpendium is a derivative wrk f the NCCN Guidelines. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, and NCCN GUIDELINES are trademarks wned by the Natinal Cmprehensive Cancer Netwrk, Inc. T view the mst recent and cmplete versin f the Cmpendium, g nline t NCCN.rg. Accessed July Referenced with permissin frm the NCCN Drugs & Bilgics Cmpendium (NCCN Cmpendium ) Nn-Small Cell Lung Cancer. Versin Natinal Cmprehensive Cancer Netwrk, The NCCN Cmpendium is a derivative wrk f the NCCN Guidelines. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, and NCCN GUIDELINES are trademarks wned by the Natinal Cmprehensive Cancer Netwrk, Inc. T view the mst recent and cmplete versin f the Cmpendium, g nline t NCCN.rg. Accessed July 2018.