Local Coverage Determination (LCD): Chemotherapy Drugs and their Adjuncts (L28576)

Local Coverage Determination (LCD): Chemotherapy Drugs and their Adjuncts (L28576) Contractor Information Contractor Name Wisconsin Physicians Service Insurance Corporation LCD Information Document Information LCD ID L28576 LCD Title Chemotherapy Drugs and their Adjuncts AMA CPT / ADA CDT / AHA NUBC Copyright Statement CPT only copyright 2002-2014 American Medical Association. All Rights Reserved. CPT is a registered trademark of the American Medical Association. Applicable FARS/DFARS Apply to Government Use. Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein. The Code on Dental Procedures and Nomenclature (Code) is published in Current Dental Terminology (CDT). Copyright American Dental Association. All rights reserved. CDT and CDT-2010 are trademarks Original Effective Date For services performed on or after 05/16/2009 Revision Effective Date For services performed on or after 09/01/2015 Revision Ending Date N/A Retirement Date ANTICIPATED 09/30/2015 Notice Period Start Date 06/01/2012 Notice Period End Date N/A

of the American Dental Association. UB-04 Manual. OFFICIAL UB-04 DATA SPECIFICATIONS MANUAL, 2014, is copyrighted by American Hospital Association ( AHA ), Chicago, Illinois. No portion of OFFICIAL UB-04 MANUAL may be reproduced, sorted in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior express, written consent of AHA. Health Forum reserves the right to change the copyright notice from time to time upon written notice to Company. CMS National Coverage Policy Jurisdiction "8" Notice: Jurisdiction "8" comprises the states of Indiana and Michigan. WPS is responsible for claims payment and Local Coverage Determination (LCD) development for this jurisdiction. This LCD was created as a part of the legacy transition (7/16/2012-8/20/2012); and, is a consolidation of the previous legacy contractors' policies. Coverage of each LCD begins when the state/contract number combination officially is integrated into the Jurisdiction. On the CMS MCD, this date is known as either the Original Effective Date or the Revision Effective Date. The following table details the official effective dates for each state/contract number combination. ST Legacy A Contractor & Contract Number Legacy B Contractor & Contract Number J "8" MAC A Contractor & Contract Number J "8" MAC B Contractor & Contract Number J "8" Effective Date IN NGS: 00630 WPS: 08102 08/20/12 MI WPS: 00953 WPS: 08202 07/16/12 IN NGS: 00130 WPS: 08101 07/23/12 MI NGS: 00452 WPS: 08201 07/23/12 CMS Pub. 100-02 Medicare Benefit Policy Manual, Chapter 15-Covered Medical and Other Health Services, Section 50-Drugs and Biologicals CMS Pub. 100-04 Medicare Claims Processing Manual, Chapter 12-Physician/Nonphysician Practitioners, Section 30.5-Payment for Codes for Chemotherapy Administration and

Nonchemotherapy Injections and Infusions CMS Pub. 100-04 Medicare Claims Processing Manual, Chapter 14-Ambulatory Surgical Centers, Section 10-General CMS Pub. 100-04 Medicare Claims Processing Manual, Chapter17-Drugs and Biologicals, Section 90.2- Drugs, Biologicals, and Radiopharmaceuticals CR 71111-October 2010 Integrated Outpatient Code Editor (I/OCE) Specifications Version 11.3 CR 7303 Quarterly HCPCS Drug/Biological Code July 2011 Update CR 7844 July Update to the CY 2012 Medicare Physician Fee Schedule Database (MPFSDB) CR 8338 July 2013 Update of the Hospital Outpatient Prospective Payment System (OPPS) CR 8880 October 2014 Update of the Ambulatory Surgical Center (ASC) Payment System CR 9100 April 2015 Update of the Ambulatory Surgical Center (ASC) Payment System CR 9205 July 2015 Attachment A: Drugs and Biologicals with OPPS Pass-through Status Coverage Guidance Coverage Indications, Limitations, and/or Medical Necessity A. Coverage for medication is based on the patient's condition, the appropriateness of the dose and route of administration, based on the clinical condition and the standard of medical practice regarding the effectiveness of the drug for the diagnosis and condition. The drug must be used according to the indication and protocol listed in the accepted compendia ratings listed below. National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium Thomson Micromedex DrugDex American Hospital Formulary Service-Drug Information (AHFS-DI) Clinical Pharmacology The compendia employ various rating and recommendation systems that may not be readily cross-walked from compendium to compendium. In general, a use is identified by a compendium as medically accepted if the: 1. indication is a Category 1 or 2A in NCCN, or Class I, Class IIa or Class IIb in DrugDex; or 2. narrative text in AHFS-DI or Clinical Pharmacology is supportive. B. The following well-established drugs will be allowed for cancer therapy and for other therapy as indicated. (ICD-9 codes 140.0-239.9, or 259.2) 1. Bleomycin sulfate, 15 units (Blenoxane) (J9040) Verruca - 078.10-078.12, 078.19

2. Carboplatin 50 mg, (Paraplatin) (J9045) 3. Carmustine 100 mg, (BCNU, BiCNU) (J9050) 4. Cisplatin (Platinol) powder or solution, per 10 mg (J9060) 5. Cyclophosphamide (Cytoxan) 100 mg (J9070) See section F for non-oncological uses. 6. Cytarabine 100 mg. (J9100) 7. Dacarbazine (DTIC) 100 mg (J9130) 8. Dactinomycin 0.5mg (actinomycin-d, Cosmegen) (J9120) 9. Doxorubicin Hydrochloride 10 mg (Adriamycin) (J9000) 273.3 10. Diethylstilbestrol Diphosphate, 250 mg (J9165) 11. Etoposide (VePesid) 10 mg (J9181) Etopside phosphate (Etopophos) 273.3 12. Floxuridine (FUDR) 500 mg (J9200) 13. Fluorouracil (5FU, Adrucil) 500 mg (J9190) glaucoma (365.10-365.65, 365.70-365.73, 365.81-365.9) for patients at high risk for filtering surgery failure. Verruca - 078.10-078.12, 078.19 14. Ifosfamide 1 gram (J9208) 15. Leucovorin calcium, per 50 mg (J0640) 16. Levoleucovorin calcium, 0.5mg (J0641) 17. Mechlorethamine hydrochloride (Nitrogen Mustard), 10 mg (J9230) 18. Mesna 200 mg (Urothelial Protectant used in combination with cyclophosphamide or Ifosfamide) 595.9 (J9209) 19. Methotrexate Sodium ; (MTX, Folex) 5 mg (J9250), Methotrexate Sodium ; (MTX, Folex) 50 mg (J9260) See section F for non-oncological uses. 20. Plicamycin 2.5mg (Mithracin) (J9270) 21. Mitomycin (Mutomycin) 5 mg (J9280) Use/See J7315 for ophthalmic use. 22. Thiotepa 15 mg (J9340) 23. Vinblastine sulfate (Velban) 1 mg (J9360) 24. Vincristine (Oncovin) 1 mg (J9370), (273.3-Waldenstrom s Macroglobulinemia, 283.0- autoimmune hemolytic anemia or 287.49-other secondary thrombocytopenia) The following have been added: 25. BCG (Intravesical), per installation (J9031) 26. Cladribine Chlorodexyadenoside (2-CDA) (Leustatin) per 1 mg (J9065) 27. Daunorubicin, 10 mg (J9150) 28. Daunorubicin citrate, liposomal formulation, (DaunoXome) 10 mg (J9151) 29. Doxorubicin Hydrochloride, liposomal, Doxil, 10mg Not otherwise specified (Q2050 ); Doxorubicin Hydrochloride, liposomal Lipodox, 10 mg (Q2049) 30. Docetaxel (Taxotere) 1mg (J9171) 31 Epirubicin Hydrochloride (Ellence) 2 mg (J9178) 32. Fludarabine Phosphate (Fludara) 50 mg (J9185), (273.3, V42.82) 33. Fulvestrant (Faslodex ) 25mg (J9395) 34. Gemcitabine Hydrochloride (Gemzar) 200 mg (J9201) 35. Idarubicin Hydrochloride 5 mg (Idamycin) (J9211) 36. Interferon, alpha-2b, recombinant, 1 million units (Intron A) (J9214) (078.10-078.12, 078.19, 070.44, 070.54, 070.32).

37. Irinotecan (Camptosar) 20 mg (J9206) 38. Melphalan Hydrochloride (Alkeran) (J9245) per 50 mg (273.3, V42.81,V42.82) 39. Mitoxantrone (Novantrone) (J9293) per 5mg (340, Multiple Sclerosis) 40. Oxaliplatin (Eloxatin ) 0.5 mg (J9263) 41. Paclitaxel (Taxol) 30mg (J9267) 42. Pemetrexed (Alimta ), 10 mg (J9305) 43. Streptozocin (Zanosar), 1 gram (J9320) 44. Topotecan (Hycamtin) 0.1 mg (J9351) 45. Valrubicin intravesical (Valstar) 200mg (J9357) 46. Vinorelbine tartrate (Navelbine) per 10 mg (J9390) C. The following drugs are approved per FDA or NCCN guidelines for the specific indications listed: 1. ado-trastuzumab emtansine, 1mg (KADCYLA )(J9354) Patients must have a positive 2+ HER 2 and metastatic disease, or a positive 3+ HER 2 test or a positive fish test for all indications below: Is covered as a single agent, for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either: Received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy (174.0-174.9, 175.0-175.9). Effective 02/22/2013-FDA approval date. OR per NCCN: Is covered as a single agent, for the treatment of patients with HER2-positive, recurrent or metastatic trastuzumab-exposed disease. The patient therefore should previously have been treated with trastuzumab (174.0-174.9, 175.0-175.9). Effective 01/01/2015 2. Aldesleukin.per single use vial, (J9015) (Proleukin) (Interleukin-2) Acute myelogenou/s Leukemia 205.00-205.02 Melanoma 172.0-172.9, 190.9 (effective 05/16/09) Renal Cell 189.0, 189.1 Non-Hodgkin's lymphoma 200.00-200.88, 202.00-202.98 3. Arsenic Trioxide (Trisenox) 1mg (J9017) Acute Promyelocytic leukemia (APL) 205.00-205.02 Chronic Myeloid Leukemia 205.10, 205.11, 205.12 Multiple Myeloma 203.00-203.02 Myelodysplastic Syndromes 238.72-238.76 4. Asparaginase, (erwinaze), 1,000 units (J9019), Asparaginase, not otherwise

specified 10,000 units (J9020) Acute lymphocytic leukemia 204.00-204.02 Acute non-lymphocytic leukemia 205.00-205.02, 205.10-205.12, 205.20-205.22, 205.30-205.32, 205.80-205.82, 205.90-205.92, 206.00-206.02, 206.10-206.12, 206.20-206.22, 206.80-206.82, 206.90-206.92, 207.00-207.02, 207.10-207.12, 207.20-207.22, 207.80-207.82, 208.00-208.02, Chronic lymphocytic leukemia 204.10, 204.12 Hodgkin's lymphoma 201.90-201.98 Soft tissue sarcoma, melanosarcoma 172.0-172.9 Non-Hodgkin's lymphoma 200.00-200.88, 202.00-202.98 5. Azacitidine (Vidaza TM ) (J9025), 1 mg Myelodysplastic Syndrome 238.72-238.76 Acute myelogenous leukemia 205.00-205.02 Chronic Myeloid leukemia 205.10, 205.12 Monocytic leukemia 206.00-206.02 Other specified leukemia 207.00-207.02, 207.20-207.22 6. Bendamustine hydrochloride (Treanda ), 1 mg J9033 FDA indication: Bendamustine hydrochloride is covered for the treatment of patients with indolent B-cell non-hodgkin's lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. OR per NCCN: Chronic lymphocytic leukemia (CLL) 204.10-204.11, 204.12. Non-Hodgkin's Lymphoma (NHL) 200.00-200.88, 202.00-202.98 Waldenstrom's Macroglobulinemia 273.3 Multiple Myeloma 203.00-203.82, 238.6 Hodgkin s Lymphoma 201.40-201.48, 201.50-201.58, 201.60-201.68, 201.70-201.78, 201.90-201.98 Adult T- cell Leukemia/lymphoma (204.80-204.82 )- effective 03/01/2015 7. Bevacizumab (Avastin )(J9035), 10 mg Breast Cancer Covered for the treatment of recurrent or metastatic breast cancer, HER-2 negative disease, in combination with paclitaxel. 174.0-175.9 Malignant neoplasm small intestine 152.0-152.2, 152.8, 152.9 Colorectal Cancer 153.0-154.8, 152.0-152.2, 152.8, 197.0, 197.6, 197.7 Non-Small cell lung cancer 162.0-162.9 Corpus uteri -Endometrium 182.0 Glioma 191.0-191.9, 192.8, 237.5 Ovarian Cancer 183.0-183.9

Renal Cell Cancer 189.0, 189.1 Malignant neoplasm of retroperitoneum and peritoneum 158.0, 158.8, 158.9 Soft Tissue Sarcomas 171.0-171.9 Cervical Cancer 180.0-180.9 Mesothelioma 163.0, 163.1, 163.8, 163.9 8. Bortezomib (Velcade ) (J9041), 0.1mg Anaplastic large cell lymphoma 200.60-200.68 Peripheral T-cell lymphoma 202.70-202.78 Other Lymphomas 202.80-202.88 Multiple Myeloma 203.00-203.02, 203.10, 203.12, 203.80-203.82, 238.6 Mantle cell lymphoma 200.40-200.48 Amyloidosis 277.30 Waldenstrom's Macroglobulinemia 273.3 Other NHL s 229.0, 202.83, 200.80-200.88, 785.6 Or: Primary chemotherapy for progressive solitary plasmacytoma or smoldering myeloma (asymptomatic) that has progressed to active (symptomatic) myeloma (203.00, 203.10, 203.80 or 238.6) in: -combination with dexamethasone with or without cyclophosphamide, doxorubicin, lenalidomide, or thalidomide for transplant candidates (all preferred regimens) -combination with dexamethasone or in MPB (melphalan, prednisone, and bortezomib) regimen for nontransplant candidates (all preferred regimens) 9. Brentuximab vedotin, (ADCETRIS ) (J9042) 1mg FDA approved 08/19/2011 for: - The treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates (201.00-201.98) - The treatment of patients with systemic anaplastic large cell lymphoma (excluding cutaneous ALCL) after failure of at least one prior multi-agent chemotherapy regimen and for CD 30+ peripheral T-cell lymphoma (200.60-200.68, 202.70-202.78) Or per NCCN: Hodgkin lymphoma 200.80-200.88, 201.50-201.98 NHL s 202.10-202.18, 202.20-202.28, 200.60-200.68, 202.70-202.78

10. Cabazitaxel (Jevtana ) (J9043) 1 mg, effective 07/17/10 FDA approval date Microtubular inhibitor indicated in combination with prednisone for treatment of hormone refractory metastatic prostate cancer (185) previously treated with a docetaxel containing regimen. 11. Carfilzomib 1 mg (KYPROLIS )(J9047) KYPROLIS is a proteasome inhibitor indicated for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy (203.00-203.02). Effective 07/20/12-FDA approval date. Or per NCCN: Used in combination with lenalidomide and dexamethasone for transplant candidates with progressive solitary plasmacytoma or smoldering myeloma (asymptomatic) that has progressed to active (symptomatic) myeloma as primary chemotherapy. (203.00-203.02, 203.10, 203.12, 203.80, 203.82, 238.6). Effective 03/01/2015 As preferred therapy for previously treated myeloma on/off clinical trials for disease relapse, progressive disease or refractory disease (203.00, 203.02, 203.10, 203.12, 203.80, 203.82, 238.6). Waldenstrom s/lymphoplasmacytic Lymphoma (200.80-200.88, 273.3). 12. Cetuximab (Erbitux ) (J9055) 10 mg Colorectal Cancer 152.0-152.2, 152.8, 152.9, 153.0-154.8, 197.0, 197.6, 197.7 Head and Neck Cancer 140.0-149.9, 160.0-161.9, 173.00, 173.02, 173.09, 195.0, 196.0, 198.89, 235.1, 235.6, 235.9 Non-Small cell lung cancer 162.2-162.9 Squamous Cell Skin Cancer of the head and neck 173.02, 173.12, 173.22, 173.32, 173.42, 173.52, 173.62, 173.72, 173.82, 173.92 Squamous Cell Skin Cancer for Regional Recurrences or Distal Metastases 239.2 or V10.83. Penile 187.1-187.4, 187.8, 187.9 Cetuximab is covered when: Used in combination with irinotecan, is indicated for the treatment of metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. -Administered as a single agent for the treatment of patients with metastatic colorectal carcinoma in patients who are intolerant to irinotecan based chemotherapy.

The patient must not have K-RAS mutation when using this drug for the treatment of colorectal cancer. -As a single agent or in combination with irinotecan after first progression except in patients receiving capecitabine or fluorouracil and leucovorin with bevacizumab. Cetuximab is a recombinant, human/mouse (chimeric) monoclonal antibody. If the patient has disease progression on an Epidermal Growth Factor Receptor (EGRF) monoclonal antibody, it would not be appropriate to use this drug. 13. Cytarabine Liposome (Depocyt ) 10 mg (J9098) Intrathecal treatment of lymphomatous meningitis-secondary malignant neoplasm of other parts of nervous system 198.4 CNS Cancers/AML 205.00, 205.02, 206.00, 206.02, 207.00, 207.02, 207.20, 207.22 14. Decitabine (Dacogen) (J0894) Myelodysplastic Syndrome 238.72-238.76 Acute Myeloid Leukemia 205.00, 205.01, 205.02, 206.00, 206.01, 206.02, 207.00, 207.01, 207.02, 207.20, 207.21, 207.22 Chronic Myelomonocytic leukemia 205.10, 205.12 15. Eribulin mesylate (Halaven) (J9179), 0.1mg FDA Approved 11/15/2010 For the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included anthracycline and a taxane in either the adjuvant or metastatic setting (174.0-174.9, 175.0-175.9). Soft tissue Sarcomas: 158.0, 158.8, 158.9, 171.0, 171.2-171.9 16. Interferon, Alfa-N3 (Human Leukocyte Derived) 250,000 IU (Alferon N)(J9215) Bladder 188.0-188.9, 233.7 Chronic Myelocytic Leukemia 205.10, 205.11, 205.12 Hairy Cell Leukemia 202.40-202.48 Kaposi's Sarcoma 176.0-176.9 Kidney 189.0, 189.1 Melanoma 172.0-172.9 Multiple Myeloma 203.00-203.02, 203.10, 203.12 Non-Hodgkin's Lymphomas 200.00-200.88, 202.00-202.98 Other Indications: Condylomata Acuminata 078.10-078.12, 078.19

17. Ipilimumab (Yervoy ) 1mg, (J9228) effective 03/25/11 (FDA approval date) For the treatment of unresectable or metastatic melanoma 172.0-172.9, 184.0-184.4, 187.1, 187.2, 187.4, 187.7 Or per NCCN: Melanoma: single-agent therapy for metastatic or unresectable disease: first-line therapy if clinical stability is anticipated for >12 weeks; secondline or subsequent therapy for disease progression or following maximum clinical benefit from BRAF targeted therapy for patients with performance status 0-2; and reinduction therapy in select patients who experienced no significant systemic toxicity during prior ipilimumab therapy and who relapse after initial clinical response or progress after stable disease > 3 months (172.0-172.9, 190.9, 198.3, 199.0, 199.1). 18. Ixabepilone (Ixempra ), 1mg (J9207 ) Breast (174.0-175.9) Ixabepilone is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting. Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting. Ixabepilone is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine. 19. Nelarabine (Aarron) (J9261) 50 mg Acute lymphoblastic Leukemia 204.00, 204.01, 204.02 Lymphoblastic lymphoma, T-cell 200.10-200.18 20. Obinutuzumab (GAZYVA) (J9301) is a CD20-directed cytolytic antibody and is indicated, in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia. (204.10). Effective FDA approval date (11/01/2013). Or per NCCN: Small lymphocytic lymphoma 200.10-200.18-effective 02/01/2015 Used in combination with chlorambucil as first-line therapy for patients with stage II-IV disease. Chronic lymphocytic leukemia and small lymphocytic lymphoma 204.10, 204.12,

200.10-200.18 for relapsed or refractory disease; and if unable to tolerate purine analogs as a single agent or in combination with chlorambucil-effective 04/01/2015. 21. Octreotide, Depot Form for Intramuscular Injection, 1 mg.(sandostatin LAR Depot) (J2353) Acromegaly 253.0 Carcinoid Syndrome 259.2 Neuroendocrine tumors 209.00-209.03, 209.10-209.17, 209.20-209.29, 209.30, 209.70 Pancreas 157.0-157.9 Vasoactive intestinal peptide tumors (VIPomas) 159.0 (For the control of diarrhea associated with VIPomas) Chemotherapy induced diarrhea 787.91 Angiodysplasia of intestine with hemorrhage 569.85 Enterocolic fistula of intestine 569.81 22. Omacetaxine mepesuccinate, (SYNRIBO) 0.01 mg (J9262) is covered for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI). (205.10-205.12) 23. Paclitaxel protein-bound particles, 1 mg (Abraxane ) (J9264) Breast 174.0-175.9 Non-Small cell lung cancer 162.2-162.9 Malignant neoplasm of specified parts of peritoneum 158.8 Ovarian- Recurrence therapy as a single agent for progressive, stable or persistent disease on primary chemotherapy, or relapse after complete remission following primary chemotherapy, or stage II-IV disease showing partial response to primary treatment 183.0-183.9 Pancreatic - In combination with gemcitabine for patients with locally advanced or unresectable or metastatic disease and good performance status 157.0-157.3, 157.8, 157.9 Melanoma 172.0-172.9, 198.3, 199.0, 199.1 24. Panitumumab (Vectibix), 10 mg (J9303) Colorectal cancer 152.0-152.2, 152.8, 152.9, 153.0-154.8, 197.0, 197.6, 197.7 Panitumumab (Vectibix TM ) is indicated for the treatment of metastatic colorectal carcinoma. Patient must not have K-RAS mutation. Panitumumab is a recombinant human monoclonal antibody. If the patient has disease progression on an Epidermal Growth Factor Receptor (EGFR) monoclonal antibody, it would not be appropriate to use this drug.

25. Pentostatin (Nipent) 10 mg (J9268) Hairy Cell Leukemia 202.40-202.48 Acute Lymphocytic Leukemia 204.00, 204.01, 204.02 Prolymphocytic Leukemia 204.90, 204.91, 204.92 Chronic Lymphocytic Leukemia 204.10, 204.11, 204.12 Cutaneous T-Cell Lymphomas, Mycosis Fungoides, Sézary's Disease 202.00-202.98 Mantle Cell 200.40-200.48 NHL 204.80, 204.82, 200.10-200.18 26. Pegaspargase (Oncaspar) per single dose vial (J9266) (When patient has developed a hypersensitivity to native forms of L-asparaginase) Acute lymphocytic leukemia 204.00, 204.01, 204.02 NHL 202.80-202.88 27. Pertuzumab, 1 mg (PERJETATM ) (J9306) Pertuzumab is indicated in combination with trastuzumab and docetaxel or paclitaxel for the treatment of patients with HER2-positive breast cancer (174.0-175.9). May be considered in combination with trastuzumab with or without cytotoxic therapy (eg, vinorelbine or taxane) or in cancer in combination with docetaxel or carboplatin. Patients must have a positive 2+ HER 2 and metastatic disease, or a positive 3+ HER 2 test or a positive fish test. 28. Pralatrexate (Folotyn) 1 mg (J9307) Relapsed or refractory peripheral T-cell lymphoma (PTCL) 200.60-200.68, 202.10-202.18, 202.20-202.28, 202.70-202.78, 202.80-202.88 NHL 200.80, 204.80, 204.82 29. Radium Ra 223 dichloride (Xofigo) ( A9606) Coverage is for the FDA approved indication: the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. It is administered at 4 week intervals for a total of 6 doses. Use diagnosis codes 185 and 198.5. Coverage is effective 05/15/2013 FDA approval date. Off label use is not covered. Do not use both diagnosis codes if the indications have not been met. 30. Romidepsin (Istodax) 1 mg (J9315) Cutaneous T- cell lymphoma (CTCL) in patients that have received at least one prior systemic therapy (202.00-202.98). (Effective 11/05/2009) Peripheral T-cell lymphoma (PTCL) in patients that have received at least one

prior therapy. (202.70-202.78) (Effective FDA approval date-06/16/2011 Second line therapy for relapsed or refractory angioimunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, anaplastic large cell lymphoma or enteropathy-associated T-cell lymphoma 200.60-200.68. Or per NCCN: T cell leukemia/lymphoma 204.80, 204.82 Mycosis Fungoides/Sezary 202.10-202.18, 202.20-202.28 PTCL 200.60-200.68, 200.80, 202.70-202.78, 202.83 Lymphoproliferative disorders 200.80-200.88 31. Temsirolimus (Torisel ) 1 mg (J9330) Advanced Renal Cell Carcinoma 189.0, 189.1 Corpus uteri -Endometrium 182.0 Sarcoma 171.8, 171.9, 239.2 32. Teniposide (Vumon) 50 mg Q2017 Acute Lymphocytic Leukemia 204.00, 204.01, 204.02 Neuroblastoma 160.0-160.9, 194.0-194.9 Non-Hodgkin's Lymphoma 200.00-200.88, 202.00-202.98 33. Vincristine sulfate, liposome, 1 mg (Marqibo) (J9371) is covered for the treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies (204.02) 34. ziv-aflibercept 1 mg (ZALTRAP), (J9400) In combination with 5-fluorouracil, leucovorin, irinotecan-(folfiri), is indicated for patients with metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin-containing regimen (153.0-154.8). Effective 08/03/12- FDA approval date. Or per NCCN: Colorectal Cancer: 152.0-152.2, 152.8, 152.9, 153.0-153.9, 154.0, 154.1, 154.8, 197.0, 197.7 D. Not otherwise Classified Agents (NOC) (A9699, J3590, J9999, C9399) 1. Ramucirumab (Cyramza) (J9999, C9025) Covered for advanced gastric cancer or gastro-esophageal junction adenocarcinoma, as a single agent after prior fluoropyrimidine or platinum containing chemotherapy (150.0-150.8,151.0-151.9). Effective 04/21/2014 FDA approval date.

Covered in combination with paclitaxel for treatment of advanced gastric or gastro-esophageal junction adenocarcinoma, with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy (150.0-150.8, 151.0-151.9). Effective 11/05/2014-FDA approval date. Covered in combination with docetaxel, for treatment of metastatic nonsmall cell lung cancer with disease progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA. (162.0, 162.2-162.5, 162.8, 162.9) Effective 12/12/2014-FDA approval Date. Covered in combination with FOLFIRI, for the treatment of metastatic colorectal cancer with disease progression on or after prior therapy with bevacizumab, oxaliplatin and a fluoropyrimidine. (153-154.8). Effective 04/24/2015, FDA approval date. Or per NCCN: Colorectal Ca 152.0-152.2, 152.8, 152.9, 153.0-154.8, 197.0, 197.6, 197.7 Esophageal Cancer 150.0-150.5, 150.8, 150.9, 151.0, 235.5 Gastric Cancer 151.0-151.6, 151.8, 151.9, 235.2 NSCLC: 162.0, 162.2-162.5, 162.8, 162.9 2. Belinostat (Beleodaq) (J9999/C9442) is indicated for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) (202.70-202.78). Effective 07/03/2014-FDA approval date. 3. Pembrolizumab (Keytruda) (J9999/C9027) is indicated for the treatment of patients with unresectable or metastatic melanoma (172.0-172.9) and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Effective 09/04/2014 -FDA approval date. Clarification of above FDA approval: First line therapy for unresectable or metastatic melanoma. Second line therapy for disease progression following ipilimumab. Or per NCCN: Melanoma metastatic or unresectable disease: 172.0-172.9, 190.9, 198.3, 199.0, 199.1 4. Nivolumab (OPDIVO) (J9999, C9453) Covered for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. (172.0-172.9). Effective 12/22/2014-FDA approval date.

Metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy (162.0, 162.2-162.5, 162.8, 162.9, V10.11). Effective 03/04/2015-FDA approval date. Or per NCCN: Melanoma: single-agent therapy for metastatic or unresectable disease: first line and second line or subsequent therapy for disease progression or following maximum clinical benefit from BRAF targeted therapy for patients with performance status 0-2. (172.0-172.9, 190.9, 198.3, 199.0, 199.1). 5. Blinatumomab (BLINCYTO ) (J9999, C9449 effective 04/01/2015) For the treatment of Philadelphia chromosome-negative relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL) 204.02. Effective 12/03/2014- FDA approval date. E. Monoclonal Antibodies that are useful in chemotherapeutic regimens: 1. Rituximab (Rituxan) 100 mg, (J9310) Non-Hodgkin's Lymphoma 200.00-200.88, 202.00-202.98 Acute Lymphoid Leukemia 204.00-204.02 Chronic Lymphocytic Leukemia 204.10-204.11, 204.12 Hodgkin's Lymphoma 201.40-201.48 Waldenstrom Macroglobulinemia 273.3 Idiopathic thrombocytopenia 287.30-287.39 Autoimmune hemolytic anemia 283.0 Rheumatoid Arthritis & retreatment (in combination with methotrexate for mod-severe RA with inadequate response to 1 or or more TNF antagonist therapies) 714.0-714.2 Post Stem cell transplant and Epstein Barr virus V42.82 and 075 Refractory chronic graft versus host disease 996.80-996.89 and 279.52 Acute refractory and relapsed refractory thrombotic thrombocytopenic purpura (TTP) due to immune-mediated ADAMTS-13 deficiency. 446.6 Wegener's granulomatosis 446.4 Post transplant lymphoproliferative disorder 996.80-996.89 and 238.77 Multicentric Castleman's disease effective 05/21/2015 785.6 229.0 Microscopic polyangiitis (MPA) (Effective-FDA approval date 04/19/11) 446.0 Dermatomyositis 710.3 Acquired hemophilia 286.52 Acquired coagulation factor deficiency 286.7 (effective 12/01/2011) Polymyositis 710.4 Pemphigus 694.4 Relapsing and remitting multiple sclerosis 340

Neuromyelitis optica 341.0 Arteritis, unspecified- is covered for Henoch-Schonlein purpura. Effective 10/15/2013 447.6 Pemphigoid (bullous) when corticosteroid refractory 694.5 Pemphigoid (cicatricial) when corticosteroid refractory 694.61 2. Trastuzumab (Herceptin) 10 mg (J9355) Patients must have a positive 2+ HER 2 and metastatic disease, or a positive 3+ HER 2 test or a positive fish test for all diagnosis below: Breast 174.0-175.9 Gastric Cancer -used in combination with systemic chemotherapy for the treatment of patients with advanced gastric cancer that is HER-2 151.0-151.9 Esophageal when used in combination with systemic chemotherapy for the treatment of patients with advanced esophageal or gastroesophageal junction adenocarcinoma that is HER-2-positive 150.0-150.9 Malignant neoplasm of parotid gland that is HER-2 positive 142.0 Non-Small Cell Lung Cancer (NSCLC) that is HER-2 positive 162.0, 162.2-162.5, 162.8, 162.9 3. Ofatumumab (Arzerra) 10 mg (J9302) Ofatumumab is covered for the treatment of Chronic Lymphocytic Leukemia (CLL) that is refractory to fludarabine and Alemtuzumab or relapsed CLL (204.10, 204.12, 200.10-200.18). Used in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. (204.10, 204.12, 200.10-200.18). Effective 04/17/2014-date of FDA approval. Or per NCCN: Single agent or combination salvage therapy in rituximab intolerant patients for disease that does not respond to primary therapy or for progressive or relapsed disease for: Lymphoplasmacytic lymphoma (200.00-200.88) Waldenstrom s Macroglobulinemia (273.3) o Coverage of Cyclophosphamide (J9070) and Methotrexate (J9250, J9260) for indications other than oncologic diseases.

1. Cyclophosphamide (J9070) a. Wegener's granulomatosis 446.4 b. Rheumatoid arthritis 714.0 c. Systemic Lupus Erythematosus 710.0 d. Systemic sclerosis 710.1 e. Vasculitis 447.6 f. Polyarteritis nodosa 446.0 g. Multiple sclerosis 340 h. Nephrotic syndrome in children 581.0-581.9 i Immune thrombocytopenia (severe) 287.30-287.39 j. Autoimmune hemolytic anemia (severe) 283.0 k Multifocal motor neuropathy 356.4 l. Cryoglobulinemia/Macroglobulinemia 273.0-273.3 m. Castleman Disease 785.6 n. Systemic light chain amyloidosis 277.30 2. Methotrexate (J9250, J9260) a. Rheumatoid arthritis (severe) 714.0 b. Psoriasis (severe) 696.1 c. Psoriatic arthritis (severe) 696.0 d. Reiter's Disease 711.10-711.19 e. Lupus glomerulonephritis 710.0, 583.81 f. Temporal arteritis 446.5 g. Still's Disease 714.2, 714.30 h. Autoimmune bullous pemphigoid (severe) 694.5 i. Pulmonary interstitial fibrosis 516.30, 516.31, 516.32, 516.33, 516.36, 516.37 j. Severe polymyositis 710.4 k. Vasculitis 447.6 l. Ectopic Pregnancy 633.00-633.81, 633.90, 633.91 m. Unspecified Inflammatory polyarthropathy 714.9 n. Ankylosing spondylitis 720.0 o Requests for off label Chemotherapy drug coverage consideration should be submitted via the LCD reconsideration process described on our website http://www.wpsmedicare.com/ or submit a request with a copy of the compendia documenting the medically accepted category or narrative and or peer reviewed literature that is published in a CMS accepted journal supporting its use via e-mail to policycomments@wpsic.com

Coding Information Bill Type Codes: Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims. N/A Revenue Codes: Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes. N/A CPT/HCPCS Codes Group 1 Paragraph: See section "Indications and Limitations of Coverage" Group 1 Codes: XX000 Not Applicable ICD-9 Codes that Support Medical Necessity Group 1 Paragraph: See section "Indications and Limitations of Coverage" Group 1 Codes: XX000 Not Applicable ICD-9 Codes that DO NOT Support Medical Necessity

Paragraph: N/A Codes: XX000 Not Applicable General Information Associated Information Documentation Requirements The medical record should include the disease being treated with the name and dosage of the drug being administered. Medical Records should be made available upon Contractors request. Utilization Guidelines Coverage for medication is based on the patient's condition, the appropriateness of the dose and route of administration, based on the clinical condition and the standard of medical practice regarding the effectiveness of the drug for the diagnosis and condition. The drug must be used according to the indication and protocol listed in the accepted compendia ratings listed in this LCD. Sources of Information and Basis for Decision Allegra, C. J., & et.al. (2009). American society of clinical oncology provisional clinical opinion: Testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti epidermal growth factor receptor monoclonal antibody therapy. Journal of Clinical Oncology, 27(12), 2091-2096. Accessed March 3, 2015. De Claro, A. R., & et.al. (2012). U.S. Food and Drug Administration summary: Brentuximab vedotin for the treatment of relapsed hodgkin lymphoma or relapsed systemic anaplastic largecell lymphoma. American Association for Cancer Research, 18(21), 5845-5849. Accessed March 3, 2015. Ettinger, D. S., & et.al. (2012). Non-small cell lung cancer clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 10(10), 1236-1271. Accessed March 3, 2015. Jett, J.R., & et.al. (2013). Treatment of small cell lung cancer diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. CHEST, 143(5), 400S-149S. Accessed March 2, 2015. Kantoff, P.W., & et.al. (2010). Sipuleucel-T immunoptherapy for castration-resistant prostate cancer. The New England Journal of Medicine, 363(5), 411-422. Accessed March 2, 2015. Merseburger, A.S., Bellmunt, J., Jenkins, C., Parker, C., & Fitzpatrick, J.M. (2013). Perspective on treatment of metastatic castration-resistant prostate cancer. The Oncologist, (18), 558-567. Accessed March 3, 2015.

Piccart-Gebhart, M.J., & et.al. (2005). Trastuzumab after adjuvant chemotherapy in her2-positive breast cancer. The New England Journal of Medicine, 353(16), 1659-1672. Accessed March 2, 2015. Rahib, L., & et. al. (2014). Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. American Association for Cancer Research, 74(11), 2913-2921. Accessed March 3, 2015. Reichert, Janice M. (2013). Antibodies to watch in 2013, mabs. Landes Bioscience, 5(4), 513-517. Accessed March 3, 2015. Slamon, D. J., & et.al. (2001). Use of chemotherapy plus a monoclonal antibody against her2 for metastatic breast cancer that overexpresses her2. The New England Journal of Medicine, 344(11), 783-792. Accessed March 3, 2015. Slamon, D.J., & et.al. (2011). Adjuvant trastuzumab in her2-positive breast cancer. The New England Journal of Medicine, 365(14), 1273-1283. Accessed March 2, 2015. Tol, J., & et.al. (2009). Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. The New England Journal of Medicine, 360(6), 563-572. Accessed March 3, 2015. Warren, J.L. & et.al. (2013). Multiple myeloma treatment transformed: A population-based study of changes in initial management approaches in the United States. Journal of Clinical Oncology, 31(16), 1984-1989. Accessed March 3, 2015. Compendia Based Drug Bulletin, CAC - Each Revision MCM 2049.2; Pharmaceutical inserts; USPDI update Vol. 1 & 2; Corr-00-06-627; PM AB-02-072. National Comprehensive Cancer Network-Drugs & Biologics Compendium-website: www.nccn.org U.S. Department of Health and Human Services, U.S. Food and Drug Administration -website: www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm Contractor Advisory Committee Meeting Notes Meeting Date: Wisconsin 09/26/2008 Illinois 09/17/2008 Michigan 09/24/2008 Minnesota 09/11/2008 Iowa 10/16/2008 Kansas 10/16/2008

Missouri 10/17/2008 Nebraska 10/16/2008 Any Contractor Advisory Committee (CAC) related information, including Start Date and End Date of Comment Period, reflects the last time this LCD passed through the Comment and Notice process. Formal comment is not required for LCDs being adopted as part of the MAC transition. Start Date of Comment Period 10/18/2008 End Date of Comment Period 12/03/2008 Start Date of Notice Period 06/01/2012 Revision History Information Please note: Most Revision History entries effective on or before 01/24/2013 display with a Revision History Number of "R1" at the bottom of this table. However, there may be LCDs where these entries will display as a separate and distinct row. Revision History Date 09/01/2015 R28 Revision History Number Revision History Explanation 09/01/2015: Under Section C and D added the following ICD 9 codes to update per NCCN: J9055 added 152.0-152.2, 152.8, 152.9, 197.0, 197.6, 197.7, 173.00, 173.02, 173.09,198.89, 235.1, 235.6, 235.9, 173.52, 173.62, 173.72, 173.82, 173.92, 187.1-187.4, 187.8, 187.9; J9098 added 205.00, 205.02, 206.00, 206.02, 207.00, 207.02, 207.20, 207.22; J0894 added 206.00, 206.01, 206.02, 207.00, 207.01, 207.02, 207.20, 207.21, 207.22; J9179 added 158.0, 158.8, 158.9, 171.0, 171.2-171.9; J9264 added 172.0-172.9, 198.3, 199.0, 199.1; J9303 added 152.0-152.2, 152.8, 152.9, 197.0, 197.6, 197.7; J9268 added 200.40-200.48, 204.80, 204.82, 200.10-200.18; J9266 added 202.80-202.88; J9307 added Reason(s) for Change ICD-9-CM Code Reconsideration Request Other

08/01/2015 R27 204.80, 204.82, 200.80.; J9315 added 204.80, 204.82, 202.10-202.18, 202.20-202.28, 200.60-200.68, 200.80, 202.70-202.78, 202.83, 200.80-200.88; J9330 added 171.8, 171.9, 239.2; J 9400 added 152.0-152.2, 152.8, 152.9, 153.0-153.9, 154.0, 154.1, 154.8, 197.0, 197.7; J9999 /C9025 added 152.0-152.2, 152.8, 152.9, 153.0-154.8, 197.0, 197.6, 197.7, 150.0-150.5, 150.8, 150.9, 235.5, 151.0-151.6, 151.8, 151.9, 235.2, 162.0, 162.2-162.5, 162.8, 162.9; J9999/C9027 added: 172.0-172.9, 190.9, 198.3, 199.0, 199.1. Per reconsideration request the following was added: J9035 added 163.0, 163.1, 163.8, 163.9. J9070 corrected per NCCN/reconsideration; 277.30 was added and 277.39 was removed (removal of 277.39 effective in 45 days-10/15/2015). Updated J5 National list. 08/01/2015: Under Section C added the following language: The following drugs are approved per FDA or per NCCN guidelines for the specific indications listed. Added the following ICD 9 codes to update per NCCN. (J9025): 206.00-206.02, 207.00-207.02, 207.20-207.22. J9033: 203.82, 238.6, and removed language that was no longer up to date per NCCN.( J9035): 152.0-152.2, 152.8, 197.0, 197.6, 197.7, 162.0-162.9, 192.8, 237.5, 158.8, and added recurrent and removed for first line therapy to breast cancer indications per NCCN. (J9041): 203.10, 203.12, 203.80-203.82, 238.6, 229.0, 202.83, 200.80-200.88, 785.6. (J9042): 200.80-200.88, 201.50-201.98, 202.10-202.18, 202.20-202.28, 200.60-200.68, 202.70-202.78. (J9047): 203.10, 203.12, 203.80, 203.82, 238.6, 200.80-200.88, 273.3 and added new wording per NCCN guidelines for myeloma. Removed Denileukin (J9160) as indication that was listed is no longer recommended by NCCN and there are no recommendations for its usage. J9310: removed outdated wording and moved any current wording ICD-9-CM Code Other

07/01/2015 R26 next to appropriate ICD 9 code. Removed Porfirmer (J9600) as no longer recommended by NCCN for the indications listed. Added the following language to adotrastuzumab (J9354) and pertuzumab (J9306) for consistency: Patients must have a positive 2+ HER 2 and metastatic disease, or a positive 3+ HER 2 test or a positive fish test. Removed the word squamous from the NSCLC indications for Nivolumab (J9999, C9453). 07/01/2015: The following drugs were moved under Section B: BCG (Intravesical), per installation (J9031) Cladribine Chlorodexyadenoside (2-CDA) (Leustatin) per 1 mg (J9065) Daunorubicin, 10 mg (J9150) Daunorubicin citrate, liposomal formulation, (DaunoXome) 10 mg (J9151) Doxorubicin Hydrochloride, liposomal, Doxil, 10mg Not otherwise specified(q2050) Doxorubicin Hydrochloride, liposomal Lipodox, 10 mg (Q2049) Docetaxel (Taxotere) 1mg (J9171) Epirubicin Hydrochloride (Ellence) 2 mg (J9178) Fludarabine Phosphate (Fludara) 50 mg (J9185)(273.3, V42.82) Fulvestrant (Faslodex ) 25mg (J9395) Gemcitabine Hydrochloride (Gemzar) 200 mg (J9201) Idarubicin Hydrochloride 5 mg (Idamycin) (J9211) Irinotecan (Camptosar) 20 mg (J9206) Melphalan Hydrochloride (Alkeran)(J9245) per 50 mg (273.3, V42.81,V42.82) Oxaliplatin (Eloxatin ) 0.5 mg (J9263) Paclitaxel (Taxol) 30mg (J9267) Pemetrexed (Alimta?), 10 mg (J9305) Streptozocin (Zanosar), 1 gram (J9320) Topotecan (Hycamtin) 0.1 mg (J9351) Valrubicin intravesical (Valstar) 200mg (J9357) Vinorelbine tartrate (Navelbine) per 10 mg (J9390) ICD-9-CM Code Reconsideration Request Other

06/01/2015 R25 05/01/2015 R24 Mitoxantrone (Novantrone) (J9293) per 5mg (340, Multiple Sclerosis). Interferon, alpha-2b, recombinant, 1 million units (Intron A) (J9214)(078.10-078.12, 078.19, 070.44, 070.54, 070.32). Under section B added: 259.2 (carcinoid) to ICD 9 codes Under Section C: Gemtuzumab (J9300) and Raltitrexed (J9999/C9399) are removed; no longer available. Rituximab (J9310): for Multicentric Castleman s disease removed associated with human herpes virus infection in HIVinfected patients effective 05/21/2015. Added 229.0 to Rituximab. Nivolumab: added C9453 per CR 9205 and a BRAF inhibitor to language associated with ICD 9 codes 172.0-172.9. Also, added 190.9, 198.3, 199.0, and 199.1 for first and second line disease per NCCN. Ipilimumab (J9228): added 172.0-172.9, 190.9, 198.3, 199.0, 199.1 for first and second line and reinduction therapy per NCCN. 06/01/2015: Added 153-154.8 (metastatic colorectal cancer) to Ramucirumab (J9999, C9025) Effective 04/24/2015, FDA approval date; Added 154.2 (sq cell cancer of anal canal) to Paclitaxel (J9267); Added 140.0, 140.1, 140.3-140.6, 140.8, 140.9, 141.0-141.6, 141.8, 141.9, 143.0, 143.1, 143.8, 143.9, 144.0, 144.1, 144.8, 144.9, 145.0, 145.2, 145.3, 145.6, 145.8, 145.9, 146.0-146.2, 146.7, 147.0-147.3, 147.8, 147.9, 148.0-148.3, 148.8, 148.9, 149.0, 149.1, 149.8, 149.9, 160.2, 160.3, 161.0-161.3, 161.8, 161.9, 173.0, 195.0, 196.0, 198.89, 235.1, 235.6, 235.9 to Vinorelbine (J9390); Added clarification note to pembrolizumab coverage. 05/01/2015-Under NOC: Added 162.0, 162.2-162.5, 162.8, 162.9, V10.11 (metastatic squamous NSCLC) to Nivolumab J9999, C9399. Effective 03/04/2015-FDA approval date. Added C9449 to Blinatumomab effective 04/01/2015 per CR 9100. Annual review ICD-9-CM Code ICD-9-CM Code CPT/HCPCS Code

04/01/2015 R23 03/01/2015 R22 02/01/2015 R21 01/01/2015 R20 date 04/01/2015. Updated sources of information. 04/01/2015-Added 694.5 and 694.61 (pemphigoid) to J9310; and 204.10, 204.12, 200.10-200.18 (CLL/SLL) for relapsed or refractory disease; and if unable to tolerate purine analogs as a single agent or in combination with chlorambucil to J9301. 03/01/2015-J9047-Added new indication for transplant candidates 203.00-203.02, added 204.80-204.82 to J9033; J9302-Added FDA approved indication for previously untreated CLL (204.10, 204.12, 200.10-200.18)- effective 04/17/2014 FDA approval date; Added 200.50, 200.51 to J9305. 02/01/2015- Added 171.2 to J9267, Added 200.10-200.18 to J9301-efffective 02/01/2015, Updated section D- added 162.0, 162.2-162.5, 162.8, 162.9 to Ramucirumab (J9999, C9025) effective 12/12/2014 and added it was covered in combination with paclitaxel, for treatment of advanced gastric or gastro-esophageal junction adenocarcinoma, with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy 150.0-150.8, 151.0-151.9- Effective 11/05/2014-FDA approval date. Added Nivolumab (J9999/C9399) for 172.0-172.9 effective 12/22/2014-FDA approval date. Added to J9354 Is covered as a single agent, for the treatment of patients with HER2-positive, recurrent or metastatic trastuzumab-exposed disease. The patient therefore should previously have been treated with trastuzumab (174.0-174.9, 175.0-175.9)- Effective 01/01/2015. Added Blinatumomab (J9999, C9399) for 204.02 & added 184.0-184.4, 187.1, 187.2, 187.4, 187.7 to J9228. 01/01/2015- Added new codes A9606, C9027, C9442, J9267, J9301; moved drugs with true codes from section D to section C & renumbered. Removed deleted codes Other (Annual review ) ICD-9-CM Code Other (Coverage change and addition of ICD-9 codes) ICD-9-CM Code Other (Coverage change and addition of ICD-9 codes) ICD-9-CM Code Other (Coverage change and addition of ICD-9 codes) CPT/HCPCS Code

12/01/2014 R19 11/01/2014 R18 09/01/2014 R17 06/01/2014 R16 05/01/2014 R15 04/01/2014 R14 03/01/2014 R13 A9699, C9021, J9265 Removed J9010- coverage indicator changed to I-not payable by Medicare. 12/01/2014- Added systemic light chain amyloidosis dx code 277.39 to J9070. 11/01/2014 -Added Pembrolizumab (Keytruda) to section D -NOC agents, covered for (172.0-172.9) effective 09/04/2014 -FDA approval date; Added 142.0 & 162.0, 162.2-162.5, 162.8, 162.9 to J9355; added C9025 to section D. #4 based on CR 8880 effective 10/01/2014; Removed underlining in sources of information section. 09/01/2014- Added Belinostat (Beleodaq) (J9999/C9399) for 202.70-202.78; effective 07/03/2014-FDA approval date. Add 150.0-150.8 to Ramucirumab (J9999/C9399) - Effective 04/21/2014 FDA approval date.; Added 200.60-200.68 to J9315. 06/01/2014-See indications for coverage info-added 202.70-202.78 to J9042; Added 164.0 to J9201; J9355 clarification of testing; Section D-added 151.0-151.9 to Ramucirumab (J9999/C9399)- Effective 04/21/2014 FDA approval date. 05/01/2014-J9306 removed metastatic, who have not received prior Her2 therapy or chemotherapy for metastatic disease. Added or in cancer in combination with docetaxel, or carboplatin. Added 569.81-Enterocolic fistula of intestine toj2353; Annual Review. 04/01/2014- Added 182.0 to J9035 & J9330; Added C9021 to obinutuzumab per CR8675- April 2014 Update of the Ambulatory Surgical Center (ASC) Payment System -effective 04/01/2014. 03/01/2014- Updated Section D-Added J9999 obinutuzumab & ICD-9 code 204.10, effective FDA approval date 11/01/2013; J9035- removed the following statement from our cervical cancer coverage: second Other (Code update ) ICD-9-CM Code Other (Coverage change & ICD-10 addition) ICD-10-CM Code ICD-9-CM Code Other (Coverage change & ICD-9 addition ) Other (Coverage change ) ICD-9-CM Code Other (Coverage change ) ICD-9-CM Code ICD-9-CM Code Other (Coverage Change (actual

01/01/2014 R12 01/01/2014 R11 12/01/2013 R10 11/01/2013 R9 09/07/2013 R8 09/01/2013 R7 line therapy as a single agent for local/regional recurrence; distant metastases. 01/01/2014- Code update- added new codes J9047, J9262, J9306, J9354, J9371, J9400. Added 204.02 to J9371; added 205.10-205.12 to J9262; added 171.0-171.4, 171.6-171.8 to J9390- range is now listed as 171.0-171.9; Removed deleted codes C9131, C9292, C9295, C9296. Drugs with true codes moved from Section D to section C & renumbered. 01/01/2014- Code update- added new codes J9047, J9262, J9306, J9354, J9371, J9400. Added 204.02 to J9371; added 205.10-205.12 to J9262; added 171.0-171.4, 171.6-171.8 to J9390- range is now listed as 171.0-171.9; Removed deleted codes C9131, C9292, C9295, C9296. Drugs with true codes moved from Section D to section C & renumbered. 12/01/2013-Added 152.0-152.2, 152.8, 152.9 to J9035 11/01/2013- Added Henoch-Schonlein purpura ICD-9 code 447.6 to J9310- effective 10/15/2013; added C9399 to Radium RA 223 dichloride (Xofigo) for outpatient hospital billing based on CR 8338. The WPS Carrier Contract Numbers 00951(WI), 00952(IL), and 00954(MN) were removed from this LCD. Effective 09/07/2013, the Jurisdiction 6 Part B MAC contractor for Illinois, Wisconsin, and Minnesota is National Government Services (NGS). 09/01/2013 Added A9699 Radium Ra 223 dichloride (Xofigo) to Section D- Not otherwise Classified Agents. Covered for FDA approved indication (185 and 198.5 )- effective 05/15/2013; Added or paclitaxel to our coverage of Pertuzumab (J9999/C9292). J9201- changed wording to change in medical parameters)) Other ICD-9-CM Code CPT/HCPCS Code ICD-9-CM Code ICD-9-CM Code Change in Assigned States or Affiliated Contract Numbers ICD-9-CM Code Reconsideration Request

08/01/2013 R6 07/01/2013 R5 06/01/2013 R4 04/01/2013 R3 03/01/2013 R2 02/01/2013 R1 Occult primary tumors; carcinoma not otherwise specified for diagnosis codes 199.0, 199.1 08/01/2013 posted update- J9035- added Cervical Cancer- second line therapy as a single agent for local/regional recurrence; distant metastases. 180.0-180.9-effective 07/01/2013; Corrected typo- FDA approval date changed to 02/22/2013 for adotrastuzumab emtansine. 07/01/2013-Code updates based on CR 8328- July 2013 Update of the Ambulatory Surgical Center (ASC) Payment System & CR 8286- Quarterly (HCPCS) Drug/Biological Code - July 2013 Update: Added C9131 ado-trastuzumab emtansine, 1mg & Q2050 Injection, Doxorubicin Hydrochloride, Liposomal, Not Otherwise Specified, 10 mg and removed J9002- no longer payable for Medicare. Reconsideration requests: added 187.1-187.9 to J9265; added 341.0 & 340- relapsing and remitting MS to J9310. 06/01/2013- Added 157.0-157.3, 157.8, 157.9 to J9264; Added 201.40-201.48 to J9002 & Q2049 & J9390; Added 180.1, 180.8 and 189.0 to J9201 (01/01/2012); Added ado-trastuzumab emtansine (KADCYLA (J9999/C9399) for (174.0-174.9, 175.0-175.9)-effective 02/26/2013 FDA approval date. Annual review completed 04/01/2013-Reconsideration Request-Added 193 to J9002, Q2049 & J9265; Added 202.20-202.28 to J9307; Added 201.40-201.48, 201.50-201.58, 201.60-201.68, 201.70-201.78, 201.90-201.98 to J9033; J9305- corrected typo 185.0 changed to 185. 03/01/2013-Added 157.0-157.3, 157.8, 157.9, 199.0 & 199.1 to J9171 effective 1/23/13; Added152.0-152.2, 152.8, 152.9 to J9206 effective 03/01/2013 02/01/2013- Added 200.10-200.18, 273.3, 200.00-200.88 to J9302, removed effective FDA approval date; Noting previous update ICD-9-CM Code Reconsideration Request CPT/HCPCS Code ICD-9-CM Code Reconsideration Request ICD-9-CM Code Reconsideration Request ICD-9-CM Code ICD9 Addition/Deletion

(01/01/2013) Revision history explanation listed an update to J9035 and should have been J9305. 01/01/2013- Added 189.1, 189.2, 185, 164.0, 212.6 to J9035 effective 12/01/2012; Code Update- new codes added-j9002, J9019, J9042, C9292, C9295, C9296. Removed deleted codes- J9001, C9287 Description changed J9020; J9999/C9292- added May be considered in combination with trastuzumab with or without cytotoxic therapy (eg, vinorelbine or taxane) for one line of therapy beyond first-line therapy in patients previously treated with chemotherapy and trastuzumab in the absence of Pertuzumab; J9033- added First line therapy in combination with Rituximab for the treatment of Non-Hodgkin s Lymphoma. J9310- added First-line therapy for NHL stage II-IV disease as single-agent therapy or in combination with chlorambucil in patients unable to tolerate purine analogs. Information on using Mitomycin for eye surgery was removed. Refer to J7315 which is informational only. It is not subject to the diagnosis code list in the LCD. J9213 moved to our SAD list. 12/06/12- Posted 11/01/2012- added 287.49 to J9370-effective 11/01/2012; clarification to section G.- added chemotherapy drug. 12/06/2012 - In accordance with Section 911 of the Medicare Modernization Act of 2003 and CMS Change request 8059, contract numbers in this LCD were updated due to the transition from WPS Fiscal Intermediary Contract Number 52280 to WPS Part A MAC Contract Number 05901. For contract number 05901, this LCD is in a "Notice Period" from 10/22/12 through 12/05/12. For all other contract numbers this LCD continues to be in effect with no coverage changes. This LCD will be

effective for Contract number 05901 on 12/06/2012. 09/01/2012-added 694.4 to J9310, Added the following FDA approved drugs added to Section D: to Carfilzomib (KYPROLIS TM ) for 203.00-203.02, Pertuzumab (PERJETA TM ) for 174.0-175.9 and zivaflibercept (ZALTRAP) for 153.0-154.8. 08/20/2012: This LCD was revised to add the Jurisdiction 8 (J-8) Indiana Part B MAC Contract Number 08102. The CMS Statement of Work for the J8 Medicare Administrative Contract (MAC) requires that the contractor retain the most clinically appropriate LCD within the jurisdiction. This WPS policy is being promulgated to the J8 MAC as the most clinically appropriate LCD within this jurisdiction. No coverage changes were made to this LCD for this revision. Posted 08/01/2012- added 158.8, 158.9 to J9263. 07/23/2012: This LCD was revised to add the Jurisdiction 8 (J-8) Indiana and Michigan Part A MAC Contract Numbers 08101 and 08201. The CMS Statement of Work for the J8 Medicare Administrative Contract (MAC) requires that the contractor retain the most clinically appropriate LCD within the jurisdiction. This WPS policy is being promulgated to the J8 MAC as the most clinically appropriate LCD within this jurisdiction. No coverage changes were made to this LCD for this revision. 07/16/2012: This LCD was revised to add the Jurisdiction 8 (J-8) Michigan Part B MAC Contract Number 08202 and remove the legacy Michigan Part B Carrier Contract Number 00953. The CMS Statement of Work for the J8 Medicare Administrative Contract (MAC) requires that the contractor

retain the most clinically appropriate LCD within the jurisdiction. This WPS policy is being promulgated to the J8 MAC as the most clinically appropriate LCD within this jurisdiction. No coverage changes were made to this LCD for this revision. Posted 07/01/2012-Added Q2048 & Q2049, removed J9001- Procedure status changed to I (not valid for Medicare purposes)- effective 07/01/2012 see CR 7844 July Update to the CY 2012 Medicare Physician Fee Schedule Database (MPFSDB); Typos corrected-173.0 invalid code removed from J9265. J9201-186.0.0 changed to186.0, J9150-2205.00 corrected to read 205.00., J9213 & J9214- duplicate code range removed (173.00-173.99) 12/01/2010-Added 204.00-204.12 to J9310 and added 173.1-173.9 to J9265, Updated NOC listing (J9999/C9399) Ofatumumab is covered for the treatment of CLL (204.10) that is refractory to fludarabine and Alemtuzumab or relapsed CLL (ICD 204.12). 11/01/2010- Added 996.80-996.89 and 238.77 to J9310 10/01/2010-Added J0641 to Section B, October 2010 Integrated Outpatient Code Editor (I/OCE) update Added C9273- Sipuleucel-T, per infusion and changed will develop for records to may develop. Added ICD-9 codes 182.0-182.8 to J9171 09/01/2010- Added 171.0-171.9 to J9001, added 170.0-170.9 to J9206, added Cabazutaxel (J9999) and ICD-9 code 185 effective 07/17/10- FDA approval date. 08/01/2010- Added Provenge (sipuleucel-t) (J3590/C9399) effective 04/29/10- FDA approval date & added 446.4 to J9310 effective 07/01/10

07/01/2010- Added V42.82 to J9185, Added 163.0, 163.1, 163.8, 163.9 to J9390 06/01/2010- Removed "progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens" from J9303 as it will be covered as first line therapy for the treatment of Colorectal cancer & added 446.6 to J9310, added 189.0 to J9171. 05/01/2010-Added 164.0 to J9265; 152.0-152.9 to J9263, Added 202.10-202.18, 202.20-202.28 to J9010, added 205.10, 205.12 to J0894, added 189.1, 189.2 to J9171, added V42.82 and 075, 996.80-996.89 and 279.52 to J9310; added or a positive fish test to J9355. 04/01/2010- Added ICD-9 710.1 to J9070- J9097; Typo corrected in section C. #7 03/01/2010- Typo corrected- J9062 Cisplatin changed to 50 mg. 02/01/2010- Added 150.0-150.9 to J9355; added 188.0-188.9, 233.7 to J9305; added 209.00-209.03, 209.10-209.17, 209.20-209.29, 209.30, 209.70 to J2353. 01/01/2010-Added 171.0, 171.3, 171.5, 171.9 to J9265; added 201.50-201.58, 201.60-201.68, 201.70-201.78, 201.90-201.98 to J9390 & J9001, added 199.0 & 199.1 to J9201; added 273.3 to J9041; Annual code updates Added J9171, deleted J9170; J9015 effective date of ICD-9 code 190.9 changed to 05/16/09; *12/01/09-Added 277.30 to J9041 & 785.6 to J9070-J9097 *Published 11/01/09 Added Pralatrexate (Folotyn) (J9999/C9399) & 202.70-202.78

effective 9/24/09 FDA approval date; added 190.9 to J9015-Effective 09/01/09 ; *Published 10/01/09 added 180.0-180.9 to J9305, Added 151.0-151.9 to J9355, added 183.0-183.9 and 186.0, 186.9 to J9263, and added 180.0-180.9 to J9305. Language changes to J9055 and J9303; 09/18/2009 *Published 09/01/09 added 200.60-200.68, 202.70-202.78, 202.80-202.88 to (J9041) Published 08/01/09- added ICD-9 codes 156.0-156.9,157.0-157.3, 157.8, 157.9 to J9263, added 196.0 to J9055, added 273.3 to J9370, J9375, J9380, J9250 replaced 710.9 with 714.2 & 714.30 for Still s disease, J9390-added 171.5, 171.9, J9025 added 205.10, 205.12; 6/29/09 Removed contractor number 05392 because as of 8/1/09 E MO will join with the current number for W MO *Effective 05/16/09 added ICD-9 codes 183.0-183.9 to J9305 and 200.50 to J9350, J9245 corrected typo for range 203.10-203.12 Clarification of the need for K-RAS test for treatment of colorectal cancer for J9055, Added 205.01 and 205.02 to J9025, 205.12 added to J9213, Added 162.2-162.9 to J9264, added 200.00-200.88, 202.00-202.98 to J9263 added 182.0-182.8 to J9350 effective 05/16/09; Effective 5/16/09-Added AML ICD-9 codes 205.00, 205.01, and 205.02 to J0894 Decitabine (Dacogen) 8/1/2010 - The description for Bill Type Code 11 was changed 8/1/2010 - The description for Bill Type Code 12 was changed

8/1/2010 - The description for Bill Type Code 13 was changed 8/1/2010 - The description for Bill Type Code 18 was changed 8/1/2010 - The description for Bill Type Code 21 was changed 8/1/2010 - The description for Bill Type Code 22 was changed 8/1/2010 - The description for Bill Type Code 23 was changed 8/1/2010 - The description for Revenue code 0250 was changed 8/1/2010 - The description for Revenue code 0259 was changed 8/1/2010 - The description for Revenue code 0636 was changed 01/01/2011-HCPCs code update- Added J9302, J9307, J9351, C9276;Removed deleted codes J9080, J9090, J9091, J9092, J9093, J9094, J9095, J9096, J9097, J9110, J9140, J9290, J9291, J9350, J9375, J9380; Added ICD-9 codes 209.31-209.36, 209.75 to J9351, added 785.6 to J9310; Added 158.8 to J9305 & J9264; added 158.0, 158.8, 158.9 171.0-171.9 to J9035, added 174.0-174.9, 175.0-175.9 to Eribulin mesylate (Halaven) (J9999) 02/01/2011-removed deleted code J9062- effective 01/01/2011 03/01/2011- Added 182.0 to J9001, added 156.2 & 156.8 to J9201; added 200.60-200.68, 202.10-202.18, 202.80-202.88 to J9307, added 174.0-175.9 to J9206; added 273.3 to J9033; added new FDA approved indication to J9310 -as single-agent maintenance therapy of follicular in patients achieving a complete or partial response to Rituxan in combination with first line chemotherapy. 04/01/2011- added 203.00-203.02 to J9033

05/01/2011- Added 170.0-170.9 to J9171 & J9201; J9264 added 183.0-183.9, Added J9999-Ipilimumab- 172.0-172.9- effective 03/25/11 (FDA approval date) 07/01/2011- Add new code Q2043 & removed C9273; Added 155.1 & 204.10, 204.12 to J9263; Added 720.0 to J9250, J9260 08/01/2011-Added 201.40-201.48 to J9310, added 179, 180.0, 182.0-182.8 to J9201; added 200.00-200.88, 202.00-202.98 and V42.81, V42.82 to J9245; added J9315 & 202.00-202.98 effective 11/05/2009 -FDA approval date & 202.70-202.78-effective 06/16/2011 -FDA approval date; added As a single agent or in combination with irinotecan after first progression except in patients receiving capecitabine or fluorouracil and leucovorin with bevacizumab to J9055; Moved information on Q2043 Sipuleucel-T (Provenge ) from the LCD to the billing and coding guidelines and included information from the new NCD -Section 110.22 Autologous Cellular Immunotherapy Treatment (Effective June 30, 2011)(CR 7431-Transmittal 133 ) and Claims Processing Manual Change Request 7431-transmittal 2254. 09/01/2011-J9201-added 156.1, 156.2, 156.8, 156.9; Added 446.0 to J9310 effective 04/19/11-FDA approval date, J9320-added 209.00-209.29, 209.70-209.74 10/01/2011-ICD-9 code update-added 365.70, 365.71, 365.72, 365.73 to J9190, Added 173.00-173.99 to J9213, J9214, J9040, J9045, J9050, J9060, J9070; Added 516.30-516.37 to J9250, J9260, Added 173.01, 173.11, 173.21, 173.31, 173.41, 173.51, 173.61, 173.71, 173.81, 173.91, 189.0 to J9265 & removed 239.2, added 516.30, 516.31, 516.32, 516.33, 516.36,

516.37 to J9250, J9260, added 173.00-173.99 to J9040, J9045, J9050, J9060, J9070 & added (J9999/C9399) Brentuximab vedotin (ADCETRIS TM ) effective 08/19/2011-FDA approval date for - The treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates (201.00-201.98) and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen (200.60-200.68) 12/01/2011- Added 710.3, 286.52 to J9310. 01/01/2012-2012 Code update: Removed deleted code C9276 & Added C9287, J9043, J9179, and J9228 & Removed J9999 & C9399 for drugs that now have a true 2012 HCPC s code. 02/01/2012-Article Added 286.7 to J9310- effective 12/01/2011 03/01/2012 Article posted- Added 173.02, 173.12, 173.22, 173.32, 173.42, 239.2, V10.83 to J9055. Added 203.80, 238.6 to J9041 04/01/2012- article posted-added 204.80, 204.82 to J9010; added 199.0, 199.1 to J9206, added 710.4 to J9310 Associated Documents Attachments Billing and Coding Guidelines (PDF - 396 KB ) Related Local Coverage Documents N/A Related National Coverage Documents N/A

Public Version(s) Updated on 08/18/2015 with effective dates 09/01/2015 - N/A Updated on 07/20/2015 with effective dates 08/01/2015-08/31/2015 Updated on 06/15/2015 with effective dates 07/01/2015-07/31/2015 Updated on 05/19/2015 with effective dates 06/01/2015-06/30/2015 Updated on 04/21/2015 with effective dates 05/01/2015-05/31/2015 Updated on 03/17/2015 with effective dates 04/01/2015-04/30/2015 Updated on 02/16/2015 with effective dates 03/01/2015-03/31/2015 Updated on 01/20/2015 with effective dates 02/01/2015-02/28/2015 Updated on 12/16/2014 with effective dates 01/01/2015-01/31/2015 Updated on 11/18/2014 with effective dates 12/01/2014-12/31/2014 Updated on 10/21/2014 with effective dates 11/01/2014-11/30/2014 Updated on 08/20/2014 with effective dates 09/01/2014-10/31/2014 Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

Billing and Coding Guideline for HONC-010 Chemotherapy Drugs and their Adjuncts Medicare Regulation Excerpts: PUB.100-20 One time Notification (OTN); Change Request (CR) 3818, 3631, 3028) For services furnished on or after January 1, 2005, chemotherapy administration codes apply to parenteral administration of nonradionuclide anti-neoplastic drugs and also to anti-neoplastic agents provided for the treatment of noncancer diagnoses (e.g., cyclophosphamide for autoimmune conditions) or to substances such as monoclonal antibody agents and other biologic response modifiers. Administration of anti-anemia drugs and anti-emetic drugs by injection or infusion for cancer patients is not considered chemotherapy administration. Excerpts from CMS internet only Manual (IOM): Publications 100-02 Medicare Benefit Policy Manual: Chapter 15 Section 50.4.5 - Unlabeled Use for Anti-Cancer Drugs If a use is identified as not indicated by CMS or the FDA or if a use is specifically identified as not indicated (in one or more of the three compendia mentioned) or if it is determined (based on peer reviewed medical literature) that a particular use of a drug is not safe and effective, the off-label usage is not supported and, therefore, the drug is not covered. In this instance, the administration is also not covered. Publications 100-02 Medicare Benefit Policy Manual: Chapter 15 Section 60.1 Incident to Physician Professional Services To be covered, supplies, including drugs and biologicals, must be an expense to the physician or legal entity billing for the services or supplies. For example, where a patient purchases a drug and the physician administers it, the drug is not covered. However, the administration of the drug, regardless of the source, is a service that represents an expense to the physician. Therefore, administration of the drug is payable if the drug would have been covered if the physician purchased it. Publications 100-04 Medicare Claims Processing Manual Chapter 12 Section 30.5 - Payment for Codes for Chemotherapy Administration and Nonchemotherapy Injections and Infusions D. Chemotherapy Administration Chemotherapy administration codes apply to parenteral administration of nonradionuclide anti-neoplastic drugs; and also to anti-neoplastic agents provided for treatment of noncancer diagnoses (e.g., cyclophosphamide for auto-immune conditions) or to substances such as monoclonal antibody agents, and other biologic response modifiers. The following drugs are commonly considered to fall under the category of monoclonal antibodies: infliximab, rituximab, alemtuzumb, gemtuzumab, and trastuzumab. Drugs commonly considered to fall under the category of hormonal antineoplastics include leuprolide acetate and goserelin acetate. The drugs cited are not intended to be a complete list of drugs that may be administered using the chemotherapy administration codes. Local carriers may provide additional guidance as to which drugs may be considered to be chemotherapy drugs under Medicare. The administration of anti-anemia drugs and anti-emetic drugs by injection or infusion for cancer patients is not considered chemotherapy administration. If performed to facilitate the chemotherapy infusion or injection, the following services

and items are included and are not separately billable: 1. Use of local anesthesia; 2. IV access; 3. Access to indwelling IV, subcutaneous catheter or port; 4. Flush at conclusion of infusion; 5. Standard tubing, syringes and supplies; and 6. Preparation of chemotherapy agent(s). Payment for the above is included in the payment for the chemotherapy administration service. If a significant separately identifiable evaluation and management service is performed, the appropriate E & M code should be reported utilizing modifier 25 in addition to the chemotherapy code. For an evaluation and management service provided on the same day, a different diagnosis is not required. Publications 100-04 Medicare Claims Processing Manual Chapter 17 Section 90.2 90.2 - Drugs, Biologicals, and Radiopharmaceuticals (Rev. 1657, Issued: 12-31-08, Effective: 01-01-09, Implementation: 01-05-09) A. General Billing and Coding for Hospital Outpatient Drugs, Biologicals, and radiopharmaceuticals Hospitals should report charges for all drugs, biologicals, and radiopharmaceuticals, regardless of whether the items are paid separately or packaged, using the correct HCPCS codes for the items used. It is also of great importance that hospitals billing for these products make certain that the reported units of service of the reported HCPCS code are consistent with the quantity of a drug, biological, or radiopharmaceutical that was used in the care of the patient. Payment for drugs, biologicals and radiopharmaceuticals under the OPPS is inclusive of both the acquisition cost and the associated pharmacy overhead or nuclear medicine handling cost. Hospitals should include these costs in their line-item charges for drugs, biologicals, and radiopharmaceuticals. Under the OPPS, if commercially available products are being mixed together to facilitate their concurrent administration, the hospital should report the quantity of each product (reported by HCPCS code) used in the care of the patient. Alternatively, if the hospital is compounding drugs that are not a mixture of commercially available products, but are a different product that has no applicable HCPCS code, then the hospital should report an appropriate unlisted drug code (J9999 or J3490). In these situations, it is not appropriate to bill HCPCS code C9399. HCPCS code C9399, Unclassified drug or biological, is for new drugs and biologicals that are approved by FDA on or after January 1, 2004, for which a specific HCPCS code has not been assigned. The HCPCS code list of retired codes and new HCPCS codes reported under the hospital OPPS is published quarterly via Recurring Update Notifications. The latest payment rates associated with each APC and HCPCS code may be found in the most current Addendum A and Addendum B, respectively, that can be found under the CMS quarterly provider updates on the CMS Web site at: http://www.cms.hhs.gov/hospitaloutpatientpps/au/list.asp Publications 100-04 Medicare Claims Processing Manual Chapter 14 Section 10 Ambulatory Surgery Center

Billing for Drugs and Biologicals ASCs are strongly encouraged to report charges for all separately payable drugs and biologicals, using the correct HCPCS codes for the items used. ASCs billing for these products must make certain that the reported units of service of the reported HCPCS code are consistent with the quantity of the drug or biological that was used in the care of the patient. ASCs should not report HCPCS codes and separate charges for drugs and biologicals that receive packaged payment through the payment for the associated covered surgical procedure. We remind ASCs that under the ASCPPS, if two or more drugs or biologicals are mixed together to facilitate administration, the correct HCPCS codes should be reported separately for each product used in the care of the patient. The mixing together of two or more products does not constitute a "new" drug as regulated by the Food and Drug Administration (FDA) under the New Drug Application (NDA) process. In these situations, ASCs are reminded that it is not appropriate to bill HCPCS code C9399. HCPCS code C9399, Unclassified drug or biological, is for new drugs and biologicals that are approved by the FDA on or after January 1, 2004, for which a HCPCS code has not been assigned. Unless otherwise specified in the long description, HCPCS descriptions refer to the non-compounded, FDA-approved final product. If a product is compounded and a specific HCPCS code does not exist for the compounded product, the ASC should report an appropriate unlisted code such as J9999 or J3490. Publication 100-02 Chapter 15 Excerpt 50.4.5 - Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen (Rev.96, Issued: 10-24-08, Effective: 06-05-08 NCCN/06-10-08 Thomson Micromedex/07-02-08 Clinical Pharmacology, Implementation: 11-25-08) A. Overview Effective January 1, 1994, off-label, medically accepted indications of Food and Drug Administration-(FDA) approved drugs and biologicals used in an anti-cancer chemotherapeutic regimen are identified under the conditions described below. A regimen is a combination of anticancer agents clinically recognized for the treatment of a specific type of cancer. Off-label, medically accepted indications are supported in either one or more of the compendia or in peer-reviewed medical literature. The contractor may maintain its own subscriptions to the listed compendia or peer-reviewed publications to determine the medically accepted indication of drugs or biologicals used off-label in an anti-cancer chemotherapeutic regimen. Compendia documentation or peerreviewed literature supporting off-label use by the treating physician may also be requested of the physician by the contractor. Current compendia: American Hospital Formulary Service-Drug Information (AHFS-DI) Effective June 5, 2008 - National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium Effective June 10, 2008 - Thomson Micromedex DrugDex Effective July 2, 2008 - Clinical Pharmacology In general, a use is identified by a compendium as medically accepted if the indication is a Category 1 or 2A in NCCN, or Class I, Class IIa, or Class IIb in DrugDex; or, narrative text in AHFS or Clinical Pharmacology is supportive. Publication 100-03 Medicare NCD Manual, Section 110.22 Autologous Cellular Immunotherapy Treatment (Effective June 30, 2011)(CR 7431-Transmittal 133)

A. General Prostate cancer is the most common non-cutaneous cancer in men in the United States. In 2009, an estimated 192,280 new cases of prostate cancer were diagnosed and an estimated 27,360 deaths were reported. The National Cancer Institute states that prostate cancer is predominantly a cancer of older men; the median age at diagnosis is 72 years. Once the patient has castration-resistant, metastatic prostate cancer the median survival is generally less than two years. In 2010 the Food and Drug Administration (FDA) approved sipuleucel-t (PROVENGE ; APC8015), for patients with castration-resistant, metastatic prostate cancer. The posited mechanism of action, immunotherapy, is different from that of anti-cancer chemotherapy such as docetaxel. This is the first immunotherapy for prostate cancer to receive FDA approval. The goal of immunotherapy is to stimulate the body's natural defenses (such as the white blood cells called dendritic cells, T-lymphocytes and mononuclear cells) in a specific manner so that they attack and destroy, or at least prevent, the proliferation of cancer cells. Specificity is attained by intentionally exposing a patient's white blood cells to a particular protein (called an antigen) associated with the prostate cancer. This exposure "trains" the white blood cells to target and attack the prostate cancer cells. Clinically, this is expected to result in a decrease in the size and/or number of cancer sites, an increase in the time to cancer progression, and/or an increase in survival of the patient. Sipuleucel-T differs from other infused anti-cancer therapies. Most such anti-cancer therapies are manufactured and sold by a biopharmaceutical company and then purchased by and dispensed from a pharmacy. In contrast, once the decision is made to treat with sipuleucel-t, a multi-step process is used to produce sipuleucel-t. Sipuleucel-T is made individually for each patient with his own white blood cells. The patient s white blood cells are removed via a procedure called leukapheresis. In a laboratory the white blood cells are exposed to PA2024, which is a molecule created by linking prostatic acid phosphatase (PAP) with granulocyte/macrophage-colony stimulating factor (GM- CSF). PAP is an antigen specifically associated with prostate cancer cells; GM-CSF is a protein that targets a receptor on the surface of white blood cells. Hence, PAP serves to externally manipulate the immunological functioning of the patient's white blood cells while GM-CSF serves to stimulate the white blood cells into action. As noted in the FDA's clinical review, each dose of sipuleucel-t contains a minimum of 40 million treated white blood cells, however there is "high inherent variability" in the yield of sipuleucel-t from leukapheresis to leukapheresis in the same patient as well as from patient to patient. The treated white blood cells are then infused back into the same patient. The FDA-approved dosing regimen is three doses with each dose administered two weeks apart. The total treatment period is four weeks. Nationally Covered Indications Effective for services performed on or after June 30, 2011, The Centers for Medicare and Medicaid Services (CMS) proposes that the evidence is adequate to conclude that the use of autologous cellular immunotherapy treatment - sipuleucel-t; PROVENGE improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for this on-label indication under 1862(a)(1)(A) of the Social Security Act. Effective for services performed on or after June 30, 2011, coverage of all off-label uses of autologous cellular immunotherapy treatment sipuleucel-t; PROVENGE for the treatment of prostate cancer is left to the discretion of the local Medicare Administrative Contractors. Publication 100-04 Medicare Claims Processing Manual -Chapter 32 Billing Requirements for Special Services (CR 7431-transmital 2339, CR 7431-transmittal 2254) Excerpts:

280 Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer 280.1 - Policy 280.2 Healthcare Common Procedure Coding System (HCPCS) Codes and Diagnosis Coding 280.3 - Types of Bill (TOB) and Revenue Codes Coverage for PROVENGE, Q2043, for asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer is limited to one (1) treatment regimen in a patient s lifetime, consisting of three (3) doses with each dose administered approximately two (2) weeks apart for a total treatment period not to exceed 30 weeks from the first administration. 280.1 Policy (Rev. 2339, Issued: 11-02-11, Effective: 06-30-11, Implementation: 08-08-11) Effective for services furnished on or after June 30, 2011, a National Coverage Determination (NCD) provides coverage of sipuleucel-t (PROVENGE ) for patients with asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone refractory) prostate cancer. Conditions of Medicare Part A and Medicare Part B coverage for sipuleucel-t are located in the Medicare NCD Manual, Publication 100-3, section 110.22. 280.2 Healthcare Common Procedure Coding System (HCPCS) Codes and Diagnosis Coding (Rev. 2339, Issued: 11-02-11, Effective: 06-30-11, Implementation: 08-08-11) Effective for claims with dates of service on and after July 1, 2011, Medicare providers shall report the following HCPCS code: Q2043 Sipuleucel-T, minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF, including leukapheresis and all other preparatory procedures, per infusion; short descriptor, Sipuleucel-T auto CD54+. ICD-9 Diagnosis Coding : For claims with dates of service on and after July 1, 2011, for PROVENGE, the on-label indication of asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone refractory) prostate cancer, must be billed using ICD-9 code 185 (malignant neoplasm of prostate) and at least one of the following ICD-9 codes: ICD-9 Description code 196.1 Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes 196.2 Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes 196.5 Secondary and unspecified malignant neoplasm of lymph nodes of inguinal region and lower limb 196.6 Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes 196.8 Secondary and unspecified malignant neoplasm of lymph nodes of multiple sites 196.9 Secondary and unspecified malignant neoplasm of lymph node site unspecified - The spread of cancer to and establishment in the lymph nodes. 197.0 Secondary malignant neoplasm of lung Cancer that has spread from the original (primary) tumor to the lung. The spread of cancer to the lung. This may be from a primary lung cancer, or from a cancer at a distant site. 197.7 Malignant neoplasm of liver secondary - Cancer that has spread from the original (primary) tumor to the liver. A malignant neoplasm that has spread to the liver from another (primary) anatomic site. Such malignant neoplasms may be carcinomas (e.g., breast, colon), lymphomas, melanomas, or sarcomas.

198.0 Secondary malignant neoplasm of kidney - The spread of the cancer to the kidney. This may be from a primary kidney cancer involving the opposite kidney, or from a cancer at a distant site. 198.1 Secondary malignant neoplasm of other urinary organs 198.5 Secondary malignant neoplasm of bone and bone marrow Cancer that has spread from the original (primary) tumor to the bone. The spread of a malignant neoplasm from a primary site to the skeletal system. The majority of metastatic neoplasms to the bone are carcinomas. 198.7 Secondary malignant neoplasm of adrenal gland 198.82 Secondary malignant neoplasm of genital organs Coding for Off-Label PROVENGE Services The use of PROVENGE off-label for the treatment of prostate cancer is left to the discretion of the Medicare Administrative Contractors. Claims with dates of service on and after July 1, 2011, for PROVENGE paid off-label for the treatment of prostate cancer must be billed using either ICD-9 code 233.4 (carcinoma in situ of prostate), or ICD-9 code 185 (malignant neoplasm of prostate) in addition to HCPCS Q2043. WPS does not cover Provenge for any off label indications. 280.3 - Types of Bill (TOB) and Revenue Codes (Rev. 2339, Issued: 11-02-11, Effective: 06-30-11, Implementation: 08-08-11) The applicable TOBs for PROVENGE are 12X, 13X, 22X, 23X, 71X, 77X, and 85X. On institutional claims, TOBs 12X, 13X, 22X, 23X, and 85X, use revenue code 0636 - drugs requiring detailed coding 280.4 Payment Method (Rev. 2339, Issued: 11-02-11, Effective: 06-30-11, Implementation: 08-08-11) Payment for PROVENGE is as follows: TOBs 12X, 13X, 22X and 23X - based on the Average Sales Price (ASP) + 6%, TOB 85X based on reasonable cost, TOBs 71X and 77X based on all-inclusive rate. For Medicare Part B practitioner claims, payment for PROVENGE is based on ASP + 6%. Contractors shall not pay separately for routine costs associated with PROVENGE, HCPCS Q2043, except for the cost of administration. (Q2043 is all-inclusive and represents all routine costs except for its cost of administration) Coding Guidelines 1. ICD-9 codes must be listed to the most specific number. The fifth digit in the section on Neoplasms should be 0 - without mention of remission. The fifth digit 01 indicates the patient is in remission and therefore would not require chemotherapy. Accordingly, other sections of the ICD-9 classifications carry some sections out to the fifth place to indicate specific information. Carry out all ICD-9 codes out to the fifth space where indicated. 2. Use the appropriate J code to report the drug being used.

3. True codes reflect the dosage of the drug; the number of units should indicate the total number of units given in 2400/SV1-04 data element of the ANSI 837 5010 or in item 24G of the CMS 1500 form. 4. NOC billing: Office/Clinic: When using a drug/radiopharmaceutical NOC code (J9999, J3490, or J3590, A9699) list the name of the drug, the amount of the drug that is administered and wasted if applicable; method of administration in the electronic narrative 2400/SV101-7 which is equivalent to line 19 of the CMS 1500 form. List the units of service as one in 2400/SV1-04 data element of the ANSI 837 5010 or in item 24G of the CMS 1500 form. Occasionally, the strength of the drug will also be needed on NOC claims. If the NOC ASP pricing file lists the name of the drug with its strength it must also be included on line 19. Example: Sodium Bicarbonate 8.4%. Hospital Outpatient Departments: Hospital outpatient departments are allowed to bill for new drugs, biologicals, and therapeutic radiopharmaceuticals that are approved by the FDA on or after January 1, 2004 for which pass-through status has not been approved and a C-code and APC payment have not been assigned using the unclassified drug/biological HCPCS code C9399 (Unclassified drugs or biological). Drugs, biologicals, and therapeutic radiopharmaceuticals that are assigned to HCPCS code C9399. 5. Coverage for medication is based on the patient s condition, the appropriateness of the dose and route of administration, based on the clinical condition and the standard of medical practice regarding the effectiveness of the drug for the diagnosis and condition. The drug must be used according to the indication and protocol listed in the accepted compendia ratings listed below. National Comprehensive Cancer Network (NCCN) Drugs and Biologies Compendium Thomson Micromedex DrugDex American Hospital Formulary Service-Drug Information (AHFS-DI) Clinical Pharmacology The compendia employ various rating and recommendation systems that may not be readily cross-walked from compendium to compendium. In general, a use is identified by a compendium as medically accepted if the: 1. indication is a Category 1 or 2A in NCCN, or Class I, Class IIa or Class IIb in DrugDex; or 2. narrative text in AHFS-DI or Clinical Pharmacology is supportive. 6. Self-administered drugs are not covered and should not be submitted to Medicare unless requested to do so by the beneficiary. 7. An invoice may be requested if pricing is not available on the ASP pricing file. This file contains lists for NOC and true codes. This file can be located using the following web link. http://www.cms.hhs.gov/mcrpartbdrugavgsalesprice

Electronic submitters should indicate they have additional documentation or an invoice, which Medicare may require, by indicating DOCUMENTATION AVAILABLE UPON REQUEST in the electronic equivalent of item 19. If the additional documentation or an invoice you have is needed for Medicare to make its payment determination, a development letter will be sent requesting the information. If you do not indicate the availability of the additional documentation, or the information is not returned timely, the claim will be returned as unprocessable. 8. To be covered, drugs and biologicals must be an expense to the physician or legal entity billing for the services or supplies. If the drug was supplied free to the physician, donated, or the patient brings in the drug to the physicians office to be administered, the drug would not be billable. The administration of the drug would be covered if the drug is given for a covered indication. a. When submitting a claim for the administration of a drug that was given for a covered indication, that the beneficiary brings in or was donated to them, indicate on line 19 the name of the drug. Failure to include the name of the drug in line 19 may result in denial. b. Drug administration services are not covered when the drug is given for a non-covered indication. 9. Requests for off label coverage consideration should be submitted via the LCD reconsideration process described on our Website http://www.wpsmedicare.com/ or submit a request with a copy of the compendia documenting the medically accepted category or narrative and or peer reviewed literature that is published in a CMS accepted journal supporting its use via e-mail to Policy Comments@wpsic.com Reason for Denial: Non-covered Published/Website: 11/01/2013; 09/01/2013; 09/01/2012, 12/01/2011; 08/01/2011; 03/01/2009 Revision History and Explanation: 05/01/2015: Annual review done 04/01/2015. 11/01/2013- updated #4 NOC billing under Hospital Outpatient Departments. Added information for therapeutic radiopharmaceutical billing based on Change Request 8338. 09/01/2013-Added A9699 to Coding Guideline section, #4. 09/01/2012- #3 & 4- NOC billing instructions updated with 5010 information. 06/01/2012 - This LCD was revised to add the Jurisdiction 8 (J-8) MAC contractor numbers. 08101, 10/22/2012: In accordance with Section 911 of the Medicare Modernization Act of 2003 and CMS Change Request 8059, contractor numbers in this LCD policy were updated due to the transition from WPS Fiscal Intermediary Contract Number 52280 to WPS Part A MAC Contractor Number 05901. No other changes were made to this LCD policy. Posted 09/01/2012 -Added 704.41, 704.42 08/20/2012: This LCD was revised to add the Jurisdiction 8 (J-8) Indiana Part B MAC Contract Number 08102. The CMS Statement of Work for the J8 Medicare Administrative Contract (MAC) requires that

the contractor retain the most clinically appropriate LCD within the jurisdiction. This WPS policy is being promulgated to the J8 MAC as the most clinically appropriate LCD within this jurisdiction. No coverage changes were made to this LCD for this revision. 07/23/2012: This LCD was revised to add the Jurisdiction 8 (J-8) Indiana and Michigan Part A MAC Contract Numbers 08101 and 08201. The CMS Statement of Work for the J8 Medicare Administrative Contract (MAC) requires that the contractor retain the most clinically appropriate LCD within the jurisdiction. This WPS policy is being promulgated to the J8 MAC as the most clinically appropriate LCD within this jurisdiction. No coverage changes were made to this LCD for this revision. 12/01/2011- Provenge information updated based on CR 7431 transmittal 2339: Q2043 is all-inclusive and represents all routine costs except for its cost of administration & limit of one (1) treatment regimen in a patient s lifetime, consisting of three (3) doses with each dose administered approximately two (2) weeks apart for a total treatment period not to exceed 30 weeks from the first administration.. 08/01/2011-Added Autologous Cellular Immunotherapy treatment of Metastatic Prostate Cancer information from Change Request (CR) 7431 Transmittals 133 and 2254.