Yescarta (Axicabtagene Ciloleucel) Policy Number: Current Effective Date: MM.02.036 September 27, 2019 Lines of Business: Original Effective Date: HMO; PPO; QUEST Integration June 1, 2018 Precertification: Place(s) of Service: Required, see section IV Inpatient

I. Description Diffuse large B-cell (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma and accounts for approximately 25% of non-Hodgkin lymphoma cases. DLBCL exhibits large heterogeneity in morphologic, genetic, and clinical aspects and multiple clinicopathologic entities are defined by the 2016 World Health Organization classification, which are sufficiently distinct to be considered separate diagnostic categories.

The spontaneous regression of certain cancers (e.g., renal cell carcinoma, melanoma) supports the idea that a patient’s immune system can delay tumor progression and, on rare occasions, can eliminate tumors altogether. These observations have led to research into various immunologic therapies designed to stimulate a patient’s own immune system. Adoptive immunotherapy is a method of activating lymphocytes and/or other types of cells for the treatment of cancer and other diseases. Cells are removed from the patient, processed for some period of time, and then infused back into the patient.

Axicabtagene Ciloleucel For individuals who are adults with a histologically confirmed diagnosis of aggressive non-Hodgkin lymphoma (eg, diffuse large B-cell lymphoma not otherwise specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed ) who receive axicabtagene ciloleucel, the evidence includes a single-arm prospective trial. Relevant outcomes are overall survival, disease-specific survival, quality of life, and treatment-related mortality and morbidity. The pivotal single-arm trial reported a 72% overall response rate (measured by complete or partial remission) in heavily pretreated patients. After a median follow-up of 7.9 months, the median duration of response was 9.2 months. The observed benefits were offset by a high frequency and severity of adverse events. Cytokine release syndrome was observed in more than half (63%) of the patients, and 44% had an adverse event at grade 3 or higher. Long- term follow-up and real-world evidence are required to assess the generalizability of axicabtagene ciloleucel efficacy and safety outside of the clinical trial setting. The manufacturer has agreed to a postmarketing requirement observational registry study to collect safety information for patients treated with the marketed product. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Similar to tisagenlecleucel, axicabtagene ciloleucel is adoptive immunotherapy in which the T-cells of a patient are modified genetically using a retroviral vector. The resulting genetically modified cells express a CD-19-directed chimeric antigen receptor protein that has a murine single-chain variable fragment with specificity for CD19. Once injected, the genetically modified T-cells selectively target and bind to CD19 antigen expressed on the surface of normal and malignant B cells. PAGE 10 OF POLICY

Yescarta (Axicabtagene Ciloleucel) III-2

Axicabtagene ciloleucel (Yescarta™; ) was FDA-approved for the treatment of adults with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

II. Policy Criteria Axicabtagene Ciloleucel (Yescarta) is covered (subject to Limitations and Administrative Guidelines) when all of the following criteria are met: A. The patient has been diagnosed with relapsed/refractory B-cell lymphoma* including any of the following: 1. Diffuse large B-cell lymphoma (DLBCL) not otherwise specified; or 2. Primary mediastinal large B-cell lymphoma; or 3. High grade B-cell lymphoma; or 4. Diffuse large B-cell lymphoma (DLBCL) arising from follicular lymphoma; and B. The patient is 18 years of age or older; and C. The patient has not received prior CD-19-directed CAR therapy treatment or any other or being considered for treatment with any other gene therapy, and D. The patient received adequate prior therapy which included all of the following: 1. Anti-CD20 monoclonal antibody for CD20—positive tumor 2. Anthracycline-containing chemotherapy regimen 3. For patients with transformed follicular lymphoma, prior chemotherapy for follicular lymphoma and subsequently have chemo-refractory disease after transformation to diffuse large B-cell lymphoma E. Documentation of all of the following: 1. Absolute neutrophil count of >/ (greater or equal to) 1,000/uL 2. Absolute lymphocyte count of > 100/uL 3. Platelet count of >/ (greater or equal to) 75,000 /uL F. The patient will not be treated with more than 2.0 x 108 CAR-positive viable T cells; AND G. If the patient is under 100kg in weight, they will receive weight-based dosing 2.0 x 106 CAR-positive viable T cells; and H. The patient has received or will receive lympho-depleting cyclophosphamide 500mg/m2 intravenously and fludarabine 30 mg/m2 intravenously on the fifth, fourth, and third day before infusion of Yescarta; and I. The patient has adequate organ and bone marrow function with no significant deterioration in organ function expected within 4 weeks after apheresis; and J. The patient does not have primary central nervous system (CNS) lymphoma; and K. The patient does not have human immunodeficiency virus (HIV), active hepatitis B or hepatitis C, active uncontrolled infection and any autoimmune disease requiring immune suppression; and L. The prescriber will submit documentation of response to Yescarta within 3 months following therapy as a follow-up to the prior approval request. * Relapsed or refractory disease, defined as progression after 2 or more lines of systemic therapy.

III. Limitations A. Axicabtagene Ciloleucel is not covered for all other indications including but not limited to the following as they are not know to be effective in improving long-term health outcomes: 1. Relapsed or refractory non-Hodgkin’s lymphoma when criteria in II.A. is not met; Yescarta (Axicabtagene Ciloleucel) IV-3

2. Any central nervous system (CNS) disease (eg., brain metastases, CNS lymphoma, and a history or presence of CNS disorders such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement); 3. History of allogeneic stem cell transplant, chimeric antigen receptor therapy or other genetically modified T-cell therapy; 4. Active, uncontrolled infection; 5. Human immunodeficiency virus (HIV); 6. Hepatitis B or C (if viral load is detectable).

IV. Administrative Guidelines A. Precertification is required. To pre-certify, complete HMSA’s Precertification Request form and fax or mail the form, or use iExchange with the following documentation: 1. Clinical Notes of past and current treatment 2. Confirmation of diagnosis (e.g. imaging, path) 3. Recent laboratory results B. Autologous lymphocytes used as part of adoptive immunotherapy may be harvested in a pheresis procedure or may be isolated from resected tumor tissue. C. The recommended target dose of axicabtagene ciloleucel for patients with large B-cell lymphoma is 2×106 CAR-positive viable T cells per kg body weight, with a maximum of 2×108 chimeric antigen receptor- positive viable T cells intravenously. D. Axicabtagene Ciloleucel has a black box warning because of the risk of cytokine release syndrome and neurologic toxicities that include fatal or life-threatening reactions. It should not be administered to patients with active infection or inflammatory disorders. It is recommended that severe or life- threatening cytokine release syndrome should be treated with tocilizumab. Patients should be monitored for neurologic events after treatment. E. Axicabtagene Ciloleucel is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the Yescarta REMS. The requirement for the REMS components are as follows: 1. Health care facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. 2. Certified health care facilities must have onsite, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for administration within 2 hours after Yescarta infusion, if needed for treatment of cytokine release syndrome. 3. Certified health care facilities must ensure that health care providers who prescribe, dispense or administer Yescarta are trained about the management of cytokine release syndrome and neurologic toxicities.

HCPCS Codes Description Q2041 Axicabtagene Ciloleucel, up to 200 Million Autologous Anti-CD19 CAR T Cells, Including Leukapheresis And Dose Preparation Procedures, Per Infusion J9999 Not Otherwise Classified, Antineoplastic Drugs J3490 Unclassified Drugs J3590 Unclassified Biologics CPT Codes Description 0537T Chimeric antigen receptor T-cell (CAR-T) therapy; harvesting of blood-derived T Yescarta (Axicabtagene Ciloleucel) V-4

lymphocytes for development of genetically modified autologous CAR-T cells, per day 0538T Chimeric antigen receptor T-cell (CAR-T) therapy; preparation of blood-derived T lymphocytes for transportation (eg, cryopreservation, storage) 0539T Chimeric antigen receptor T-cell (CAR-T) therapy; receipt and preparation of CAR-T cells for administration 0540T Chimeric antigen receptor T-cell (CAR-T therapy; CAR-T cell administration, autologous

V. Scientific Background Axicabtagene Ciloleucel Observed outcomes in single-arm study design cannot be attributed solely to the intervention itself because they could occur as a result of a placebo effect, the natural course of the disease, or confounding by time- varying factors. However, it is unlikely the high response rate (measured by CR/CRi or CR plus partial response) seen in the pivotal trials of axicabtagene ciloleucel could be the result of a noninterventional effect. An unbiased estimate of the safety of these chimeric antigen TCR cannot be ascertained from this evidence base because of the lack of control arm, which makes it difficult to determine whether the observed adverse reactions are a consequence of background disease or the drug itself. However, axicabtagene ciloleucel is a biologic drug and therefore observed adverse reactions that have immunologic basis are likely drug-mediated. The observed benefits seen with axicabtagene ciloleucel were offset by a high frequency and severity of adverse reactions. CRS was observed in more than half of the patients in the pivotal trials and more than 40% of patients had an adverse event at grade 3 or higher. Long-term follow-up and real-world evidence are required to assess the generalizability of efficacy and safety of axicabtagene ciloleucel outside of a clinical trial setting.

Axicabtagene Ciloleucel Clinical Context and Therapy Purpose The purpose of axicabtagene ciloleucelis to provide a treatment option that is an alternative to or an improvement on existing therapies in patients who are adults with specific types of aggressive NHL.

The question addressed in this evidence review is: does the use of adoptive immunotherapy in patients with various malignancies improve the net health outcome?

The following PICOTS were used to select literature to inform this review.

• Patients The relevant population of interest is individuals who are adults with specific types of aggressive NHL. • Interventions The therapy being considered is axicabtagene ciloleucel. • Comparators Comparators of interest include standard of care. • Outcomes The general outcomes of interest are OS, DSS, QOL, treatment-related mortality, and treatment- related morbidity. • Timing Though not completely standardized, follow-up for individuals who are adults with specific types of aggressive NHL would typically occur in the months after starting treatment. Yescarta (Axicabtagene Ciloleucel) V-5

• Setting Patients who are adults with specific types of aggressive NHL are actively managed by oncologists in an outpatient clinical setting. • Study Selection Criteria Methodologically credible studies were selected using the following principles:

1. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs; 2. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies. 3. To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought. 4. Studies with duplicative or overlapping populations were excluded.

The approval of axicabtagene ciloleucel was based on the results of an open-label, multicenter phase 1/2 study called ZUMA-1, which reported CR rates and duration of response demonstrated in the phase 2 portion of the study. Trial results have not been published; data were obtained from the FDA documents and the approved label.18,72,73, Adults with aggressive B-cell NHL that was primary refractory, refractory to a second or greater line of therapy, or relapsed within one year after autologous HCT were enrolled in the study. Patients with prior allogeneic HCT, any history of central nervous system lymphoma, Eastern Cooperative Oncology Group Performance Status score of 2 or greater, absolute lymphocyte count less than 100/μL, creatinine clearance less than 60 mL/min, hepatic transaminases more than 2.5 times the upper limit of normal, cardiac ejection fraction less than 50%, or active serious infection were excluded. Most patients (74%) had de novo DLBCL and 32% had double- or triple-hit lymphoma. The median age was 58, with 24% being aged 65 years or older; the median number of prior therapies was 3; 77% had refractory disease to a second or greater line of therapy, and 21% had relapsed within 1 year after autologous hematopoietic cell transplantation.

All patients received a lymph depleting regimen consisted of cyclophosphamide and fludarabine prior to infusion of axicabtagene ciloleucel. Of the 111 patients who underwent leukapheresis, 101 received the infusion (9 were not treated due to progressive disease or serious adverse reactions following leukapheresis and there was a manufacturing failure in 1 patient). The study protocol mandated hospitalization of patients for infusion and seven days after infusion. Bridging chemotherapy between leukapheresis and lymph depleting chemotherapy was not permitted. The median time from leukapheresis to product delivery was 17 days (range, 14-51 days). The primary endpoint was objective response rate based on a modified intention- to-treat population, which was defined as all patients treated with at least 1.0 × 106 chimeric antigen receptor-positive T cells per kilogram. Table 1 summarizes the trial results.

Table 1. Summary of Efficacy Results of the Pivotal Study Outcomes Results, n (%) (95% Confidence Interval) Primary end point N=101 Objective remission rate (CR + PR)a 73 (72) (62 to 81) CR 52 (51) (41 to 62) PR 21 (21) (13 to 30) Secondary end points N=73 Median duration of response, mob,c All patients 9.2 (5.4 to NE) CR only NE (8.1 to NE) PR only 2.1 (1.3 to 5.3) Median follow-up for duration of response, mob,c 7.9 Yescarta (Axicabtagene Ciloleucel) V-6

Adapted from Kite Pharma (2017). CR: complete response; NE: not estimable; PR: partial response. a Per 2007 revised International Working Group criteria, as assessed by the independent review committee. b Duration of response was measured from the date of the first objective response to the date of progression or death from relapse or toxicity. c Kaplan-Meier estimates.

Safety Safety data assessed 108 patients treated with axicabtagene ciloleucel. Adverse events of special interest are summarized in Table 8. All patients experienced at least 1 adverse event following infusion and 94% (n=102) experienced grade 3 or higher events. Serious adverse events were observed in 56 (52%) of patients, and serious adverse events that were grade 3 or higher occurred in 48 (44%) patients. Overall, 34 deaths were reported from the time of informed consent to the trial data cutoff (January 27, 2017). Thirty patients died of progressive disease and 4 deaths were attributed to axicabtagene ciloleucel as per the FDA analysis, of which 3 occurred within 30 days of infusion.

The median time to onset for CRS was 2 days (range, 1-12 days), and the median time to resolution was 7 days (range, 2-58 days). Forty-five percent (49/108) of patients received tocilizumab for CRS management. The median time to onset of neurologic toxicity was 4 days (range, 1-43 days). The median duration was 17 days. Prolonged encephalopathy lasting up to 173 days was noted. Most common neurologic toxicities included encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia, and anxiety. Neurologic toxicities were managed with supportive care and/or corticosteroids. Almost all neurologic toxicities at grade 2 or higher occurred within seven days following infusion.

Table 2. Summary of Serious Adverse Events of Special Interest in the Pivotal Study (N=108) Adverse Events All Grades, n (%) Grades ≥3, n (%) Cytokine release syndrome 101 (63) 14 (13) Neurologic toxicitiesa 94 (21) 34 (31) Serious infections 41 (38) 25 (23) Febrile neutropenia 39 (36) 35 (32) Prolonged cytopenia not resolved by day 30 - 30 (28) Hypogammaglobulinemia 16 (15) 0 Adapted from Food and Drug Administration (2017).72 a Ninety-eight percent of all neurologic toxicities occurred within first 8 weeks of axicabtagene ciloleucel infusion.

Summary of Evidence Axicabtagene Ciloleucel For individuals who are adults with a histologically confirmed diagnosis of aggressive NHL (eg, DLBCL not otherwise specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed follicular lymphoma) who receive axicabtagene ciloleucel, the evidence includes a single-arm prospective trial. The relevant outcomes are OS, DSS, QOL, and treatment-related mortality and morbidity. The pivotal single-arm trial reported a 72% overall response rate (measured by complete or partial remission) in heavily pretreated patients. After a median follow-up of 7.9 months, the median duration of response was 9.2 months. The observed benefits were offset by a high frequency and severity of adverse events. The CRS was observed in more than half (63%) of the patients, and 44% had an adverse event at grade 3 or higher. Long- term follow-up and real-world evidence are required to assess the generalizability of axicabtagene ciloleucel efficacy and safety outside of the clinical trial setting. The manufacturer has agreed to a postmarketing requirement observational registry study to collect safety information for patients treated with the marketed product. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. Yescarta (Axicabtagene Ciloleucel) VI-7

VI. Supplemental Information Practice Guidelines and Position Statements Current guidelines from the National Comprehensive Cancer Network do not include recommendations for adoptive immunotherapy to treat cancers of the bladder, central nervous system, head and neck, hepatobiliary system, kidney, pancreatic, stomach, or thyroid, melanoma, Hodgkin lymphoma r non-small- cell lung cancer. Current Network guidelines for B-cell recommend (category 2A) axicabtagene ciloleucel or tisagenlecleucel as a treatment option

• For histological transformation to diffuse large B-cell lymphoma after multiple lines of prior therapies which include ≥2 chemo-immunotherapy regimens for indolent or transformed disease. • For relapse or refractory disease diffuse large B-cell lymphoma after multiple lines of prior therapies which include ≥2 chemo-immunotherapy regimens for indolent or transformed disease.

U.S. Preventive Services Task Force Recommendations - Not applicable.

Medicare National Coverage There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

ONGOING AND UNPUBLISHED CLINICAL TRIALS Some currently unpublished trials that might influence this review are listed in Table 4. Table 4. Summary of Key Trials Planned NCT No. Trial Name Completion Date Enrollment Cytotoxic T lymphocytes Lymphokine-activated killer cells Targeted Natural Killer (NK) Cell Based Adoptive Immunotherapy for the NCT02118415 Treatment of Patients With Non-Small 90 Feb 2018 Cell Lung Cancer (NSCLC) After Radiochemotherapy (RCT) Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive NCT02229266 56 Sep 2020 Immunotherapy With NK Cells in High- risk AML (HINKL) Tumor-infiltrating lymphocytes TIL Therapy in Metastatic Melanoma NCT01995344 90 Dec 2018 and IL2 Dose Assessment (METILDA) A Phase II Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor NCT01993719 64 Sep 2029 Infiltrating Lymphocytes Plus IL-2 Comparing Two Different Chemotherapy Preparative Regimens A Pilot Study of SGI-110 in Combination With an Allogeneic Colon NCT01966289 Cancer Cell Vaccine (GVAX) and 18 Dec 2019 Cyclophosphamide (CY) in Metastatic Colorectal Cancer (mCRC) as Yescarta (Axicabtagene Ciloleucel) VI-8

Maintenance Therapy Prospective Randomized Study of Cell Therapy for Metastatic Melanoma Using Short-Term Cultured Tumor Infiltrating Lymphocytes Plus IL-2 NCT01319565 102 Jun 2020 Following Either a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Alone or in Conjunction w/1200 TBI Randomized Phase III Study Comparing a Non-myeloablative Lymphocyte Depleting Regimen of Chemotherapy NCT02278887 Followed by Infusion of Tumor 168 Sep 2020 Infiltrating Lymphocytes and Interleukin-2 to Standard Ipilimumab Treatment in Metastatic Melanoma Autologous dendritic cells Study of a Drug [DCVax®-L] to Treat NCT00045968a 348 Nov 2016 (ongoing) Newly Diagnosed GBM Brain Cancer A Phase II Clinical Trial Evaluating Autologous Dendritic Cells Pulsed With NCT01204684 Tumor Lysate Antigen +/- Toll-like 60 Oct 2019 Receptor Agonists for the Treatment of Malignant Glioma Lymph depletion Plus Adoptive Cell NCT00338377a Transfer With or Without Dendritic Cell 189 Feb 2019 Immunization Dendritic cells/cytokine-induced killer cells Concurrent Chemo radiation With or Without DC-CIK Immunotherapy in NCT01691625a 50 Sep 2019 Treating Locally Advanced Esophageal Cancer Axicabtagene ciloleucel A Phase 2 Multicenter Study Evaluating NCT02601313 Subjects With Relapsed/Refractory 130 Mar 2035 Mantle Cell Lymphoma (ZUMA-2)

A Study Evaluating KTE-C19 in Adult Subjects With Relapsed/Refractory B- NCT02614066 100 precursor Acute Lymphoblastic Mar 2034

Leukemia (r/r ALL) (ZUMA-3) (ZUMA-3)

A Multi-Center Study Evaluating KTE- C19 in Pediatric and Adolescent Oct 2034 NCT02625480 Subjects With Relapsed/Refractory B- 100

precursor Acute Lymphoblastic Leukemia (ZUMA-4) A Phase 2 Multicenter Study of NCT03105336 Axicabtagene Ciloleucel in Subjects With 80 Mar 2034 Relapsed/Refractory Indolent Non-

Hodgkin Lymphoma (ZUMA-5) Yescarta (Axicabtagene Ciloleucel) VIII-9

NCT: national clinical trial. a Denotes industry-sponsored or cosponsored trial.

VII. Important Reminder The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is intended to discourage or prohibit providing other medical advice or treatment deemed appropriate by the treating physician. Benefit determinations are subject to applicable member contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. This Medical Policy has been developed through consideration of the medical necessity criteria under Hawaii’s Patients’ Bill of Rights and Responsibilities Act (Hawaii Revised Statutes §432E-1.4), generally accepted standards of medical practice and review of medical literature and government approval status. HMSA has determined that services not covered under this Medical Policy will not be medically necessary under Hawaii law in most cases. If a treating physician disagrees with HMSA’s determination as to medical necessity in a given case, the physician may request that HMSA reconsider the application of the medical necessity criteria to the case at issue in light of any supporting documentation.

VIII. References 1. Berry DA, Zhou S, Higley H, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA Oncol. Jul 13 2017;3(7):e170580. PMID 28494052 2. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. Oct 15 2015; 373(16):1541-1552. PMID 26465987 3. Maude SL, Teachey DT, Porter DL, et al. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. Jun 25 2015; 125(26):4017-4023. PMID 25999455 4. Pui CH, Carroll WL, Meshinchi S, et al. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol. Feb 10 2011; 29(5):551-565. PMID 21220611 5. Tallen G, Ratei R, Mann G, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. May 10 2010; 28(14):2339-2347. PMID 20385996 6. Bajwa R, Schechter T, Soni S, et al. Outcome of children who experience disease relapse following allogeneic hematopoietic SCT for hematologic malignancies. Bone Marrow Transplant. May 2013; 48(5):661-665. PMID 23128573 7. Jeha S, Gaynon PS, Razzouk BI, et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. Apr 20 2006; 24(12):1917-1923. PMID 16622268 8. von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. Dec 20 2016;34(36):4381-4389. PMID 27998223 9. Food and Drug Administration (FDA). FDA Briefing Document: Oncologic Drugs Advisory Committee Meeting (BLA 125646,Tisagenlecleucel). n.d.; https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Oncolo gicDrugsAdvisoryCommittee/UCM566166.pdf. Accessed July 24, 2017.

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10. Food and Drug Administration (FDA). FDA Presentations for the July 12, 2017 Meeting of the Oncologic Drugs Advisory Committee. 2017; https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Oncolo gicDrugsAdvisoryCommittee/UCM567383.pdf. Accessed July 24, 2017. 11. Novartis Briefing Document::Oncologic Drugs Advisory Committee Meeting (BLA 125646,Tisagenlecleucel). https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Oncolo gicDrugsAdvisoryCommittee/UCM566168.pdf. Accessed July 24, 2017. 12. Novartis Presentations for the July 12, 2017 Meeting of the Oncologic Drugs Advisory Committee (PDF - 2.6MB). https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Oncolo gicDrugsAdvisoryCommittee/UCM567385.pdf. Accessed July 24, 2017. 13. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: bladder cancer. Version 4.2018. http://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. 14. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: central nervous system cancers. Version 1.2018. http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. 15. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: head and neck cancers. Version 1.2018. http://www.nccn.org/professionals/physician_gls/pdf/head- and-neck.pdf. 16. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: hepatobiliary cancers. Version 2.2018. http://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. 17. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: kidney cancer. Version 4.2018. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. 18. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma. Version 1.2018. http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. 19. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: gastric cancer. Version 2.2018. http://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. 20. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: thyroid carcinoma. Version 1.2018. http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. 21. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: melanoma. Version 2.2018. https://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. 22. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: Hodgkin lymphoma. Version 3.2018. http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf. 23. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: non-small cell lung cancer. Version 4.2018. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. 24. National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology: acute lymphoblastic leukemia. Version 1.2018. https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. 25. Blue Cross Blue Shield Association. Adoptive Immunotherapy. 8.01.01. Revised February 2019.