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This is a new policy published on 8/25/2020. It will be effective on 9/26/2020 or later.
  
Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:211
Effective Date: 09/26/2020
Original Policy Date:08/25/2020
Last Review Date:
Date Published to Web: 08/25/2020
Subject:
Brexucabtagene autoleucel (Tecartus)

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

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Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma (NHL) in which the tumor cells originate from the “mantle zone” of the lymph node. The incidence of MCL increases with age and most often affects men over the age of 60 years. Approximately 7% of adult non-Hodgkin lymphomas are MCL. The incidence in the United States and Europe is estimated to be 4 to 8 cases per million persons per year. The majority of patients are diagnosed with advanced disease and present with lymphadenopathy; however, a small percentage may present with extranodal disease. Treatment is not curative, and, therefore, patients will have refractory or recurrent disease. Despite treatment advances, relapsed and refractory MCL remains difficult to treat.

On July 24, 2020, the FDA approved Tecartus® (brexucabtagene autoleucel), a cell-based gene therapy for treatment of adult patients diagnosed with mantle cell lymphoma (MCL) who have not responded to or who have relapsed following other kinds of treatment. Tecartus® (brexucabtagene autoleucel) was the first cell-based gene therapy approved by the FDA for the treatment of MCL.

Tecartus® (brexucabtagene autoleucel) suspension for intravenous infusion is a CD19-directed genetically modified autologous T cell immunotherapy. Each dose of Tecartus® (brexucabtagene autoleucel) is a customized treatment created using a patient’s own immune system to help fight the lymphoma. The patient’s T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells. These modified T cells are then infused back into the patient.

Tecartus® (brexucabtagene autoleucel) is a CD19-directed genetically modified autologous T cell immunotherapy, binds to CD19-expressing cancer cells and normal B cells. Studies demonstrated that following anti-CD19 CAR T cell engagement with CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines. This sequence of events leads to killing of CD19- expressing cells.

The safety and efficacy of Tecartus® (brexucabtagene autoleucel) was established in an open-label, multicenter clinical trial (ZUMA-2; NCT02601313) of 74 adults with refractory or relapsed MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor. A single infusion of Tecartus® (brexucabtagene autoleucel was given to 68 of 74 patients who were leukapheresed. The primary efficacy outcome measure was objective response rate (ORR). 60 patients were evaluated for efficacy based on a minimum duration of follow-up for response of six months, the ORR was 87% (95% CI: 75, 94), with a complete remission (CR) rate of 62% (95% CI: 48, 74). The median time to response was 28 days (range 24-92 days) with a median follow-up time of 8.6 months.

Tecartus® (brexucabtagene autoleucel) has a black boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and for neurologic toxicities. Both CRS and neurologic toxicities can be fatal or life-threatening. Because of the risk of CRS and neurological toxicities, Tecartus® (brexucabtagene autoleucel) is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The risk mitigation measures for Tecartus® (brexucabtagene autoleucel) are identical to those of the current REMS program for another CAR-T therapy, Yescarta®.

Warnings for Tecartus® (brexucabtagene autoleucel) include hypersensitivity reactions, severe infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and effects on ability to drive and use machines. The most common non-laboratory adverse reactions (incidence greater than or equal to 20%) from use of Tecartus® (brexucabtagene autoleucel) are: pyrexia, CRS, hypotension, encephalopathy, fatigue, tachycardia, arrhythmia, infection – pathogen unspecified, chills, hypoxia, cough, tremor, musculoskeletal pain, headache, nausea, edema, motor dysfunction, constipation, diarrhea, decreased appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia.
The recommended dose of Tecartus® (brexucabtagene autoleucel) is a single intravenous infusion  of 2 x 106 CAR-positive viable T cells per kg body weight (maximum 2 x 108 CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

    I. Tecartus (brexucabtagene autoleucel) is considered medically necessary for the FDA approved indication of the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) when members meet ALL of the following criteria:
        A. Member was previously treated with an anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor (BTK; e.g.: ibrutinib or acalabrutinib)
        B. Member had disease progression after their last regimen or refractory disease to the most recent therapy
        C. Member does not have active or serious infections
        D. Member has not had prior allogeneic hematopoietic stem cell transplant (HSCT)
        E. Member does not have detectable cerebrospinal fluid malignant cells or brain metastases
        F. Member does not have any history of central nervous system (CNS) lymphoma or CNS disorders
        G. Member has not received CAR-T cell therapy
        H. Will be used as a single agent (this does not include pretreatment regimens or supportive care such as pre-infusion and post-infusion medications)
        I. Requirements of the Tecartus REMS Program have been met:
            1. Healthcare facility that dispense and administer drug must be enrolled and comply with the REMS requirements. Certified healthcare facility must have on-site, immediate access to tocilizumab and ensure that a minimum of two doses of tocilizumab are available for each patient for administration within 2 hours after Brexucabtagene autoleucel (Tecartus) infusion, if needed for treatment of CRS.
            2. Certified healthcare facility must ensure that healthcare providers who prescribe, dispense, or administer Brexucabtagene autoleucel (Tecartus) are trained about the management of CRS and neurological toxicities.
        J. Vaccination with live vaccines will not be administered for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Brexucabtagene autoleucel (Tecartus) treatment, and until immune recovery folllwing treatment with Brexucabtagene autoleucel (Tecartus).
        K. The prescriber is a specialist in the area of the member’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the member’s diagnosis.


    II. When Tecartus (brexucabtagene autoleucel) is considered medically necessary, therapy will be approved once-per-lifetime based on FDA-approved labeling:
        A. One treatment course consists of a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously on each of the fifth, fourth, and third days before infusion of Tecartus (brexucabtagene autoleucel).
        B. Tecartus (brexucabtagene autoleucel) is administered as a single infusion of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells.
        C. After administration of Tecartus (brexucabtagene autoleucel), signs and symptoms of Cytokine Release Syndrome (CRS) and other neurological toxicities should be monitored and supportive care should be provided as appropriate. Monitor patients at the certified healthcare facility daily for at least seven days following infusion.
        D. Tecartus will be approved for 60 days duration. A maximum of one dose per lifetime will apply.
          [INFORMATIONAL NOTE: Based on the FDA approved prescribing information, the following is stated in regards to dosing and administration of Tecartus (brexucabtagene autoleucel):
          Preparation for Infusion:
            1. Ensure tocilizumab and emergency equipment are available prior to infusion and during the recovery period.
            2. Premedicate with acetaminophen and diphenhydramine or another H1-antihistamine approximately 30 to 60 minutes prior to brexucabtagene autoleucel (Tecartus) infusion. Avoid prophylactic use of systemic corticosteroids as it may interfere with the activity of Brexucabtagene autoleucel (Tecartus).

          Based on FDA prescribing information, cytokine release syndrome (CRS) should be identified based on clinical presentation. If CRS is suspected, manage according to the recommendations in Table 1. Patients who experience Grade 2 or higher CRS (e.g., hypotension, not responsive to fluids, or hypoxia requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry. For patients experiencing severe CRS, consider performing an echocardiogram to assess cardiac function. For severe or life-threatening CRS, consider intensive care supportive therapy.
            Table 1. CRS Grading and Management Guidance
            CRS GradeTocilizumabCorticosteroids
            Grade 1
            Symptoms require symptomatic treatment only (e.g., fever, nausea, fatigue, headache, myalgia, malaise)
            If not improving after 24 hours, administer tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg)N/A
            Grade 2
            Symptoms require and respond to moderate intervention.

            Oxygen requirement less than 40% FiO2 or hypotension responsive to fluids or low-dose of one vasopressor or Grade 2 organ toxicity
            Administer tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg).

            Repeat tocilizumab every 8 hours as needed if not responsive to intravenous fluids or increasing supplemental oxygen. Limit to a maximum of 3 doses in a 24- hour period; maximum total of 4 doses.

            If improving, discontinue tocilizumab.
            Manage per Grade 3 if no improvement within 24 hours after starting tocilizumab.

            If improving, taper corticosteroids.
            Grade 3
            Symptoms require and respond to aggressive intervention.

            Oxygen requirement greater than or equal to 40% FiO2 or hypotension requiring high-dose or multiple vasopressors or Grade 3 organ toxicity or Grade 4 transaminitis
            Per Grade 2

            If improving, discontinue tocilizumab.
            Administer methylprednisolone 1 mg/kg intravenously twice daily or equivalent dexamethasone (e.g., 10
            mg intravenously every 6 hours) until Grade 1, then taper corticosteroids.

            If improving, manage as Grade 2.
            If not improving, manage as Grade 4.
            Grade 4
            Life-threatening symptoms.

            Requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis).
            Per Grade 2

            If improving, discontinue tocilizumab.
            Administer methylprednisolone 1000 mg intravenously per day for 3 days.

            If improving, taper corticosteroids, and manage as Grade 3.

            If not improving, consider alternate
            immunosuppressants
            Based on FDA prescribing information, signs and symptoms of neurologic toxicities should be monitored, according to Table 2. Other causes of neurologic symptoms should be ruled out. Patients who experience Grade 2 or higher neurologic toxicities should be monitored with continuous cardiac telemetry and pulse oximetry. Intensive care supportive therapy for severe or life threatening neurologic toxicities should be provided. Non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis for any Grade 2 or higher neurologic toxicities should be considered.

            Table 2. Neurologic Toxicity Grading and Management Guidance
            Grading AssessmentConcurrent CRSNo concurrent CRS
            Grade 1Administer tocilizumab per Table 1 for
            management of Grade 1 CRS.
            Supportive care.
            Grade 2Administer tocilizumab per Table 1 for management of Grade 2 CRS.

            If not improving within 24 hours after starting tocilizumab, administer dexamethasone 10 mg intravenously every 6 hours until the event is Grade
            1 or less, then taper corticosteroids.

            If improving, discontinue tocilizumab.

            If still not improving, manage as Grade 3.
            Administer dexamethasone 10 mg intravenously every 6 hours until the event is Grade 1 or less.

            If improving, taper corticosteroids.
            Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis
            Grade 3 Administer tocilizumab per Table 1 for management of Grade 2 CRS.

            In addition, administer dexamethasone 10 mg intravenously with the first dose of tocilizumab and repeat dose every 6 hours. Continue dexamethasone use until the event is Grade 1 or less, then taper corticosteroids.

            If improving, discontinue tocilizumab and manage as Grade 2.

            If still not improving, manage as Grade 4.
            Administer dexamethasone 10 mg intravenously every 6 hours.

            Continue dexamethasone use until the event is Grade 1 or less, then taper corticosteroids

            If not improving, manage as Grade 4.

            Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
            Grade 4Administer tocilizumab per Table 1 for
            management of Grade 2 CRS.

            Administer methylprednisolone 1000 mg intravenously per day with first dose of tocilizumab and continue methylprednisolone 1000 mg
            intravenously per day for 2 more days.

            If improving, then manage as Grade 3.

            If not improving, consider alternate immunosuppressants.

            Administer methylprednisolone 1000 mg intravenously per day for 3 days.

            If improving, then manage as Grade 3.

            If not improving, consider alternate
            immunosuppressants
            Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
          III. Tecartus (brexucabtagene autoleucel) is considered medically necessary for the following off-label uses:
              A. Useful in certain circumstances without regard to response duration to prior chemoimmunotherapy or expected median progression free survival as subsequent therapy for patients with relapsed or refractory disease (only given after chemoimmunotherapy and bruton tyrosine kinase inhibitor)
              [INFORMATIONAL NOTE: The off-label uses are supported by a rating of 'Category 1' or 'Category 2A' in the recommendations in the National Comprehensive Cancer Network (NCCN) compendium.]

          IV. All other uses of Tecartus (brexucabtagene autoleucel) are considered investigational, including but not limited to: relapsed/refractory chronic lymphocytic leukemia; relapsed/refractory small lymphocytic lymphoma; acute lymphoblastic leukemia; relapsed non-Hogkin’s lymphoma; refractory Non-Hodgkin’s lymphoma.


          Medicare Coverage:
          Per Final Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N) issued 8/09/19, autologous treatment for cancer with T-cells expressing at least one chimeric antigen receptor (CAR) is covered when administered at healthcare facilities enrolled in the FDA risk evaluation and mitigation strategies (REMS) and used for a medically accepted indication as defined at Social Security Act section 1861(t)(2) i.e., is used for either an FDA-approved indication (according to the FDA-approved label for that product), or for other uses when the product has been FDA-approved and the use is supported in one or more CMS-approved compendia. For additional information and eligibility, refer to Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N). Available at: https://www.cms.gov/medicare-coverage-database/indexes/ncd-alphabetical-index.aspx

          The use of non-FDA-approved autologous T-cells expressing at least one CAR is non-covered. Autologous treatment for cancer with T-cells expressing at least one CAR is non-covered when the requirements above are not met.

          Note: For Calendar Years (CYs) 2019 and 2020 only, original fee-for-service Medicare will pay for CAR T-cell therapy when Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N) criteria is met. Therefore, providers must submit all claims for CAR-T Cell Therapy and associated costs to the local MAC. Claims should not be submitted to the Medicare Advantage plan.
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        Horizon BCBSNJ Medical Policy Development Process:

        This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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        Index:
        Brexucabtagene autoleucel (Tecartus)
        Tecartus (Brexucabtagene autoleucel)

        References:
        1. Tecartus [package insert]. Santa Monica, CA: Kite Pharma, Inc. July 2020.

        2. Kite Pharma, Inc. Press Reelease. US FDA Approves Kit’s Tectarus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma. Available at https://www.kitepharma.com/news/press-releases/2020/7/us-fda-approves-kites-tecartus-the-first-and-only-car-t-treatment-for-relapsed-or-refractory-mantle-cell-lymphoma. Accessed July 30, 2020.

        3. FDA Press Release. FDA Approves First Cell-based Gene Therapy for Adult Patients with Relapsed or Refractory MCL. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-adult-patients-relapsed-or-refractory-mcl. Accessed July 30, 2020.

        4. Micromedex® Healthcare Series. n.d. Thomson Healthcare, Greenwood Village, CO. December 2019. http://www.thomsonhc.com.

        5. ClinicalTrials.gov. Study of Brexucabtagene Autoleucel (KTE-X19) for the Treatment of Individuals with Relapsed/Refractory B-Cell Malignancies. July 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04162756. Accessed August 3, 2020.

        6. ClinicalTrials.gov. Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ZUMA-8). July 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02625480. Accessed August 3, 2020.
        7. ClinicalTrials.gov. Study Evaluating Brexucabtagene Autoleucel (KTE-X19) in Pediatric and Adolescent Participants With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia or Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (ZUMA-4). June 2020. Available at:
        https://clinicaltrials.gov/ct2/show/NCT02625480. Accessed August 3, 2020.

        8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 2.2020. July 9, 2020. Accessed July 31, 2020.

        9. IPD Analytics: New Drug Review. Tecartus (brexucabtagene autoleucel). August 2020.
          Codes:
          (The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

          CPT

          HCPCS


          * CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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          Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

          The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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