Brexucabtagene Autoleucel (Tecartus) Form

Brexucabtagene autoleucel (Tecartus®) is a CD19-directed chimeric antigen receptor (CAR) T cell therapy. FDA Approved Indication(s) Tecartus is indicated for the treatment of:
• Adult patients with relapsed or refractory mantle cell lymphoma (MCL) • Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic lymphoma (ALL) ____ This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
All requests reviewed under this policy require medical director review. It is the policy of health plans affiliated with Centene Corporation® that Tecartus is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Mantle Cell Lymphoma (must meet all):
Only for initial treatment dose; subsequent doses will not be covered.

1. Diagnosis of relapsed or refractory MCL;
2. Prescribed by or in consultation with an oncologist or hematologist;
3. Age ≥ 18 years;
4. Recent (within the last 30 days) absolute lymphocyte count (ALC) ≥ 100 cells/μL;

5. Member has previously received 2 to 5 prior regimens that included all of the following (a, b, and c):
   a. Anthracycline (e.g., doxorubicin) or bendamustine-containing chemotherapy; b. Anti-CD20 monoclonal antibody therapy (e.g., rituximab); c. Bruton tyrosine kinase (BTK) inhibitor (e.g., Imbruvica®, Calquence®, Brukinsa™);

   6. Member does not have a history of or current central nervous system (CNS) disease or CNS disorders as detected by magnetic resonance imaging [MRI] (i.e., detectable Page 1 of 9

   CLINICAL POLICY Brexucabtagene Autoleucel
   cerebrospinal fluid malignant cells or brain metastases, CNS lymphoma, seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement);

   7. Member does not have a history of allogeneic stem cell transplantation;
6. Member has not previously received treatment with CAR T-cell immunotherapy (e.g., Abecma®, Breyanzi™, Carvykti™, Kymriah™, Yescarta™);
   9. Tecartus is not prescribed concurrently with other CAR T-cell immunotherapy (e.g., Abecma, Breyanzi, Carvykti, Kymriah, Yescarta);
   10. Dose does not exceed 2 x 108 CAR-positive viable T cells. Approval duration: 3 months (1 dose only, with 4 doses of tocilizumab (Actemra) if requested at up to 800 mg per dose) B. Acute Lymphoblastic Leukemia (must meet all): Only for initial treatment dose; subsequent doses will not be covered.
7. Diagnosis of B-cell precursor ALL;
8. Prescribed by or in consultation with an oncologist or hematologist;
9. Age ≥ 18 years;
10. Recent (within the last 30 days) ALC ≥ 100/μL;

11. Request meets one of the following (a or b): a. Member has relapsed or refractory disease defined as one of the following (i - iv): i. Primary refractory disease; ii. First relapse if first remission ≤ 12 months;
    iii. Relapsed or refractory disease after 2 or more lines of systemic therapy; iv. Relapsed following allogeneic stem cell transplantation (allo-SCT) and must be ≥ 100 days from allo-SCT at the time of Tecartus infusion; b. Disease is relapsed or refractory, Philadelphia chromosome positive, and member has received 2 tyrosine kinase inhibitors (e.g., imatinib, Sprycel®, Tasigna®, Bosulif®, Iclusig®); *Prior authorization may be required for tyrosine kinase inhibitors

    6. If previously treated with Blincyto®, documentation of CD19 tumor expression on blasts obtained from bone marrow or peripheral blood after completion of the most recent prior line of therapy;
    7. Member does not have CNS-3 disease or have a history or presence of any CNS disorder (e.g., seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema); CNS-3 disease is defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 white blood cells (WBCs) per mm3
    8. If member has CNS-2 disease, documentation of no clinically evident neurological changes; CNS-2 disease is defined as CSF blast cells with < 5 WBC/mm3
    9. Member has not previously received treatment with CAR T-cell immunotherapy (e.g., Abecma, Breyanzi, Carvykti, Kymriah, Yescarta);
    10. Tecartus is not prescribed concurrently with other CAR T-cell immunotherapy (e.g., Abecma, Breyanzi, Carvykti, Kymriah, Yescarta);
    11. Dose does not exceed 1 x 108 CAR-positive viable T cells. Page 2 of 9

    CLINICAL POLICY Brexucabtagene Autoleucel
    Approval duration: 3 months (1 dose only, with 4 doses of tocilizumab (Actemra) if requested at up to 800 mg per dose) C. Other diagnoses/indications (must meet 1 or 2):

    1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
    2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
       II. Continued Therapy A. All Indications in Section I
    3. Continued therapy will not be authorized as Tecartus is indicated to be dosed one time only. Approval duration: Not applicable B. Other diagnoses/indications (must meet 1 or 2):
    4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
    5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
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    CLINICAL POLICY Brexucabtagene Autoleucel
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. MCL: History of or current CNS disease or CNS disorders as detected by MRI (i.e., detectable cerebrospinal fluid malignant cells or brain metastases, CNS lymphoma, seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement); C. MCL: History of allo-SCT; D. ALL: History or presence of any CNS disorder, such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema; E. ALL: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 white blood cells (WBCs) per mm3 with or without neurological changes. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALC: absolute lymphocyte count Allo-SCT: allogeneic stem cell transplantation
    ALL: acute lymphoblastic leukemia CAR: chimeric antigen receptor CNS: central nervous system
    CSF: cerebrospinal fluid FDA: Food and Drug Administration MCL: mantle cell lymphoma MRI: magnetic resonance imaging WBC: white blood cells Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Mantle Cell Lymphoma HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone/methotrexate/ cytarabine) + rituximab NORDIC (rituximab + cyclophosphamide, vincristine, doxorubicin, prednisone/rituximab + cytarabine) RCHOP/RDHAP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)/(rituximab, dexamethasone, cisplatin, cytarabine) Varies Varies Varies Varies Varies Varies Page 4 of 9

    CLINICAL POLICY Brexucabtagene Autoleucel
    Drug Name Dosing Regimen Varies Varies Varies Varies Varies Varies Varies 560 mg PO QD 100 mg PO BID 160 mg PO BID or 320 mg PO QD 20 mg/day for week 1, 50 mg/day for week 2, 100 mg/day for week 3, 200 mg/day for week 4, 400 mg/day for week

12. Week 6 and thereafter: 800 mg/day Adults with Ph+ ALL: 600 mg/day Pediatrics with Ph+ ALL: 340 mg/m2/day Ph+ ALL: 140 mg per day Ph+ ALL: 45 mg per day Resistant or intolerant Ph+ CML-CP and CML-AP: 400 mg twice per day Ph+ CML: 500 mg per day
    Ph- ALL: varies RDHA (rituximab, dexamethasone, cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin) RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
    Bendeka® (bendamustine) ± rituximab VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone) Revlimid® (lenalidomide) + rituximab bortezomib ± rituximab lenalidomide ± rituximab Imbruvica® (ibrutinib) ± rituximab Calquence® (acalabrutinib) Brukinsa® (zanubrutinib) Venclexta® (venetoclax) Acute Lymphoblastic Leukemia imatinib mesylate (Gleevec®) Sprycel® (dasatinib) Iclusig® (ponatinib) Tasigna® (nilotinib) Bosulif® (bosutinib) Various combination regimens that may include the following: daunorubicin, doxorubicin, vincristine, dexamethasone, prednisone, pegaspargase, nelarabine, methotrexate, cyclophosphamide, cytarabine, rituximab, 6-mercaptopurine Page 5 of 9 Dose Limit/ Maximum Dose Varies Varies Varies Varies Varies Varies Varies 560 mg/day 400 mg/day 320 mg/day 800 mg/day Adults: 800 mg/day Pediatrics: 600 mg/day 180 mg/day 45 mg/day
    800 mg/day
    600 mg/day Varies

    CLINICAL POLICY Brexucabtagene Autoleucel
    Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s):
    o Cytokine release syndrome: do not administer Tecartus to patients with active infection or inflammatory disorders; treat severe or life-threatening cytokine release syndrome with tocilizumab or tocilizumab and corticosteroids o Neurologic toxicities: monitor for neurologic toxicities after treatment with Tecartus; provide supportive care and/or corticosteroids, as needed Appendix D: General Information • The ZUMA-2 trial included only patients with MCL and an ALC ≥ 100 cells/μL and a magnetic resonance imaging (MRI) of the brain showing no evidence of CNS lymphoma. Subjects with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of CNS lymphoma were excluded. The trial also excluded patients with history or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement. Additionally, patients with a history of allogeneic stem cell transplantation or prior CAR therapy or other genetically modified T-cell therapy were excluded. • Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program. • Refractory disease is defined as an inability to achieve a complete response to therapy. • The ZUMA-3 trial in patients with ALL excluded patients with:
    o Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3 with or without neurological changes; o Presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a sample of CSF with <5 WBCs per mm3 with neurological changes; o History or presence of any CNS disorder, such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema. V. Dosage and Administration Indication MCL ALL Dosing Regimen Target dose: 2 × 106 CAR-positive viable T cells per kg body weight 1 x 106 CAR-positive viable T cells/kg Maximum Dose 2 × 108 CAR-positive viable T cells 1 x 108 CAR-positive viable T cells/kg
    VI. Product Availability Single-dose unit infusion bag: frozen suspension of genetically modified autologous T-cells labeled for the specific recipient Page 6 of 9

    CLINICAL POLICY Brexucabtagene Autoleucel
    VII.