Drug and Biologic Coverage Policy Effective Date .......................................... 5/15/2021 Next Review Date… ..................................... 5/1/2022 Coverage Policy Number .................................. 1808 Chimeric Antigen Receptor T-Cell (CAR-T) and Advanced Cellular/Immune Effector Cell Therapy Table of Contents Related Coverage Resources Coverage Policy ................................................... 1 Adoptive Immunotherapy - (0225) FDA Approved Indications ................................... 3 Immunomodulators - (1805) Recommended Dosing ........................................ 4 General Background ............................................ 6 Coding/Billing Information .................................... 7 References .......................................................... 7 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. Coverage Policy Chimeric Antigen Receptor T-Cell (CAR-T) and Advanced Cellular/Immune Effector Cell Therapy includes the following products: • Yescarta™ (axicabtagene ciloleucel) • Tecartus™ (brexucabtagene autoleucel) • Kymriah™ (tisagenlecleucel) I. Axicabtagene ciloleucel (Yescarta) is considered medically necessary when ALL of the following criteria are met: A. Age 18 years of age and older B. ANY of the following: i. Diagnosis of any of the following large B-cell lymphoma subtypes: diffuse large B-cell lymphoma [DLBCL] not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, AIDS-related B-cell lymphoma, human herpes virus 8-positive DLBCL, and post-transplant lymphoproliferative disorders [B-cell type]); AND a. Disease is relapsed or refractory after two or more lines of systemic therapy ii. Diagnosis of DLBCL arising from follicular lymphoma; AND Page 1 of 8 Coverage Policy Number: 1808 a. The individual has received prior treatment with two or more chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated iii. Diagnosis of DLBCL arising from nodal marginal zone lymphoma; AND a. The individual has received prior treatment with two or more chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated C. Individual is not being treated for primary central nervous system lymphoma D. No prior use of axicabtagene ciloleucel (Yescarta) or another CD19-directed CAR-T therapy Authorization is for a single dose. Axicabtagene ciloleucel (Yescarta) is considered not medically necessary for all other uses including the following: • Repeat administration of axicabtagene ciloleucel (Yescarta) • Acute lymphocytic leukemia • Burkitt lymphoma • Chronic lymphocytic leukemia • Mantle cell lymphoma • Small lymphocytic leukemia • Solid tumors • Splenic marginal zone lymphoma II. Brexucabtagene autoleucel (Tecartus) is considered medically necessary when ALL of the following criteria are met: A. Individual is 18 years of age or older B. Diagnosis relapsed or refractory of Mantle Cell Lymphoma (MCL) C. Individual has previously received chemoimmunotherapy (for example, anthracycline- or bendamustine- based chemotherapy, anti-CD20 monoclonal antibody) AND a Bruton tyrosine kinase inhibitor D. Individual has received lymphodepleting (for example, cyclophosphamide and fludarabine) chemotherapy prior to Tecartus infusion E. Tecartus is prescribed by, or in consultation with, a hematologist or oncologist F. No prior use of another CD19-directed CAR-T therapy (for example, Kymriah or Yescarta) Authorization is for a single dose. Brexucabtagene autoleucel (Tecartus) is considered not medically necessary for all other uses. III. Tisagenlecleucel (Kymriah) is considered medically necessary when ALL of the following criteria are met: A. EITHER of the following: 1) Treatment for an individual up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is ONE of the following: a. Disease is refractory, or in second or later relapse b. Minimal residual disease positive after consolidation therapy c. Philadelphia chromosome-positive and ONE of the following: i. Less than complete response ii. High-risk genetics iii. Tyrosine kinase inhibitor (TKI) intolerant or refractory (TKIs include: Sprycel® [dasatinib tablets], imatinib tablets, Iclusig® [ponatinib tablets], Tasigna® [nilotinib capsules], and Bosulif® [bosutinib tablets]) iv. Relapse post-hematopoietic stem cell transplantation 2) Treatment for an adult when ANY of the following criteria are met: Page 2 of 8 Coverage Policy Number: 1808 a. Diagnosis of any of the following large B-cell lymphoma subtypes: diffuse large B- cell lymphoma [DLBCL] not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, AIDS-related B-cell lymphoma, human herpes virus 8-positive DLBCL, and post-transplant lymphoproliferative disorders [B- cell type]); AND i. Disease is relapsed or refractory after two or more lines of systemic therapy b. Diagnosis of DLBCL arising from follicular lymphoma; AND i. The individual has received prior treatment with two or more chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated c. Diagnosis of DLBCL arising from nodal marginal zone lymphoma; AND i. The individual has received prior treatment with two or more chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated B. Individual is not being treated for primary central nervous system lymphoma C. No prior use of axicabtagene ciloleucel (Yescarta) or another CD19-directed CAR-T therapy Authorization is for a single dose. Tisagenlecleucel (Kymriah) is considered not medically necessary for all other uses including the following: • Repeat administration of tisagenlecleucel (Kymriah) • Acute Myeloid Leukemia (AML) • Chronic lymphocytic leukemia • Hodgkin lymphoma • Mantle cell lymphoma • Plasma cell disorders • Solid tumors • T-cell leukemia/lymphoma When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to therapy. Note: Receipt of sample product does not satisfy any criteria requirements for coverage. FDA Approved Indications FDA Approved Indication Axicabtagene ciloleucel (Yescarta) Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Limitation of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. REMS Program • Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS • The required components of the Yescarta REMS are: o Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate Page 3 of 8 Coverage Policy Number: 1808 access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS o Certified healthcare facilities must ensure that healthcare