BlueCross BlueShield of Tennessee Medical Policy Manual

Axicabtagene Ciloleucel (Yescarta®)

NDC CODE(S)

71287-0119-XX YESCARTA PLASTIC BAG, INJECTION (KITE PHARMA, IN)

DESCRIPTION

Axicabtagene ciloleucel is a CD19-directed genetically modified autologous T cell immunotherapy.  To prepare the product an individual’s own T cells are harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising a murine anti-CD19 single chain variable fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains. The anti-CD19 CAR T cells are expanded and infused back into the individual.

Axicabtagene ciloleucel 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.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

Submission of medical records related to the medical necessity criteria is REQUIRED on all requests for authorizations. Records will be reviewed at the time of submission. Please provide documentation via direct upload through the PA web portal or by fax.

Large B-Cell Lymphoma

Follicular Lymphoma (FL)

RENEWAL CRITERIA

Coverage cannot be renewed.

DOSAGE/ADMINISTRATION

INDICATION

DOSE

Large B-Cell Lymphoma and Follicular Lymphoma

Lymphodepleting chemotherapy:

·         Administer cyclophosphamide 500 mg/m2 and fludarabine 30 mg/m2 intravenously on the fifth, fourth, and third day before infusion of Yescarta

Yescarta Infusion:

·         Premedicate with 650 mg acetaminophen and 12.5 mg diphenhydramine 1 hour prior to infusion. Avoid prophylactic system corticosteroids which may interfere with Yescarta activity.

·         Infuse the entire contents of the Yescarta bag within 30 minutes by either gravity or a peristaltic pump.

·         Each single infusion bag of Yescarta contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The target dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells.

Monitoring:

·         Monitor patients at least daily for 7 days at the certified healthcare facility following

infusion for signs and symptoms of CRS and neurologic toxicities.

·         Instruct patients to remain within proximity of the certified healthcare facility for at least 4 weeks following infusion.

For autologous use only. For intravenous use only.

·         Yescarta is prepared from the patient’s peripheral blood mononuclear cells, which are obtained via a standard leukapheresis procedure.

·         One treatment course consists of lymphodepleting chemotherapy followed by a single infusion of Yescarta.

·         Confirm Yescarta availability prior to starting the lymphodepleting regimen.

·         Store infusion bag in the vapor phase of liquid nitrogen (less than or equal to minus 150°C). Thaw prior to infusion.

·         In case of manufacturing failure, a second manufacturing may be attempted.

·         Additional chemotherapy (not the lymphodepletion) may be necessary while the patient awaits the product.

·         Ensure that 2 doses of tocilizumab and emergency equipment are available prior to infusion and during the recovery period.

LENGTH OF AUTHORIZATION

Coverage will be provided for one treatment course (1 dose of Yescarta) and may not be renewed.

DOSING LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

1.     Yescarta [package insert]. Santa Monica, CA; Kite Pharma, Inc., March 2021. Accessed March 2021.

2.     Locke FL, Neelapu SS, Bartlett NL, et al. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295.

3.     Mejstrikova E, Hrusak O, Borowitz MJ, et al. CD19-negative relapse of pediatric B-cell precursor acute lymphoblastic leukemia following blinatumomab treatment. Blood Cancer J. 20177; 659. DOI 10.1038/s41408-017-0023-x

4.     Ruella M, Maus MV. Catch me if you can: Leukemia Escape after CD19-Directed T Cell Immunotherapies. Computational and Structural Biotechnology Journal 14 (2016) 357–362.

5.     Braig F, Brandt A, Goebeler M, et al. Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking. Blood; 129:1, 2017 Jan.

6.     Majzner RG, Mackall CL. Tumor Antigen Escape from CAR T-cell Therapy. Cancer Discov 2018;8:1219-1226.

7.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) axicabtagene ciloleucel. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2021.

8.     Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42. doi:10.1016/S1470-2045(18)30864-7.

9.     Neelapu SS, Jacobson CA, Oluwole OO, et al. Outcomes of older patients in ZUMA-1, a pivotal study of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2020;135(23):2106-2109. doi:10.1182/blood.2019004162.

10.  Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi: 10.1056/NEJMoa1707447.

11.  Jacobson CA, Chavez JC, Sehgal AR, et al. Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL). Journal of Clinical Oncology 2020 38:15_suppl, 8008-8008.

12.  MICROMEDEX Healthcare Series. Drugdex Evaluations. (2021, March). Axicabtagene ciloleucel. Retrieved April 19, 2021 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  12/14/2017

MOST RECENT REVIEW DATE:    8/31/2021

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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