Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Chimeric Antigen Receptor (CAR) Therapy
Policy #:MA08.093e

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

Coverage and reimbursement for CAR-T Cell Therapy for the Company’s Medicare Advantage members will be processed through the local Medicare Administrative Contractor (MAC), as this therapy has been identified as meeting Medicare's the significant cost threshold. 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.

Policy Guidelines

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Tisagenlecleucel (Kymriah™) was approved by the FDA on August 30, 2017 for the treatment of individuals up to age 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Supplemental approvals for tisagenlecleucel (Kymriah™) have since been issued by the FDA. In the pediatric population, the safety and effectiveness of tisagenlecleucel (Kymriah™) has been established for the treatment of relapsed or refractory B-cell ALL; the safety and effectiveness of tisagenlecleucel (Kymriah™) has not been established for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

Axicabtagene ciloleucel (Yescarta™) was approved by the FDA on October 18, 2017 for the treatment of adult individuals 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. The safety and effectiveness of axicabtagene ciloleucel (Yescarta™) in the pediatric population has not been established.


Description

Acute lymphoblastic leukemia (ALL) is a rapidly progressing cancer of immature forms of white blood cells (lymphocytes) in the bone marrow and blood. These cancerous cells grow quickly and crowd the bone marrow, preventing it from making normal red blood cells, white blood cells, and platelets. ALL is the most common form of cancer in children and the median age at diagnosis is 15 years old. There are approximately 5970 new cases per year, with 2500-3500 being children, in the United States. Lymphoblastic leukemias are classified in 2 categories: precursor B cell lymphoblastic leukemia, which account for approximately 70-80% of childhood ALL cases, and precursor T cell lymphoblastic leukemia.

Lymphoma is the most common blood cancer, and is divided into 2 categories: Hodgkin lymphoma and non-Hodgkin lymphoma. Lymphoma occurs when lymphocytes grow abnormally. There are two main types of lymphocytes in the body: B-lymphocytes and T-lymphocytes. Non-Hodgkin lymphoma is the most common cancer of the lymphatic system, with over 74,000 cases diagnosed annually in the United States. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL, accounting for 32% of all cases.

TISAGENLECLEUCEL (KYMRIAH)

Tisagenlecleucel (Kymriah™) is a genetically modified autologous T-cell immunotherapy. Each dose of tisagenlecleucel (Kymriah™) is customized to the individual. The individual's T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a chimeric antigen receptor (CAR). The modified T-cells target and bind to CD19 expressing leukemia cells and eliminates them. Prior to initiating the Kymriah™ infusion, individuals must undergo lymphodepleting chemotherapy to reduce the level of white blood cells and help the body accept the reprogrammed CAR-T cells.

On August 30, 2017, the United States Food and Drug Administration (FDA) approved tisagenlecleucel (Kymriah™) for the treatment of individuals up to 25 years old with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later stage relapse. Efficacy and safety of tisagenlecleucel (Kymriah™) in pediatric individuals with relapsed and refractory B-cell acute lymphoblastic leukemia (ALL) were established in a single-arm, open-label, phase 2 study (ELIANA). The primary outcome of this trial is the overall remission rate within 3 months of infusion of tisagenlecleucel (Kymriah™). Secondary outcomes included duration of remission, overall survival, and safety. Of the 63 individuals infused with tisagenlecleucel (Kymriah™), 52 (83%) achieved complete response and were minimal residual disease (MRD) negative. Duration of remission was defined as the time since onset of complete remission to relapse or death due to underlying cancer, whichever is earlier. A median duration of remission was not reached by any of the 52 individuals.

On May 1, 2018, the FDA approved tisagenlecleucel (Kymriah™) for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Efficacy and safety of tisagenlecleucel (Kymriah™) were established in a retrospective subgroup analysis of an open-label, single-arm trial (JULIET) of 68 individuals. The study included adults with relapsed or refractory DLBCL who had received 2 or more lines of chemotherapy, including rituximab and anthracycline, or relapsed following autologous hematopoietic stem cell transplantation. Tisagenlecleucel (Kymriah™) was administered as a single infusion, following 2-11 days after completion of lymphodepleting chemotherapy. The complete response (CR) rate and partial response (PR) rate was 32% and 18%, respectively; median duration of response was longer in those with CR compared with PR (not reached vs 3.4 months). Median time to first response was 0.9 months (range, 0.7 to 3.3 months).

AXICABTAGENE CILOLEUCEL (YESCARTA)

On October 18, 2017, the United States Food and Drug Administration approved axicabtagene ciloleucel (Yescarta™) for the treatment of adult individuals with relapsed or refractory large B-cell lymphoma after 2 or more lines of therapy. Axicabtagene ciloleucel (Yescarta™) is the second CD 19-directed genetically modified autologous T cell immunotherapy available in the United States. Like tisagenlecleucel (Kymriah™), axicabtagene ciloleucel (Yescarta™) is customized to the individual after the T cells are harvested. The T cells are genetically modified to express a chimeric antigen receptor that targets CD19 expressing cells.

Safety and efficacy of axicabtagene ciloleucel (Yescarta™) for the treatment of adult individuals with relapsed or refractory B-cell non-Hodgkin lymphoma were established in a single arm, open-label, multicenter trial (ZUMA-1). Individuals eligible for the trial had refractory disease to the most recent therapy or relapse within 1 year of autologous hematopoietic stem cell transplant. Of the 101 individuals who received the axicabtagene ciloleucel (Yescarta™) infusion, 52 (51%) achieved complete remission and 21 (21%) achieved partial remission. At the median follow up of 7.9 months, individuals in complete remission had not reached the estimated duration of response.

RISK EVALUATION AND MITIGATION STRATEGY (REMS) PROGRAM

Due to the risk of cytokine release syndrome (CRS) and neurological toxicities, tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™) are only available through a Risk Evaluation and Mitigation Strategy (REMS) program. The requirements of the REMS include:
  • Healthcare facilities that dispense and administer tisagenlecleucel (Kymriah™) or axicabtagene ciloleucel (Yescarta™) must be enrolled in the program
  • Certified healthcare facilities must have on-site, immediate access to tocilizumab (Actemra®) and ensure that a minimum of two doses are available for each patient for administration within 2 hours after tisagenlecleucel (Kymriah™) or axicabtagene ciloleucel (Yescarta™) infusion if needed to treat CRS
  • Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer tisagenlecleucel (Kymriah™) or axicabtagene ciloleucel (Yescarta™) are trained about the management of CRS and neurological toxicities

References

Centers for Medicare & Medicaid Services (CMS). Decision memo for chimeric antigen receptor (CAR) T-cell therapy for cancers (CAG-00451N). [CMS Web site]. 08/07/2019. Available at:
https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=291. Accessed September 17, 2019.

Centers for Medicare & Medicaid Services (CMS). Medicare learning network (MLN) Matters SE19009 . Chimeric Antigen Receptor (CAR) T-Cell Therapy Revenue Code and HCPCS Setup Revisions. [CMS Web site]. 05/28/2019. Available at:
https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNMattersArticles/downloads/SE19009.pdf. Accessed September 17, 2019.

Centers for Medicare & Medicaid Services (CMS). Medicare learning network (MLN) Matters SE19024. Billing instructions for beneficiaries enrolled in Medicare Advantage (MA) plans for services covered by Decision Memo CAG-00451N. [CMS Website]. Effective 08/07/2019. Article release 10/24/2019. Available at: https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNMattersArticles/Downloads/SE19024.pdf. Accessed November 14, 2019.

Centers for Medicare & Medicaid Services (CMS). Medicare managed care manual chapter 4 - benefits and beneficiary protections. [CMS Web site]. 04/22/2016. Available at: https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/mc86c04.pdf . Accessed September 17, 2019.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

Claims for Chimeric Antigen Receptor (CAR) T-cell therapy for Medicare Advantage members to be processed through the local Medicare Administrative Contractor (MAC)


0537T, 0538T, 0539T, 0540T



Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

N/A


HCPCS Level II Code Number(s)



Claims for Chimeric Antigen Receptor (CAR) T-cell therapy for Medicare Advantage members to be processed through the local Medicare Administrative Contractor (MAC)

Q2041 Axicabtagene ciloleucel, up to 200 million autologous anti-cd19 car positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose

Q2042 Tisagenlecleucel, up to 600 million car-positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References




Policy History

MA08.093e
01/01/2019This version of the policy is effective 01/01/2019.

This policy has been updated to communicate coverage and reimbursement for CAR-T Cell Therapy for the Company’s Medicare Advantage members will be processed through the local Medicare Administrative Contractor (MAC), as this therapy has been identified as meeting Medicare's the significant cost threshold.

The following CPT codes have been added to this policy:

0537T, 0538T, 0539T, 0540T

All ICD-10 CM codes have been deleted from Attachment A of this policy.

MA08.093d
01/01/2019This policy has been identified for the CPT/HCPCS code update, effective 01/01/2019.

The following HCPCS code has been added to this policy:
Q2042 Tisagenlecleucel, up to 600 million car-positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose

The following HCPCS code has been termed from this policy:
Q2040 Tisagenlecleucel, up to 250 million car-positive viable t cells, including leukapheresis and dose preparation procedures, per infusion

The following HCPCS codes has been revised in this policy:
FROM: Q2041 Axicabtagene ciloleucel, up to 200 million autologous anti-cd19 car t cells, including leukapheresis and dose preparation procedures, per infusion
TO: Q2041 Axicabtagene ciloleucel, up to 200 million autologous anti-cd19 car positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose

MA08.093c
07/30/2018This version of the policy will become effective 07/30/2018.

This policy has been updated in consideration of revisions within the US Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia for Axicabtagene ciloleucel (Yescarta™) and Tisagenlecleucel (Kymriah™), including the new coverage criteria for Tisagenlecleucel (Kymriah™) for relapsed or refractory large B-cell lymphoma.

MA08.093b
04/01/2018This policy has been identified for the HCPCS code update, effective 04/01/2018.

The following HCPCS codes have been added to this policy:
Q2041 Axicabtagene ciloleucel, up to 200 million autologous anti-cd19 car t cells, including leukapheresis and dose preparation procedures, per infusion

MA08.093a
01/01/2018This policy has been identified for the HCPCS code update, effective 01/01/2018.

The following HCPCS codes have been added to this policy:
Q2040 Tisagenlecleucel, up to 250 million car-positive viable t cells, including leukapheresis and dose preparation procedures, per infusion

Revisions from MA08.093
11/29/2017New policy number MA08.093 was issued as a result of of a new FDA approval of tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™).

This version of the policy will become effective 11/29/2017.

This new policy has been developed to communicate the Company’s coverage criteria for tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™).





Version Effective Date: 01/01/2019
Version Issued Date: 12/09/2019
Version Reissued Date: N/A