Medical Policy: 08.01.33 

Original Effective Date: September 2020 

Reviewed: September 2020 

Revised:  

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

Tecartus (brexucabtagene autoleucel) a chimeric antigen receptor (CAR) T-cell therapy and is the first cell-based gene therapy approved by the FDA for the treatment of refractory or relapsed mantle cell lymphoma (MCL).

 

Mantle cell lymphoma (MCL) is a rare form of cancerous B-cell non-Hodgkin’s lymphoma that usually occurs in middle-aged or older adults. In patients with MCL, B-cells, a type of white blood cell which help the body fight infection, change into cancer cells that start to form tumors in the lymph nodes and quickly spread to other areas of the body.

 

Tecartus is a CD19-directed, genetically-modified autologous T-cell immunotherapy, also known as chimeric antigen receptor (CAR) T-cell therapy. CAR T-cells are made by first collecting T-cells from the patient. The cells are then sent to a laboratory where they are genetically engineered to produce chimeric antigen receptors. The modified T-cells, now known as CAR T-cells, have the ability to better recognize an antigen (the CD19 protein) on targeted tumor cells. After the CAR T-cells have multiplied in the laboratory, they are then infused back into the patient. The modified CAR T-cells help the body’s immune system better target and treat the tumor cells.

 

While Tecartus shares the same design as another FDA-approved anti-CD19 CAR-T cell therapy Yescarta (axicabtagene ciloleucel), the difference lies in the manufacturing process for Tecartus. Tecartus undergoes a white blood cell enrichment process, which is necessary for certain types of B-cell blood cancers, such as mantle cell lymphoma, where circulating lymphoblasts are a common feature.

 

The FDA has approved Tecartus for relapsed or refractory mantle cell lymphoma under its accelerated approval program. Continued approval is based on verification of clinical benefit in confirmatory trials.

 

The safety and efficacy of Tecartus was established in a single-arm, open-label trial of 60 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 (2020 Wang et. al.). A total of 74 patients were enrolled. KTE-X19 was manufactured for 71 patients and administered to 68. The primary efficacy analysis showed that 93% (95% confidence interval [CI], 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred. The authors concluded Tecartus (KTE-X19) induced durable remissions in a majority of the patients with relapsed or refractory mantle cell lymphoma.

 

Tecartus has a black box warning for cytokine release syndrome (CRS), and should not be administered in patients with active infection or inflammatory disorders due to risk of life-threatening reactions and death. Severe or life-threatening CRS should be treated with tocilizumab with or without corticosteroids. Tecartus also has black box warning for causing neurological toxicities, which could also be severe and life-threatening. Monitoring for neurological events after administration is recommended. Due to these black box warnings, Tecartus is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.

 

Summary of Evidence

Tecartus is a CD19-directed, genetically-modified autologous T-cell immunotherapy, also known as chimeric antigen receptor (CAR) T-cell therapy. The FDA has approved Tecartus for relapsed or refractory mantle cell lymphoma (MCL) under its accelerated approval program. Continued approval is based on verification of clinical benefit in confirmatory trials. The safety and efficacy of Tecartus was established in a single-arm, open-label trial of 60 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 (2020 Wang et. al.). This trial concluded that Tecartus (KTE-X19) induced durable remissions in a majority of the patients with relapsed or refractory mantle cell lymphoma (of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response). Due to the risk of CRS (cytokine release syndrome) and neurologic toxicities, Tecartus was approved with a Risk Evaluation and Mitigation Strategy (REMS), which includes elements of safe use. The evidence is sufficient to determine that the technology results in meaningful improvement in net health outcomes.

 

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

B-Cell Lymphomas Version 4.2020
Mantel Cell Lymphoma

Second-Line Therapy

  • Useful in Certain Circumstances
    • Brexucabtagene autoleucel (only give after chemoimmunotherapy and BTK inhibitor)

 

Guidance for the Treatment of Patients with Brexucabtagene Autoleucel

  • Patient selection
    • Brexucabtagene autoleucel is recommended in the treatment of adult patients with relapsed or refractory MCL Lymphoma only after chemoimmunotherapy and BTK inhibitor
    • Healthcare facilities that dispense and administer brexucabtagene autoleucel must be enrolled and comply with Risk Evaluation and Mitigation Strategies (REMS) requirements.
  • Cytokine release syndrome (CRS) management – See CAR-T Cell Related Toxicities in the NCCN Guidelines for Management of Immunotherapy-Related Toxicities
  • Neurological toxicity management -See CAR-T Cell Related Toxicities in the NCCN Guidelines for Management of Immunotherapy-Related Toxicities
  • Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in brexucabtagene autoleucel
  • Severe infections: Severe or life-threatening infections occurred in patients after brexucabtagene autoleucel infusion. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.
  • Prolonged cytopenias
    • Patients may exhibit cytopenias for serval weeks following lymphodepleting chemotherapy and brexucabtagene autoleucel infusion
  • Hypogammaglobulinemia
    • B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with brexucabtagene autoleucel
  • Secondary malignancies may develop. Monitor life-long for secondary malignancies.

 

Regulatory Status

On July 24, 2020, the FDA approved Tecartus (brexucabtagene autoleucel) for intravenous infusion for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

 

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.

 

Black Box Warning

 

Warning: Cytokine Release Syndrome and Neurologic Toxicities

  • Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving TECARTUS. Do not administer TECARTUS to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
  • Neurologic toxicities, including life-threatening reactions, occurred in patients receiving TECARTUS, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with TECARTUS. Provide supportive care and/or corticosteroids, as needed.
  • TECARTUS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS Program.

 

Dosage

Dosing of TECARTUS is based on the number of chimeric antigen receptor (CAR)-positive viable T cells.

  • The TECARTUS dose is 2 × 106CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108CAR-positive viable T cells.

 

Prior Approval:

Prior approval required

 

Policy:

See Related Medical Policies

  • 08.01.27 Cellular Immunotherapy for Prostate Cancer – Provenge (Sipuleucel-T)
  • 08.01.29 Yescarta (Axicabtagene Ciloleucel)*
  • 08.01.30 Kymriah (Tisagenlecleucel)*

 

Tecartus (Brexucabtagene Autoleucel) as a one-time, single administration intravenous infusion treatment is considered medically necessary when ALL of the following criteria are met:

  • Individual is 18 years or older; AND
  • Individual has a diagnosis of mantel cell lymphoma; AND
  • Individual has a histologically confirmation of one of the following:
    • Cyclin D1 overexpression; or
    • Presence of the translocation t(11;14); AND
  • Individual has relapsed or refractory disease; AND
  • Previous therapy must have included ALL of the following
    • Bendamustine OR Anthracycline containing chemotherapy; and
    • Anti-CD20 monoclonal antibody, such as rtuximab; and
    • Bruton’s Tyrosine Kinase (BTK) Inhibitors such as acalabrutinib, ibrutinib, zanubrutinib); AND
  • Individual has at least one measurable lesion per Lugano Classification (lymph nodes: the longest diameter in axial plane should be >1.5 cm; extranodal lesions the longer diameter in the axial plane should be >1.0 cm); AND
  • Individual has adequate bone marrow reserve defined by all of the following:
    • Platelet count ≥ 75,000/uL; and
    • Absolute neutrophil count (ANC) ≥ 1000 cells/uL; and
    • Absolute lymphocyte count (ALC) ≥ 100 cells/uL; and
  • Individual has adequate renal, cardiac and pulmonary function defined as the following:
    • Creatinine clearance ≥ 60 mL/min
    • Cardiac ejection fraction ≥ 50% and there is no evidence of pericardial effusion as determined by an echocardiogram
    • Baseline oxygen saturation >92% on room air; AND
  • Tecartus (Brexucabtagene Autoleucel) will be provided based on the FDA recommended dosing and administration:
    • The patient will receive weight-based dosing of 2 × 106CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108CAR-positive viable T cells in approximately 68 ML; AND
  • The member will receive Tecartus (Brexucabtagene Autoleucel) at a treatment center that is certified to administer Tecartus (Brexucabtagene Autoleucel) (see Policy Guidelines below); AND
  • The individual does not have any of the following:
    • Prior treatment with chimeric antigenreceptor therapy or other genectically modified T-cell therapy including, but not limited to, Tecartus (Brexucabtagene Autoleucel), Yescarta (axicabtagene ciloleucel) or Kymriah (tisagenleucelucel); or are being considered for treatment with any other gene therapy;
    • Active hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive), if viral load is detectable; a history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing);
    • Presence of fungal, bacterial, viral or other infection that is uncontrolled requiring IV antimicrobials (antibiotics, antifungals, antiprotozoals, antivirals) for management prior to Tecartus (Brexucabtagene Autoleucel) infusion);
    • Active inflammatory disorders;
    • Active central nervous system (CNS) lymphoma or CNS disorders by imaging.

 

Tecartus (Brexucabtagene Autoleucel) is considered investigational for all other indications, including when the above medical necessity criteria are not met as the safety and efficacy has not yet been established in the peer reviewed medical literature. The evidence is insufficient to determine the effects on net health outcomes.

 

Repeat Treatment

Repeat treatment of Tecartus (Brexucabtagene Autoleucel) for any indication is considered investigational, as the safety and efficacy beyond one dose has not been studied. The evidence is insufficient to determine the effects on net health outcomes.

 

Required Documentation

The patient’s medical records submitted for review should document the above medical necessity criteria is met and should also include the following:

  • Office notes that contain the confirmed diagnosis and clinical features of the diagnosis (including laboratory results confirming the diagnosis), relevant history and physical and prior cancer treatment history
  • Include patient's weight for dosing and administration review.
  • Lab work within 7 to 14 days of the approval request to determine the individual has adequate organ and bone marrow function and meets the medical necessity criteria above.

 

Policy Guidelines

Anthracycline containing chemotherapy for the treatment of mantle cell lymphoma (MCL) may include the following:

  • RDHA [rituximab, dexamethasone, cytarabine] + platinum [carboplatin, cisplatin, or oxaliplatin];
  • Alternating RCHOP/RDHAP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]/[rituximab, dexamethasone, cytarbine, cisplatin]
  • NORDIC regimen [dose intensified induction immunochemotherapy with rituximab + cyclophosphamide, vincristine, doxorubicin, prednisone [maxi-CHOP] alternating with rituximab and high dose cytarabine];
  • HyperCVAD [cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine + rituximab];
  • VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone];
  • RCHOP;
  • Lenalidomide + retuximab

 

Black Box Warning

Warning: Cytokine Release Syndrome and Neurologic Toxicities

  • Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving TECARTUS. Do not administer TECARTUS to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
  • Neurologic toxicities, including life-threatening reactions, occurred in patients receiving TECARTUS, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with TECARTUS. Provide supportive care and/or corticosteroids, as needed.
  • TECARTUS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS Program.

 

Tecartus (Brexucabtagene Autoleucel) is available only through a restricted program under a risk evaluation and mitigation strategy (REMS). The requirement for the REMS components is as follows:

  • Health care facilities that dispense and administer Tecartus (Brexucabtagene Autoleucel) must be enrolled and comply with the REMS requirements.
  • Certified health care facilities must have onsite, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for administration within 2 hours after infusion Tecartus (Brexucabtagene Autoleucel), if needed for treatment of cytokine release syndrome (CRS).
  • Certified health care facilities must ensure that health care providers who prescribe, dispense or administer Tecartus (Brexucabtagene Autoleucel) are trained about the management of cytokine release syndrome (CRS) and neurologic toxicities.

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD diagnosis codes.

  • C9073 Brexucabtagene autoleucel, up to 200 million autologous anti-cd19 car positive viable t-cells, including leukapheresis and dose preparation procedures, per therapeutic dose
  • 0537T Chimeric antigen receptor T-cell (CAR-T) therapy; harvesting of blood-derived T lymphocytes for development of genetically modified autologous CAR-T cells, per day
  • 0538T Chimeric antigen receptor T-cell (CAR-T) therapy; preparation of blood-derived T lymphocytes for transportation (eg, cryopreservation, storage)
  • 0539T Chimeric antigen receptor T-cell (CAR-T) therapy; receipt and preparation of CAR-T cells for administration
  • 0540T Chimeric antigen receptor T-cell (CAR-T) therapy; CAR-T cell administration, autologous
  • Revenue Code 0891 Special Process Drugs – FDA Approved Cell Therapy

 

 

Selected References:

  • National Comprehensive Cancer Network (NCCN) B-Cell lymphomas Version 4.2020
  • FDA Labeling for Tecartus
  • Tecartus
  • Yescarta and Tecartus REMS
  • Wang et. al. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma N Engl J Med 2020;382:1331-134

 

Policy History:

  • September 2020 - New Medical Policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

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