Oscar Yescarta (axicabtagene ciloleucel) (CG063) Form

Eligibility for CAR T-cell Therapy

The Plan members who have certain types of treatment-resistant lymphoma or leukemia may be eligible for chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell treatment involves genetically modifying a patient’s white blood cells to specifically target the cancer cells in the body. This type of therapy is also known as adoptive immunotherapy.

The process starts by filtering the white blood cells from the patient’s blood. The filtered cells are then genetically modified to target the tumor receptors and expanded to a greater quantity. The patient’s existing immune system is then depleted, often with chemotherapy, prior to infusion in order to allow for a more effective environment for the CAR T-cells to function.

As there are potentially serious side effects, treatment should only be performed when the benefits outweigh the risks, under the care of a licensed physician and in an inpatient facility that is certified to administer CAR T-cell therapy. The facility must provide adequate inpatient monitoring during the infusion or extremely close outpatient monitoring with transplant or CAR T-cell experience. The facility must also have at least two doses of tocilizumab immediately available should a severe adverse reaction occur. Patients are also expected to be available and within appropriate proximity of the treatment location to be monitored for 4 weeks after treatment.

Yescarta can only be accessed at specific treatment centers. To obtain more information, contact the REMS Call Center at 1-844-454-KITE (5483) or visit www.YescartaTecartusREMS.com.

This guideline does not address adoptive T-cell therapy for metastatic prostate cancer: Sipuleucel-T (Provenge™). For sipuleucel-T (Provenge™), please review the criteria outlined in MCG Sipuleucel-T (A-0661).

Definitions:

AIDS

Acquired Immunodeficiency Syndrome. It is a condition caused by the Human Immunodeficiency Virus (HIV), which attacks the immune system and weakens its ability to fight off infections and diseases. AIDS is considered the most advanced stage of HIV infection and is characterized by severe immune deficiency, leading to life-threatening opportunistic infections, cancers, and neurological disorders.

Allogeneic Stem Cell Transplant

A treatment where donor stem cells are harvested and transferred into patients with cancer or disorders (after their own immune system has been depleted using chemotherapy or total body irradiation) to repopulate their entire bone marrow with healthy cells.

Autologous Stem Cell Transplant

Similar to allogeneic stem cell transfer, except the patient’s own stem cells are used instead of a matched donor.

B-cell lymphomas

A group of non-Hodgkin’s lymphomas developing from cancerous white blood cells (specifically B-lymphocytes), often involving lymph nodes or other extranodal tissues. This group of lymphomas includes, but is not limited to, the following:

• Burkitt lymphoma
• Diffuse large B-cell lymphoma (DLBCL)
• Primary mediastinal B-cell lymphoma (PMBCL)
• Mantle cell lymphoma
• Marginal zone lymphomas
• Transformed follicular lymphoma

CAR T-cell or Chimeric Antigen Receptor T-cell

A type of adoptive immunotherapy where a patient’s white blood cells (specifically T-lymphocytes) are genetically engineered to specifically target the receptors on the cancer cells (CD19 receptor in the case of B-cell lymphomas and leukemias), B-cell maturation antigen (BCMA) or prostatic acid phosphatase (PAP) in the case of prostate cancer).

CAR-T cell-related encephalopathy syndrome (CRES)

An inflammatory immune response that can occur with CAR-T treatment and is treated in the same way as CRS.

Cytokine release syndrome (CRS)

An inflammatory immune response that may occur with CAR T-cell treatment.

It often manifests as fever, hypotension, nausea, and other symptoms, and is an emergent condition that may require prompt treatment with tocilizumab (treatment binds to and inhibits IL-6 to reduce inflammatory and immune excessive response) and/or corticosteroids.

"ECOG score" (Eastern Cooperative Oncology Group)

is a measure of a patient's general well-being and ability to participate in activities of daily living. The score ranges from 0 (fully active with restrictions) to 5 (dead) and is available at https://ecog-acrin.org/resources/ecog-performance-status.

"HHV8 (Human herpesvirus 8)"

, also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is a virus that can cause several types of cancers including Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease.

"Leukemia"

refers to a type of malignancy affecting the bone marrow and circulating cells in the bloodstream. Acute lymphoid leukemia (ALL) is one example.

"MALT"

stands for mucosa-associated lymphoid tissue, which is a type of tissue found in various mucosal surfaces of the body.

"Metastatic Castrate-Resistant Prostate Cancer"

is prostate cancer that has metastasized or spread outside of the pelvis. Castrate-resistant refers to the state of the cancer not responding to medications or systemic agents that typically inhibit progression by blocking hormonal signals.

"Relapsed"

refers to a lymphoma or leukemia that had previously responded to treatment with remission, but has returned after a period since the last treatment.

"Refractory"

refers to a lymphoma or leukemia that has not responded, has progressed, or has not achieved remission.

Medical Necessity Criteria for Authorization

The Plan considers a single dose of YESCARTA® (axicabtagene ciloleucel) medically necessary when ALL the following criteria are met:

1. Prescribed by or in consultation with a hematologist-oncologist; AND
2. The member is 18 years of age or older; AND
3. Treatment is for ONE of the following histologically confirmed CD19-positive large B-cell lymphomas, under the following conditions:

• If the patient has had prior treatment with first-line chemoimmunotherapy and has any of the following B-cell lymphoma subtypes:
  1. AIDS-related B-cell lymphomas; or
  2. Diffuse large B-cell lymphoma (DLBCL); or
  3. Monomorphic post-transplant lymphoproliferative disorder (B-cell type); or
  4. Other high-grade B-cell lymphomas; or
  5. Primary mediastinal large B-cell lymphoma; or
• If the patient has had prior treatment with two or more lines of systemic therapy and has any of the following B-cell lymphoma subtypes:
  1. AIDS-related B-cell lymphomas; or
  2. Diffuse large B-cell lymphoma (DLBCL); or
  3. DLBCL arising (histologic transformation) from follicular lymphoma or nodal marginal zone lymphoma; or
  4. Follicular lymphoma; or
  5. Gastric MALT lymphoma; or
  6. Non-gastric MALT lymphoma; or
  7. HHV8-positive diffuse large B-cell lymphoma; or
  8. Monomorphic post-transplant lymphoproliferative disorder (B-cell type); or
  9. Nodal marginal zone lymphoma; or
  10. Other high-grade B-cell lymphomas; or
  11. Primary mediastinal large B-cell lymphoma; or
  12. Splenic marginal zone lymphoma; AND

#aFor members with CD20-positive tumors, previous chemoimmunotherapy regimens should have included an anti-CD20 monoclonal antibody (e.g., Rituxan or rituximab biosimilars), unless contraindicated.

#bFor diffuse large B-cell lymphoma arising from follicular lymphoma or nodal marginal zone lymphoma, treatment should have included at least one anthracycline or anthracenedione-based regimen, unless contraindicated.

4.

Documented evidence of ALL of the following:

1. The member is scheduled for and can safely undergo lymphodepleting therapy (including chemotherapy and/or total body irradiation) before CAR T-cell treatment; and

2. The healthcare facility administering Yescarta is enrolled and adheres to the Yescarta REMS (Risk Evaluation and Mitigation Strategy), which includes:
   • Immediate, on-site availability of tocilizumab; and
   • Provision of a minimum of two tocilizumab doses per patient, ensuring administration within 2 hours after Yescarta infusion if required for cytokine release syndrome treatment; and
3. Healthcare providers involved in prescribing, dispensing, or administering Yescarta are trained in managing cytokine release syndrome and neurological side effects; and
4. The member has undergone screening and does NOT have any of the following:
   • Active uncontrolled infection or inflammatory disorders; or
   • Active or latent hepatitis B; or
   • Active hepatitis C; or
   • NOTE: history of hepatitis B or C is acceptable if the viral load is currently non-detectable.
   • A positive Human Immunodeficiency Virus (HIV) test; or
   • Previous treatment with Yescarta or any other CD19-targeted CAR T-cell therapy; AND
5. No contraindications (listed in "Experimental or Investigational / Not Medically Necessary" exclusions) are present.

Length of Stay

Initial Inpatient Admission- Up to 7 days

Extension Stay Criteria

Additional inpatient hospital days after 7 days are medically necessary when:

1. Patient has cytokine release syndrome (CRS); or
2. Patient has neurotoxicity, CAR-T Related Encephalopathy Syndrome (CRES); or
3. Patient has developed any adverse reaction continuing after infusion that include, but are not limited to, fever, hypoxia, hypotension, tachycardia, hypersensitive reactions, hypogammaglobulinemia, infections-pathogen unspecified, bleeding episodes, diarrhea, nausea, vomiting, headache, acute kidney injury, edema, and delirium; or
4. Patient is not stable for discharge, as outlined in the general recovery course and discharge criteria in MCG General Recovery Care > Problem Oriented General Recovery Guidelines >Medical Oncology GRG (PG-ONC).

Experimental or Investigational / Not Medically Necessary

CAR T-cell therapy for any other indication is considered experimental, investigational, or unproven. Non-covered indications and contraindications include, but are not limited to, the following:

• Any lymphoma subtype not mentioned above, including primary CNS lymphoma and Mantle cell lymphoma; or
• Any leukemia; or
• Any other cancer type or condition not included in the Clinical Indications criteria above; or
• When any other newly diagnosed malignancy or other malignancy that is under active treatment or not currently in remission is present; or
• Patients with an ECOG score of 3-4, as the efficacy and evidence for use in patients with poor performance status is limited; or
• Any of the following contraindications:
  • Live vaccination within 6 weeks of planned treatment date; or
  • Current pregnancy; or
  • Active, severe systemic infection including but not limited to those currently requiring IV antibiotics; or
  • Active HIV; or
  • Hepatitis B or Hepatitis C with detectable viral load; or
  • Uncontrolled central nervous system disease, including but not limited to brain metastases, positive CSF disease, seizure disorder, dementia, history of stroke, cerebellar disease, or autoimmune CNS disease.