Breyanzi (lisocabtagene maraleucel) Form

Overview Clinical criteria Overview Coding Document history References This document addresses the use of Breyanzi (lisocabtagene maraleucel), a CD19-directed immunotherapy, for treatment of relapsed or refractory large B-cell lymphomas.
The FDA approved indications for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B who have:
• • • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
relapsed or refractory disease after two or more lines of systemic therapy Breyanzi is the third CAR-T therapy indicated for large B-cell lymphoma, following Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel).
Breyanzi (lisocabtagene maraleucel, also called liso-cel) 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. Of note, Breyanzi’s TRANSCEND study originally allowed individuals with an ECOG score of 2 to be enrolled, but the protocol was amended in 2017 (2 years after study initiation) to restrict to only ECOG of 0 to 1 for unknown reasons. A total of 4 patients (1% of study population) had ECOG of 2. Breyanzi 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. Breyanzi 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, Breyanzi is only available through a Risk Evaluation and Mitigation Strategy (REMS) program. The National Comprehensive Cancer Network® (NCCN) provides additional recommendations with a category 2A level of evidence for the following uses: • Primary Mediastinal Large B-Cell Lymphoma • Diffuse Large B-Cell Lymphoma • Histologic Transformation of Indolent Lymphomas to Diffuse Large B-Cell Lymphoma • High-Grade B-Cell Lymphomas • HIV-Related B-Cell Lymphomas • Post-Transplant Lymphoproliferative Disorders Definitions and Measures Allogeneic cells: Harvested from a histocompatible donor. 1

Autologous cells: Harvested from the individual's own cells. Bone marrow: A spongy tissue located within flat bones, including the hip and breast bones and the skull. This tissue contains stem cells, the precursors of platelets, red blood cells, and white cells. Chemotherapy: The medical treatment of a disease, particularly cancer, with drugs or other chemicals. Chimerism: Cell populations derived from different individuals; may be mixed or complete. Complete Response (CR): The disappearance of all signs of cancer as a result of treatment; also called complete remission; does not indicate the cancer has been cured. Cytotoxic: Treatment that is destructive to cells, preventing their reproduction or growth. ECOG or Eastern Cooperative Oncology Group Performance Status: A scale and criteria used by doctors and researchers to assess how an individual’s disease is progressing, assess how the disease affects the daily living abilities of the individual, and determine appropriate treatment and prognosis. This scale may also be referred to as the WHO (World Health Organization) or Zubrod score which is based on the following scale: • • • • • • 0 = Fully active, able to carry on all pre-disease performance without restriction 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 5 = Dead Hematopoietic stem cells: Primitive cells capable of replication and formation into mature blood cells in order to repopulate the bone marrow. Line of Therapy: • First-line therapy: The first or primary treatment for the diagnosis, which may include surgery, chemotherapy, radiation therapy or a combination of these therapies. • Second-line therapy: Treatment given when initial treatment (first-line therapy) is not effective or there is disease progression. • Third-line therapy: Treatment given when both initial (first-line therapy) and subsequent treatment (second-line therapy) are not effective or there is disease progression. Refractory Disease: Illness or disease that does not respond to treatment. Relapse or recurrence: After a period of improvement, during which time a disease (for example, cancer) could not be detected, the return of signs and symptoms of illness or disease. For cancer, it may come back to the same place as the original (primary) tumor or to another place in the body. Clinical Criteria When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose. Breyanzi (lisocabtagene maraleucel) Requests for Breyanzi (lisocabtagene maraleucel) for large B-cell lymphoma may be approved if the following criteria are met: I. II. Individual is 18 years of age or older; AND Individual has a histologically confirmed diagnosis of one of the following: A. Diffuse large B-cell lymphoma (DLBCL), not otherwise specified; OR B. Transformed DLBCL from indolent histology; OR
C. High-grade B-cell lymphoma; OR D. Primary mediastinal large B-cell lymphoma; OR E. Follicular lymphoma Grade 3B; OR F. HIV Related B-Cell Lymphomas (NCCN 2A); OR G. Monomorphic Post-Transplant Lymphoproliferative (B-cell type) Disorders (PTLD) (NCCN 2A); AND 2

III. Is using in one of the following ways:
A. Relapsed or refractory disease, defined as progression after two or more lines of systemic therapy (which may or
may not include therapy supported by haematopoietic stem cell transplant), including all of the following:

1. Anti-CD20 monoclonal antibody, such as rituximab; AND
2. An anthracycline-containing chemotherapy regimen; AND Individual has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
   B. OR C. Refractory disease to first-line chemotherapy or relapse within 12 months of first-line chemotherapy including all of the following:
   
   1. Anti-CD20 monoclonal antibody, such as rituximab; AND
3. An anthracycline-containing chemotherapy regimen; AND D. Individual has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
   OR E. Refractory disease to first-line chemotherapy or relapse after first-line chemotherapy including all of the following:
   1. Anti-CD20 monoclonal antibody, such as rituximab; AND

4. An anthracycline-containing chemotherapy regimen; AND F. Are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; AND Individual has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
   G. AND IV. V. VI. VII. Individual has adequate bone marrow reserve; AND If individual has a history of an allogeneic stem cell transplant, there are no current signs of active graft versus host disease (GVHD); AND Individual has not received prior treatment with CAR T-cell therapy or other genetically modified T-cell therapy; AND Individual is using as a one-time, single administration treatment. Breyanzi (lisocabtagene maraleucel) may not be approved for the following: I. II. III. IV. V. VI. VII. VIII. Repeat administration; OR Diagnosis of primary central nervous system lymphoma; OR Cardiac ejection fraction (EF) less than 40%, or other clinically significant cardiac disease; OR Using in combination with other chemotherapy agents (not including the use of lymphodepleting chemotherapy prior to infusion); OR
   History or presence of CNS disorders such as epilepsy/seizure disorder, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or pyschosis; OR If prescribed in combination with other CAR T-cell immunotherapy (e.g. Abecma, Carvykti, Kymriah, Tecartus, Yescarta); OR Individual has active GVHD; OR Active or latent hepatitis B, active hepatitis C, or other active, uncontrolled infection; OR IX. When the above criteria are not met, and for all other indications. Coding The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. HCPCS
   Q2054 ICD-10 Diagnosis C82.40 C82.41 C82.42 C82.43 C82.44 Lisocabtagene maraleucel, up to 110 million autologous anti-cd19 car-positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose [Breyanzi] All diagnosis pend (applies to NOC codes only) Follicular lymphoma grade IIIb Follicular lymphoma grade IIIb, lymph nodes of head, face, and neck Follicular lymphoma grade IIIb, intrathoracic lymph nodes Follicular lymphoma grade IIIb, intra-abdominal lymph nodes Follicular lymphoma grade IIIb, lymph nodes of axilla and upper limb 3

   C82.45 C82.46 C82.47 C82.48 C82.49 C83.30 C83.31 C83.32 C83.33 C83.34 C83.35 C83.36 C83.37 C83.38 C83.39 C83.90 C83.91 C83.92 C83.93 C83.94 C83.95 C83.96 C83.97 C83.98 C83.99 C85.10 C85.11 C85.12 C85.13 C85.14 C85.15 C85.16 C85.17 C85.18 C85.19 C85.20 C85.21 C85.22 C85.23 C85.24 C85.25 C85.26 C85.27 C85.28 Follicular lymphoma grade IIIb, lymph nodes of inguinal region and lower limb Follicular lymphoma grade IIIb, intrapelvic lymph nodes Follicular lymphoma grade IIIb, spleen Follicular lymphoma grade IIIb, lymph nodes of multiple sites Follicular lymphoma grade IIIb, extranodal and solid organ sites Diffuse large B-cell lymphoma, unspecified site Diffuse large B-cell lymphoma, lymph nodes of head, face, and neck Diffuse large B-cell lymphoma, intrathoracic lymph nodes Diffuse large B-cell lymphoma, intra-abdominal lymph nodes Diffuse large B-cell lymphoma, lymph nodes of axilla and upper limb Diffuse large B-cell lymphoma, lymph nodes of inguinal region and lower limb Diffuse large B-cell lymphoma, intrapelvic lymph nodes Diffuse large B-cell lymphoma, spleen Diffuse large B-cell lymphoma, lymph nodes of multiple sites Diffuse large B-cell lymphoma, extranodal and solid organ sites Non-follicular (diffuse) lymphoma, unspecified Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of head, face, and neck Non-follicular (diffuse) lymphoma, unspecified, intrathoracic lymph nodes Non-follicular (diffuse) lymphoma, unspecified, intra-abdominal lymph nodes Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of axilla and upper limb Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of inguinal region and lower limb Non-follicular (diffuse) lymphoma, unspecified, intrapelvic lymph nodes Non-follicular (diffuse) lymphoma, unspecified, spleen Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of multiple sites Non-follicular (diffuse) lymphoma, unspecified, extranodal and solid organ sites Unspecified B-cell lymphoma, unspecified site Unspecified B-cell lymphoma, lymph nodes of head, face, and neck Unspecified B-cell lymphoma, intrathoracic lymph nodes Unspecified B-cell lymphoma, intra-abdominal lymph nodes Unspecified B-cell lymphoma, lymph nodes of axilla and upper limb Unspecified B-cell lymphoma, lymph nodes of inguinal region and lower limb Unspecified B-cell lymphoma, intrapelvic lymph nodes Unspecified B-cell lymphoma, spleen Unspecified B-cell lymphoma, lymph nodes of multiple sites Unspecified B-cell lymphoma, extranodal and solid organ sites Mediastinal (thymic) large B-cell lymphoma, unspecified site Mediastinal (thymic) large B-cell lymphoma, lymph nodes of head, face, and neck Mediastinal (thymic) large B-cell lymphoma, intrathoracic lymph nodes Mediastinal (thymic) large B-cell lymphoma, intra-abdominal lymph nodes Mediastinal (thymic) large B-cell lymphoma, lymph nodes of axilla and upper limb Mediastinal (thymic) large B-cell lymphoma, lymph nodes of inguinal region and lower limb Mediastinal (thymic) large B-cell lymphoma, intrapelvic lymph nodes Mediastinal (thymic) large B-cell lymphoma, spleen Mediastinal (thymic) large B-cell lymphoma, lymph nodes of multiple sites 4

   C85.29 C85.80 C85.81 C85.82 C85.83 C85.84 C85.85 C85.86 C85.87 C85.88 C85.89 Z51.12 Mediastinal (thymic) large B-cell lymphoma, extranodal and solid organ sites Other specified types of non-Hodgkin lymphoma, unspecified site Other specified types of non-Hodgkin lymphoma, lymph nodes of head, face, and neck Other specified types of non-Hodgkin lymphoma, intrathoracic lymph nodes Other specified types of non-Hodgkin lymphoma, intra-abdominal lymph nodes Other specified types of non-Hodgkin lymphoma, lymph nodes of axilla and upper limb Other specified types of non-Hodgkin lymphoma, lymph nodes of inguinal region and lower limb Other specified types of non-Hodgkin lymphoma, intrapelvic lymph nodes Other specified types of non-Hodgkin lymphoma, spleen Other specified types of non-Hodgkin lymphoma, lymph nodes of multiple sites Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites Encounter for antineoplastic immunotherapy Document History Revised: 11/19/2023