Anthem Blue Cross California Kymriah (tisagenlecleucel) Form

Overview Clinical criteria Overview Coding Document history References This document addresses the use of Kymriah (tisagenlecleucel). Kymriah is a CD19-directed immunotherapy that is used to treat B-cell precursor acute lymphoblastic leukemia (ALL) and large B-cell lymphoma. The FDA approved indications for Kymriah include individuals up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (also called acute lymphocytic leukemia) that is refractory or in second or later relapse, for adults 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, high grade B-cell lymphoma, and DLBCL from follicular lymphoma, and for adults with relapsed or refractory follicular lymphoma after two or more line of systemic therapy. Kymriah 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. Kymriah 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. Kymriah 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, Kymriah 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: • Acute Lymphoblastic Leukemia • B-cell Lymphomas – o Follicular Lymphoma, o Diffuse Large B-Cell Lymphoma, o Histologic Transformation of Indolent Lymphomas to DBLCL, o High Grade Cell Lymphomas, o HIV-Related B-Cell Lymphomas, o Post-Transplant Lymphoproliferative Disorders, Definitions and Measures Allogeneic cells: Harvested from a histocompatible donor. 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. 1 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. Karnofsky Performance Status: A scale and criteria used by doctors and researchers to assess an individual’s prognosis, measure changes in their function and abilities, and determine their ability to tolerate therapies. The lower the score (from 0-100), the worse the likelihood of survival. • • • • • • • • • • • 100 = Normal, no complaints 90 = Able to carry on normal activities 80 = Normal activity with effort 70 = Care for self. Unable to carry on normal activity or to do active work 60 = Requires occasional assistance, but able to care for most of his needs 50 = Requires considerable assistance and frequent medical care 40 = Disabled. Requires special care and assistance 30 = Severely disabled. Hospitalization indicated though death nonimminent 20 = Very sick. Hospitalization necessary. Active supportive treatment necessary 10 = Moribund 0 = Dead Lansky Score: A measure of the individuals overall physical health, judged by their level of activity; the score uses the following scale (generally reserved for individuals less than 16 years of age): • • • • • • • • • • • 100 Fully active, normal 90 Minor restrictions in physically strenuous activity 80 Active, but tires more quickly 70 Both greater restriction of and less time spent in play activity 60 Up and around, but minimal active play; keeps busy with quieter activities 50 Gets dressed but lies around much of the day, no active play but able to participate in all quiet play and activities 40 Mostly in bed; participates in quiet activities 30 In bed; needs assistance even for quiet play 20 Often sleeping; play entirely limited to very passive activities 10 No play; does not get out of bed 0 Unresponsive 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. Tyrosine kinase inhibitor: Type of drug which works by blocking several enzymes that promote cell growth, which has been found to be an effective approach to treat a variety of cancers. Examples include imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), bosutinib (Bosulif), and ponatinib (Iclusig). Clinical Criteria 2 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. Kymriah (tisagenlecleucel) Requests for Kymriah (tisagenlecleucel) for B-cell acute lymphoblastic leukemia may be approved if the following criteria are met: I. II. III. IV. V. VI. VII. VIII. Individual is 25 years of age or younger; AND Individual has diagnosis of B-cell acute lymphoblastic leukemia; AND Individual has confirmed CD19 tumor expression; AND Individual has relapsed or refractory disease defined by any of the following (NCT02228096): A. Second or later bone marrow relapse; OR B. Bone marrow relapse after allogeneic stem cell transplant; OR C. Primary refractory disease defined as failure to achieve complete response after two cycles of standard chemotherapy; OR D. Chemo-refractory after relapse defined as failure to achieve complete response after 1 cycle of standard chemotherapy for relapse leukemia; AND Using for one of the following types of disease: A. If individual has Philadelphia chromosome positive (Ph+) ALL with refractory disease or ≥ 2 relapses following therapy that has included at least two tyrosine kinase inhibitor (TKI) therapies (NCCN 2A, NCT02228096); OR If individual has Philadelphia chromosome negative (Ph -) ALL with refractory disease or ≥ 2 relapses (NCCN 2A); AND B. Individual has a Karnofsky or Lansky performance score of greater than or equal to 50%; 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. Kymriah (tisagenlecleucel) for B-cell acute lymphoblastic leukemia may not be approved for the following (Label, NCT02228096): I. II. III. IV. V. VI. VII. VIII. IX. Repeat administration; OR Using in combination with other chemotherapy agents (not including the use of lymphodepleting chemotherapy as labeled prior to Kymriah infusion); OR If prescribed in combination with other CAR T-cell immunotherapy (e.g. Abecma, Breyanzi, Carvykti, Kymriah, Yescarta); OR Active central nervous system (CNS) 3 leukemia (CNS-3) found in cerebral spinal fluid (CSF), defined as white blood cell (WBC) count greater than or equal to 5 WBC/mcL with presence of lymphoblasts (NCCN); OR Other forms of active CNS-3 leukemia with CSF involvement, such as CNS parenchymal or ocular disease, cranial nerve involvement, or significant leptomeningeal disease; OR Any acute or ongoing neurologic toxicity greater than Grade 1 as defined by the National Cancer Institute (NCI CTCAE v.5), not including history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past three months; OR Diagnosis of Burkitt’s lymphoma/leukemia; OR Active or latent hepatitis B, active hepatitis C, human immunodeficiency virus (HIV) positive, or other active, uncontrolled infection; OR Active neurological autoimmune or inflammatory disorders (for example, Guillain Barre Syndrome, Amyotrophic Lateral Sclerosis) (Label, NCT02445248); OR Individual has active GVHD; OR X. XI. When the above criteria are not met, and for all other indications. Requests for Kymriah (tisagenlecleucel) for large B-cell lymphoma may be approved if the following criteria are met: I. II. III. IV. 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. High-grade B-cell lymphoma; OR C. DLBCL from follicular lymphoma; OR D. Monomorphic Post-transplant lymphoproliferative (B-cell type) disorders (NCCN 2A); OR E. HIV-Related B-cell Lymphomas (NCCN 2A); OR F. Histologic Transformation of Indolent Lymphomas to DLBCL (NCCN 2A); AND Relapsed or refractory disease, defined as progression after two or more lines of systemic therapy (which may or may not include therapy supported by autologous stem cell transplant), including all of the following: A. An anthracycline-containing chemotherapy regimen; AND B. Rituximab; AND Individual has adequate bone marrow reserve without transfusion defined by all of the following: A. Absolute neutrophil count (ANC) ≥ 1000 cells/uL; AND B. Absolute lymphocyte count (ALC) > 300 cells/uL; AND 3 C. Platelet count ≥ 50,000 cells/uL; AND D. Hemoglobin > 8.0 g/dl; 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 has a current ECOG performance status of 0-1; AND Individual is using as a one-time, single administration treatment. V. VI. VII. VIII. Kymriah (tisagenlecleucel) for large B-cell lymphoma may not be approved for the following (Label, NCT02445248): I. II. III. IV. V. VI. VII. VIII. IX. 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 as labeled prior to Kymriah infusion); OR Diagnosis of Burkitt’s lymphoma/leukemia (NCT02228096); OR If prescribed in combination with other CAR T-cell immunotherapy (e.g. Abecma, Breyanzi, Carvykti, Tecartus, Yescarta); OR Individual has active GVHD; OR Active or latent hepatitis B, active hepatitis C, human immunodeficiency virus (HIV) positive, or other active, uncontrolled infection; OR Active neurological autoimmune or inflammatory disorders (for example, Guillain Barre Syndrome, Amyotrophic Lateral Sclerosis); OR X. When the above criteria are not met, and for all other indications. Requests for Kymriah (tisagenlecleucel) for Follicular Lymphoma may be approved if the following criteria are met (NCT03568461): I. II. III. IV. V. VI. Individual is 18 years of age or older; AND Individual has received ≥ 2 prior lines of systemic therapy or autologous hematopoietic stem cell transplant (HSCT); AND Individual has an ECOG performance status of 0-1; AND 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. Kymriah (tisagenlecleucel) for Follicular Lymphoma may not be approved for the following criteria (NCT03568461): Repeat administration; Evidence of histologic transformation; OR Individual has a diagnosis of follicular lymphoma, grade 3B; OR I. AND II. III. IV. V. VI. VII. Individual has active CNS involvement by malignancy; OR Active neurological autoimmune or inflammatory disorders (for example, Guillan – Barre syndrome, amyotrophic lateral sclerosis); OR Using in combination with other chemotherapy agents (not including the use of lymphodepleting chemotherapy prior to infusion); OR If prescribed in combination with other CAR T-cell immunotherapy (e.g. Abecma, Breyanzi, Carvykti, Kymriah, Tecartus); OR Individual has active GVHD; OR VIII. IX. X. 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. CPT 0537T 0538T 0539T 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 [for Kymriah] Chimeric antigen receptor T-cell (CAR-T) therapy; preparation of blood-derived T lymphocytes for transportation (eg, cryopreservation, storage) [for Kymriah] Chimeric antigen receptor T-cell (CAR-T) therapy; receipt and preparation of CAR-T cells for administration [for Kymriah] 4 Chimeric antigen receptor T-cell (CAR-T) therapy; CAR-T cell administration, autologous [for Kymriah] Tisagenlecleucel, up to 600 million CAR-positive viable T cells, including leukapheresis and dose preparation procedures, per therapeutic dose [Kymriah] Introduction of engineered autologous chimeric antigen receptor T-cell immunotherapy into peripheral vein, percutaneous approach, new technology group 3 [when specified as Kymriah] Introduction of engineered autologous chimeric antigen receptor T-cell immunotherapy into central vein, percutaneous approach, new technology group 3 [when specified as Kymriah] Follicular lymphoma grade I Follicular lymphoma grade II Follicular lymphoma grade IIIa 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 Acute lymphoblastic leukemia not having achieved remission Acute lymphoblastic leukemia, in relapse Encounter for antineoplastic immunotherapy 0540T HCPCS Q2042 ICD-10 Procedure XW033C3 XW043C3 ICD-10 Diagnosis C82.00-C82.09 C82.10-C82.19 C82.30–C82.39 C83.30 C83.31 C83.32 C83.33 C83.34 C83.35 C83.36 C83.37 C83.38 C83.39 C91.00 C91.02 Z51.12 Document History Revised: 11/19/2023