Chimeric Antigen Receptor (CAR) T-cell immunotherapy is a cell-based gene therapy in which immune cells are removed from a patient, armed with new proteins that allow them to recognize cancer, and then reinfused into the patient in large numbers. These cells persist in the body, becoming “living drugs.”
Changes have been made to resolve the conflict for the intravenous administration of CAR T-cell therapies, which had been classified to two different tables. The two codes in Table XW0, Anatomical Regions, Introduction, were not product-specific, with Substance value C, Engineered Autologous Chimeric Antigen Receptor T-cell Immunotherapy. Yescarta® (axicabtagene ciloleucel) and KYMRIAH® (tisagenlecleucel) were previously reported with the non-product-specific codes. On the other hand, the two codes in Table XW2, Anatomical Regions, Transfusion, were product specific with Substance value 4 Brexucabtagene Autoleucel Immunotherapy, and 7, Lisocabtagene Maraleucel Immunotherapy. For more information on Brexucabtagene Autoleucel Immunotherapy, and Lisocabtagene Maraleucel Immunotherapy, please refer to Coding Clinic, Fourth Quarter 2020, pages 77-78.
As noted in Coding Clinic, Fourth Quarter 2020, page 77, the root operation Transfusion was originally utilized based on the root operation definitions and receipt of public comments. CAR T-cell therapy is comprised of blood/blood product, and therefore, the root operation Transfusion was originally determined to be more clinically accurate. The full definition for the root operation Introduction is “Putting in or on a therapeutic, diagnostic, nutritional, physiological, or prophylactic substance except blood or blood products.”
Based on a proposal discussed at the September 2020 ICD-10 Coordination and Maintenance (C&M) Committee meeting and additional public comments, changes have been made so that all CAR T-cell immunotherapies are classified to a single root operation in code Table XW0, Anatomical Regions, Introduction, for consistency in the classification of CAR T-cell immunotherapy. During the comment period, many felt that CAR T-cell and other cell-derived immunotherapies were not a blood or blood product as traditionally understood; and, therefore the root operation Transfusion was not ideal. As a result, the codes for CAR T-cell products in Table XW2, Anatomical Regions, Transfusion, were deleted and replaced with new codes in Table XW0, Anatomical Regions, Introduction. Please note that all of the new CAR T-cell immunotherapy codes below have a qualifier of 7, New Technology Group 7.
New non-product-specific codes have been created to distinguish autologous from allogeneic engineered CAR T-cell immunotherapy. The non-product-specific codes for Engineered Autologous Chimeric Antigen Receptor T-cell Immunotherapy with a qualifier of 3, New Technology Group 3 have been deleted. Substance Value C, Engineered Autologous Chimeric Antigen Receptor T-cell Immunotherapy, was revised and a new Substance Value G was created as shown below. The new codes may be used to identify the infusion of new engineered autologous or allogeneic CAR-T cell immunotherapy products that do not have unique codes. Please note the new non-product-specific CAR T-cell immunotherapy codes have a qualifier of 7, New Technology Group 7.
C Engineered Chimeric Antigen Receptor T-cell Immunotherapy, Autologous
G Engineered Chimeric Antigen Receptor T-cell Immunotherapy, Allogeneic
Engineered autologous CAR T-cell immunotherapy involves use of the patient’s own blood, separating out the T-cells and genetically engineering them to produce receptors on their surface called chimeric antigen receptors, or CARs. These special receptors allow the T-cells to recognize and attach to a specific protein, or antigen, on tumor cells. The engineered CAR T-cells reinfused into the patient further multiply in the patient’s body and kill cancer cells that harbor the antigen on their surfaces.
Engineered allogeneic CAR T-cell immunotherapy is derived from healthy donors; is engineered in advance; and stored in large numbers. Once infused into the patient, similar to autologous CAR T-cell immunotherapies, the allogeneic CAR T-cells will target and kill the diseased cells. They are also referred to as “off the shelf” since they are more rapidly available when compared to autologous CAR T-cell immunotherapies that have to be generated individually from a patient’s own cells. Complications such as graft-versus-host disease and rejection of the allogeneic cells are more likely to occur with allogeneic CAR T-cells. However, gene editing and other strategies are being developed to reduce or eliminate these limitations.
New product-specific Substance values have been created for existing products as noted below:
H Axicabtagene Ciloleucel Immunotherapy
J Tisagenlecleucel Immunotherapy
M Brexucabtagene Autoleucel Immunotherapy
N Lisocabtagene Maraleucel Immunotherapy
In addition, new product-specific Substance values were created for new CAR T-cell immunotherapy products as noted below.
A Ciltacabtagene Autoleucel
K Idecabtagene Vicleucel Immunotherapy
Ciltacabtagene autoleucel (cilta-cel) is an autologous CAR T-cell therapy directed against B-cell maturation antigen (BCMA) for the treatment of patients with relapsed or refractory multiple myeloma. Cilta-cel is designed to recognize myeloma cells and destroy them. Its CAR T-cell technology consists of harvesting the patient’s own T-cells, programming them to express a chimeric antigen receptor that identifies BCMA, and reinfusing these modified cells back into the patient. The modified T-cells bind to the myeloma cells displaying the BCMA antigen. The T-cells become activated and proliferate resulting in the release of pro-inflammatory cells to kill malignant myeloma cells.
Idecabtagene vicleucel (ide-cel), is a B-cell maturation antigen-directed genetically modified autologous CAR T-cell therapy for the treatment of adult patients with relapsed or refractory multiple myeloma. Ide-cel is administered as a single IV infusion through the central or peripheral vein, primarily in the hospital inpatient setting as a standalone procedure.