Axicabtagene ciloleucel, sold under the brand name Yescarta, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used for the treatment for large B-cell lymphoma that has failed conventional treatment.

T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...

are removed from a person with lymphoma and genetically engineered to produce a specific

T-cell receptor The T-cell receptor (TCR) is a protein complex, located on the surface of T cells (also called T lymphocytes). They are responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. ...

. The resulting chimeric antigen receptor T cells (CAR-Ts) that react to the cancer are then given back to the person to populate the bone marrow. Axicabtagene treatment carries a risk for cytokine release syndrome (CRS) and neurological toxicities. Due to

CD19 B-lymphocyte antigen CD19, also known as CD19 molecule ( Cluster of Differentiation 19), B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene ''CD19''. In human ...

being a pan-B cell marker, the T-cells that are engineered to target

receptors on the cancerous

B cells B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

also influence normal

, except some

plasma cells Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances c ...

Adverse effects

Because treatment with axicabtagene carries a risk of cytokine release syndrome and neurological toxicities, the Food and Drug Administration (FDA) has mandated that hospitals be certified for its use prior to treatment of any patients. In April 2024, the FDA label

boxed warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears near the beginning of the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administratio ...

was expanded to include T cell malignancies.

History

It was developed by California-based Kite Pharma. Axicabtagene ciloleucel was awarded U.S. FDA

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

designation in October 2017, for

diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 ...

, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma. It also received

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and orphan drug designation. Based on the ZUMA-1 trial, Kite submitted a

biologics license application A biologics license application (BLA) is defined by the U.S. Food and Drug Administration (FDA) as follows: The biologics license application is a request for permission to introduce, or deliver for introduction, a biologic product into inters ...

for axicabtagene in March 2017, for the treatment of

non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredn ...

. The FDA granted approval in October 2017, for the

second-line treatment A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx. As a rule, each therapy has indications an ...

of diffuse large B-cell lymphoma. In April 2022, the FDA approved axicabtagene ciloleucel for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within twelve months of first-line chemoimmunotherapy. It is not indicated for the treatment of patients with primary central nervous system lymphoma. Approval was based on ZUMA-7, a randomized, open-label, multicenter trial in adults with primary refractory LBCL or relapse within twelve months following completion of first-line therapy. Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT). A total of 359 participants were randomized 1:1 to receive a single infusion of axicabtagene ciloleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or to receive second-line standard therapy, consisting of two or three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in participants who attained complete remission or partial remission. In the ZUMA-7 trial, patients treated with axicabtagene ciloleucel had superior clinical outcomes compared with the previous standard of care, including improved overall survival with an estimated 4-year overall survival rate of 54.6% for axicabtagene ciloleucel, compared with 46% for the previous standard of care. In January 2023, the National Institute for Health and Care Excellence (NICE) recommended axicabtagene ciloleucel to treat adult patients with diffuse large B-cell lymphoma (DLBCL) or primary mediastinal large B-cell lymphoma (PMBCL) who have already been treated with two or more systemic therapies.

Society and culture

Names

Axicabtagene ciloleucel is the international nonproprietary name.

References

External links

* * {{DEFAULTSORT:Axicabtagene Ciloleucel Cancer treatments Approved gene therapies CAR T-cell therapy Gilead Sciences Orphan drugs Antineoplastic drugs