How it is administered

Lisocabtagene maraleucel is administered as a single intravenous (IV) infusion. The medication is a genetically modified autologous T cell immunotherapy, meaning it is made from your own T cells, which are collected, modified, and then returned to your body. The dose is based on the number of CAR-positive viable T cells and is supplied as separate vials for CD8 and CD4 T cell components. Before receiving the infusion, patients undergo a lymphodepleting chemotherapy regimen (usually fludarabine and cyclophosphamide) to prepare the body for the CAR-T cells. The product is shipped frozen and thawed just before administration.

Administration is performed in a healthcare setting with close monitoring, especially for the first 7 days after infusion. Patients are advised to stay near the treatment center for at least 2 weeks after receiving the infusion.

How it works

Lisocabtagene maraleucel is a type of CAR-T cell therapy. It works by taking your own T cells (a type of immune cell), genetically modifying them in a laboratory to express a chimeric antigen receptor (CAR) that targets CD19, a protein found on the surface of most B cells, including those in large B-cell lymphoma (LBCL).

Once these modified T cells are infused back into your body, they recognize and bind to CD19 on the cancerous B cells. This binding activates the T cells, causing them to multiply, release inflammatory molecules (cytokines), and directly kill the cancer cells. The therapy is designed to provide a targeted, potent immune response against the lymphoma cells, while minimizing damage to other tissues. The CAR-T cells can persist in the body for months, continuing to seek out and destroy cancerous B cells.

Who Should take it

Lisocabtagene maraleucel is indicated for adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. It is used in patients who:

• Have disease that is refractory to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
• Are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age, and have relapsed or refractory disease after first-line chemoimmunotherapy.
• Have relapsed or refractory disease after two or more lines of systemic therapy.

This therapy is also approved for certain other blood cancers, but its main use in this context is for LBCL when other treatments have not worked or are not suitable.

Who should not take it

There are no absolute contraindications listed for lisocabtagene maraleucel. However, it should not be used in patients with active, uncontrolled infections or in those with unresolved serious adverse events from previous therapies. It is not indicated for patients with primary central nervous system lymphoma.

Caution should be exercised in patients with significant organ dysfunction, active graft-versus-host disease, or those who are pregnant, as the effects on pregnancy and the fetus are unknown. Patients with active hepatitis B, C, or HIV infections should be evaluated and managed according to clinical guidelines before starting therapy.

Commonly used with

Before receiving lisocabtagene maraleucel, patients are typically given a lymphodepleting chemotherapy regimen with fludarabine and cyclophosphamide to prepare the body for CAR-T cell infusion. Acetaminophen and an antihistamine (such as diphenhydramine) are given as premedication to reduce the risk of infusion reactions.

Tocilizumab (an anti-IL-6 receptor antibody) and corticosteroids may be used to manage side effects such as cytokine release syndrome or neurologic toxicities if they occur after the infusion.

Commonly tested with

Lisocabtagene maraleucel is often studied in combination with standard lymphodepleting chemotherapy agents (fludarabine and cyclophosphamide) as part of the treatment protocol. In clinical trials, supportive medications like tocilizumab and corticosteroids are used for management of side effects.

It is not typically combined with other anti-cancer therapies at the time of infusion, but may be given after other treatments have failed or as part of a sequence of therapies in relapsed or refractory LBCL.