Cell dispersion for infusion in adults for the gene therapy of relapsed or refractory mantle cell lymphoma (third-line treatment)

About the medicinal product

Tecartus contains the active substance brexucabtagene autoleucel and is a genetically modified autologous^[1] T-cell immunotherapy directed against CD19 for adult patients with mantle cell lymphoma (MCL) who have not responded to 2 or more treatments, including those with a Bruton tyrosine kinase (BTK) inhibitor.

Mantle cell lymphoma is a rare, usually aggressive, form of non-Hodgkin's lymphoma, a cancer of the lymphatic system. It predominantly affects men and is usually diagnosed in the elderly. This type of cancer develops from certain immune cells, the B cells, which occur in the lymph nodes. A genetic defect that is present in most MCL patients results in the increased formation of a protein named cyclin D1, causing the cells to grow and multiply uncontrollably.

The disease is often detected only at a late stage, when the cancer cells have already spread to many lymph nodes, and frequently to other organs as well, including the spleen, bone marrow, or gastrointestinal tract. Consequently, the prognosis is often poor.

The treatment of MCL usually starts with a combination of chemotherapy and an antibody that attacks the cancer cells. These treatments often show good results initially, but relapses are common. For these cases, stronger chemotherapies and a BTK inhibitor that blocks certain mechanisms of the cancer cells are available.

Tecartus is used as third-line treatment for recurrent (relapsed) or refractory^[2] MCL.

Since MCL is a rare and life-threatening disease, the medicine has been authorised as an orphan drug. The term "orphan drug" is used to refer to important medicines for rare diseases.

^[1] _{Autologous: belonging to the same person, i.e. here the patient's own T cells}

^[2] _{In the context of cancer, refractory means that the cancer does not respond to the treatment and fails to regress, or even progresses, despite the treatment.}

Mode of action

The active substance brexucabtagene autoleucel is a so-called CD19-directed cellular immunotherapy (CAR T-cell therapy^[3]). The active substance brexucabtagene autoleucel binds to the CD19 antigen on the surface of tumour cells. This binding triggers downstream signals, thereby activating the CAR T cells and causing them to multiply.

As a result of this mechanism of action, the body's immune system is able to fight and kill the lymphoma cells that cause the cancer. 

^[3] _{CAR T-cell therapy is a specific immunotherapy for cancer in which the patients’ own immune cells are collected and modified using gene technology so that they recognise cancer cells and specifically destroy them. The modified CAR T cells are administered to the patient via an infusion.} 

Administration

Tecartus is a prescription-only medicine.

Tecartus is a patient-specific anti-CD19-CAR T-cell dispersion for infusion into a vein.

It is administered in the following steps. First, the patient's T lymphocytes (a subgroup of white blood cells) are collected. These cells are then used to produce the CAR T cells individually for each patient. Before Tecartus is administered, the number of lymphocytes in the blood and bone marrow must be reduced by chemotherapy. The CAR T-cell infusion is then administered directly afterwards.

Tecartus is administered in a treatment centre with immediate access to appropriate intensive care units for the treatment of possible severe reactions. The patients should visit the hospital daily for at least 10 days after the Tecartus treatment or remain in hospital as inpatients, and then stay within reach of the treating hospital for at least 4 weeks.

Efficacy

The efficacy of Tecartus was investigated in the ZUMA-2 study with 74 MCL patients. Although the patients had already been pretreated with chemotherapy, antibodies, and BTK inhibitors, their cancer returned. The response rate to the treatment with Tecartus in the ZUMA-2 study was much higher than would be expected on the basis of historical controls (similar MCL patients who had been given a different treatment). While the times for progression-free survival (PFS) and overall survival (OS) have not yet been fully evaluated at the time of authorisation, the data so far indicate that many MCL patients live longer.

Precautions, undesirable effects & risks

Tecartus must not be used in those who are hypersensitive to the active substance or any of the excipients.

The most frequent adverse effects are infections (28 %), encephalopathy (disease of the brain) (26 %), and cytokine release syndrome^[4] (15 %).

All precautions, risks, and other possible undesirable effects are listed in the Information for patients (package leaflet) and the Information for healthcare professionals.

^[4] _{CRS: Cytokine release syndrome is a systemic inflammatory response to the massive secretion of cytokines (proteins), which activate the white blood cells.}

Why the medicinal product has been authorised

Mantle cell lymphoma is a life-threatening disease. There is a high medical need for treatments for patients whose cancer recurs or progresses despite various therapeutic approaches.

For the authorised indication, i.e. for patients who meet the criteria of the ZUMA-2 study, the benefit-risk ratio of Tecartus treatment is positive, particularly since these patients have very few alternative treatment options.

The ZUMA-2 study will be continued by the authorisation holder so that the long-term effects can be better assessed. It should be noted that not all patients benefit from Tecartus therapy in the long term, and its effect may be less durable in some. Tecartus patients must be entered in a registry that monitors the long-term safety and efficacy of this CAR T-cell therapy.

Taking all the risks and precautions into account, and based on the available data, the benefits of Tecartus outweigh the risks. Swissmedic has therefore authorised the medicinal product Tecartus, containing the active substance brexucabtagene autoleucel, for use in Switzerland.

Further information on the medicinal product

Information for healthcare professionals:

Information for patients (package leaflet):

Healthcare professionals can answer any further questions.

^{The date of revision of this text corresponds to that of the SwissPAR. New information concerning the authorised medicinal product in question will not be incorporated into the Summary report on authorisation.}

^{Swissmedic monitors medicinal products authorised in Switzerland. Swissmedic initiates the necessary action in the event of newly discovered adverse drug reactions or other safety-relevant signals. New findings that could impair the quality, efficacy, or safety of this medicinal product are recorded and published by Swissmedic. If necessary, the medicinal product information is adapted.}