Dispersion for infusion for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) after at least two prior therapies

About the medicinal product

Breyanzi, containing the active substance lisocabtagene maraleucel, is used to treat specific types of blood cancer called "diffuse large B-cell lymphoma (DLBCL)" and "primary mediastinal large B-cell lymphoma" (PMBCL) in adults.

DLBCL and PMBCL are malignant cancers of the lymphatic system^[1], which originate from mature degenerated B lymphocytes (white blood cells). DLBCL and PMBCL are aggressive and rapidly growing forms of non-Hodgkin lymphoma (NHL).
DLBCL develops primarily in lymph nodes in the chest or abdomen or in superficial lymph nodes in the neck or armpit. PMBCL develops in the mediastinum, an area in the centre of the chest behind the breastbone.

The medicinal product Breyanzi is an immunotherapy with genetically modified cells. Breyanzi is used to treat recurrent (relapsed) or refractory^[2] DLBCL and PMBCL in patients who have previously received at least two lines of systemic therapy^[3]. Despite these treatments, the cancer DLBCL or PMBCL has recurred or continues to progress.

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

^[1] _{Lymphatic system: The lymphatic system includes all the lymph pathways in the body plus the lymphatic organs, including the lymph nodes, the spleen, the lymphatic tissues in the gastrointestinal tract and throat, and the thymus gland.}

^[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.}

^[3] _{Systemic therapy: In contrast to local therapy (treatment at the site of the disorder), systemic therapy involves treatment of the entire body to eliminate a disorder.}

Mode of action

The active substance lisocabtagene maraleucel is a so-called CD19-directed cellular immunotherapy (CAR T-cell therapy^[4]). The active substance lisocabtagene maraleucel 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. 

^[4] _{CAR T-cell therapy is a specific immunotherapy for cancer in which the patients’ own immune cells are taken 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

Breyanzi, containing the active substance lisocabtagene maraleucel, is a prescription-only medicine.

The medicinal product Breyanzi is a dispersion for infusion with CAR-positive viable T cells. Each vial contains 4.6 ml of cell suspension with either CD8 or CD4 cell components and is injected intravenously.

Treatment with Breyanzi is initiated and monitored by a healthcare professional with experience in the administration of cancer treatments.

Before receiving the treatment with Breyanzi, the patients are pretreated with chemotherapy.

Before using Breyanzi, the doctor will give the patient suitable medicines for minimising possible infusion reactions.

Breyanzi is administered in a treatment centre with immediate access to appropriate intensive care units for the treatment of possible severe reactions.

Efficacy

The efficacy of Breyanzi was investigated in the TRANSCEND study (CSR 017001) in adult subjects with aggressive large cell non-Hodgkin lymphoma (DLBCL and PMBCL).

The pivotal study (authorisation study) showed that the subjects treated with Breyanzi had an overall response rate (ORR)^[5] of 43 %. The median^[6] survival was 14 months.

^[5] _{Overall response rate: Overall response rate (ORR) is defined as the percentage of patients who respond to the treatment.}

^[6] _{Median: the value that lies exactly in the middle of a distribution of data is called the median or central value. Half of the data values are always less than the median, the other half are always greater.}

Precautions, undesirable effects & risks

The medicinal product Breyanzi must not be used in those who are hypersensitive to the active substance or any of the excipients.

The most common adverse effects (affecting more than 1 in 10 or more than 10 %) are a reduced number of a specific group of white blood cells (69 %), anaemia (45 %), cytokine release syndrome (CRS; 41 %)^[7], reduced platelet count (39 %) and fatigue (34 %).

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

^[7] _{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

DLBCL and PMBCL are life-threatening cancers. There is a major medical need for safe and effective treatments for the affected patients.

The pivotal study showed that patients with relapsed or refractory DLBCL and PMBCL profited from the treatment with Breyanzi. The study demonstrated benefit in both the overall response rate and overall survival.

The efficacy of Breyanzi in patients who have previously received at least two lines of systemic therapy is therefore very promising.

Taking all the risks and precautions into account, and based on the available data, the benefits of Breyanzi outweigh the risks.

Swissmedic has therefore authorised the medicinal product Breyanzi, containing the active substance lisocabtagene maraleucel, 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 Public Summary SwissPAR.}

^{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.}