23 December, 2021

The Hospital Clínic Group develops a second CAR-T, suitable for multiple myeloma resistant to treatment

The Hospital Clínic Group of Barcelona along with the August Pi and Sunyer Biomedical Research Institute (IDIBAPS) have developed a new CAR-T, the ARI-0002h, for patients with multiple myeloma resistant to habitual treatments. The results of a clinical trial, recently presented in the American Society of Hematology (ASH), which was held in Atlanta, have demonstrated that this new CAR-T for multiple myeloma is capable of getting a response rate of up to 75% after a year of treatment and that in 60% of patients that have complete remission and without residual disease, results that are, without doubt, very hopeful.

“These results are comparable in efficacy to the existing commercial CAR-T for multiple myeloma and with less toxicity”, points out Dr. Álvaro Urbano-Ispizua, director of the Hemato-Oncological Disease Clinical Institute. “Now we are preparing all the documentation based on the results in order to request the use as an advanced therapy of non-industrial fabrication from the Spanish Agency of Medicines and Medical Devices (AEMPS)”, concludes Dr. Urbano-Ispizua.

“These results are comparable in efficacy to the existing commercial CAR-T for multiple myeloma and with less toxicity”

Dr. Álvaro Urbano-Ispizua,

director of the Hemato-Oncological Disease Clinical Institute at Hospital Clínic of Barcelona

The study was carried out with the collaboration of the University Clinic of Navarra, which has collaborated with the professionals from the Clínic in order to be able to produce this type of therapy, along with three other Spanish hospitals: University Hospital of Salamanca, Virgen de la Arrixaca Hospital of Murcia and the Virgen del Rocío Hospital of Sevilla. In order to carry out the clinical study, as well as the support from the “laCaixa” Foundation, specific financing was also received from the Carlos III Health Institute and the Bosch Aymerich Foundation.

Dr. Josep Maria Campistol, general manager of the Hospital Clínic, points out that “this is the second CAR-T therapy developed in our hospital, which shows the researcher and innovative vocation of the Clínic, focused on proportioning the best therapeutic alternatives to our patients. The CAR-T ARI-0002h is the result of the effort of the many professionals at the hospital who have participated in the many stages of the development of this treatment, from the CAR-T for multiple myeloma to the carrying out of the trial to demonstrate its efficacy”.

“This is the second CAR-T therapy developed in our hospital, which shows the researcher and innovative vocation of the Clínic, focused on proportioning the best therapeutic alternatives to our patients”

Dr. Josep Maria Campistol, director general del Hospital Clínic de Barcelona

WHAT ARE CAR-T THERAPIES?

CAR-T is a type of cellular and genetic therapy in which the patient becomes their own donor. Via an apheresis, a technique that allows for the separation of the blood components, T lymphocyte is obtained, a type of white globule charged with the immunitary response from the patient themself. Subsequently, in the laboratory, these T lymphocytes are reprogrammed genetically so that, when they are transfused again into the patient, they can recognise specifically the tumoural cells and attack them.

In order to obtain this specificity, a concrete antigen must be selected, meaning a protein which is present in the surface of the majority of the tumoural cells. The T lymphocytes have their own proteins, called receptors, which join with these antigens and help to cause other parts of the immune system to destroy the tumoural cells. The relationship between the antigens and the immune receptors is like a lock and a key so each foreign antigen has a unique immune receptor to join with. This way different types of CAR-T therapies can be developed using one antigone or another as a target, meaning that the immune response is centred solely on the tumoural cells.

In the specific case of ARI-002h, the antigen BCMA has been used, which is found in the surface of the myeloma tumoural cells. So the researchers of the IDIBAPS who have developed it -Dr. Beatriz Martín-Antonio, Dr. Guillermo Suñé and Dr. Lorena Pérez-Amill– experimentally demonstrated in the laboratory that this therapy was very specific and effective against malignant cells of multiple myeloma, something that led the Spanish Agency of Medicines and Medical Devices (AEMPS) to approve the clinical trial which is now giving results.

ABOUT MULTIPLE MYELOMA

Multiple myeloma is a type of blood cancer that affects bone marrow, where plasmatic cells are found -a type of white globule- charged with producing the necessary antibodies to combat infection. In multiple myeloma the plasmatic cells go through an abnormal growth process and form tumours in areas of the bone.

It’s a relatively frequent disease that makes up between 10 and 15% of all hematologic cancers, being the second most common cancer of the blood, behind lymphoma. The most common age for this disease is between 65 and 70, being slightly more frequent in men than women. Afro Americans have the highest risk of getting this disease, while Asians have the lowest.

Despite being considered an, in general, incurable disease, it’s one of the areas where new medicines and treatments have been developed to improve the quality of life of the patients and make the disease chronic. And although different alternatives exist, from chemotherapy to bone marrow transplant, there is still a percentage of people who don’t respond and therefore have a limited life expectancy. This new CAR-T therapy for multiple myeloma can be an alternative for those patients.

Photo: Francisco Avia