2023-07-04 01:03:54
More than 3,000 people in Spain are diagnosed each year with multiple myeloma, a blood cancer that represents the second most frequent of all hematological tumors. In addition, it accounts for 10% of cancers in the bone marrow, which is where the plasma cells (a type of white blood cell) are in charge of producing the antibodies that help fight infections. In multiple myeloma, these cells go through an abnormal growth process and form tumors in the bones.
In total and according to data provided by the Spanish Society of Hematology and Hemotherapy (SEHH), in Spain some 27,000 hematological cancers will be diagnosed in 2023, of which 18,000 will correspond to lymphoid neoplasms, the most frequent of which are multiple myeloma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia.
In recent years, the hope for these tumors and specifically for multiple myeloma lies in CAR-T therapies, that is, a type of immunotherapy that consists of helping our immune system detect and find cancer cells. In other words, it would be our own immune system that is in charge of destroying those “bad cells”.
In this line, the Hospital Clínic Barcelona-IDIBAPS has shown that a type of CAR-T therapy, specifically called CAR-T ARI0002h, can be used to treat patients with multiple myeloma resistant to standard treatments through a multicenter study. The results, which have just been published in the scientific journal The Lancet Oncology, show that all patients treated with this CAR-T respond to treatment, of which about 70% are complete remissions after 18 months and the rest are partial.
The research has been directed by Dr. Carlos Fernández de Larrea, hematologist at the Clínic and head of the IDIBAPS group on myeloma, amyloidosis, macroglobulinemia and other gammopathies, and has at all times had the support of the Carlos III Health Institute and the ‘la Caixa’ Foundation. As well as with the collaboration with other hospitals in Spain: the Clínica Universidad de Navarra, which has collaborated with the Hospital Clínic to be able to produce this type of therapy, the University Hospital of Salamanca, the Virgen de la Arrixaca Hospital in Murcia and the Virgen Hospital del Rocío in Seville.
First CAR-T developed in Europe for multiple myeloma
CAR-T (Chimeric Antigen Receptor T-Cell) therapy represents a promising option in the treatment of resistant multiple myeloma. As explained by the Clínic, it is “a type of cell and gene therapy in which the patient becomes his own donor. It consists of modifying the patient’s T lymphocytes so that they have the capacity to attack tumor cells”.
He CAR-T ARI0002h -they continue explaining- it is directed against the BCMA antigen, which is found on the surface of myeloma tumor cells. Preclinical studies demonstrated that ARI0002h was highly specific and effective against malignant multiple myeloma cells.
This is the second CAR-T developed at the Clínic-IDIBAPS and it makes a difference with respect to previous CAR-Ts, in addition to the therapeutic target, which in this case is the BCMA antigen, is that on this occasion it is humanized.
“Many times mouse antibodies are used for the development of CAR-T and in this case we have humanized it so that it has greater durability in the patient and less probability of rejection”, as explained by Dr. Manel Juan, head of the Clínic Immunology Service, from the IDIBAPS group Immunogenetics and immunotherapy of the autoinflammatory and immune response and responsible for the joint platforms of the Hospital Sant Joan de Déu and Banc de Sang i Teixits.
In general, the survival of patients with multiple myeloma has improved significantly thanks to the incorporation of certain treatments, although there is a significant proportion of patients who relapse and generate resistance to therapies. It is there, in that group of patients with which this new therapy has been worked.
Positive response of patients with multiple myeloma
To evaluate the efficacy of the CAR-T ARI0002h, the Clínic-IDIBAPS began a trial with four other hospitals to treat 30 patients with myeloma who had relapsed after two or three previous treatments. All the centers performed apheresis to obtain the lymphocytes from the patients, and the CAR-T was performed at the Hospital Clínic Barcelona and at the Clínica Universidad de Navarra.
“Thanks to the learning from previous trials with the CAR-T developed in the hospital, we observed that administering the initial dose in a divided manner could reduce the severity of the adverse effects without reducing the efficacy”, explains Dr. Fernández de Larrea. “Thus, the first dose is administered in three aliquots and, 100 days after the first infusion, a booster dose is administered that provides a sustained response over time with low toxicity.”
The results of the study show that, after a follow-up of 18 months, there is a response of all the patients to the treatment and of these, 67% are complete, 27% are very good partial responses and 7% are partial responses. At 3 months, in 24 of the 26 patients with bone marrow samples, no residual disease was identified. On the other hand, no neurological toxicity was seen and immunological adverse effects were mild.
Although the results are promising, patients treated with the ARI0002h continue to relapse, requiring strategies to overcome this obstacle. “We have carried out studies that reveal that there are different mechanisms that could be responsible for relapse after treatment with this CAR-T. And on the other hand, we have detected a permanence of CAR-T cells for 5 months in blood and “Although this time is similar to that of other CAR-T for this disease, it is still short. Thus, our research is aimed at finding out how we can lengthen the persistence of CAR-T,” says Dr. de Larrea.
Now, as they underline and conclude from the hospital, the Spanish Agency for Medicines and Health Products (AEMPS) is evaluating the documentation based on the results of this study for its approval as a non-industrially manufactured advanced therapy drug.
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