SUS studies adoption of promising cancer treatment

The treatment of some types of cancer, developed by the Butantan Institute, University of São Paulo (USP) and Blood Center of Ribeirão Preto, has shown good results and its use in the Unified Health System (SUS) has been studied. Called CAR-T Cell therapy, the procedure is already adopted in the United States and other countries to treat lymphomas and advanced leukemias, as a last resort.

In this form of treatment, the patient’s T cells (a type of immune system cell) are altered in the laboratory to recognize and attack cancer or tumor cells. The term CAR refers to a chimeric antigen receptor (chimeric antigen receptorin English).

“OT comes from T lymphocytes, which are blood cells responsible for fighting infections and some types of cancer”, explains professor of hematology, hemotherapy and cell therapy at the Faculty of Medicine of the University of São Paulo (USP) Vanderson Rocha, also national coordinator of cell therapy for the D’Or network.

Cancer is very ‘smart’, says Rocha. “The T cells ‘escape’ a little from the recognition of the cancer cells. In the treatment, we remove these cells from the patient, through the blood, and put them in the laboratory, to be genetically modified, to ‘arm’ them against the cancer cells.”

In the treatment program, one of the patients had non-Hodgkin’s lymphoma. “About a month after these cells are produced, we can infuse them into the blood. So, the cells will direct themselves against the tumor cells, because they are able to do that, to be able to fight the tumors, in the case of this patient, the lymphoma. He had a complete remission a month after the injection of these cells”, adds the specialist.

As cell therapy is still in an experimental phase in Brazil, patients have so far been treated compassionately, that is, by medical decision, when the cancer is in an advanced stage and there are no alternative therapies.

Patients began treatment at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, in the interior of São Paulo, in 2019. In the United States, the FDA (the country’s health regulatory agency) released it for use by the pharmaceutical industry in 2017.

In Brazil, the use of the pharmaceutical industry began in January of this year. For those who can afford the treatment, the cost is around BRL 2 million. The Brazilian challenge is to make the therapy accessible on a large scale through public health, but there is still a way to go for it to be available for free.

“The cells are removed, sent to the United States and returned to the patients. In the specific case of the study group, all this production was done in Brazil, through research and science, by FAPESP [Fundação de Amparo à Pesquisa do Estado de São Paulo]by CNPq [Conselho Nacional de Desenvolvimento Científico e Tecnológico], by Instituto Butantã, by Fundação Hemocentro, Faculdade de Medicina at USP, in the capital and in Ribeirão Preto. It was a whole team of scientists who allowed the manufacture of these cells”, emphasizes Rocha.

The first case of disease remission using this technique in the country occurred in 2019, but the patient died of another cause two months after treatment. “The patient obtained a partial remission, but it may be that, at that moment, he still had time to respond [totalmente ao tratamento]”, details the doctor.

In 2019, the report by Agência Brasil told the story of retiree Vamberto Castro, who, at the age of 62, had lymphoma in a serious condition and unresponsive to conventional treatments. About 20 days after starting the treatment, the patient’s health response was promising: the tests started to show that the cancer cells had disappeared. At the end of the same year, however, Vamberto died as a result of a domestic accident, unrelated to the disease.

In 2022, the São Paulo government expanded the program’s capacity. Two health centers, one in São Paulo and one in Ribeirão Preto, have since then produced compounds for CAR-T cell therapy. The initial treatment capacity will be up to 300 patients per year. The program is part of a cooperation agreement between the Butantan Institute, USP and the Blood Center of Ribeirão Preto.

Prompt answer

So far, 14 patients have been treated with CAR-T Cell with funding from FAPESP and CNPq. All patients had remission of at least 60% of the tumors. The recovery was in the SUS network. “The responses we are getting here, of course in a small number of patients, are very similar to those we have outside Brazil. This is very important”, observes Rocha.

For one of these patients, Paulo Peregrino, the response was immediate, says the hematology professor. “In this case, what is impressive is the immediate response of a patient who had many tumors. So, the images [pet scan do corpo do paciente] show: all that is black [os tumores] disappear completely within a month. We recently repeated the images, and everything is still in remission. I mean, he’s tumor free at this point. However, to talk about a cure, it takes a few years, because even if you do that, the disease can come back ”, he emphasizes.

Faced with the news of the complete remission of the cancer, Peregrino said he was surprised. “First, I didn’t believe I was like that, I didn’t know that image [pet scan]I didn’t know I had reached that point, and even after reaching that point [de remissão]after Car T Cell”.

For him, the willingness to participate in the study was not just for the possibility of a cure. “When I decided on Car T Cell, I knew it was a compassionate study that could be used — and should be used — so that other people in the future can have a better quality of life treatment. That, for me, was one of the goals from the beginning. When I am willing to take part in the study and leave something of knowledge that can help others in the future, I am doing good”, says the advertiser, who is 61 years old.

Paulo had been treating cancer for 13 years. First, it was prostate cancer, in 2010, which he treated until 2014. Then, in 2018, he discovered non-Hodgkin’s lymphoma, recalls the professor. “He underwent six cycles of chemotherapy, but the disease came back after a few years, so he had an autologous bone marrow transplant. However, in Paulo, the disease returned after the transplant, there was no longer any therapeutic possibility, and the cancer grew. We were able to infuse the T cell, and he had this wonderful response, he is already discharged.” On Sunday (28), Paulo left the hospital and is recovering at home.

The doctor says it was exciting to see the patient’s response. “It is a treatment developed in Brazil, relatively recently, and we have had experience with other cases, but this one really impressed everyone. The team was surprised by the response of this patient, who we wouldn’t have much more to offer and who would go to palliative care”, admits Rocha.

Adverse reactions

The therapy has been shown to be effective, but like most complex health treatments, it has had adverse reactions. In the ‘war’ between laboratory-altered T cells and cancer, the body becomes inflamed with the ‘debris’ of cancer, and the patient often needs to be monitored in an intensive care unit (ICU), explains Rocha.

“The patient, after the infusion of the cells, will have a reaction, an important inflammation of these. Fifty percent of the patients who receive these cells will be treated in the ICU, because they have to be monitored, take anti-inflammatories and corticoids.

There is also the immune neurotoxicity syndrome, in which the patient may have neurological problems, such as difficulty writing and walking. “This all passes with time, but they are important and adverse reactions.”

According to Rocha, the side effects can even lead patients to death. “However, as we gained more experience in treating this type of syndrome, the results of the so-called cytokine release syndrome, which occurs in severe and inflammatory processes, have greatly improved. There is also immune deficiency: patients who receive CAR-T cells for a long time will receive drugs to improve immunity.”

Expectations

According to Rocha, there is still a lack of funds for science and research for the therapy to be made available on a large scale. “It is very expensive to produce these cells, and phase 1 and 2 studies are still missing, which will start next month, to demonstrate that it works, that it is not more toxic to patients and that it can be used in the public service. But it is a stage that still takes a few years, so it is important to invest in research.”

The expert points out that there is still the possibility of using the technique in case of solid tumors. “The big problem is that T cells cannot [se] infiltrate the tumor. So, one of the possibilities is to find other types of cells that can penetrate the tumor and, for that, we need funding and support from the scientific community.”

Anvisa

In a note, the National Health Surveillance Agency (Anvisa) informs that the procedure for obtaining the product based on CAR-T cells, used in the patient Paulo Peregrino, was notified in January of this year and evaluated with priority, favoring scientific research and experimental use for the treatment of lymphoma.

“The Agency emphasizes that this is not a routine therapy and does not apply to all types of cancer, and that additional studies need to be conducted”, says the note.

The regulatory agency adds that it is committed to the evaluation of new advanced therapies and that it recently selected two projects, through a call for proposals, with the objective of supporting the approval of clinical trials and the production of the promising therapy in Brazil.

“The Blood Center of Ribeirão Preto has been administering the product in an experimental context, outside the framework of a controlled clinical trial. This feature is applicable in circumstances where there is immediate risk to the patient’s life or when dealing with diseases for which there are no therapeutic alternatives available in the country. Experimental use must be notified to the Agency, as provided for in its technical regulation (RDC 505/2022)”, completes the note.

Pilot project

Anvisa informs that it has a regulatory technical cooperation pilot project for the development of advanced therapy products (APTs) of interest to the SUS. The Butantan Institute and the Blood Center of Ribeirão Preto were approved by the call notice, which aims to select national developers to participate in the initiative.

The aim of the project is to establish a dynamic and effective regulatory cooperation model. “Such cooperation will involve Anvisa, Brazilian researchers and developers and the national health productive sector. This collaborative effort aims to stimulate the development of PTAs for use in the SUS, addressing the demand of an increasing number of patients with a wide variety of diseases without adequate therapeutic alternatives. These diseases include rare genetic disorders, autoimmune and oncological diseases.

The principle of the pilot project is to seek strategies to achieve high standards of safety, efficacy and quality of the products under study, to satisfy the needs of Brazilian patients in a timely manner, boosting the development and approval of these advanced therapies in an agile way, informs the agency. .

Although the developers have already started interactions with the agency, the pre-clinical and clinical protocols of the product in question are still in the adjustment phase, says Anvisa. In March 2023, after submission of the initial documentation for the study, Anvisa requested further clarification on specific preclinical safety trial requirements, issues related to the proposed clinical trial, and necessary safety assessments.

“It should also be noted that the documentation related to the manufacture of the product and the respective controls is being prepared and has not yet been submitted to the Agency for analysis”, he adds.

Thus, only after receiving answers to the questions asked and the documentation related to the production of the therapy, Anvisa will be able to pronounce on the approval of the proposed clinical trial. It is worth mentioning that the project has already been classified as a priority for analysis by the agency”, concludes the note.

*With information from Agência Brasil

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