Seven Centers authorized for administration, the highest number among the Italian Regions. The participation of specialists and researchers in the development and testing of therapies. The network of AIL sections, which supports the treatment path of patients and their families and collaborates with the Centers to monitor the effectiveness of treatments.
These are some factors that place Lombardy at the forefront of CAR-T, the treatments that engineer T lymphocytes to help them fight tumors and that represent the great hope in the treatment of oncological and oncohematological diseases.
Three of those already approved at European level, as many in the home straight, with complete remission rates up to 82% for Acute Lymphoblastic Leukemia, the most frequent cancer in children, between 40 and over 50% for two very aggressive non-Hodgkin’s lymphomas (Diffuse large B-cell lymphoma and Primary mediastinal lymphoma) and an important improvement in survival (2 years for 51% of patients) in myeloma. Currently these therapies are also being studied for use against other haematological diseases and solid tumors.
CAR-T are an increasingly concrete hope for those patients who do not respond to conventional therapies, but they also raise questions on aspects such as security, organization, costs, access methods. What are the actual benefits of CAR-T? What forms of cancer can they cure? Who are the patients who can benefit from it? Where are they administered? How are side effects managed? And how to make them sustainable for the Health Service, in light of their costs?
The “Lombard laboratory” is the optimal observation point to answer these questions and for this reason it is Milan that hosts the first stage of CAR-T – Future destination, traveling and online campaign promoted by AIL – Italian Association against Leukemia, Lymphoma and Myeloma and made with the non-conditioning support of Celgene (now part of Bristol Myers Squibb), Janssen and Novartis: a real “journey into the future” of the fight against cancer, in which patients, families, doctors and institutions are invited to participate, divided into events on the territory and digital activities aimed at increasing information, measuring expectations, bringing out needs and criticalities.
What are CAR-T
Le CAR-T (Chimeric Antigen Receptor T cell therapies), are the new frontier of personalized medicine in the field of cancer and represent a therapeutic option in those patients in whom the previous standard therapeutic strategies (chemotherapy and hematopoietic stem cell transplantation) have failed: the T lymphocytes taken from the patient’s blood are “Armed” in such a way as to express the CAR receptor on their surface which helps them recognize malignant cells and kill them, to then be reinfused into the patient himself.
“The arrival of CAR-T has opened new perspectives for some haematological diseases, has triggered great expectations among patients and their families and has aroused great enthusiasm even among us haematologists: but correct, timely and transparent information is needed to clarify doubts and uncertainties about such an innovative therapy – he claims Sergio Amadori, AIL National President – for this AIL has decided to take the field with an itinerant and online information campaign on therapy, carried out with the support of the primary pharmaceutical companies engaged in the production of CAR-T. The goal is to explain to patients and their families that the CAR-T weapon is there and is effective, but at the moment it is not a weapon for everyone, it is only indicated for certain types of haematological diseases and only for patients with adequate requirements, in authorized centers. The other objective is to open a dialogue with specialists and decision-makers at national and local level to evaluate the critical issues and to create the conditions for this innovation to be fully successful “.
Campaign activities include one landing page dedicated on the AIL website (www.ail.it) with all the most important information relating to CAR-T therapies, together with a map of the Centers authorized for administration. The regional capitals that host Centers authorized for administration host events involving specialists, patients, caregivers, AIL volunteers and the media to take stock of the state of the art on CAR-T therapy, the critical issues in the Region, the expectations and questions of patients. The information activities are enriched by a oral video story, available on the campaign landing page, in which Andrea Grignolio, Professor of History of Medicine and Bioethics at the San Raffaele University of Milan – CNR Ethics tells the path of discovery that led to this revolutionary approach in the treatment of tumors.
“CAR-T can be considered as the therapy for patients who have no other therapeutic options – he claims Paolo Corradini, Director of the Hematology Division, IRCCS Foundation National Cancer Institute of Milan, Chair of Hematology, University of Milan and President of the Italian Society of Hematology – these therapies combine at least two fundamental aspects: they are intelligent therapies, as they identify a single receptor expressed by tumor cells and sparing the patient’s healthy tissues; second, they are highly personalized and targeted therapies because they are produced starting from the lymphocytes of the individual patient to which they are reinfused after the engineering process that arms the lymphocytes against cancer cells and, another peculiarity, can remain for a long time in the patient’s body. which are reinfused, ensuring a prolonged mechanism of action over time and able to reactivate each time the disease reappears ».
What do we know today
Much remains to be understood and studied with respect to the safety and efficacy of these treatments, the use of which is associated with the risk of sometimes serious events, the cytokine release syndrome, which is caused by an excessive immune response due to infusion of modified T lymphocytes. In addition, reduction of B lymphocytes and antibodies and persistence of late cytopenia may occur. Acute criticalities can be remedied with a good organizational and training system and with close contact with intensive care. Chronic criticalities must make use of a good pathology team that leverages dedicated hematologists. For this reason, CAR-T therapies can be administered in a limited number of pediatric and adult hematology and oncohematology centers, highly specialized in the treatment of leukemia and lymphomas, with specific requirements (including the availability of access to intensive, the certification of the National Transplant Center in accordance with EU Directives, the JACIE 7.0 accreditation for allogeneic transplantation; the presence of an apheresis center and a laboratory for cryopreservation).
“CAR-T therapy represents an articulated and specialized development of the characteristic activity of advanced transplant centers – he claims Fabio Ciceri, Full Professor of Hematology, Vita-Salute San Raffaele University, Director of the Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Hospital – the transplant centers where CAR-T are administered are experts in complex transplantation, in particular in the transplant performed by a donor from the registry, because from the clinical point of view it is necessary to know how to manage any complications that are not very dissimilar from the serious complications of the transplant as a donor. Furthermore, these Centers are already used to managing the coming and going of the material as they are sometimes also Centers for the collection of voluntary donors. Ours is the second center in Italy that takes from voluntary donors and we send cells around the world ».
I haematological tumors, leukemias and lymphomas, are those globally more frequent in pediatric age, from 0 to 18 years, acute lymphoblastic leukemia is the most common form. The first clinical trials and the first scientific evidences on CAR-T occurred precisely on pediatric blood cancers, and specifically the Acute Lymphoblastic Leukemia of children.
“Thanks to the progress made in recent years, Acute Lymphoblastic Leukemia can be considered curable in 80% of children but the challenge is to heal more, because 15-20% do not recover and, unfortunately, still die today due to this disease – he claims Andrea Biondi, Professor of Pediatrics, University of Milano Bicocca, Director of the Pediatric Clinic of the MBBM Foundation, San Gerardo Hospital of Monza, European Reference Network (ERN) PaedCan, EuroBloodNet, MetabERN – for patients who experience relapse or are resistant to multiple lines of treatment, CAR-T cell therapies have yielded extraordinary results. The ML Verga Center of Monza participated in the registration studies but we must be aware that we are only at the beginning of this new page of medicine. We need research to have CAR-T with a better safety profile, more effective, that is, able to prevent the relapse of the disease that often loses the target against which we have developed these therapies, and finally that they are more sustainable from a point of view. from an economic point of view “.
A difficult physical and psychological path
Treatment with CAR-T therapies involves a long journey marked by fears, doubts and expectations. Each phase of treatment needs a special accompaniment. The AIL section of Milan has activated the psychological clinic in March 2021 to support and listen to haematological patients which is enjoying considerable success with dozens of requests.
“Psychological support guarantees a protected space in which the person is free to share the experience lived in all its dimensions and in which he can find the resources and strengths necessary to face the entire therapeutic path – he comments Eleonora Criscuolo, Head of Psychological Support Clinic AIL Milan – moreover, psychological support allows to evaluate the emotional impact of CAR-T therapies and helps to improve adherence to the therapeutic path ».
Enormous commitment and work of the AIL section of Milan, at the service of the hematological community of the territory since 1976, which not only deals with the project ‘AIL welcomes. Actually close to the needs of patients and their families, in particular supporting the most vulnerable, but has always supported scientific research on blood cancers.
“We are proud to support active projects at the National Cancer Institute on CAR-T – explains Matilde Cani, Head of Institutional Projects AIL Milan – a prospective study on myeloproliferative diseases and a study on primary mediastinal lymphoma, both for the monitoring of CAR-T therapy and the biological and clinical characteristics predicting efficacy to evaluate its progress and be able to anticipate any relapses, so as to customize treatment as much as possible “.
The campaign promoted by the AIL, which will cover this last part of the year and will continue also in 2022, will be an initiative in progress: the information conveyed through the site and in the events will be updated in relation to the news that will arrive from the research front, the AIFA authorizations and the clinical experiences.