The CAR-Ts in the treatment of Acute Lymphoblastic Leukemia they represent a great revolution, but for some patients they do not always work as expected. To try to understand why this happens AIL, thanks to the proceeds of bequests, has financed the “National multicenter retrospective and prospective observational study of chimeric antigen receptor T cell (CAR T) therapy in childhood and adult acute B lymphoblastic leukemia (B ALL). The study is promoted by the GIMEMA Foundation (Italian Group of Adult Hematological Diseases) in collaboration with AIEOP (Italian Association of Pediatric Hematology and Oncology). Alessandro Rambaldi, Professor of Hematology, Scientific Director of the Foundation for Clinical Research – FROM Papa Giovanni XXIII Hospital in Bergamo and Member of the AIL Scientific Committee talks about it
Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia (ALL) represents the most common form of pediatric cancer, however after an initial peak of incidence in childhood, there is a second peak which also affects the adult population. The term Acute Lymphoblastic Leukemia is defined a constellation of different diseases, characterized by biological complexity, that researchers and hematologists have learned about over the last thirty years. In Italy, this was possible thanks to the work of molecular biology laboratories which were largely supported by AIL.
The most recent innovations in the treatment of Acute Lymphoblastic Leukemia concern the availability of CAR-T therapies.
In ALL, the aim of treatment has always been to obtain a first long-lasting remission of the disease. To achieve this result the heart of the treatment was based on intensive chemotherapy programs which is usually possible to administer in pediatric age but which in adult patients is associated with toxicity that is often difficult to tolerate.
All of this, including the transplant, is done to avoid disease recurrence which, when it occurs, is unfortunately associated with a significant reduction in the chances of a definitive cure of the disease. In the recent past, there were in fact few available and effective therapeutic options for the treatment of relapsed disease and this condition represented a moment of dramatic hardship for patients and families.
The drama of a patient’s clinical picture, at the time of disease relapse, for many years it remained a clinical scenario without new valid therapeutic choices. The arrival of immunotherapy and CAR-T cell therapy it therefore has meaning an extraordinary revolution, not only for the effectiveness that this therapeutic option has proven to possess, but also for its feasibility.
In the majority of patients this therapy is in fact well tolerated although in some patients very intensive forms of supportive therapy may be necessary. Unfortunately, even this extraordinary treatment can in some cases prove ineffective. Numerous studies are currently underway around the world to try to understand the reasons why CAR-T therapy fails in some patients.
It should not be forgotten that it is a biological therapy, a real living drug, made up of the patient’s T lymphocytes which, after being taken from the peripheral blood, are genetically modified and then infused back into the patient himself.
It is therefore necessary to keep in mind that exposure to prolonged chemotherapy treatments and often also a previous allogeneic bone marrow transplant, can make the patient’s lymphocytes more fragile and less effective after genetic modification. These are the problems that research will have to address in the near future to try to optimize the quality of this therapeutic intervention.
The objectives of the study financed by AIL
The project financed by AIL is aimed at collecting data from normal clinical practice and measuring the therapeutic outcomes that we are achieving with CAR-T cells in this indication. Why is this so important? What is the difference compared to a clinical study?
The Registrative clinical study is a controlled study that is conducted in very homogeneous groups of patients who may not be entirely representative of the patients we encounter in normal clinical practice.
Conducting clinical studies in this way is a necessity, but it is equally true that it is important to confirm the data in common clinical practice. Furthermore, it must be said that up to now the results of the initial registration studies have been largely reproducible in normal clinical practice.
However, the therapeutic context in which patients are brought to CAR-T therapy today is different from that which characterized patients five-seven years ago, the period in which the first studies with these cells were conducted. Therefore, in this ever-changing scenario, AIL’s initiative takes on an extraordinary importance for generating updated data for today’s clinical practice.
What predictions for the future of these innovative and promising therapies
The future scenario of use of CAR-T cells in this clinical context is destined to change quickly because the therapeutic progress that has been observed in Acute Lymphoblastic Leukemia depends on other extraordinary therapeutic protagonists that are entering, or have already entered, the therapeutic armamentarium. Therefore, the indication for the use of CAR-T cells, currently available in Italy in the very advanced stages of the therapeutic strategy, could undergo changes. We therefore hope that the placement of CAR-T cells in therapy can be brought forward to an earlier phase of treatment. So, we are convinced that in the near future we will be able to document not only progress in the effectiveness of CAR-T cells, but also that this therapeutic modality will lead to a reduction in the overall toxicity of the treatment that we offer to patients with Acute Lymphoblastic Leukemia. In conclusion, CAR-T cells along with other forms of immunotherapy, they represent not only an effective therapy for otherwise incurable patients, but they will probably be able to represent a treatment tool that can be used earlier as a more effective and less toxic alternative.
HELP US BUILD A FUTURE WITHOUT BLOOD CANCER
Thanks to the bequests the Italian Association against Leukemia, Lymphoma and Myeloma finances important projects Scientific Research And guarantees social and healthcare assistance to haematological patients. To find out more or to request the Bequest Guide go to www.lasciti.ail.itwrite to [email protected] or call 800 85 78 78.
