About 800 adult patients and 40 children with blood cancer in Italy could soon benefit from Car-T, a new, revolutionary treatment against incurable leukaemia and lymphoma that do not respond to traditional treatments. And among all the eligible patients the rate of recovery is 40%, if not actually 50 per cent. These are some of the figures announced by professor Paolo Corradini, President of the Italian Society of Haematology and Director of the Haematology Division of IRCSS Foundation, National Cancer Institute of Milan, and professor of Haematology at the University of Milan, and by Professor Franco Locatelli, President of the National Board of Health and Director of the department of Paediatric Oncology and haematology, at the “1st Italian Workshop on Car T- Cell Therapy” held in Milan, with such guests as Carl June, director of the Centre for Cellular Immunotherapies at the University of Pennsylvania and a pioneer of Car-T Cells. The meeting brought together all the scientific associations working in the field: Sie (Italian Haematology Association), Sies (Italian Experimental Haematology Association), Aieop (Italian Association for Paediatric Haematology and Oncology), Gitmo (Italian group for bone marrow and haematopoietic stem cell transplantation and cell therapy) and Fil (Italian Lymphoma Foundation).
Car-T therapy (Chimeric Antigen Receptor T-cell) is a next-generation immunotherapeutic treatment that uses special white blood cells, the so-called T lymphocytes, engineered to activate the immune system. “The patient’s T lymphocytes are taken and then genetically modified in the laboratory to enable them to recognise cancer cells: when they are put back into the patient, they get into the blood flow and can recognise cancer cells and remove them by activating an immune response”, Corradini explained.
Car-T Cell therapy is currently used on patients who have failed traditional treatments. “More specifically, the European Medicines Agency (EMA) approved Car-T Cell therapy in patients up to 25 years of age suffering from B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) on a second relapse of the disease or a disease that is refractory to traditional treatments or on first relapse after a haematopoietic transplant and in adult patients suffering from diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) that are refractory or resistant to one or more lines of a systemic therapy”, Locatelli added.
This is, then, a new, complex therapeutic approach to the disease, intended only for selected patients and relying on very expensive drugs that need to be approved by governmental authorities, in Italy the Italian Medicines Agency (Aifa). “In Italy, potential patients with lymphoma might be 300 to 400 a year and for the time being only compassionate use of one of the Car-Ts is available, so that one patient a month can be treated at Fondazione IRCCS Istituto Nazionale dei Tumori”.
In a survey conducted by Ospedale Bambino Gesù in Rome using Car-T cells in BCP-ALLs and B-Cell lymphomas, “the therapy showed a definitely favourable response in the 15 treated patients with over 80% of remission of the disease”, Locatelli explained. “Even the first few figures about the initial response in children with neuroblastoma are promising and widely encourage us to go on along this way”.
Therefore, Car-T Cell therapy can provide a real chance of a final recovery for those patients who, having failed traditional treatments, would not have any other therapeutic option. However for the time being the therapy is not completely risk-free. “Potential side effects that have been reported are cytokine release syndrome and neurological adverse effects. The cytokine release syndrome is due to the activity of the Car-T cells and can occur in about 25% of patients with a high temperature, low pressure, problems breathing and kidney failure”, Corradini pointed out. The death rate with this treatment is 5%. That’s why it is essential to move quickly as soon as the first symptoms of this complication appear, and with appropriate treatments (corticosteroids or antibodies that stop the cytokines involved in the physiopathology of the condition).
“This consideration highlights how important it is for Car-T Cell therapy to be carried out in highly-qualified and experienced selected centres. Another fearful complication of Car-T Cell therapy is neurotoxicity that, in the very few cases occurred in adult patients, turned out to be lethal. To increase the safety of the Car-T cells used in our academic trial, while the T lymphocytes are formed, we have developed a change: the addition of a gene, known as suicide, which is activated if there is no response to pharmacological treatments for cytokine release syndrome, instead of neurotoxicity, thus causing the Car-T Cells to be promptly removed”, Locatelli ended.
Lastly, while Car-T cells are not used as a first-line treatment now, work is being done to administer them earlier. In a not too distant future, cell therapy could become a basis for the treatment of many types of cancer. What about Italy? “Hopefully, Aifa will give its authorisation as soon as possible so we can start to treat some patients before the end of the year”, Corradini stated. “This is not a drug, this is a complex cell therapy procedure that, where previous treatments have failed, can be the only life-saving option”.