There are more and more studies that shed hope on the effectiveness of CAR-T therapies in solid tumors considered incurable until now. A group of scientists from Stanford University (United States) launched a clinical trial in 2020 with 11 patients diagnosed with diffuse midline glioma, a tumor that affects the nervous system, has a very poor prognosis and appears in children and young people. . The results, published this Wednesday in the magazine Nature, are encouraging: the treatment has achieved complete remission of the disease in one of them, 17 years old. The patient has had no detectable pathology for four years. In addition, the tumor reduced its volume between 52 and 91% in three other cases and in the majority there was a “neurological benefit,” according to the researchers.
The work, far from being definitive – at the moment it is a phase I trial – “is very promising as a suggester of efficacy,” says Manel Juan, head of the Immunology Service at the Hospital Clínic of Barcelona, in statements to the Science Media Centre. It opens the door to making a disease that is incurable today through a treatment that “can last and integrate into the body as it is a living drug, unlike chemo or radiotherapy, which only act while they are applied” , he explains.
CAR-T are personalized therapies that are based on reprogramming immune system cells to attack tumor cells. They have a high cost, but the Spanish public health system is beginning to produce them in its own hospitals at a significantly lower price to treat blood tumors, where the evidence of their effectiveness is more solid.
The experts receive the results of the trial, which is rigorous and well designed despite the small volume of patients, as a “authentic boost to this immunotherapy in terms of safety and efficacy,” in the words of Luis Álvarez-Vallina, head of the Unit of Cancer Immunotherapy at the 12 de Octubre University Hospital and the National Cancer Research Center.
However, it is important to measure the aggressiveness of this tumor. Although signs of improvement were seen, these did not prevail for the majority of patients. The trial began with 13 people: two of them were discharged early due to the rapid evolution of the disease and, 30 months after the first infusion, only two of the remaining 11 had survived. They were on average 15 years old.
Diffuse midline glioma is associated with symptoms that were significantly reduced during the trial. For example, the patient who responded best – to the point that the disease remitted – had “sensory and motor deficits” that forced him to use a wheelchair. After receiving the treatment, his motor coordination improved “to the point of independence.” Another 30-year-old patient, whose tumor shrank by 90% at the best time, had, before the first infusion, “severe paraplegia, neuropathic pain, and intestinal and bladder dysfunction.” The pain improved and so did the function of his extremities. He was able to walk with a cane.
Few cases and very selected
One of the problems with this treatment, as with others to attack cancer, is toxicity. This study demonstrates, several experts agree, that there is a route of administration – directly into the central nervous system – that is less toxic and more effective. “The most interesting thing about the study is that intracavitary locoregional administration (in the same area where the tumor of origin is) is the way to go. Through this intratumoral administration route, the performance of CAR-T cells against solid tumors can be optimized with maximum exposure,” analyzes Ignacio Melero, professor of Immunology at the University of Navarra and CIMA researcher.
The work, however, has limitations. There are few cases treated and only one of them achieved a complete response after four years; Furthermore, “patients were highly selected so that they were in a good functional state and had tumors of an adequate size,” emphasizes Marta María Alonso, researcher in the Solid Tumors Program at CIMA and the Clínica Universidad de Navarra. The researchers themselves admit that it is still “difficult to discern whether GD2-CAR T cell therapy favorably impacts overall survival” with such a small and selected sample. and “should be evaluated in future phase II trials.”
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