CAR-T cells: treatment of blood cancers at the threshold of a major revolution
The placing on the market in the United States of the first two gene therapies based on the CAR-T cell technology of using the patient's own genetically modified immune cells to destroy tumor cells, are a possible revolution for the treatment of blood cancers.
The placing on the market of this type of treatment is a major step forward for patients. The results observed on the complete response rate are unpublished and very encouraging. We are in a paradigm shift to treat blood cancers and therefore probably at the threshold of a major revolution, says Prof. Gilles Salles, head of Clinical hematology service at the Hospices Civiles de Lyon (Centre Hospitalier Lyon-Sud) and President of the LYSA.
The LYSA (Lymphoma Study Association) is a co-operating group of over 500 physicians, clinicians and researchers from 120 centres in Europe. He works for clinical research against lymphoma, the first blood cancer and the sixth most common cancer.
The American Drug Agency (FDA) has approved in the last three months the placing on the US market of two drugs based on the CAR-T cell technology. Kymriah (Novartis), approved in August for a very aggressive form of leukemia in children and young adults, showed a remission in 83% of patients. A request for extension of indication has been filed for the third-line treatment of recurrent or refractory diffuse large cell lymphoma B (DLBCL) in patients who cannot undergo autologous stem cell transplantation. The second drug, approved in October, is Yescarta (Kite/Gilead) for the treatment of large-cell diffuse B lymphoma, an aggressive non-Hodgkin's lymphoma. They are aimed at patients in failure of conventional treatments.
"Today, for large-cell lymphoma, the most common of lymphomas, there is no reference treatment when the patient is in his second relapse." The immunochimiothérapie gives poor results, with less than 10% remission, while the Yescarta allows to have a remission rate of 50%. So it's quite remarkable, says Dr. Richard Delarue, hematologist at Necker Hospital (AP-HP) in Paris and a member of the LYSA board of Directors.
Available for French patients from 2018?
Applications for authorisation to put on the European market of these therapies are in progress. In France, with more than 4,000 new cases of large cell B lymphomas Newly diagnosed each year, and although the majority of them will cure with the first treatment, one can estimate to several hundred patients those who could Benefit from this type of treatment, especially if one can better foresee and/or control the side effects of the CAR-T.
"We hope that national health firms and authorities in different countries will be able to quickly allow patients to benefit from these innovative treatments." For French patients, we hope that through clinical trials that will be implemented in France and temporary authorisation devices (ATU), patients will be able to benefit from access to these treatments as early as 2018», Specifies the Pr Salles.
The issue of reimbursement and assumption by national health authorities also remains to be resolved because, if only one injection is sufficient, it is nevertheless currently charged in the United States between 373,000 and 475,000 (only when the Treatment was successful).
These costs must be related to those of other therapies recently approved for various cancers and the results obtained. Our solidarity health system is being put to the test with the cost of new medicines, but this is a major innovation, a technological rupture, and we must consider the possibility that seems open to cure with the CAR-T some Patients whose other treatments had failed, says Prof. Salles.
New challenges for Hematologists
Many studies are still needed because, for the time being, these treatments are not effective in all patients and their side effects can be severe or even lethal.
"A greater decline will lead to a better understanding of why and how it affects the survival of these patients." Will we be able to cure some of them? If so, which ones? What will be the place of these new treatments in the therapeutic arsenal and their possible efficacy in other types of lymphoma? , asks Dr. Richard Delarue, for whom these new treatments also represent a challenge for the hematologists. ' It will be necessary to specify the setting up of the treatment circuit: collection, manipulation of cells, reinjection, management of the patient and complications, as well as a ' real life ' analysis from the point of view of the efficacy and toxicity of these Treatments. These are points that we feel are urgent.
The toxicity of these therapies, essentially general (fever, respiratory problems, drop of tension, etc.) and sometimes neurological (confusion, convulsions, etc.), requires today the administration of this treatment in Hospital structures allowing the management of these complications, sometimes fatal.
LYSA, as a co-operative Group of researchers on lymphoma, continues to work for the rapid development and evaluation of innovative therapies. A very limited number of centres attached to the LYSA have been able to access the trials evaluating this therapy so far. "We hope that other LYSA centres will be able to quickly become part of this dynamic," said Prof. Gilles Salles.
What are CAR-T cells?
Treatment using chimeric antigen receptor cells (Chimeric antigen receptor) is a cellular immunotherapy. T lymphocytes (cells of the organism responsible for the so-called adaptive immune response – i.e., which responds specifically to an antigen) are taken from a patient and then genetically modified in the laboratory to express at their Surface an artificial receptor (called a chimeric). Once they are injected into the patient, they can specifically recognize and destroy cancer cells.
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