2023-10-18 08:05:23
by Health Editorial Staff
40-45% of treated patients recover, for the others a step forward has now been made: possible predictive biomarkers of response to treatment have been identified. The time elapsed before relapse is important
CAR-T therapies represent one of the biggest innovations in recent years for the treatment of blood cancers. They are essentially based on a procedure that makes T lymphocytes, an important component of our immune system, capable of attacking the tumor. To achieve this objective, a blood sample is taken from the patient, from which the T lymphocytes are selected. These are then engineered in the laboratory so that they express the CAR (Chimeric Antigen Receptor) receptor on their surface, responsible for recognize the CD19 antigen present on neoplastic cells. Once reinfused into the patient, the engineered T lymphocytes, or CAR-T cells, can target and destroy tumor cells. CAR-T-based therapy has been successfully applied on some types of hematological malignancies, such as non-Hodgkin lymphomas and lymphoblastic leukemias, in patients who have not responded or responded incompletely to conventional therapies. The problem is that there is a significant portion of subjects who do not even respond to CAR-T therapies, or respond only partially.
Healing for 40-45% of patients
Now a new study coordinated by Paolo Corradini, director of the Complex Hematology Structure of the National Cancer Institute of Milan, in collaboration with the Humanitas Institute of Rozzano, has clarified some important aspects of these lack of therapeutic responses, opening up interesting perspectives, both for clinical practice and for research. CAR-Ts are offered to patients with lymphomas who have a relapse of the disease after conventional treatments and no longer have therapeutic alternatives: 40-45% of the subjects subjected to this therapy survive in the long term, that is, alive and in remission at a year and recovered, because late relapses, beyond one year, are very rare events – says Corradini -. This leaves the problem of 55-60% of the remaining subjects who do not respond to CAR-T tests, or respond only partially and have a new relapse in the short term. Hence the research project, carried out with the experts in statistics and pathological anatomy of the INT, in collaboration with Carmelo Carlo Stella’s group of the Humanitas Institute, dedicated to the analysis of possible predictive biomarkers of response to CAR-T. The results of the study, which involved a total of 51 patients, are published in the British Journal of Haematology
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Possible options for disease progression
From the analysis of this fairly large sample of patients, some fundamental data emerged: the first is that a level of free circulating tumor DNA above a certain threshold, identified in the study, predicts a poor response to CAR-T therapy – adds Corradini -. This result is particularly important because drugs are currently available, such as immune checkpoint inhibitor antibodies or bispecific antibodies (such as glofitamab) that could modulate the response in some patients, if identified early. A very encouraging result, which however depends crucially on the type of therapeutic failure: if the patient has never responded to CAR-T, and therefore undergoes a clear progression, unfortunately there are no effective therapeutic options. However, the case of a patient who has had a partial response to CAR-T and in whom perhaps the disease progresses after a few months is different – explains the expert -: in this case the disease is better controlled, obtaining a better response and greater survival if, at the same time, some immunological treatment is given, or even chemotherapy or radiotherapy. This is the second important result we have obtained, which confirms what has already emerged from other studies.
The results of the study
The time that passes from CAR-T treatment to disease progression is also relevant for clinical outcomes. Let’s take the example of a patient who responds to CAR-T for four months, and then undergoes disease progression again: if a bi-specific antibody is subsequently intervened, his probability of responding to the treatment is decidedly higher than a subject who progresses after 30 days and therefore shows a very short response or even no response at all – adds Corradini -. It leads us to consider the first as a partially immune-sensitive disease and the second as a completely immune-resistant disease. All these data, considered together, suggest that the clinical outcome ultimately depends on multiple variables, many of which still remain unknown, even if research is gradually shedding light on some fundamental mechanisms. In conclusion, we have a positive message: in this latest work, we show that patients who have relapsed after CAR-T therapy still have a 30% chance of two-year survival – concludes the hematologist -. It may seem like a limited number, but it must be considered that these are patients who previously would have had a very rapid decline in their clinical situation. The objective of our research is now to be able to identify in advance the share of patients who are most likely to respond to CAR-T therapy and the share that would instead be better sent directly to therapy with bispecific antibodies, from a perspective of greater personalization of oncological treatments.
October 18, 2023 (modified October 18, 2023 | 08:04)
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