2023-10-16 15:49:48
An Italian study indicates possible biomarkers useful for predicting the response of cancer patients to Car-T therapies, and suggests immunological treatments capable of prolonging survival in about a third of patients who only partially react to the treatment. The work, published in the ‘British Journal of Haematology’, was conducted by Paolo Corradini, director of the Complex Hematology Structure of the National Tumor Institute (Int) of Milan, together with experts in statistics and pathological anatomy of the Int, in collaboration with Carmelo Carlo Stella’s group from the Humanitas Clinical Institute of Rozzano, Milan.
Car-T therapies, based on T lymphocytes taken from patients and engineered in the laboratory to recognize and kill cancer cells, represent one of the biggest innovations in recent years – they recall from Int – for the treatment of blood tumors. They have been used successfully against some hematological malignancies such as non-Hodgking’s lymphomas and lymphoblastic leukemias, in patients who have not responded or responded incompletely to conventional treatments. However, there is a significant portion of patients who do not even respond to CAR-T therapies, or respond only partially. When CAR-Ts are used in “patients with lymphomas who have a relapse of the disease after conventional treatments and no longer have therapeutic alternatives – specifies Corradini – 40-45% of the subjects subjected to this therapy survive in the long term, that is, alive and in remission at one year and is cured, because late relapses beyond one year are very rare events. However, the problem remains of the 55-60% who do not respond to CAR-T, or respond only partially and have a new relapse short term”.
From the analysis of 51 patients, a “fairly large” sample, underlines Corradini, “some fundamental data emerged: the first is that a level of free circulating tumor DNA above a certain threshold, identified in the study, is predictive of a poor response to Car-T therapy. This is particularly important – highlights the specialist – because drugs are currently available, such as immune checkpoint inhibitor antibodies or bispecific antibodies, such as glofitamab, which could modulate the response in some patients , if identified in time”. A result defined by the authors as “very encouraging, which however depends crucially on the type of therapeutic lack of response”.
Corradini clarifies: “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 is different and in which perhaps the disease progresses after a few months: in this case, the disease is better controlled, obtaining a better response and greater survival, if some immunological treatment is performed concurrently, or even chemotherapy or radiotherapy. It is the second important result we have obtained, which confirms what has already emerged from other studies.”
“The time that passes from Car-T treatment to disease progression is also relevant for clinical outcomes”, emerges from the research. “Let’s take the example – explains the Int oncohaematologist – of a patient who responds to Car-T for 4 months and then undergoes disease progression again: if a bispecific antibody is subsequently intervened, his probability of respond to the treatment is decidedly higher than in a subject who unfortunately already progresses after 30 days and therefore shows a very short response or even no response at all. This leads us to consider the first as a partially immune-sensitive disease and the second a completely immune-resistant disease.”
“In conclusion”, for Corradini “we can send a positive message: in this latest work, we show that patients who have relapsed after Car-T therapy still have a 30% chance of survival at 2 years. It may seem a limited number, but it must be considered that these are patients who previously would have had a very rapid collapse of the clinical situation. The objective of our research – concludes the coordinator – is now to be able to identify in advance the share of patients who with greater probability will respond to therapy with CAR-Ts and the portion that would instead be better sent directly to therapy with bispecific antibodies, with a view to ever greater personalization of oncological treatments”.
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