CAR-T against lymphoma improves survival

CAR-T against lymphoma improves survival

When they arrived, CAR-T-based therapies – an immunotherapy technique that enhances the action of the immune system against tumors thanks to gene therapy – were reserved for the most severe cases. Those who no longer had other treatment options. Over time we then found ourselves, strengthened by the results that came from the clinic, wondering if the use of these innovative third-line therapies could not be anticipated and replace the standard of care. And the recently concluded results from two of the major oncology congresses confirm that CAR-T can be used in the second line in the treatment of some cancers in difficult-to-treat patients and can improve survival compared to standard treatments. This is the case of some lymphomas, against which the treatment axicabtagene ciloleucel has been used, among the first to arrive in the panorama of CAR-T.

CAR-T for patients ineligible for transplantation

The results in question are those coming from the congress of the European Hematology Association (EHA) in Frankfurt and the American Society of Clinical Oncology (ASCO) in Chicago and concern large B-cell lymphoma. In Frankfurt, the data presented concern the ALYCANTE study , which used the therapy as second-line treatment in patients with relapsed or refractory disease ineligible for transplantation and high-dose chemotherapy. In fact, this is usually the standard of care: an initial treatment with chemo-immunotherapy followed by high-dose chemotherapy and stem cell transplantation. Sixty-two patients included in the final evaluation.

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The ALYCANTE study

In the ALYCANTE study – supported by the Lymphoma Study Association and the Lymphoma Academic Research Organization – the complete metabolic response (PET negative during or after treatment) was 71% at three months versus 12% at standard of care from historical controls, remaining just under 60% at six months. At three months, approximately 75% of patients had a partial or complete response, while overall survival at twelve months was approximately 78%, and median overall survival (OS) was not reached. Analysis of liquid biopsies - which aim to trace the presence of tumor DNA circulating in patients - have observed that the early disappearance of tumor traces, such as those of DNA, was predictive of response to therapy. That is: in patients in whom the disappearance of the tumor DNA was observed early, the responses to therapies were better.

“Transplant-ineligible patients with aggressive lymphomas such as large B-cell lymphoma have had a poor prognosis to date. The ALYCANTE study is the first to evaluate CAR-T therapy with axicabtagene ciloleucel as second-line therapy for people with relapsed or refractory large B-cell lymphoma who are ineligible for transplant. The results showed high response rates and durable remission in this type of difficult-to-treat patient,” commented Stefano Luminari, Full Professor of Medical Oncology, University of Modena and Reggio Emilia, director of the oncohematology research program at the Institute for Scientific Research and Treatment (IRCCS) of Reggio Emilia. "The Alycante study, moreover, completes the results of the Zuma-7 study: axicel is the only treatment that demonstrates a statistically significant improvement compared to the second-line standard of care in large B-cell lymphoma".

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Car-T better than second-line standard of care, the ZUMA-7 study

The other interesting data for this cancer therapy are in fact those arriving from Chicago from the Zuma-7 study and anticipated in recent months by a publication in the New England Journal of Medicine. In the study, involving 359 patients, second-line CAR-T cell therapy against relapsed or refractory large B-cell lymphoma was compared to standard of care.

“At a median follow up of 47.2 months, Zuma 7 demonstrated a 27% reduction in the risk of death compared with standard of care. At four years, 54.6% of patients receiving axicel are alive compared with 46% in the comparator arm. It is important to underline that within this arm, 57% received third-line cell therapy - explained Luminari - These are data that are unprecedented in the last thirty years in the treatment of aggressive lymphomas, a very important piece of news for the scientific community and for patients. This reinforces the role of CAR-T therapy with axicel as a new standard of care in the second line of patients with large B-cell lymphoma". And that confirms what has already been recognized by the regulatory authorities of the drug, which last year, precisely on the wave of the results that arrived from Zuma 7, had in fact approved the use of this therapy also in the second line for these tumours.

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In fact, the conclusions of the study are that in the second line against this tumor CAR-T is superior in terms of event-free survival and response, although in the face of important, albeit expected and already known adverse events (such as cytokine release syndrome and neurological events). But if these data, as stated in the editorial accompanying the NEJM study, help better understand how and when to use CAR-T cells for large B-cell lymphoma, they still need to be interpreted with caution. Other studies (such as the BELINDA trial), the authors recall, lead us to believe that not always, not for all patients with aggressive B-cell lymphomas, CAR-T is superior to the standard of care, especially if the disease is rapidly progressing and very extensive.

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