Home Health Blood cancers: more and more Car-T

Blood cancers: more and more Car-T

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IN ITALY, 7 out of 10 patients with blood cancers are now alive 10 after diagnosis or are considered cured. A word, healing, which can rarely be used in oncology. This is also and above all thanks to the Italian research that continues to lead the way. In particular in the last two years, the natural history of two diseases – large B cell lymphoma and acute lymphoblastic leukemia – has changed radically thanks to the studies conducted in our country on two frontiers of immunotherapy: therapies with Car-T cells. and with bi-specific antibodies. Many of the studies that are presented in these days in Milan, at the National Congress of the Italian Society of Hematology (SIE) concern these two strategies. And among these, the real life study on nearly 200 patients with aggressive non-Hodgkin’s lymphomas treated in Italy with Car-T. The data is striking: today 40% of patients are considered cured, while previously only 5% survived at 6 months. “A result obtained with a single infusion, therefore without the need for maintenance therapy, in people without any therapeutic alternative”, underlines Paolo Corradini, President of SIE: “At the same time, today just 5% of patients need intensive care for complications – which are increasingly managed – while mortality is around 3%: much lower than that for transplantation. With Gimema, we are also currently conducting a study on how these people return to life after therapy, but what we observe every day tells us that they have an exceptional quality of life, much better than post-transplant. “.

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To date, 25 Car-T centers are active or are about to be activated throughout the peninsula. However, the patients treated treated to date are few compared to those expected: an exclusively organizational problem, underline the SIE experts, and which requires a greater effort in selecting and referring eligible patients from peripheral hospitals.

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The near future of Car-T

A problem that must absolutely be overcome, because in the coming months it is expected that Car-T therapies will no longer be usable only after the third line of treatment, but already after the second. In addition, they are also entering the world of other lymphomas – in particular mantle and follicular lymphomas – and multiple myeloma (for which the European Commission has already approved the use of one of the two commercial therapies currently used in Italy). “The disease causes 5,800 new cases to be registered every year in Italy”, continues Corradini: “In the KarMMa study on 128 heavily pretreated patients, the overall response rate reached 73%. Median overall survival exceeded two years. Very important results, if we consider that for these patients with multiple myeloma without alternative treatment, before the arrival of CAR T, the median life expectancy was between 6 and 9 months “. Finally, two international studies concern chronic lymphatic leukemia, with 8-9 patients treated in Italy with excellent results.

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The “bridge” antibodies for acute lymphoblastic leukemia

Spotlight also on bispecific antibodies for acute lymphoblastic leukemia. These molecules allow to build a “bridge” between the cells of the immune system and the leukemic cells, so that the former can go directly to the latter, and kill them. “Acute lymphoblastic leukemia is a rare cancer of the lymphocytes, which causes nearly 800 new diagnoses every year in our country. However, it is the most frequent in children: it represents 80% of leukemias and about 25% of all cancers in the under 14s. The incidence peaks between the ages of 2 and 5 and then decreases with the increase of age ”, explains Pier Luigi Zinzani, President of the Training Activities Commission of the SIE:“ Two Italian studies can change the history of the disease. In the first, in 149 patients, thanks to the combination of the sequence consisting of chemotherapy with a bispecific antibody, a complete response of 90% was shown and the molecular remission went from 73% to 96% after the addition of the antibody: this means that even molecular tests cannot ‘see’ diseased cells. The second study shows that it is possible to treat the disease without chemotherapy. Remission was achieved in 98% of cases “.

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Costs and suspicion

But if the number of patients who can benefit from these therapies in the near future is much larger, will the system be able to bear the costs? “Aifa has obtained a payment mechanism based on the result, ensuring our country the most expensive drugs in the world at the lowest costs”, replies Emanuele Angelucci, Vice President of SIE: “Full payment takes place one year after administration and we are thinking that this time may not be sufficient to evaluate effectiveness. Both Car-T and bi-specific antibodies, however, are one-shot therapies, which means that patients do not have to continue to follow a treatment for the rest of their life ”.

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Covid, vaccines and thrombosis risk

Could not miss the Covid theme, vaccinations and thrombosis risk. “We know that the anti-SARS-CoV-2 vaccination could be less effective in people affected by a neoplastic haematological pathology and in active treatment with chemotherapy”, explains Sergio Siragusa, Vice President of SIE: “Almost all haematological therapies, in fact, are immunosuppressive and this may make vaccination less effective, but not dangerous. SIE has produced guidelines on the management of anti Covid vaccination in patients suffering from neoplastic and benign haematological diseases “. In both cases, in fact, the type and timing of vaccination must take into account the concomitant therapy and the severity of the underlying disease, it being understood that no haematological disease and its therapy constitute a contraindication to vaccination. “Indeed – continues Siragusa – vaccination not only protects patients from the risks of infectious complications, but also from thrombotic complications that affect 4 to 20% of patients with active Covid-19 infection. The extremely rare cases of atypical thrombosis recorded in women under the age of 50 and subjected to viral vector vaccine are still being studied. The SIE has produced an expert consensus on the management of patients who may present with signs or symptoms suggestive of these very rare complications; to date, no new cases have been recorded in Italy. It should be borne in mind that the risk of thrombosis that can occur following Covid is also much higher “. In general, the Covid mortality rate of haematological patients highlighted by a study of the SIE last year is equal to 37%. The scientific society has suggested the use of mRNA vaccines for most patients suffering from haematological diseases.

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