Blood cancers: 70% of patients can recover with Car-T and bispecific antibodies

A ‘research bridge’ that connects Italy with the United States: it will be possible to travel ideally until 26 October in Rome, where the fourth edition of the SOHO Italy annual Conference takes place. SOHO Italy is the Italian extension of the “Society of Hematologic Oncology”, founded in the United States in 2012 by researchers from the MD Anderson Cancer Center in Houston. Indeed, research today allows 70% of people affected by blood cancers to heal. Fifteen years ago this percentage did not exceed 30%. A very important result, obtained thanks to the innovation of therapies, which does not stop and sees Italy at the top of research. ‘SOHO Italian Conference’ is an event that aims to promote dialogue between international researchers at the highest level to bring innovative therapies to the patient’s bed as soon as possible.

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The ‘awakening’ of the immune system thanks to Car-T

The most frequent blood cancers are lymphomas, leukemias and multiple myeloma, which each year in our country register about 30 thousand new cases. The most advanced frontiers of research are constituted by Car-T, ie cell therapy, and bispecific antibodies. Car-T are now reimbursed and available in our country in the most aggressive lymphomas and acute lymphoblastic leukemia, in patients already undergoing various lines of therapy and with a very short life expectancy in the absence of adequate therapy, equal to a few months. Today 60-70% of the population treated with Car-T lives more than one year. “Cell therapy based on Car-T has fostered an epochal revolution in the fight against blood cancers”, explains Giovanni Martinelli, Scientific Director of the Romagnolo Institute for the Study of Tumors ‘Dino Amadori’ – IRST IRCCS, Meldola and president of SOHO Italy. The goal is to ‘awaken’ the immune system, which has tolerated tumor growth for too long ”.

Few production workshops in Italy

In aggressive lymphomas, such as non-Hodgkin’s, 40% of patients recover from a single infusion thanks to Car-T. And promising studies are underway for their use also in multiple myeloma, acute lymphoblastic leukemia of the elderly and acute myeloid leukemia. “The Car-T – continues Martinelli – are based on the patient’s genetically modified lymphocytes. The procedure is complex and includes various phases: from the collection of T lymphocytes from the blood, to their engineering and expansion in specialized laboratories inside sterile bioreactors, up to their reinfusion in the patient. The cells must be shipped to the United States, where the engineering process centers are located. In Italy, academic institutions with a Car-T production workshop can be counted on the fingers of one hand, far too few. A change of pace is needed to make these innovative weapons available to the greatest number of patients ”.

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Bispecific monoclonal antibodies for multiple myeloma

In multiple myeloma, bispecific monoclonal antibodies are able to target cancer cells with extreme precision, comparable to a laser. In acute myeloid leukemia, which until a few years ago had a poor prognosis especially in the elderly, increasingly selective weapons make it possible to remove the fuel from the leukemia cells. “In multiple myeloma, which originates in the bone marrow and affects about 5,750 people in Italy every year, the median survival has passed in the last twenty years from 36 months to about 7 years”, he explains Claudio Circle, executive medical researcher of the Hematology Division of the IRST “Dino Amadori” IRCCS and president of SOHO Italy. “Today we can talk about the chronicization of the disease thanks to research. We are able to treat even refractory and relapsed disease in the best possible way thanks to immunotherapy “.

The ‘medullary microenvironment’

The therapeutic innovation was represented by the introduction of drugs with direct action towards the plasma cells and the ‘medullary microenvironment’, first of all immunomodulators. Proteasome inhibitors and monoclonal antibodies have also further enriched the therapeutic scenario. “These drugs were usefully used first in patients with relapsed-refractory disease and, subsequently, in newly diagnosed ones, combined in chemo-free regimens, without chemotherapy drugs”, continues Cerchione who adds: “The therapy of multiple myeloma is profoundly changing, after the excellent results obtained with monospecific monoclonal antibodies (anti-CD38), which today are used since the first line and which have revolutionized the history of the disease making it chronic. We can talk about the sequence and choice of therapies, based on parameters that also include the quality of life ”.

Therapies for relapsed patients

Above all, we begin to evaluate the depth of response even in the relapsed and refractory patient, analyzing the minimal residual disease. And there are therapies that can also be used starting from the fourth relapse (anti-BCMA), with important results in terms of balanced efficacy, with good tolerability in patients who previously lacked therapeutic opportunities. “Today drugs with even more innovative mechanisms of action are appearing, namely bispecific antibodies, which represent the most extreme frontier of precision medicine, waiting to have Car-T available in our country as well”, explains Cerchione. “We are reaching very important milestones in smoldering myeloma, where identifying high-risk patients can allow us to slow down the progression into multiple myeloma.”

Acute myeloid leukemia personalized therapy model

The therapies in acute myeloid leukemia, which affects over 3,000 people in Italy every year, especially the elderly, are also increasingly precise. “This blood cancer represents the model par excellence of personalized medicine”, continues Martinelli. On the one hand, we have new drugs available, the progenitor of which is the inhibitor of BCL2, a molecule produced by leukemic cancer cells, which are very selective and can also be used in combination with other therapies. On the other hand, it is important to act on the metabolic mechanisms by removing the fuel, ie glucose, from the diseased cells. In this way, even in elderly patients, it is possible to obtain a long disease-free survival and reduce the costs for families and the health system ”.

The history of targeted therapies began precisely with blood cancers, in particular chronic myeloid leukemia, which every year, in Italy, records about 1,000 new diagnoses, especially in the elderly. “In this haematological neoplasm, over 20 years ago, a genetic lesion was identified for the first time, which was the target of the parent molecule of targeted therapies, a tyrosine kinase inhibitor,” he explains. Giuseppe Saglio, emeritus professor of Hematology at the University of Turin. “Chronic myeloid leukemia therefore constitutes the real paradigm of molecularly targeted therapies. Before these molecules, the only alternatives were bone marrow transplant, which requires a compatible donor, and interferon, to which less than 20% of patients responded. With the first and second generation tyrosine kinase inhibitors, the scenario has changed and for these patients life expectancy is excellent “.

‘Functional’ healing

In short, so many advances that can make us say today that 70% of people affected by blood cancers recover or get a complete remission. “Sometimes – specifies Martinelli – there is no complete eradication of the disease but a ‘functional’ recovery is obtained”. “These patients are in a similar condition to those with arterial hypertension or diabetes, that is, they have to take daily therapy, but they can lead a normal life.”