Experts say there is promising news for those with aggressive lymphoma, for the elderly with acute myeloid leukemia and for patients with myelofibrosis and polycythemia vera.
Every year they register in Italy 70 new cases of blood cancers per 100 thousand inhabitants and about 40 thousand compatriots have to deal with a diagnosis of leukemia, lymphoma, myeloma or with one of the dozens of different subtypes of haematological neoplasms that mainly affect after the age of 65. Diseases that are more and more treatable for many years and that in an increasing number of cases we are also able to cure – underlines Paolo Corradini, president of the Italian Society of Hematology (Sie) -. Not a slogan, but a reality: thanks to new treatments and advances in scientific research we have made important steps forward which allow those who fall ill to live longer and better. The major innovations were exhibited in recent days in Rome, during the national congress of the Sie, which from biennial now becomes annual, because with the constant arrival of innovative treatments It is important to update more quickly, says Corradini.
Aggressive non-Hodgkin’s lymphoma
Time matters a lot, especially if you have an aggressive tumor, as it happens to some patients who are diagnosed with non-Hodgkin B-cell lymphoma. A neoplasm that is diagnosed every year at approx 4,500 people, 60-65% of whom recover with first-line therapy. They are used for further effective treatments for those who do not respond (in medical terms refractory) or have a relapse and in this context the new bispecific antibodies can be useful, which are being studied even after the failure of CAR-T cells: they are also called double target, because they bind to two target targets at the same time, connecting T cells, the most powerful agents of the immune system, to cancer cells. Thanks to this bridge, T cells can act at close range on cancerous ones, recognizing them, binding to specific antigens and releasing molecules that cause their death. Preliminary data from a 60-patient trial indicate that from combination of polatuzumab and glofitamab we are able to obtain 50% of complete answers – explains Corradini, director of Hematology at the IRCCS National Cancer Institute (Int) Foundation in Milan -: it means that, with a cure with a limited duration (12 infusions, approximately 12 months), there is no trace of the disease. And it seems that some of the complete answers are lasting, i.e. there are no relapses. Of course, confirmation is needed, but the data is promising and this is a remarkable advance.
Acute myeloid leukemia in the elderly
A greater number of patients who benefit from the treatment and see them persist over time are the closest goals today even for those suffering from acute myeloid leukemia (typical of adulthood and advanced age): they are About 3 thousand new diagnoses every year in our country and at five years unfortunately only 20% of the sick survive, not only because it is often about an aggressive disease that progresses rapidlybut also because older people who are affected cannot tolerate it aggressive treatments that would be necessary to achieve healing. In those who are not candidates for intensive chemotherapy and transplantation, but who have a mutation of the IDH1 genebased on the results of the Time.newsLE study, months of survival can be gained, with a good quality of lifefrom the combination of the targeted drug ivosidenib with the hypomethylating therapy azacitidine versus azacitidine alone, he says Francesco Passamonti, Professor of Hematology at the University of Insubria in Varese -. We manage to extend the survival of these patients, which they have a multidrug-resistant disease and they have no other options with this well-tolerated target drug mix.
How and why even CAR-T’s fail
A session of the Sie congress was also dedicated to the challenges of scientific research, with the intervention of a young Italian flagship transferred to the United States: Marco Ruellaa professor of hematology at the University of Pennsylvania and scientific director of the Lymphoma Program at the Perelman School of Medicine, tried to answer open-ended questions for hematologists. Because the tumor manages to escape the most innovative therapies such as CAR-T, built in a very sophisticated way to recognize the cancer cells of the individual patient and kill them? How does? And what can be done? There are now several CAR-T approved and in use for patients with different types of haematological neoplasms – explains Ruella -. Data from a recent study published in the New England Journal of Medicine they tell us that, five years after the cure, 30-40% of patients with treated lymphoma live without the disease and they seem to indicate, in the long run, that most of those who respond to CAR-T recover. There remain for those two thirds of patients (the remaining 60-70%) who undergo a relapse. The reasons we have identified are different: we are studying why the cure does not work in some, but we have also identified strategies that the tumor puts in place to escape. And then the tumor microenvironment plays a role, inhibiting the correct functioning of CAR-T. And so the researchers study strategies to circumvent these obstacles by exploiting genetic engineering and trying, for example, to shorten the production time of CAR-T, going from about 20 days to less than a week. And then we are trying to create new products that target multiple cancer targets together, in order to hit the tumor harder, on several fronts. The same goal we are trying to achieve combining different drugs and T lymphocytes together.
Myelofibrosis drug mix
Myelofibrosis is a chronic, rare myeloproliferative neoplasm (affects approx one individual for every 100 thousand), which determines the gradual appearance in the bone marrow of a fibrous tissue that changes its structure and no longer allows it to function properly, with a consequent alteration in the production of blood cells. Myelofibrosis mainly affects the over 60s and it is estimated, in Italy, about 700 new cases every year – explains Passamonti, Director of Hematology ASST Sette Laghi di Varese -. The characteristic manifestation enlargement of the spleen (splenomegaly) is a heterogeneous and difficult to treat pathology, because it can cause not only grave anemiabut also decrease in leukocytes and platelets. Treatment options are limited, but research is progressing. Recent studies indicate that by combining ruxolitinib with navitoclax or pelabresib, two target drugs that inhibit the activity of specific targets, we are able to reduce the disease (both clinically, with improvement of symptoms and spleen, both molecular or medullary) and to give a good quality of life for patients. Another relevant thing that we have understood more clearly the key role of some genes which have an impact on the prognosis of secondary myelofibrosis and this can help us Better “calibrate” the therapies on the individual case and to opt for bone marrow transplantation or new therapies with greater precision.
polycythemia vera
Polycythemia vera is also a chronic myeloproliferative neoplasm: characterized byprogressive increase in red blood cellsthis disease can expose sufferers to greater probabilities than thrombosis, stroke, myocardial infarction and can evolve into myelofibrosis. Therapy must therefore take into account the vascular risk factors that each patient can have: today the standard for first-line therapy with hydroxyurea, but a part of the sufferers resistant or intolerant. What to do then? The answer comes from two pivotal studies (RESPONSE 1 and 2) that compared the drug ruxolitinib (a JAK2 inhibitor) with the best therapy so far, which does not meet our needs – he explains. Valerio De Stefano, Professor of Hematology at the Catholic University of the Sacred Heart of Rome and director of the Department and DH of Hematology at the Gemelli Hospital -. Approximately 350 patients with polycythemia in Europe were enrolled in the post-authorization phase IV study, of which 182 only in Italy. On the latter we made specific sub-analyzes, also because they represented an interesting category: they were more “difficult” patients, 65% were resistant to treatmenthad a longer history of illness, many needed a significant number of bloodletting. The results are very satisfactory: after two years of therapy, in 96% of patients the disease was under control and we have achieved such a reduction in red blood cells as to greatly stem the risk of thrombosis (only 7 patients out of 182 have had thrombotic episodes) – concludes the expert -. Not only that: ruxolitinib well tolerated, with few side effects and a better quality of life for the sick.
October 13, 2022 (change October 13, 2022 | 18:13)
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