a hereditary genetic blood disorder classified as rare, but very widespread in the Mediterranean area and in particular in Italy, where it is estimated that there are 7 thousand people who suffer from it and about 3 million healthy carriers. Severe beta-thalassemia (or beta-thalassemia) forces patients to repeat blood transfusions, at intervals of 2-3 weeks, in addition to taking a therapy every day that helps them limit the accumulation of iron in organs such as the heart, liver and pancreas. Now for a medicine (administered by subcutaneous infusion) he can halve the need, significantly improving the quality of life of young and elderly patients. To remember the important achievements of scientific research are some of the leading Italian experts on the occasion of the World Thalassemia Day, which is celebrated every year on May 8th with the aim of making the population aware of this pathology and the needs of the sick.
Italy is one of the most affected countries in the world
The new drug, luspatercept (whose ability to grow red blood cells was discovered by accident while being tested as a cure for osteoporosis), had already been the focus of specialists at the 2018 American Society of Hematology congress, when he was presented among the most important innovations of the conference because it proved capable of reducing both the transfusion needs of patients and the complications of iron accumulation, often the cause of other pathologies associated with reduced survival. At the base of thalassemia there is a genetic defect that leads to an ineffective erythropoiesis: that is, in practice, the stem cells in the marrow are damaged and cannot produce an adequate amount of red blood cells. this which obliges patients to continuous blood transfusions which must be performed in the hospital approximately every 20 days, for life. In the world, they live approx 90 million carriers of the genetic mutation, able to determine one of the types of beta-thalassemia – he explains Maria Domenica Cappellini, full professor of Internal Medicine at the University of Milan -. If only one gene of the beta chains of hemoglobin changes, it is called beta-thalassemia minor, which causes no relevant symptoms and does not need therapy. If both genes of the beta chains that form hemoglobin are mutated, it has the form of beta-thalassemia major, presenting a severe clinical picture, with severe anemia. Italy is one of the most affected countries in the world: the disease was present above all among the populations of malarious areas, such as the islands, the southern regions and the Po delta area, since malaria was a factor of natural selection of the thalassemia defect. Symptoms of beta-thalassemia major appear in the first months of life and, if you do not intervene with adequate therapies, the consequences can be severe anemia, bone deformations, enlargement of the spleen and liver, growth problems, hepatic, endocrine and cardiovascular complications.
The damage caused by the accumulation of iron
Today the disease is widespread in the Mediterranean basin, in the Middle East, North Africa, India and Southeast Asia, areas still endemic for malaria. From the mid-eighties, with the spread of prenatal diagnosis (which allows parents who want a child to understand if both are healthy carriers of the genetic mutation that causes the disease and therefore to know if the unborn child will be thalassemic), cases in Italy are decreasing, but thanks to the arrival of treatments always more effective, many couples decide to still have a child, aware of the fact that they can still have a good quality of life. In the sixties of the last century, in fact, patients suffering from thalassemia major did not survive beyond 10/15 years, today thanks to the combination of transfusion and iron chelating therapy their life expectancy can exceed 50 years. On the one hand, regular blood transfusions represent a remedy against ineffective erythropoiesis of the marrow, i.e. the lack or insufficient production of red blood cells which is the cause of severe anemia. Raffaella Origa, medical director at the Microcitemico A. Cao Hospital in Cagliari and researcher in Pediatrics at the University of Cagliari -. On the other, transfusions result in an accumulation of iron, which patients are unable to eliminate naturally and which can cause, for example, heart failure, liver fibrosis or cirrhosis, diabetes, hypogonadism, hypoparathyroidism or hypothyroidism.
The situation of Sardinia
Hence the importance of a so-called iron chelating treatment, which allows the elimination of excess iron, and to perform specific and regular laboratory and instrumental checks. Sardinia is the second Region, after Sicily, with the highest number of patients with transfusion-dependent beta-thalassemia, equal to about 900 people, in the center of Cagliari we follow 460 – continues Origa -. These numbers require a dedicated organizational structure. First of all, there is the problem of lack of blood, a time limited to the summer period but, in the last year, worsened due to the Covid-19 pandemic. Sardinia imports about 27 thousand units of blood every year from other regions. In some periods, patients have to postpone the transfusion or receive less blood than necessary. Furthermore, in Cagliari, we have set up a multidisciplinary team, which guarantees 360-degree assistance to both adult and pediatric patients. Thalassemologists are at the center of a network, which includes other specialists such as cardiologists, hepatologists, endocrinologists, gynecologists, nephrologists, as well as a transplant center. We are also involved in international clinical trials. Where research is done, patients are best looked after, even in the administration of traditional therapies.
Transfusions: 5 hours in hospital approximately every 20 days
If blood represents a real lifesaver, transfusion therapy has a significant impact because on average it must be performed every 20 days and each session in the hospital lasts up to 5 hours. As highlighted by a survey presented on the occasion of World Day last year, more than half of patients perceive the disease as a cumbersome presence in everyday life, a limitation that affects the family and social sphere, as well as representing an obstacle to education and at work, with significant repercussions on physical and mental well-being. The burden of thalassemia on patients’ daily lives is really important – remember Raffaele Vindigni, president of United Onlus (National Federation of thalassemia, sickle cell disease and rare anemia associations) -. It is estimated that these people spend, on average, more than 30 days a year in the hospital for transfusions and follow-up examinations. time taken from family, study, work, free time and holidays. Their life, in fact, revolves around the transfusion center. Furthermore, in Italy, the disease is not treated uniformly throughout the territory. Beta-thalassemia requires not only blood transfusions, but also very clear protocols with instrumental tests to be performed with precise frequency. Today there are centers that carry out these analyzes every 4 or 6 months, others every 2 years. a very serious situation. In 2017, with the Italian Society of Thalassemia and Hemoglobinopathies (SITE), we presented to the Ministry of Health the proposal to establish the Thalassemia network, so that all centers are connected with a digital platform, where they can exchange information to improve care and, above all, standardize them across the territory. The implementing ministerial decree has been signed and is now being examined by the State-Regions Conference. In addition, the expectation of patients towards the terapie innovative, able to improve the quality of life and offer the opportunity to reduce the need for blood. We ask the institutions to listen to the needs of the sick, who cannot wait.
The results of the study with the medicine
The new drug luspatercept has not yet received the green light from the Italian Medicines Agency (Aifa), but is available for Italian patients before marketing thanks to the compassionate use which provides for free supply to hospital centers by the pharmaceutical company (Bristol Myers Squibb) during the price negotiation period with Aifa. Today, for the first time, luspatercept can reduce the need for transfusions – underlines Cappellini, head of the Rare Disease Center at the IRCCS Ca ‘Granda Ospedale Maggiore Policlinico Foundation -. Consists of one subcutaneous injection every 21 days and can potentially be administered to all patients affected by beta-thalassemia, unlike other available options such as bone marrow transplant, the only therapy that can lead to recovery, but with the limit of availability of a compatible donor, or gene therapy , still to be consolidated. Luspatercept reduces ineffective erythropoiesis by allowing the production of mature red blood cells. This is demonstrated by the results of the phase three study, BELIEVE, published in the New England Journal of Medicine. 336 patients with transfusion-dependent thalassemia were enrolled in 65 centers in 15 countries. The primary objective of the study was to reduce the need for transfusions by at least 33% (with a drop of at least 2 units of blood) from baseline, i.e. the units the patient was accustomed to transfusing in the six months prior to taking the drug. The result was achieved by 70% of patients. The second objective was to evaluate a reduction of more than 50% in transfusion requirements, observed in more than 40% of patients. Furthermore, the response has been maintained over time.
The experience with the new cure in Italy
In Cagliari, the compassionate use program with the new molecule started in February 2021, with the enrollment of 13 patients: We cannot draw conclusions yet, but it is possible to confirm in a preliminary manner the results of the BELIEVE pivotal study – concludes Origa -. In some of the patients we begin to observe a lengthening of the transfusion intervals. It should be noted that these “real life” patients are not selected and often present with poor health and complications. The reduction of the transfusion requirement determines a series of positive cascading consequences. the effect on the quality of life is immediate with fewer hospital visits, therefore more freedom and normality. Furthermore, Luspatercept can make the national transfusion system “breathe”, particularly in Regions such as Sardinia that do not achieve self-sufficiency in blood production. Finally, decreasing the number of transfusions means reduce iron intake which can damage organs and possible complications also related to the side effects of iron chelating drugs.
May 7, 2021 (change May 7, 2021 | 20:29)
© REPRODUCTION RESERVED