Summer, anti-Covid restrictions on and there is an immediate desire for freedom. Without exception, not even for those who carry a disease that has always limited them as in the case of beta-thalassemia which requires continuous transfusions. But from Vienna, where the congress of the European Association of Hematology has just been held, there is good news that will set free even thalassemia patients. The results of the Believe study show that after three years of treatment with luspatercept, about half of patients reduce their need for transfusions by 50% and 12% gain independence for more than two months. The new data was unveiled today at a virtual press conference, sponsored by Celgene now part of Bristol Myers Squibb.
The ‘major’ and the intermediate form
Beta-thalassemia is a genetic disease transmitted by two asymptomatic parents or healthy carriers, which affects about 7,000 people in Italy, 5,000 in the most severe form, the ‘major’. It requires continuous transfusions, every 2-3 weeks and for life, with the risk of incurring iron accumulations that can damage the heart, liver and pancreas. For this reason, iron chelating drugs must be taken, which in turn can cause side effects. “We know of more than 350 different mutations in the beta-globin gene that cause the disease, but from a clinical point of view, thalassemias are classified into transfusion-dependent forms (thalassemia major) and non-transfusion-dependent forms (intermediate forms),” he says. Maria Domenica Cappelliniformer director of the Internal Medicine Operational Unit, head of the Rare Disease Center, Coordinator of the Rare Diseases Unit at Irccs Fondazione Cà Grande Ospedale Maggiore Policlinico di Milano.
Dependence on transfusions
Thalassemia major affects about 80% of patients, is the most severe and requires continuous transfusion therapy, while the intermediate forms require periodic checks and occasional transfusions at particular times, such as pregnancy, surgery or infections. “In the most severe form – continues Cappellini – the manifestations of the disease already occur in infants, with very low hemoglobin levels, an increase in the volume of the liver and spleen and a slowdown in growth. The intermediates, on the other hand, can occur later in time and with less severe symptoms “.
50% reduction in transfusions
The main cause of severe anemia and clinical manifestations is ineffective erythropoiesis, a consequence of the lack of production of the globin chains that form hemoglobin. “The new drug – says Cappellini – reduces it and consequently also decreases anemia. It has a tolerable safety profile and represents a prospect of enormous interest as an alternative to traditional transfusion and iron chelation therapy. After 3 years of therapy, 50% of patients achieved a 50% reduction in transfusions, in each 12-week interval, compared with 40% of patients who achieved this endpoint after 1 year. 12% of patients achieved transfusion independence for more than 8 weeks after 3 years, compared with 10.7% after 1 year. Obviously, the reduction in hospital admissions has an important impact on the quality of life “.
Lo studio Believe
The new drug, reimbursed by AIFA in 2021, reduces the need for blood by more than 30%, with a great improvement in the quality of life. The international Believe study, already published in the ‘New England Journal of Medicine’, showed that, out of more than 300 patients suffering from transfusion dependent thalassemia, 70% thanks to luspatercept achieved an initial reduction of 33% in transfusion requirements. “Luspatercept had also given excellent results during phase two of the clinical trial – he declares Silverio Perrotta, head of the Pediatric Hematology and Oncology Unit of the University of Campania ‘L. Vanvitelli ‘, head of the Center for the Diagnosis and Treatment of Hemoglobinopathies and of the ERN-EuroBloodNet Center – but the data we now have allows us to guarantee its long-term safety. The group of patients in the Believe study who received the placebo joined those on treatment, for a total of 315 patients who received the drug ”.
Possible beneficial effects on malleolar ulcers
Among these patients, who continued the treatment for three years, only 7% stopped it due to side effects, ranging from bone pain, manageable with mild painkillers, to thromboembolic events. “In this last case, however – explains Perrotta – it should be pointed out that the patients were already at risk, because they had undergone the removal of the spleen. Luspatercept does not appear to have significantly increased this risk. Not only that, it also seems to have beneficial effects on malleolar ulcers, a common complication, which in some cases even heals with the drug, and on the bones, with an improvement in the osteoporosis picture. It also improves the problem of iron overload caused by transfusions by reducing the intake of iron chelators. It is therefore capable of significantly changing the life of people suffering from beta-thalassemia, with a significant reduction in periods of absence from work and a minor impact on family tasks “.
The trial for children
The new drug has been reimbursed by AIFA since 202: “Today the indications are for adults, but there is already a trial underway for approval in the pediatric range, with the age of 18: a great proof of its safety . In many Italian regions there are still difficulties in prescribing transfusion-dependent adult patients, but it will soon be available throughout the country ”, concludes Perrotta.
there are more than 7 thousand people affected by beta-thalassemia in Italy. Most are affected by the most severe form, the ‘major’, which causes dependence on transfusions, with the risk of incurring side effects due to the accumulation of iron, which can damage vital organs such as the heart, liver and pancreas. The international BELIEVE study highlighted significant results and showed how a new molecule can significantly improve the quality of life of these patients. The important innovations are illustrated in Vienna, on the occasion of the congress of the European Association of Hematology (EHA).