Myelodysplasias, green light for therapy that can make six out of ten patients independent of transfusions

A cascade of events can sometimes start from a single cell. Thus, in the case of myelodysplastic syndromes, a definition that brings together various blood cancers, improper cell maturation can set off pictures that manifest themselves in many ways. One of these, the most common on the clinical front, is severe anaemia. which weighs. And how. Severe haemoglobin deficiency forces sufferers to visit the hospital frequently to undergo blood transfusions, as well as forcing them to take daily iron chelation therapy to prevent excess iron from damaging vital organs such as the heart, liver and pancreas. This is why the extension by Aifa - the Medicines Agency - of the reimbursability of luspatercept, a therapy that acts on ineffective erythropoiesis of the marrow, i.e. the lack of or insufficient production of red blood cells, appears of great importance. The treatment has been shown to reduce the number of transfusions, with a significant impact on long-term survival and quality of life. Sixty per cent of patients even achieved transfusion independence.

In Italy, there are an estimated 3,000 new cases of myelodysplastic syndromes every year, mainly in the elderly over 70 years of age. This is probably a downward figure, because many people do not receive a correct and timely diagnostic diagnosis. In any case, myelodysplastic syndromes are clonal pathologies, i.e. linked to a single cell that becomes anarchic to control mechanisms and gives rise to offspring that are altered in terms of both shape and functional capacity. As Valeria Santini, Professor of Haematology at the University of Florence, Head of the MDS Unit at the Careggi University Hospital in Florence and President of the FISiM (Italian Foundation for Myelodysplastic Syndromes) Scientific Committee, recalls, 'the most frequent clinical manifestation is anaemia and, often, the need for blood transfusions, but these patients can also be subject to infections and haemorrhages. The symptoms and course vary significantly depending on the type of blood cell affected. The most frequent symptoms due to haemoglobin deficiency are tiredness, weight loss, breathing difficulties and an accelerated heartbeat. The impact on quality of life is enormous, especially for people with severe anaemia who have to go to hospital, in some cases every week, for blood transfusions'.

In the most severe forms, myelodysplastic syndromes can evolve into acute myeloid leukaemia, a more aggressive cancer. "In most cases," points out Matteo Della Porta, Head of the Leukaemia Unit, Humanitas Cancer Center, Milan, and Full Professor of Haematology at Humanitas University, "the causes of the disease are unknown, because the mechanism that triggers the process of DNA modification of one of the bone marrow stem cells is not known. There are also secondary forms, linked to exposure to occupational risk factors, such as chemicals like benzene, lead or solvents. In addition, some patients may develop the disease following previous treatment with chemotherapy or radiotherapy, used to treat other malignancies'.

Red blood cell insufficiency, in almost all patients, becomes severe over time and requires support with regular blood transfusions, which can also become very frequent. 'In the treatment of low-risk myelodysplastic syndromes, few patients show a lasting response to erythropoiesis-stimulating agents,' Della Porta resumes. Approximately 30% are not eligible to receive them or do not benefit from them, and for another 30% they have a time-limited effect, not exceeding one year'. In this sense, luspatercept is the first drug in 40 years to demonstrate superiority over epoetin alfa, an agent that stimulates erythropoiesis and for decades a reference therapy, substantially reducing transfusion requirements. 'The drug,' Santini emphasises, 'acts in a completely innovative way on ineffective erythropoiesis, increasing the quantity of red blood cells, interfering with the negative signals that in myelodysplasias suppress their production. In the COMMANDS study, almost twice as many patients treated with luspatercept achieved transfusion independence with a consequent increase in haemoglobin: 60% compared to 35% with epoetin alpha, including subgroups of patients with clinically relevant features. Luspatercept demonstrated a durable response, with a median duration of transfusion-free time of more than 2 years, almost 12 months longer than with epoetin alfa'.

"Myelodysplastic syndromes are still little known, even though there is more awareness among clinicians, patients and institutions, also thanks to the commitment of AIPaSIM, established in 2017 precisely to fill a knowledge gap and to make people understand the importance of pathology networks," concludes Annamaria Nosari, Vice-President AIPaSiM onlus (Associazione Italiana Pazienti con Sindrome Mielodisplastica) - "These patients present specific clinical and care needs and must be treated in specialised centres. In addition, their often advanced age and the presence of copathologies imply difficulties in therapeutic management, particularly of severe anaemia, which is its most frequent manifestation. Patients who need frequent blood transfusions often have to travel to hospital and their lives, in fact, revolve around the specialist centre, with a reduction in the quality of life itself. For the elderly, travelling to the treatment centre can become very complex. This is a condition that places a burden on the family and the health service. Thanks to the luspatercept innovation, patients' lives can really change, because they do not have to travel frequently to specialist centres to meet their blood requirements".