Myelodysplastic syndromes are a heterogeneous group of blood diseases that are caused by damage to bone marrow stem cells. Until a few years ago, myelodysplastic syndromes were considered incurable, but today they can start to benefit from personalized therapies.

Every year in Italy the new diagnoses are about 3-4 thousand, mostly concern people over 70 years of age and the number of patients is expected to grow. However, since these diseases are still little known, they are rarely discovered at an early stage. For a correct diagnosis it is necessary to perform specific tests within a specialized haematological path, to assess the risk of disease in each patient. Only in this way is it possible to choose the best treatment, taking into account the biological characteristics of the pathology, the age of the patient, any other diseases from which he suffers and his general state of health.

The importance of the biological mechanisms

“At the root of these diseases there is a defect that prevents the stem cells of the marrow to produce an adequate amount of white blood cells, red blood cells and platelets,” explains Professor Matteo Della Porta, director of the Leukaemia Unit of Humanitas and director of the scientific committee of the Italian Association of Myelodysplastic Syndrome Patients (AIPASIM,

“This causes extremely different pathologies: some patients have the same life expectancy as the average population, while others experience rapid evolution into acute myeloid leukemia. However, myelodysplastic syndromes are on the rise because they are typical of advancing age. Patients have specific care needs and for this reason it is necessary to develop targeted diagnosis, therapy and care pathways. The scientific advances of the last few years made it possible to understand the biological mechanisms underlying these diseases, making it possible to define more precisely the prognosis of each patient and, above all, to develop new targeted drugs”, continues Professor Della Porta.

Anemia and the need for transfusion

An extremely frequent symptom in the patients with myelodysplastic syndrome is anaemia (lack of haemoglobin and red blood cells), which has a great impact on the quality of the patients’ lives and also on their life expectancy. At the basis of anaemia there is a “defect” that leads to an ineffective erythropoiesis: the stem cells in the marrow are in fact “damaged” and cannot produce an adequate amount of red blood cells, with the consequent need for patients to continue blood transfusions.

“Up until recently, the therapeutic tools to combat anemia were very limited. Most patients have to perform regular transfusions of red blood cells in order to overcome the lack of bone marrow production. In the early stages of the disease, erythropoietin is helpful in reducing the need for transfusion and improving the levels of hemoglobin and the red blood cells in a percentage of patients,” explains Prof. Della Porta.

A new medication for the treatment of anemia

“In the last few months, a new drug for the treatment of anaemia in patients with myelodysplastic syndrome, called luspatercept, has completed the clinical development process. A few years ago, researchers noted that in female patients who were receiving treatment for osteoporosis with luspatercept unexpectedly increased the blood hemoglobin levels and investigated the reasons for this. Subsequent studies have shown that luspatercept was able to very specifically promote the production of red blood cells, responsible for the transport of oxygen in the blood, by the bone marrow. Thus, in 2015, trials began on patients with anemia (including cases of patients with myelodysplastic syndrome).

Today the trial on myelodysplastic syndromes is over and the results have been presented at the Congress of the American Society of Hematology (ASH) in San Diego last December. We found that luspatercept is particularly active in patients with a subtype of disease, myelodysplastic syndromes with sideroblasts ring, where it is able to significantly reduce the need for transfusions to which the patients must continuously submit in most cases. Approval in Europe for the use of luspatercept in myelodysplastic syndromes with ring sideroblasts is expected between the end of 2019 and the beginning of 2020.

It is important to note that in the last few months a controlled clinical study (COMMANDS) has been activated (also in Humanitas), aimed at patients with myelodysplastic syndrome (all low-risk subtypes are eligible) that compares the effectiveness of erythropoietin vs luspatercept in the treatment of anemia”, concluded Professor Matteo Della Porta.