Myelofibrosis and chronic myeloid leukemia are two rare oncohematological diseases, which in Italy affect respectively about 700 and 1000 people each year. There are several ongoing studies aimed at identifying personalized therapies, that is, capable of responding to the needs of the individual patient. The latest findings have just been presented at the American Society of Hematology (ASH) Congress which took place in Atlanta, Georgia, December 11-14.
Mielofibrosi
“Myelofibrosis is a complex disease with different levels of severity – explains Alessandra Iurlo, head of UOS Myeloproliferative Neoplasias at the Milan Polyclinic -. Typically, it starts over 60 years of age with very heterogeneous symptoms, which can range from simple fatigue to profuse night sweats, weight loss and an enlarged spleen. Each of these, however, may or may not present itself and in a different way from person to person. Not infrequently, this pathology is diagnosed completely randomly, following anomalies found in blood tests “.
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There are now many therapeutic innovations and the potential of some new molecules was presented during the Congress. “The goal of research today is to offer targeted treatments to patients, based on the characteristics of ‘their’ disease – underlines Iurlo -. A big step forward had been made in recent years with ruxolitinib, which positively affects the quality of life of these patients by reducing symptoms and the size of the spleen. However, this drug has a limit, namely that after a few years its effectiveness decreases or side effects appear such as to prevent the continuation of the treatment “. A very promising drug, already approved in both Europe and North America for the treatment of patients with myelofibrosis, is fedratinib, another JAK inhibitor, which has also been shown to be effective in patients who are refractory or intolerant to previous treatment with ruxolitinib. Other therapeutic strategies have also been proposed, based on the association of ruxolitinib with other molecules with a different mechanism of action, such as parsaclisib. Other drugs such as pelabresid, a BET inhibitor that works by modifying the expression profile of some genes involved in pro-inflammatory mechanisms, have also aroused much interest. “Last but not least, I would like to mention luspatercept, a drug initially used in other haematological diseases such as thalassemias and myelodysplasias, but which has proved capable of reducing the amount of transfusion requirements also in myelofibrosis”, says Iurlo. “However, it is necessary to remember that, even today, the only potentially curative therapeutic approach for myelofibrosis is stem cell transplantation, an unfortunately risky procedure and indicated only in seriously ill patients under the age of 70”.
Chronic myeloid leukemia
“Chronic myeloid leukemia is also often diagnosed in a completely random manner: the typical case is in fact that of an occasional finding of an increased number of white blood cells in routine blood tests – comments Iurlo -. Of course, there are still other cases today that can present themselves with a more challenging picture, characterized by an enlarged spleen or by severe fatigue, the latter expression of a contextual reduction in the number of red blood cells “. Compared to myelofibrosis, the age of onset of chronic myeloid leukemia is lower, typically around 55 years, although there are rare cases that arise in pediatric age. Before the 2000s, the life expectancy of patients with this form of leukemia was 5-8 years: today, thanks to the discovery of a new class of drugs, namely tyrosine kinase inhibitors, these patients can live about as much as a healthy person and, for some of them, there is also the possibility of ending the treatment in a shorter or longer time.
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“To achieve this result, it is important to select the right drug for each patient: in fact, we recall that five molecules are currently available for the treatment of chronic myeloid leukemia: imatinib, dasatinib, nilotinib, bosutinib and ponatinib. The use of second-generation drugs, such as dasatinib, nilotinib and bosutinib, already at the forefront can reduce the risk of inadequate responses. However, each of these drugs has a potential side effect profile that must be managed by the haematologist. Regarding ponatinib, a third-generation inhibitor with a safety profile that is not the best, the results of the OPTIC study were presented at the last Congress of the American Society of Hematology. In this study, a treatment strategy was identified that involves the use of ponatinib at an initial dose of 45 mg per day with subsequent reduction to 15 mg after achieving adequate response, in order to significantly reduce the risk of thrombotic events. . Another very interesting molecule is asciminib, a drug capable of acting with a different mechanism of action compared to tyrosine kinase inhibitors and therefore potentially capable of overcoming certain resistance mechanisms “, comments Iurlo
“Today, however, – concludes Iurlo – there is still no ‘perfect’ drug, especially as regards side effects: what we hematologists aim for is to find the best drug for each individual patient. For this reason, given the complexity of these pathologies, it is important to contact structures with proven experience and which have protocols with which to offer the possibility of accessing innovative molecules, well before they are placed on the market “.
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