“Anemia is one of the most important problems in patients with myelofibrosis”, a bone marrow tumor characterized by the progressive accumulation of fibrous tissue which impacts the production of red and white blood cells and platelets. “40% of patients have anemia at the time of diagnosis”, patients “who also as a consequence of current treatments of myelofibrosis become 60-70%, with a significant proportion of transfusion-dependent. The drugs to control this condition are effective in 20% of patients, but this effect is lost within a year and repeated transfusions can cause accumulation of iron in the organs with the development of consequent toxicity. This condition is associated with asthenia which has a very high impact on the quality of life Drugs are now being developed” such as momelotinib, “which despite belonging to the Jak inhibitor family can improve anemia even in a portion of anemic and transfusion-dependent patients”. Thus Alessandro Maria Vannucchi, full professor of Hematology, University of Florence and director of the Complex Hematology Structure, Careggi University Hospital, speaking today in Verona at a press meeting organized by GSK.
“Myelofibrosis, a chronic myeloproliferative neoplasm – explains Vannucchi – is sometimes diagnosed completely randomly due to the finding of altered blood test values or the symptoms that the patient reports”. Myelofibrosis “differs from polycythemia vera and essential thrombocythemia, which are other chronic myeloproliferative neoplasms. The patient with myelofibrosis generally presents with a series of symptoms which are mainly linked to the increase in volume of the spleen which, therefore, Sometimes it can cause digestive problems, such as a feeling of fullness, there are also systemic manifestations, in more advanced forms, such as weight loss, significant night sweats and, sometimes, even a low-grade fever for no other reason. . The reduction in the number of red blood cells, therefore anemia, involves all the symptoms of easy tiredness, but also difficulty concentrating.”
Myelofibrosis therapy “was largely palliative until the introduction of Jak inhibitors”, introduced starting from the understanding that most of the symptoms and clinical manifestations of myelofibrosis are due to inflammation and cytokine overload, caused by a ” problem in Jak-Stat – explains the professor – which is an important intracellular pathway for the regulation of the activity of marrow cells, but also, and above all, for the inflammatory environment. These drugs, which inhibit this signaling pathway Jak-Stat activated, were effective especially on some important clinical needs of the patient such as the increase in spleen volume and on systemic symptoms”.
“Anemia, which has a major impact on the quality of life – Vannucchi points out – is difficult to treat. There have been a whole series of attempts over the years with drugs which, however, in part continue to be used – erythropoietin, androgenic type – to stimulate the marrow. However, these are therapies that are effective in a small percentage of patients and for a generally very short time. The problem has been complicated by the fact that most Jak inhibitors have side effects very often , although not necessarily, a worsening of the anemia”. For “some patients who already started out anemic”, we are witnessing “a worsening. Others who started with a hemoglobin problem almost at the limit of normality have become anemic and, in some cases, even transfusion-dependent. This is not a rule: many patients tolerate older Jak2 inhibitors in their clinical use without developing transfusion-dependent anemia.”
More recently, however, “it has been observed that there are molecules” such as momelotinib, approved in Europe and the United States, “which belong to the family of Jak inhibitors – specifies the haematologist – however they also have additional molecular targets, compared to Jak2 alone , and which, while maintaining an efficacy on splenomegaly and symptoms, also often have an important efficacy on anemia, correcting it, these patients, who start out anemic or who develop anemia under treatment with a Jak inhibitor, represent a valid alternative.” .
At the moment “there is an extremely varied panorama of molecules that are being investigated in clinical studies as a single molecule or in addition to a Jak inhibitor – concludes Vannucchi – in order therefore to exploit the effect, the effectiveness of the Jak inhibitors, perhaps enhancing it, or trying to prevent or reduce side effects such as that of cytopenia induced by Jak inhibitors”.
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