by Vera Martinella
Study indicates that adding a new drug to standard care significantly improves disease control and reduces spleen size in more than 6 out of 10 patients
Myelofibrosis is a chronic myeloproliferative neoplasm which every year is diagnosed in approximately one thousand Italians, mostly in their sixties, but many cases occur in young people. There are therapies capable of keeping the disease under control even for years, but two important problems remain open: preventing the disease from evolving into acute myeloid leukemia (this happens in approximately 10% of patients) and preventing excessive enlargement of the spleen, very frequent, which entails serious consequences for patients. A step forward comes from one study presented at the annual meeting of the American Society of Hematology, underway in San Diego (California), whose main author is Francesco Passamonti, director of Hematology at the IRCCS Polyclinic Foundation of Milan: Obtaining a response on the spleen in a high percentage of patients and managing to maintain it for a long time implies well-being for the patient and a greater share of control over the disease – comments the expert -. This is why this result is important.
What is myelofibrosis
Myelofibrosis is a bone marrow disease characterized by the presence of alterations in the blood count (anaemia, thrombocytopenia, leukopenia or leukocytosis), accompanied by an increase in the spleen (splenomegaly) and the presence of symptoms such as fever, night sweats and a drop in weight. a rare pathology that determines the gradual appearance in the bone marrow of a fibrous tissue that no longer allows it to function correctly, with a consequent alteration in the production of blood cells – explains Passamonti – The disease is due to the presence of acquired genetic mutations in the JAK2 genes , MPL and CALR. These mutations determine the clinical manifestations of the disease, also releasing pro-inflammatory substances and a survival advantage for the diseased cells which then populate the marrow and spleen. In the early stages, myelofibrosis remains asymptomatic and the diagnosis may be made incidentally after a blood test performed for other reasons. Most patients are diagnosed in more advanced stages and manifest themselves with even serious symptoms such as anemia, enlargement of the spleen (splenomegaly) and thrombosis. It is therefore important to have new drugs available that can combat more advanced disease.
Enlarged spleen and other symptoms
The enlargement of the spleen affects approximately 8 out of 10 patients and causes symptoms such as digestive difficulties, sensations of heaviness, discomfort in the abdomen, early satiety and alterations in normal intestinal functions. In some cases the spleen is so enlarged that it occupies a large part of the abdomen and compresses the lungs (causing a dry cough). In some cases, its surgical removal is necessary. Other extremely debilitating symptoms, which can prevent you from carrying out normal daily and work activities and having a normal social and relational life, are fatigue or asthenia, a chronic sense of tiredness, to which fever, night sweats, itching can be added. widespread throughout the body (which worsens with contact with water, also known as aquagenic itching) and weight loss due to lack of appetite and digestive difficulties adds Passamonti.
The therapies
The therapies available today make it possible to extend the survival of patients and reduce debilitating symptoms, allowing, in most cases, a return to daily and work activities and a normal social life, but the only treatment that allows for definitive recovery is bone marrow transplant from a healthy donor, reserved for certain phases of the disease, for those in good general condition and under 70-75 years of age. The disease is progressive with an increase in the size of the spleen, a progressive decline in hemoglobin and platelets and increasingly disabling symptoms – says Passamonti -. It can also progress to acute leukemia. Based on the clinical characteristics of the pathology and the age of the patient, the risk of worsening of myelofibrosis is calculated: depending on the level of risk, a decision can be made for simple observation without therapy up to an allogeneic bone marrow transplant. Today, effective drugs such as JAK inhibitors (ruxolitinib and fedratinib) are available in Italy, aimed at those genetic alterations that we know are responsible for the neoplasm, allowing patients to extend their survival and reduce debilitating symptoms, allowing, in most cases, the return to daily and work activities and a normal social life. However, they have limitations: The response of the drugs on the spleen is limited and, even when they work, the validity of the treatment decreases over time – continues the expert -. And the transplant is a complex procedure, which cannot be offered to the majority of patients.
The new TRANSFORM-1 study
In short, we need new treatments that have a greater effect on the spleen and control symptoms in the long term. And they fit into this context data from the TRANSFORM-1 study, presented at the American Hematology Conference. This is a phase three trial (the last before the final approval and entry onto the market of a medicine) which enrolled over 250 patients with myelofibrosis who had not yet received any therapy, but who needed to start one . One half received the current standard treatment (ruxolitinib) and the other half ruxolitinib plus the new drug navitoclax. Navitoclax is an oral therapy which, by hitting a precise target (the BCL-2/BCL-XL proteins which promote tumor activity), causes the death of diseased cells which would otherwise live too long – clarifies Passamonti -. was administered as first line treatment with the goal of shrinking the spleen by more than 35% (measured by nuclear magnetic resonance imaging). The milestone, after six months of treatment, was reached in 63% of patients with the combination navitoclax and ruxolitinib and in 31% of those receiving standard care alone. The response was obtained in 76% and 41% in the two populations respectively. Furthermore, loss of response was recorded in 18% of patients with the combination and in 26% with ruxolitinib alone.
Chronic myeloproliferative neoplasms
In hematology, great progress in the last 20 years has been achieved thanks to the discovery of genetic mutations underlying numerous diseases and often responsible for tumor proliferation, as well as its resistance to treatment – comments Paolo Corradini, president of the Italian Society of Hematology (Sie) -. Scientific research then began to create drugs that only affected DNA alterations, sparing healthy cells. This has also led to important results in chronic myeloproliferative neoplasms, such as myelofibrosis, polycythemia vera (characterized by the progressive increase in red blood cells) and essential thrombocythemia involving the excessive increase in the number of platelets. They are rare diseases, which together cause around a thousand new cases to be recorded in Italy every year. They can accompany the patient for years without worsening, requiring only periodic checks or therapies, more or less aggressive depending on the case. The important role of our country in the TRANSFORM-1 trial demonstrates, once again, the high quality of Italian hematology.
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December 12, 2023 (modified December 12, 2023 | 5:13 pm)
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