In people with myelodysplastic syndrome (MDS), a mostly benign form of senile leukemia, the body produces too few functional blood cells. They suffer from anemia, also known as "anaemia", which can be a precursor to acute leukemia. So far, there have been hardly any treatment options for patients other than regular blood transfusions. In a study by the German MDS study group, the drug luspatercept, which acts like a “vacuum cleaner” in a figurative sense, was able to significantly improve the blood values of those affected. The worldwide follow-up study led by Prof. Dr. Uwe Platzbecker has confirmed the effectiveness of the preparation. It was recently published in the prestigious New England Journal of Medicine.
MDS is one of the most common malignant blood diseases of the bone marrow, which primarily affects older people. About 80 to 90 percent of patients are treated with regular transfusions of erythrocyte concentrates, i.e. red blood cells. In the long run, however, this cannot significantly improve the symptoms and can also lead to iron overload and organ damage. The causes of the disease are multifactorial. “We know that there must be one or more genetic changes in the stem cell of the bone marrow for MDS to develop. At the same time, our research results have also shown that the bone marrow environment and certain hormones that can have a negative effect on blood formation contribute significantly to the development of the disease," says Prof. Dr. Uwe Platzbecker, Professor of Hematology at the University of Leipzig and Head of the Department of Hematology and Cell Therapy at the local university hospital.
229 patients took part in the study
The drug luspatercept has now been tested for efficacy and side effects in a global phase III study. The substance acts like a molecular vacuum cleaner in which it removes negative "hormones" from the bone marrow and thus stimulates blood formation. 229 patients took part in the study: 153 of them received the drug luspatercept for 24 weeks, the other 76 received a placebo. As a result, around 38 percent of participants using luspatercept did not require a blood transfusion for at least eight weeks. In the placebo group, it was only 13 percent. 28 percent of the patients who took the drug were transfusion-free for more than 12 weeks (placebo: 8 percent). “Luspatercept can be a well-tolerated and, above all, highly effective therapy for many of those affected. Many participants in the study remained transfusion-independent, some for several years. We have thus developed a new therapy option for a group of patients for whom there are currently no treatment options apart from transfusions," says Platzbecker. In addition, luspatercept is characterized by a good side effect profile: The study participants only reported slightly increased fatigue, diarrhea, nausea and dizziness.
Drug captures hormones
The preparation luspatercept is referred to as a so-called ligand trap. This means it attracts and traps hormones that suppress the formation of red blood cells in the bone marrow. Once these hormones are trapped, blood formation can resume as usual. Approval for the drug has now been applied for in the USA and Europe. "We hope that it will be launched in Germany at the end of 2020," says Prof. Dr. Uwe Platzbecker. In the meantime, the German MDS study group, headed by Prof. Platzbecker, is currently planning further follow-up studies in which the active ingredient is combined with other substances in order to increase response rates. The current study was supported by Celgene in collaboration with Acceleron Pharma.
Original title of the publication in the New England Journal of Medicine:
Luspatercept in Patients with Lower Risk Myelodysplastic Syndromes,
dr Catherine Werneburg
Source: Leipzig University press release of January 20, 2020