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B. Drexler et al.
were of grade 3, including gastrointestinal disorders (nau- sea, vomiting), nervous system disorders (headache, paresthesia) and secondary malignancy (one case of breast cancer). The latter was reported as a serious adverse event and assessed as unrelated to the trial treatment. Nine adverse events were considered to be possibly related to the trial treatment by the investigators (nausea, vomiting, headache, paresthesia, insomnia, pruritus, prostatic obstruction, mucositis, vestibular disorder). No death was observed. The observed adverse events reflect the known profile of mirabegron.
Disease-related symptoms
During the trial, 20 patients (51%) suffered from at least one disease-related symptom (DRS). Considering the highest CTCAE 4.0 grade DRS per patient, only one (3%) DRS was grade 3 (abdominal distension), 6 (15%) were grade 2, and 13 (33%) grade 1. Most DRS were gastroin- testinal (abdominal distension, early satiety), general (fatigue, fever), microvascular (erythromelalgia, acropares- thesia, digital ischemia), headache, and pruritus.
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Figure 2. Reticulin fibrosis and nestin positive (nestin+) cells before and after treatment with mirabegron. (A) Bone marrow histology of a patient before (week 0) and at the end (week 24) of treatment with mirabegron. (Top) Reticulin fibers are stained black by silver impregnation (Gömöri). (Bottom) Immunohistochemical stain- ing with a monoclonal antibody against human nestin protein. Note decrease of reticulin fibrosis and increase of nestin+ cells (brown staining) after 24 weeks of treat- ment. Magnification: 200x. (B) Single patient evolutional curves of the grade of reticulin fibrosis (left) and nestin+ mesenchymal cells/mm2 (right) at study inclusion and after 24 weeks of mirabegron. n: number; PMF: primary myelofibrosis; ET: essential thrombocythemia; PV: polycythemia vera; MF: myelofibrosis.
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haematologica | 2019; 104(4)