Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant or intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes due to disease biology and inadequate efficacy and/or safety of current therapies. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with the potential to overcome resistance or intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. Two hundred and thirty-three patients were randomized to asciminib (n=157) or bosutinib (n=76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% CI, 2.19-22.30; 2-sided P=.029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and fewer adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant or intolerant to ≥2 prior TKIs. The trial is registered at www.ClinicalTrials.gov as NCT03106779.

Hypertensive crisis (HC) stands out as one type of acute elevation in blood pressure (BP) and can manifest as hypertensive emergency (HE-with target-organ damage (TOD)) or hypertensive urgency (HU-without TOD), usually accompanied by levels of diastolic BP X120 mm Hg. The aim of this study was to characterize the clinical-epidemiological profile of HC over the course of 1 year in a university reference hospital and perform a review of the literature. The study was a cross-sectional study, conducted over a period of 1 year (2006) in 362 patients who presented for treatment at the emergency hospital with HC, as described above. Among all patients examined, 231 individuals met the criteria for HE and 131 met the criteria for HU. Patients with HE were older (Po0.001) and more sedentary (P¼0.026) than those with HU. Furthermore, fewer HE patients than HU patients had previously undergone antihypertensive treatment (P¼0.006). The groups did not differ regarding BP levels, gender, smoking or body mass index. Dyspnea (41.1%), thoracic pain (37.2%) and neurological deficit (27.2%) were common signs/symptoms in those with HE. Meanwhile, in the group with HU, we most frequently found headache (42.0%), thoracic pain (41.2%) and dyspnea (34.3%). Among the forms of HE, we most frequently observed acute lung edema (30.7%), myocardial infarction/unstable angina (25.1%), and ischemic (22.9%) and hemorrhagic (14.8%) stroke. HC is a clinical entity associated with high morbidity in the emergency room. Individuals with HE are older and sedentary and have lower rates of antihypertensive treatment. Adequate control of BP should be pursued as a way to avoid this severe complication of hypertension.

HTCT 3120 1-8 hematol transfus cell ther. 2 0 2 0;x x x(x x):xxx-xxx w w w . h t c t . c o m . b r Hematology, Transfusion and Cell Therapy