Safety end points
thyroid disorders, toxicities, pyrexia, hyperbilirubinemia, Hematoma, urinary tract infections, sinus bradycardia, edema, thrombocytopenia, cerebral hemorrhage, nausea, diarrhea, fatigue, anemia, angina pectoris, sepsis, cardiac failure, neutropenia, peripheral edema, transaminitis, atrial fibrillation, hypertension
THYROID DISORDERS, CARDIOVASCULAR DISORDER, HYPERBILIRUBINEMIA, HEMATOMA, URINARY TRACT INFECTIONS, SINUS BRADYCARDIA, EDEMA, THROMBOCYTOPENIA, DISORDERS, BLOOD AND LYMPHATIC SYSTEM DISORDERS, HYPOTHYROIDISM, CEREBRAL HEMORRHAGE, ADVERSE EVENTS, ANEMIA, ADVERSE EVENT, SEPSIS, CARDIAC FAILURE, NEUTROPENIA, INFECTIONS AND INFESTATIONS, PERIPHERAL EDEMA, MITRAL VALVE INSUFFICIENCY, ATRIAL FIBRILLATION, HYPERTENSION, ARTERIAL HYPERTENSION, GASTROINTESTINAL DISORDERS
For the safety analysis, all 57 included patients who had received at least one dose of any study medication were considered. A total of 56 (98.2%) patients experienced at least one grade ≥1 adverse event during the observation period. The most common adverse events of any grade occurring during the observation period were gastrointestinal disorders (56.1%), including diarrhea (28.1%) and nausea (17.5%), general disorders (52.6%), including pyrexia (19.3%), peripheral edema (17.5%), edema (8.8%) and fatigue (8.8%), blood and lymphatic system disorders (47.4%), including anemia (19.3%), neutropenia (21.1%) and thrombocytopenia (19.3%) and infections and infestations (78.9%), including COVID-19 (22.8%) and urinary tract infections (21.1%).Cardiac toxicities, of interest in the context of BTK inhibitors, were uncommon, with one case each of angina pectoris (grade 3), cardiac failure (grade 2), cardiovascular disorder (grade 1), mitral valve insufficiency (grade 2) and sinus bradycardia (grade 1); no atrial fibrillation episodes were reported. Grade 1 to 3 hypertension was reported in three cases, of which two patients had a previous history of arterial hypertension. Hematoma was reported in five cases (grade 1 and 2) and one case of grade 3 cerebral hemorrhage occurred in a patient on prophylactic concomitating aspirin.Potentially immune-related disorders, of interest in the context of checkpoint inhibitors, included two cases of thyroid disorders (hypothyroidism, grade 2), pyrexia (12 cases, grade 1–3) and increased liver values (five cases, one hyperbilirubinemia and four transaminitis, grade 1–4).Overall, three grade 5 adverse events were reported in the safety population and all of them were related to fatal sepsis.