Safety
anaemia, immunodeficiency disorder, leucopoenia, neutropenia, fever, leukopenia, epilepsy, rAML, Hypercholesterolemia, infection, testes infection, skin infections, upper respiratory tract infections, Cancer
ANAEMIA, ADVERSE EFFECTS, IMMUNODEFICIENCY DISORDER, UPPER RESPIRATORY TRACT INFECTIONS, NEUTROPENIA, LEUKOPENIA, EPILEPSY, CNS INFECTIONS, VAGINAL INFECTION, HYPERCHOLESTEROLEMIA, COVID-19 INFECTION, SKIN INFECTION, CEREBRAL OEDEMA, ADVERSE EFFECTS, INFECTION, ULCERATION, ORAL ULCERATION, CANCER
Sixty-one of the 64 (95%) patients reported clinical adverse effects after follow-up periods of 1–12 months (n = 10), 13–24 months (n = 13), 25–36 months (n = 18), and > 36 months (n = 23) (Table Adverse effects with dose modification over time during the treatment period*Genital infection (vaginal infection n = 2, testes infection n = 1)**Cysts: (ovarian, clitoris, pilonidal)***According to the National Cancer Institute Common Terminology Criteria version 5Frequency of the most common adverse effects (stomatitis/oral ulceration, upper respiratory tract infections, fever, and skin infections) declined by ≥ 10% over time. However, a minority of the patients had stomatitis/mouth ulceration (30%) or upper respiratory tract infections (25%) regularly or almost continuously (13%). Hypercholesterolemia (41%), anaemia (30%), and leucopoenia (25%) were the most frequent laboratory abnormalities during the entire treatment period and in the first, second, and after the second treatment year. Hypercholesterolemia was mostly grade 1; only four patients had grade 2 (max cholesterol 10.2 mmol/L). Four patients required statin treatment.Table Fifty percent required dose modifications due to adverse effects. Stomatitis/oral ulceration was the most frequent cause of dose modification. Eighteen patients with symptomatic stomatitis/oral ulceration had no dose modifications.Hospitalisation or prolongation of hospitalisation was required in 34% of the sample, and one patient was diagnosed with immunodeficiency disorder and was hospitalised 10 times during 33 months of treatment. The occurrence of hospitalisation decreased after treatment with immunoglobulin for this patient.Nine patients (14%) discontinued treatment; four due to adverse effects (leukopenia, neutropenia and COVID-19 infection, cerebral oedema, oral ulceration), three due to both adverse effects and loss of effect (infections in two, infection risk due to COVID-19 pandemic in one, epilepsy in two, and rAML in one), and two due to loss of effectiveness (epilepsy).The median duration of treatment was 15 months (range 0–28, mean 13, SD: 7.9, 95% CI 6.9–19.1). The frequency of adverse effects and adverse effects ≥ grade 3 during the entire treatment period was similar in Norway and Denmark [Norway: 34/35 (97%) vs. Denmark: 27/29 (93%), Norway 14/35 (40%) vs. Denmark 9/29 (31%), respectively].