Real-world evaluation of isavuconazole in children with cancer

Isavuconazole is widely used in children. It has a favourable safety profile, fewer drug-drug interactions, predictable pharmacokinetics and broad spectrum of action compared with alternative triazoles.

To assess its place in therapy in a real-world setting, and investigate the achieved exposure.

This cohort study reports isavuconazole usage in children between 2018 and 2023 in the Princess Máxima Center, the Netherlands. Clinical data, toxicity data and isavuconazole plasma concentrations were extracted from patient records. Exposure was estimated post hoc using nonlinear mixed-effects modelling.

In total, 77 patients (median age 8.0 years) received isavuconazole during 92 episodes. Isavuconazole was primarily prescribed as second-line therapy. Out of 77 patients, 72 had a haematological malignancy and 34/77 underwent stem cell transplantation. Median episode duration was 75.5 (IQR, 44-144) days. Treatment was discontinued in 29.1% unrelated to confirmed drug side effects. 958 concentrations were available. Median Ctrough was 3.3 (range, 0.04-12.6) mg/L. The intra-patient coefficient of variation was 30.6% (IQR, 21.1%-42.8%). Predicted exposure during the first week was 79.2 (range, 35.2-95.8) mg·h/L, 81.8% > 60 mg·h/L, the 25th percentile from a pivotal trial. Median maintenance dosage for patients <18 kg, 18-32 kg and ≥32 kg was 6.4, 5.2 and 4.6 mg/kg/day.

We think that isavuconazole merits a place for treatment of invasive fungal infections in children. Isavuconazole was generally well tolerated with exposures in line with the pivotal trial. Lower-weight children required higher dosage per kg of bodyweight to achieve equivalent exposures to their older peers. Considerable inter/intra-patient variability supports the need for therapeutic drug monitoring.