Isavuconazole (referred to hereafter as ISCZ) is a broad‑spectrum triazole antifungal available in both intravenous and oral formulations. It does not generally require renal dose adjustment and has fewer clinically relevant drug–drug interactions than some other azoles. Uniquely, ISCZ has been associated with little or no risk of QTc prolongation and, in pooled analyses, with QTc shortening rather than prolongation. Because many antineoplastic agents used in hematologic malignancies, including arsenic trioxide (ATO), can prolong the QT interval, ISCZ's cardiac profile may offer an advantage when antifungal therapy is required concurrently with QT‑prolonging chemotherapy.
Real-world safety and electrophysiologic data on ISCZ in Asian and Japanese populations remain limited. This study aimed to evaluate longitudinal changes in laboratory parameters reflecting hepatic and renal function and to describe QTc dynamics during ISCZ therapy in Japanese patients with hematologic malignancies. An exploratory analysis compared QTc trajectories among patients receiving ATO with and without ISCZ.
This was a retrospective observational study conducted at the Department of Hematology and Infectious Diseases, Gifu University Hospital. The study period covered ISCZ administration between April 1, 2023 and March 31, 2025. The primary objective was to characterize clinical use and safety of ISCZ in routine practice by assessing longitudinal laboratory measures and QTc intervals recorded in electronic medical records.
Forty‑five consecutive patients aged 18 years or older who received ISCZ during the study period were included. Patients who discontinued ISCZ within 3 days of initiation were excluded because short exposure made safety evaluation difficult. Extracted data included serial laboratory tests relevant to hepatic and renal function and electrocardiographic QTc intervals using both Bazett (QTcB) and Fridericia (QTcF) corrections. Supporting de‑identified data were provided as S1 Data in the publication.
Longitudinal changes in laboratory values and QTc intervals were assessed using linear mixed‑effects models to account for repeated measures within patients over time. For the exploratory ATO subgroup analysis, QTc trajectories were compared across three groups: ATO alone, ATO plus ISCZ (ATO‑ISCZ), and ATO with other antifungals. Statistical comparisons reported point estimates and p values where applicable.
Among the 45 patients treated with ISCZ, grade ≥2 elevations in serum transaminases were observed but were infrequent and transient: AST elevation of grade ≥2 occurred in 11.1% of patients and ALT elevation of grade ≥2 in 13.3% of patients. Overall longitudinal analyses did not show significant deterioration in hepatic or renal laboratory parameters associated with ISCZ across the cohort.
These findings indicate that clinically meaningful, sustained hepatic or renal toxicity was not apparent in this real‑world Japanese cohort during the observation period. The transient nature of the transaminase elevations suggests close monitoring and routine laboratory follow‑up were adequate in these cases.
In exploratory analyses focusing on patients receiving ATO, QTc trajectories differed by antifungal exposure. The ATO‑ISCZ group demonstrated lower QTc intervals compared with the ATO‑only group beginning at Day 30. The maximal difference was observed at Day 70, with a between‑group difference of −45.5 ms for QTcB and −42.3 ms for QTcF; both differences reached statistical significance (p < 0.001).
By contrast, the subgroup receiving ATO with other antifungals showed QTc trends similar to the ATO‑only group and did not exhibit the QTc shortening seen with concomitant ISCZ. No concentration‑dependent QTc prolongation attributable to ISCZ was reported in this dataset.
No clinically significant cardiac events were observed in the cohort during ISCZ therapy. Aside from the transient transaminase elevations noted above, the study did not report sustained laboratory deterioration or cardiac adverse events attributable to ISCZ in this population.
In this single‑center retrospective cohort of Japanese patients with hematologic malignancies, ISCZ exhibited a favorable safety profile. Transient grade ≥2 transaminase elevations occurred in a minority of patients but did not translate to persistent hepatic injury in the observed period. Importantly, exploratory subgroup data in patients receiving ATO, a well‑recognized QT‑prolonging agent, showed that concomitant ISCZ was associated with lower QTc values compared with ATO alone or ATO combined with other antifungals. These observations are consistent with prior reports describing little or no QTc‑prolonging effect of ISCZ and with pooled analyses that have suggested QTc shortening with ISCZ.
From a clinical standpoint, these real‑world findings support consideration of ISCZ as an antifungal option in patients receiving QT‑prolonging chemotherapy, though individual risk assessment and monitoring remain essential.
The study's retrospective design, single‑center setting, and limited sample size constrain generalizability. The exploratory nature of the ATO subgroup analysis and potential confounding factors inherent to observational data should be recognized. Detailed dosing schedules, concomitant medications beyond the antifungal category, and patient‑level arrhythmia risk factors were not fully reported in the abstracted material and would require review of the full dataset for granular interpretation.
In this retrospective cohort of 45 Japanese patients with hematologic malignancies, isavuconazole demonstrated a favorable laboratory and cardiac safety profile. Transient AST and ALT elevations were observed in a small proportion of patients but overall laboratory function did not significantly deteriorate. In patients receiving arsenic trioxide, concomitant ISCZ was associated with lower QTc values compared with ATO alone, and no clinically significant cardiac events were reported. These real‑world data suggest ISCZ may be a safe antifungal choice during QT‑prolonging therapies, while acknowledging the study's retrospective and single‑center limitations.