Oral posaconazole (PCZ) is widely used for both prophylaxis and treatment of invasive fungal infections (IFIs) in adult leukemia patients (pts) due to its broad antifungal spectrum. However, issues with PCZ tolerability can result in treatment interruption or discontinuation, and the need for alternative oral options with comparable antifungal coverage. Isavuconazole (ISA) is the newest triazole antifungal with a similar spectrum of activity to PCZ and is increasingly used in leukemia pts. Real-world data regarding the tolerability of ISA after PCZ toxicity are lacking.
We retrospectively assessed safety and tolerability of ISA utilization after PCZ toxicity in adult (age > 18 years) leukemia pts from March 2015 to December 2016. We included all pts who received ≥ 7 days of oral or intravenous ISA 372 mg immediately after receiving at least one dose of oral PCZ. Demographic and clinical data were recorded including age, sex, underlying disease and disease status, and prior allogeneic stem-cell transplantation (alloSCT). Relevant toxicity markers were collected at three time points: prior to PCZ initiation, at switch to ISA therapy, and after ISA therapy was completed.
We identified 8 such pts, all with acute myeloid leukemia. No pt had prior alloSCT and all except one pt had relapsed or refractory disease (88%). Five pts were neutropenic at the time of ISA initiation. PCZ was administered as prophylaxis in 1 and as treatment in 7 pts. Increased liver function tests (LFTs) or total bilirubin was noted in 7 pts on PCZ, while 2 pts had confirmed Grade 3/4 QTc prolongation. No pt discontinued subsequent ISA due to toxicity. Overall, Grade 3/4 elevations in LFTs were decreased after changing to ISA (25% after PCZ vs. 0% after ISA). The two pts who experienced Grade 3/4 QTc prolongation with PCZ returned to normal EKG findings after changing to ISA.
Overall, we found ISA to be well-tolerated in pts requiring discontinuation of PCZ due to toxicity, with no pts discontinuing ISA due to toxicity. ISA was found to be a safe alternative choice in the setting of PCZ toxicity in heavily immunocompromised pts.
A. J. DiPippo,
D. P. Kontoyiannis, Merck: Consultant , Research support and Speaker honorarium . Pfizer: Consultant , Research support . Astellas: Consultant , Research support and Speaker honorarium . Gilead: Speaker's Bureau , Speaker honorarium . F2G Inc: Speaker's Bureau , Speaker honorarium . Cidara Inc: Speaker's Bureau , Speaker honorarium . Jazz Pharmaceuticals: Speaker's Bureau , Speaker honorarium .