Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice

Abstract

Background. Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical experience, nevertheless, is scarce. Methods. We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation. Results. We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy. Conclusions. Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.

Isavuconazole for the Treatment of Fungal Infections: A Real-life Experience From the Fungal Infection Network of Switzerland (FUNGINOS)

“…In our study, these IFIs accounted for most cases (87%) where ISA was used as targeted therapy. The success rate for proven/probable IFI was 54%, which is superior to rates reported in prospective trials [ 8 , 9 ] but similar to those of other real-life observational studies [ 14 , 17 ]. In addition, ISA was used as empiric therapy for possible IFI.…”

IFISTRATEGY: Spanish National Survey of Invasive Fungal Infection in Hemato-Oncologic Patients

“…Moreover, if there is a suspected breakthrough IFI while receiving echinocandin prophylactic therapy L-AMB would allow for a broad-spectrum antifungal treatment, while maintaining the antineoplastic therapy due to the lack of drug–drug interactions [ 10 ]. Isavuconazole, which appears to be a lesser CYP3A4 inhibitor has a good safety profile and a more easily managed drug–drug interaction with immunosuppressive agents, could also be a possible treatment alternative [ 52 ].…”

Real-World, Multicenter Case Series of Patients Treated with Isavuconazole for Invasive Fungal Disease in China

“…Previous reports showed that ISA had become a new option for the treatment of IFD, with an overall response rate of 35–87% [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. In our study, we had an overall response rate of 75%.…”

“…At present, the efficacy and safety of ISA have mainly been reported in clinical trials, rarely in real-world studies. Most of these studies have shown that ISA is not inferior to VOR and AmB with respect to the treatment of IFD, presenting a 35–87% clinical response and a 6–38% 42-day mortality [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Given that it was only approved in China at the end of 2021 for the treatment of IA and IM in adults, there is a lack of real-world evidence concerning the Chinese population.…”