Real-World Use of Isavuconazole as Primary Therapy for Invasive Fungal Infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant.

Abstract

(1) Introduction: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with hematologic malignancies (HM) and stem cell transplants (SCT). Isavuconazole was approved by FDA as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. The aim of this study is to look at the real-world use of Isavuconazole in patients with HM and evaluate their clinical outcomes and safety. (2) Methods: We conducted a retrospective study of HM patients at MD Anderson Cancer Center who had definite, probable or possible mold infections between 1 April 2016 and 31 January 2020 and were treated with Isavuconazole for a period of at least 7 days. Clinical and radiological findings were assessed at baseline and at 6 and 12 weeks of follow up. (3) Results: We included 200 HM patients with IFIs that were classified as definite (11), probable (63) and possible (126). Aspergillus spp was the most commonly isolated pathogen. The majority of patients (59%) received prophylaxis with anti-mold therapy and Isavuconazole was used as a primary therapy in 43% of patients, and as salvage therapy in 58%. The switch to Isavuconazole was driven by the failure of the primary therapy in 66% of the cases and by adverse effects in 29%. Isavuconazole was used as monotherapy in 30% of the cases and in combination in 70%. Adverse events possibly related to Isavuconazole were reported in eight patients (4%) leading to drug discontinuation. Moreover, a favorable response with Isavuconazole was observed in 40% at 6 weeks and in 60% at 12 weeks. There was no significant difference between isavuconazole monotherapy and combination therapy (p = 0.16 at 6 weeks and p = 0.06 at 12 weeks). Finally, there was no significant difference in outcome when Isavuconazole was used after failure of other anti-mold prophylaxis or treatment versus when used de novo as an anti-mold therapy (p = 0.68 at 6 weeks and p = 0.25 at 12 weeks). (4) Conclusions: Whether used as first-line therapy or after the failure of other azole and non-azole prophylaxis or therapies, isavuconazole seems to have a promising clinical response and a good safety profile as an antifungal therapy in high-risk cancer patients with hematologic malignancies. Moreover, combination therapy did not improve the outcome compared to Isavuconazole therapy.