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.

Comparing the Real-World Use of Isavuconazole to Other Anti-Fungal Therapy for Invasive Fungal Infections in Patients with and without Underlying Disparities: A Multi-Center Retrospective Study

“…In our study, the favorable response to isavuconazole at 6 and 12 weeks, and at the end of treatment, was 90%. This is higher than the 45% response rate reported in the SECURE trial, and the 47% and 42% reported at 6 and 12 weeks, respectively, in previous studies [ 13 , 30 ].…”

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

“…The frequent use of a second antifungal agent mirrors similar real-life studies in hematological patients. 34 The eventual synergistic effect of combining isavuconazole with L-AmB or an echinocandin remains to be established, with some supporting in vitro and animal data 35,36 and clinical reports. 37 The two factors that are found to independently predict the lack of clinical response-disseminated IMD and elevated serum AST levels-are markers of higher fungal burden and preexisting liver toxicity.…”

A Case of Primary Multifocal Cutaneous Mucormycosis in a Pediatric Patient with Newly Diagnosed Acute Lymphoblastic Leukemia

“…Multivariate analyses of studies, which include patients with hematological malignancies, show amphotericin B to be the agent of choice associated with a favorable outcome [ 21 ]. The newer triazoles, posaconazole and isavuconazole, can be alternatives to amphotericin B when stepdown therapy is needed or the patients cannot be treated with amphotericin B [ 22 , 23 ]. A drawback of these relatively new agents is the limited number of studies in the pediatric population [ 2 ].…”