Clinical Considerations of Isavuconazole Administration in High-Risk Hematological Patients: A Single-Center 5-Year Experience

Kronig, Ilona; Masouridi‐Levrat, Stavroula; Chalandon, Yves; Glampedakis, Emmanouil; Vernaz, Nathalie; Delden, Christian van; Neofytos, Dionysios

doi:10.1007/s11046-021-00583-9

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…The switches were mainly driven by the failure of the primary therapy (54%); However, 29% of cases were caused by adverse effects related to primary therapy, including elevated liver function tests (16%), a prolonged QT interval (6%), altered mental status (2%), and decreased creatinine (3%). In a study of 30 patients, isavuconazole was also indicated because of adverse events associated with prior anti-mold therapy; the most common adverse event was hepatotoxicity, followed by renal insufficiency and long QTC intervals, according to Kronig et al [33]. The study also showed that after switching to isavuconazole, liver function tests and QTc intervals decreased compared to the baseline recorded with prior azoles used (34).…”

Section: Discussionmentioning

confidence: 99%

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

Dagher

Hachem

Chaftari

et al. 2022

JoF

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(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.

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Section: Discussionmentioning

confidence: 99%

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

Dagher

Hachem

Chaftari

et al. 2022

JoF

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“…The rate of any-grade TEAEs (17.3%) was similar or lower than that reported for hematological patients. 38,39 Most events were mild to moderate in severity, mainly in the form of elevation of liver enzymes and gastrointestinal symptoms, whereas neurologic toxicity was rare. This safety profile is consistent with the results from pivotal RCTs.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…98 Other mold-active agents such as voriconazole and isavuconazole are also reasonable alternatives for prophylaxis based on observational data, some of which come from studies in patients with AML and those undergoing allo-HCT. [99][100][101][102][103][104][105] Before prescribing antifungal prophylaxis, drug-drug interactions must be carefully reviewed. Of special note, patients who are receiving venetoclax may need dose reduction if azole antifungals are used.…”

Section: Antifungal Prophylaxismentioning

confidence: 99%

Supportive Care for Patients With Myelodysplastic Syndromes

Stempel

Podoltsev²,

Dosani³

2023

Cancer J

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Myelodysplastic syndromes are a heterogeneous group of bone marrow disorders characterized by ineffective hematopoiesis, progressive cytopenias, and an innate capability of progressing to acute myeloid leukemia. The most common causes of morbidity and mortality are complications related to myelodysplastic syndromes rather than progression to acute myeloid leukemia. Although supportive care measures are applicable to all patients with myelodysplastic syndromes, they are especially essential in patients with lower-risk disease who have a better prognosis compared with their higher-risk counterparts and require longer-term monitoring of disease and treatment-related complications. In this review, we will address the most frequent complications and supportive care interventions used in patients with myelodysplastic syndromes, including transfusion support, management of iron overload, antimicrobial prophylaxis, important considerations in the era of COVID-19 (coronavirus infectious disease 2019), role of routine immunizations, and palliative care in the myelodysplastic syndrome population.

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Clinical Considerations of Isavuconazole Administration in High-Risk Hematological Patients: A Single-Center 5-Year Experience

Cited by 8 publications

References 23 publications

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

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

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

Supportive Care for Patients With Myelodysplastic Syndromes

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