(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.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries.Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers.Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03).Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality.Funding: National Cancer Institute and National Institutes of Health.

Background: Nirmatrelvir/Ritonavir has been shown to reduce the risk of COVID-19 progression by 88% compared to placebo, while Molnupiravir reduced it by 31%. However, these two agents have not been compared head-to-head. We therefore compared the safety and efficacy of both agents for the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients. Methods: We identified 240 cancer patients diagnosed with COVID-19 and treated with Molnupiravir or Nirmatrelvir/Ritonavir. Patients were matched using a 1:2 ratio based on age group (18–64 years vs. ≥65) and type of cancer. The collected data included demographics, comorbidities, and treatment outcome. Results: Both groups had comparable characteristics and presenting symptoms. However, dyspnea was more prevalent in the Molnupiravir group, while sore throat was more prevalent in the Nirmatrelvir/Ritonavir group. The rate of disease progression was comparable in both groups by univariate and multivariable analysis. Treatment with Molnupiravir versus Nirmatrelvir/Ritonavir revealed no significant difference in disease progression by multivariable analysis (adjusted OR = 1.31, 95% CI: 0.56–3.14, p = 0.70). Patients who received Nirmatrelvir/Ritonavir, however, were significantly more prone to having drug–drug interactions/adverse events (30% vs. 0%, p < 0.0001). Conclusions: In the treatment of mild-to-moderate COVID-19 in cancer patients, Molnupiravir was comparable to Nirmatrelvir/Ritonavir in preventing progression to severe disease/death and rebound events, and it had a superior safety profile.

Objective: Serial procalcitonin (PCT) monitoring has been adopted to supplement clinical judgement and help guide antibiotic therapy as part of antimicrobial stewardship programs. PCT levels peak 24 to 48 h after infection onset and decline with infection resolution. We explored the role of PCT as an infection biomarker for guiding antibiotic therapy in cancer patients hospitalized for febrile neutropenia. Design: Prospective randomized study. Methods: Patients were enrolled between October 2021 and August 2023 and received empiric intravenous broad-spectrum antibiotics (IVBSA) for at least 48 h. PCT was measured at baseline and 48–72 h after IVBSA initiation. PCT drop 48–72 h after IVBSA initiation was defined as a reduction of 30% from baseline or a PCT level < 0.25 ng/mL. De-escalation was defined as a switch from IVBSA to oral or simplified once-daily IV therapy. Results: Of the 89 patients with available PCT levels, 53 (60%) had a PCT drop, most of whom (79%) underwent IVBSA de-escalation. Compared with patients without a PCT drop, patients with a PCT drop had a higher de-escalation rate at 72 h (71% vs. 45%; p = 0.003) and a shorter median antibiotic duration (55 h vs. 98 h; p = 0.004). Patients with bacteremia had a significantly higher median PCT level than those without bacteremia (2.35 ng/mL vs. 0.370 ng/mL, p = 0.013). Conclusions: In patients with cancer and febrile neutropenia, a PCT drop was associated with earlier therapy de-escalation and shorter antibiotic duration. PCT monitoring may be useful in antimicrobial stewardship initiatives in this patient population. Clinical trials identifier: NCT04983901.

Background: Invasive aspergillosis (IA) is a life-threatening fungal infection that primarily affects immunocompromised individuals and has high morbidity and mortality rates, necessitating timely diagnosis and treatment. This study aimed to evaluate the prognostic utility of serum and bronchoalveolar lavage (BAL) fluid galactomannan levels, as well as galactomannan kinetics, in patients with IA. Methods: We retrospectively reviewed the medical records of patients who were diagnosed with proven or probable IA from March 2016 to April 2024 at a tertiary cancer center. The collected data included patient characteristics, baseline and peak galactomannan levels in serum and BAL fluid, galactomannan trends, and clinical outcomes. Subgroup analyses were performed to assess the prognostic value of dual-source galactomannan positivity (positive serum and BAL fluid galactomannan levels). Results: Elevated baseline serum galactomannan levels independently predicted treatment non-response (p = 0.039) and 12-week all-cause mortality (p < 0.001). Peak serum and BAL fluid galactomannan levels were strongly associated with poor clinical outcomes (p < 0.01). Compared to single-source galactomannan positivity, dual-source galactomannan positivity was linked to reduced treatment response (22% vs. 43%, p = 0.01) and higher IA-attributable mortality (52% vs. 27%, p = 0.002). Patients with neutropenia had poorer outcomes compared to patients without neutropenia, but neutrophil recovery dramatically improved survival (25% vs. 69% mortality, p < 0.0001). Early galactomannan kinetics and malignancy type had limited prognostic value. Conclusions: Our findings highlight the potential role of galactomannan as a key biomarker for early prognostication for IA. The strong association between galactomannan levels and clinical outcomes suggests its utility in identifying high-risk patients who may benefit from more aggressive management. Further studies are needed to introduce a nuanced and context-specific use of galactomannan into clinical practice and assess its role as a prognostic biomarker.

Background: Anti-mold azoles have improved the outcomes of invasive aspergillosis (IA) when used therapeutically, but they are extensively used as prophylaxis. There are limited data regarding the outcomes of patients with hematologic malignancy who develop breakthrough IA on anti-mold azoles. We aimed to determine whether breakthrough IA on azole prophylaxis shows worse outcomes compared to no prophylaxis. Methods: We compared outcomes including therapy response and mortality between antifungal regimens in hematologic malignancy patients with IA between July 1993 and July 2023. Results: Compared to an amphotericin B-containing regimen (AMB), an anti-mold azole as the primary therapy was independently associated with successful response at the end of therapy (OR = 4.38, p < 0.0001), protective against 42-day IA-associated mortality (OR = 0.51, p = 0.024) or all cause mortality (OR = 0.35, p < 0.0001), and protective against 84-day mortality, both IA-associated (OR = 0.50, p = 0.01) and all-cause mortality (OR = 0.27, p < 0.0001). Azole prophylaxis was independently associated with higher IA-associated mortality at 42 days (OR = 1.91, p = 0.012) and 84 days (OR = 2.03, p = 0.004), compared to fluconazole or no prophylaxis. Conclusions: Patients with breakthrough IA on anti-mold azole prophylaxis show a worse prognosis than those on other or no prophylaxis, possibly related to the emergence of azole resistance due to their widespread use as prophylaxis agents. On the other hand, anti-mold azole primary therapy is superior to AMB therapy in the treatment of IA.