Interferon-α Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Coronavirus disease 2019 (COVID-19) has now infected more than 700 million people worldwide [ 1 ], with a disproportionate impact of infection on immunocompromised patients, such as those with cancer [ 2–4 ]. Patients with cancer are more likely to have progression to lower respiratory tract disease, more frequent hospitalizations, need for oxygen, admission to an intensive care unit, and increased mortality [ 3 , 5 ]. Preventative measures, such as vaccination and monoclonal antibodies, have dramatically improved outcomes but many cancer populations experience breakthrough infections and have suboptimal vaccine responses [ 6–9 ].

Interferon-alpha (IFN-α) has biological activities such as antiviral, antimicrobial, antiproliferative, and immunomodulatory effects [ 7 , 10–12 ]. Prior studies have shown IFN pathways in the defense of COVID-19, with nasal IFN-α effective in preventing community-acquired respiratory viral infections such as rhinovirus and influenza [ 10–15 ]. When administered as postexposure prophylaxis in household contacts, IFN-α compared with placebo reduced the incidence of rhinovirus infections by 88% [ 14 ]. In the current COVID-19 era, treatment studies of IFN-α nasal spray showed reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding [ 16 ], whereas pegylated IFN-lambda reduced the incidence of hospitalization [ 17 ]. We conducted a primary prophylaxis trial to evaluate the efficacy of IFN-α nasal spray as primary prevention against COVID-19 and other respiratory viral infections in patients with cancer.

METHODS

Trial Design

This was a multicenter, randomized, double-blinded, placebo-controlled trial that evaluated 4 immunomodulatory interventions in the prevention and treatment of COVID-19 infection designed as a sequential multiple-arm randomized trial (C-SMART). We report on the primary prophylaxis intervention, which assigned participants without prior COVID-19 to receive 1:1 IFN-α 40 000 IU daily nasal spray or placebo. The trial protocol is available ( Supplementary ). The study was approved by all site human research ethics committees, and written informed consent was obtained. A trial steering committee provided oversight and an independent data safety committee board monitored the conduct of the study.

Participant Selection and Randomization

Participants were recruited from 5 tertiary-level hospitals. Inclusion criteria were adults with solid or hematological malignancy without prior COVID-19 infection. We excluded patients who had head and neck cancer, were on another interventional trial, or not suitable based on treating physician decision. Participants were randomly assigned 1:1 to receive either 40 000 IU IFN-α or normal saline via nasal spray daily. A randomization sequence was generated by using a computer-based randomization program by an independent statistician, stratified by ages older than 65 years and 65 years and younger. All participants, clinicians, investigators, coordinating staff, and trial committee members were blinded to study procedures. The central pharmacist was unblinded, with the data remaining blinded until finalization of statistical analysis. All participants were advised to follow the state and national COVID-19 precaution measures, including mask wearing, lockdowns, restricted movement, and vaccination.

IFN-α and Placebo Interventions

We evaluated an IFN dose of 40 000 IU per day based on published literature and a desire to avoid systemic side effects that could interfere with treatment of the underlying cancer. Reformulation of IFN-α-2a/β into nasal spray delivery of 20 000 IU/mL IFN per 100 μL actuation was performed at the Monash Institute of Pharmaceutical Sciences, Monash University, Australia. We first produced a suitable diluent for IFN-α-2a (Roferon-A; Roche), and IFN-α-2β (Intalfa; Intas Pharmaceuticals Ltd) with regard to compatible preservative selection, pH, and osmolarity adjustment. Nasal formulations were prepared at a concentration of 200 000 IU/mL, equivalent to 20 000 IU per 100 µL nasal actuation and administered as daily dose in each nostril (2 × 100 µL actuations). We then undertook a series of experiments to assess IFN stability through measurement of content, activity, and device performance at 2 temperatures (2°–8°C [refrigerator] and 25°C [room temperature]) on days 0, 1, 7, 14, 28, 35, 42, 50, 62, and 95. High-pressure liquid chromatography (HPLC) analysis of IFN content was performed on a Shimadzu Nexera binary ultra-HPLC system fitted with diode array and fluorescence detectors. IFN-α concentration was assessed using commercial enzyme-linked immunosorbent assay (ELISA) kits (PN:ab233622, Human IFN-α-2 kit; Abcam). Testing of device performance included mass uniformity as determined gravimetrically, droplet-size distribution via laser diffraction, device tailing studies, and microbiological testing for sterility at each time point. Nasal formulation of IFN-α-2a/β demonstrated stability of content, concentration, sterility, and device performance within specification. High-density polyethylene bottles and nasal actuation devices (preservative-free, 100-μL actuation volume; Aptar, Germany) were used. A third-party compounding pharmacy produced both the IFN-α nasal spray and placebo of 0.9% normal saline using matching bottle and actuation devices, which were then sent to a central pharmacy.

Trial Procedures

After randomization, participants were dispensed either IFN-α 40 000 IU or normal saline nasal spray daily. Study procedures included medical history, concomitant medications, baseline nasal swab, blood samples, and COVID-19 Peritraumatic Distress Index (CPDI) questionnaire. Participants were given a self-testing kit of nasal swab, viral medium, a prepaid envelope, symptom diary, and written instructions with verbal education to perform self-testing upon development of influenza-like illness (ILI) symptoms. Mandatory study visits were days 30, 60, and 90 (end of treatment) with optional sub-study follow-up at days 120 and 365. At each study visit we assessed for symptoms of ILI, adherence, and adverse events (AEs). End-of-treatment procedures included blood samples, nasal swab, and questionnaire. All biospecimens were stored at a central laboratory and sent to the Victorian Infectious Diseases Reference Laboratory for polymerase chain reaction (PCR) and SARS-CoV-2 spike and nucleocapsid antibodies testing. The respiratory PCR panel included SARS-CoV-2, Flu A, Flu B, respiratory syncytial virus (RSV), parainfluenza, adenovirus, picornavirus, seasonal coronavirus, and human metapneumovirus, with a shortened panel of SARS-CoV-2, Flu A, Flu B, and RSV for baseline and end-of-study swabs only.

Outcomes

The co-primary endpoints were incidence of COVID-19 and/or other respiratory viruses within 90 days of randomization. COVID-19 infection was defined as symptomatic ILI plus detectable SARS-CoV-2 PCR from nasal swab and/or positive rapid antigen test (available from February 2022). Other respiratory viruses were defined as symptomatic ILI plus detectable PCR from nasal swab of influenza A, B, RSV, parainfluenza, coronavirus, picornavirus, and human metapneumovirus. The trial was designed with co-primary outcomes to ensure a relevant and meaningful trial result. As IFN has broad antiviral activity, co-primary endpoints allowed the trial to evaluate an effect on COVID-19 and other respiratory viral infections that have a known serious impact on patients with cancer. Secondary outcomes included time to diagnosis, severity of illness, unplanned all-cause hospitalization, unplanned infection-related hospitalization, incidence of SARS-CoV-2 seroconversion, and all-cause mortality. Adverse events and serious AEs (SAEs) were graded according to CTCAEv5. Adverse events of special interest included epistaxis of grade 2 or higher.

Statistical Analysis

The trial used a Bayesian statistical framework to analyze the co-primary outcomes reporting on binomial regression to compare endpoints between treatment groups using risk ratios and associated 95% credible intervals (CrIs). A maximum sample size of 957 per treatment arm was calculated based on 90% power and 5% 2-sided type I error, with an expected incidence of 15% in the placebo group and 10% in the intervention group. The original design included statistical early stopping rules that maintained comparable power and type I error. As the COVID-19 pandemic evolved, recruitment rates decreased as a result of most patients becoming infected with COVID-19 (an exclusion criteria). The trial steering committee proposed to cease recruitment and analyze the available results after 2 years of recruitment following a review of the current epidemiology supporting a higher incidence of COVID-19 than the original estimate. All analyses followed a prespecified statistical analysis plan ( Supplementary ). A post hoc power analysis was performed.

The primary analysis population was according to intention-to-treat (ITT) where all participants were analyzed according to the randomly allocated group. We also performed a secondary analysis using a per-protocol population. No imputation for missing data was conducted. Five prespecified subgroup analyses of the co-primary outcomes (according to age group, sex, cancer type, any COVID-19 vaccine, and any active cancer treatment) were conducted to assess heterogeneity of the treatment effect. All analyses were conducted in R version 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria) and Stata version 18 (StataCorp, College Station, Texas).

RESULTS

Recruitment and Follow-up

A total of 433 participants were enrolled and randomly allocated to IFN-α (n = 217) or placebo (n = 216). The number of participants assessed for eligibility and screened are shown in Figure 1 . The first patient was recruited in December 2020 and the last follow-up was completed in April 2023.

Patient demographics ( Table 1 ) included a median age of 62 years (IQR: 52–69; range, 18–90), female sex (51%), and White ethnicity (91%). The primary cancer diagnoses were hematological malignancy (48%) and solid tumor cancers (52%). Of the 433 participants randomized, 3 did not receive the allocated intervention but were included in the primary ITT analysis. Of the total 433 participants, 44 (10%) did not complete the study as described in the protocol; thus, 389 participants were included in the per-protocol analysis ( Figure 1 ). Results herein are entirely from the primary prophylaxis intervention from the C-SMART protocol and no participant was enrolled in another domain of the study.

Primary Outcome

The overall incidence of COVID-19 infection was 11.3% in the ITT population, with a lower incidence observed in the IFN-α group compared with placebo (8.3% vs 14.4%; relative risk [RR]: .60; 95% CrI: .33–.97), representing a 40% reduction in the risk of infection favoring IFN-α ( Table 2 , Figure 2 ). The incidence of other respiratory viruses was 5.1%, with no difference observed between the 2 groups (5.1% vs 5.1%; RR: 1.12; 95% CrI: .43–2.34). The cumulative incidence of COVID-19 was lower in the IFN-α group compared with placebo (hazard ratio [HR]: .55; 95% CI: .32–.97; P = .04) ( Figure 3 A ). COVID-19 was the most frequently diagnosed infection during the study period (69%) compared with the other respiratory viruses (31%): picornavirus (n = 8), seasonal coronavirus (n = 7), RSV (n = 4), influenza A (n = 1), parainfluenza (n = 1), human metapneumovirus (n = 1), and influenza B (n = 0).

In the per-protocol cohort, the overall incidence of COVID-19 was 11.8%, with a lower incidence observed in the IFN-α group compared with placebo (7.7% vs 16%; RR: .50; 95% CrI: .26–.84). The incidence of other respiratory viruses was 5.1%, with no difference observed between the 2 groups (4.6% vs 5.7%). The cumulative incidence of COVID-19 was lower in the IFN-α group compared with placebo (HR: .46; 95% CI: .26–.82; P = .008) ( Figure 3 B ). As the trial was stopped early, a post hoc power analysis was performed using the per-protocol data, which determined that the trial had 95.1% power with a 5% alpha error rate to find a true result.

Subgroup Analysis

In a subgroup analysis ( Table 2 , Figure 2 ), participants in the IFN-α group compared with placebo had decreased infection risk if they were aged younger than 65 years (RR: .48; 95% CrI: .20–.92), female (RR: .44; 95% CrI: .19–.85), and had received a COVID-19 vaccine (RR: .50; 95% CrI: .26–.82). There were no differences in infection risk according to primary cancer type or if receiving active cancer treatment. In the per-protocol population subgroup analysis, there was a decrease in infection risk in patients with solid tumors (RR: .39; 95% CrI: .14–.82), with age younger than 65 years (RR: .36; 95% CrI: .13–.71), in females (RR: .36; 95% CrI: .13–.71), and with COVID-19 vaccine (RR: .49; 95% CrI: .25–.83) ( Figure 2 ).

Safety

The safety population included all those in the ITT population ( Table 2 ). There were no differences between the IFN-α and placebo groups with regard to any adverse events (10.1% vs 6%; RR: .56; 95% CrI: .16–1.33), any SAEs (4.1% vs 2.8%; RR: 1.23; 95% CrI: .36–3.12), AEs of special interest (epistaxis ≥ grade 2; 0.5% vs 0.5%), and all-cause mortality (0.5% vs 0.5%).

Secondary Outcomes

The severity of illness of COVID-19 by the World Health Organization (WHO) clinical progression scale did not differ between those receiving IFN-α compared with placebo, with 90% of participants being ambulatory and independent (score ≤2) ( Supplementary Table 1 ). There was no difference between IFN-α and placebo groups with regard to unplanned all-cause hospitalization (9.2% vs 10.2%; P = .7) and infection-related hospitalization (3.7% vs 3.7%; P = .8). Two deaths occurred during the study period, one in each of IFN-α and placebo groups, both deemed unrelated to the intervention (traumatic intracranial hemorrhage [n = 1] and progressive metastatic breast cancer [n = 1]). In 386 participants in whom baseline and end-of-treatment blood samples were available, SARS-CoV-2 seroconversion was no different between IFN-α and placebo groups (5.7% vs 8.3%; P = .3). There were no differences in quality-of-life scores between the 2 groups.

DISCUSSION

In this large randomized, double-blinded, placebo-controlled trial, nasal spray of 40 000 IU IFN-α daily for 90 days was effective in reducing the incidence of COVID-19 compared with placebo in a cohort of patients with cancer. There was a 40% reduction in the cumulative incidence of COVID-19 in the ITT population, equating to a number needed to treat of 16 to prevent 1 infection. A significant risk reduction was independently observed in the subgroups of patients younger than 65 years, females, and in those receiving COVID-19 vaccination. Furthermore, the IFN-α nasal spray was well tolerated with no significant safety concerns. In patients who completed the protocol as described, the reduction in COVID-19 incidence was 50%.

IFN-α nasal spray reduced the incidence of COVID-19 and, in particular, in those younger than 65 years and female. It may be that, during the study period, being younger and female was a marker of high risk with working and caring responsibilities and thus higher community exposure to COVID-19. We did not see any differences in the subgroup aged 65 years and older, which is recognized as having a higher risk of progression to severe disease [ 18 ]. Patients receiving IFN-α nasal spray who received a COVID-19 vaccination had a reduced risk of COVID-19 infection by 50%. COVID-19 vaccines were considered standard of care. We did not find any differences in COVID-19 incidence based on cancer type or whether patients were receiving active cancer-related treatment. Further studies with larger numbers within these subgroups may be warranted to understand any effect in the highest risk groups. Most participants with COVID-19 were managed in an ambulatory setting with mild disease and remained independent, which is in keeping with the current known epidemiology [ 3 , 8 ]. There were no differences in secondary outcomes of severity, hospitalization, and mortality, which could be a result of the evolving improvements in COVID-19 standard of care. No differences were observed in the COVID-19 seroconversion rate, likely reflecting a limitation of the assay in this immunocompromised population.

IFN-α has a broad spectrum of activity from antiviral, antimicrobial, antiproliferative, and immunomodulatory effects [ 15 , 19 ]. This study builds on prior work examining the use of type I IFN on innate immunity against respiratory virus infection [ 13 , 15 ], providing the impetus for our study design when COVID-19 treatment options were limited. During 2020–2023, the state of Victoria experienced 4 separate state government–mandated lockdowns. COVID-19 cases largely occurred from mid-2021 with the Delta wave [ 20 ].

The use of IFN for the prevention of common cold symptoms and rhinovirus infection has previously been published in randomized controlled trials [ 13 , 14 ]. Hayden et al [ 13 ] showed in a randomized trial that intranasal IFN-α2 at 5 million IU daily, given as postexposure prophylaxis within 48 hours to household family members of an index case, reduced the incidence of respiratory illness by 39%, with the greatest effectiveness in those with rhinovirus (1.3% IFN vs 15.1% placebo). When 7 days of IFN-α nasal spray was compared with placebo as postexposure prophylaxis of adults, participants on IFN-α had 41% fewer definite respiratory illnesses, with a 76% reduction in rhinovirus and a 33% reduction in nasal symptoms [ 14 ].

A randomized study of 1449 healthy participants showed that IFN-α2b was effective prophylaxis for acute adenovirus, influenza, and parainfluenza; however, this study used seroconversion to immunoglobulin M (IgM) as confirmation of infection [ 21 ]. In the current COVID-19 era, IFN-α nasal application has been used as prophylaxis in healthcare workers without effectiveness [ 22 ] and in the setting of established COVID-19 infection showing a reduction in viral shedding [ 16 ]. The strengths of this current trial include the production of IFN-α spray to reproducible manufacturing standards, conducting the trial exclusively within an immunocompromised cancer population, and the use of PCR testing to confirm clinical endpoints.

There were many challenges in conducting this trial during an evolving pandemic and a major limitation was that it did not meet the original planned sample size calculated using the best-estimated COVID-19 incidence at the time of the study design. However a post hoc analysis showed 95% power to demonstrate a robust result. Furthermore, the trial was dependent on the variable community incidence of COVID-19, but by conducting the study over 2.4 years, we could evaluate the intervention over a longer period. The study utilized self-collected nasal testing for respiratory PCR and rapid antigen testing (RAT) on the development of ILI symptoms, therefore underreporting of subclinical or asymptomatic infections is possible. Due to the predominance of COVID-19 infections and overall low event outcome of other respiratory viruses (eg, n = 1 influenza A), it is not possible to conclude whether IFN nasal spray is effective for these viruses. Much larger randomized studies need to be performed in the setting of higher community incidence of other respiratory viruses.

The trial findings showing IFN-α to be highly effective in preventing COVID-19 infection remain clinically relevant and impactful in the current post-pandemic era. We have gained knowledge that COVID-19 reinfection occurs frequently despite vaccination, hematological malignant cancer populations have suboptimal vaccine responses, and avoiding COVID-19 with subsequent delays in cancer treatment and surgery significantly reduces excess and earlier-than-expected deaths [ 9 , 23 ]. The intervention may prevent COVID-19 reinfection. The trial findings may also be relevant to other immunocompromised or comorbid populations in whom acquisition of COVID-19 is best avoided, such as prior to planned major surgery or solid-organ transplantation, or in residential care facilities.

The cancer population represents a highly vulnerable group for developing severe COVID-19 and respiratory viral infections including pandemic influenza with progression to the need for supplemental oxygen, hospitalization, intensive care admission, and mortality [ 3 ]. IFN-α nasal spray as a daily prophylactic measure is a simple, acceptable intervention, which was well tolerated and safe and avoided complex drug interactions, particularly with cancer therapies. There may be a role for short-term IFN-α nasal spray in addition to vaccination and monoclonal antibodies in preventing COVID-19. It may allow safe and vital cancer care to continue without interruption during high-risk crucial clinical periods, such as undergoing intensive chemotherapy, radiotherapy, in the pre-hematopoietic stem cell transplantation period, pre-chimeric antigen receptor CAR T-cell therapy, and presurgery.

Intranasal IFN-α nasal spray as prophylaxis was effective and safe at reducing the incidence of COVID-19 among adult patients with cancer. IFN-α may provide an additional measure to vaccination and monoclonal antibodies in preventing COVID-19.

Supplementary Material

Notes

Acknowledgments. The authors thank all the study participants and their carers. Data Safety Monitoring Board: Zoe McQuilton, Monash University; Allen C. Cheng, Monash Infectious Diseases, Monash Health and School of Clinical Sciences, Monash University; Robert Weinkove, Cancer Immunotherapy Program, Malaghan Institute of Medical Research, Wellington, New Zealand; Thomas Hills, Medical Research Institute of New Zealand, Wellington, New Zealand. Study governance and pharmacovigilance: Samantha Somers, Ruth Columbus; trial pharmacists: Vivien Chen, Genie Hong, Tim Webster; research staff: Jacinta Johnson, Jess DeMajo, Gwyn Ng, Zoe Neoh, Natalie Saunders, Nicholas Laundy, Belinda de Poi; and manufacturing: Tri-Hung Nguyen, Barry Thompson.

Financial support. This trial was funded by the National Health and Medical Research Council MRFF (grant number 2002213) and the National Health and Medical Research Council (grant number 1116876).

Contributor Information

Michelle K Yong, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Karin Thursky, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Megan Crane, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Tim Spelman, Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Robert K Mahar, Biostatistics Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia; Methods and Implementation Support for Clinical and Health (MISCH) Research Hub, The University of Melbourne, Melbourne, Victoria, Australia; Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Julie A Simpson, Biostatistics Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia; Methods and Implementation Support for Clinical and Health (MISCH) Research Hub, The University of Melbourne, Melbourne, Victoria, Australia.

Andrew M Scott, Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia; Olivia Newton-John Cancer Research Institute, Tumour Targeting Laboratory, Heidelberg, Victoria, Australia; Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia; School of Cancer Medicine, LaTrobe University, Melbourne, Victoria, Australia.

Simon J Harrison, Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Jeff Szer, Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia; Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Marc Pellegrini, Walter and Eliza Hall Institute of Medical Research, Division of Infectious Diseases and Immune Defence, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia; Centenary Institute, Executive Director, Camperdown, New South Wales, Australia; Faculty of Heath and Medical Sciences, University of Sydney, Camperdown, New South Wales, Australia.

Senthil Lingaratnam, Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; Pharmacy Department, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Ken C Pang, Clinical Sciences, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Adolescent Medicine, Royal Children's Hospital, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.

Surekha Tennakoon, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Beatrice Z Sim, Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Emily Blyth, Department of Haematology, Westmead Hospital, Westmead, New South Wales, Australia; Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.

Hui K Gan, Department of Oncology, Austin Hospital, Heidelberg, Victoria, Australia.

Hang Quach, Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia; Department of Haematology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.

Michelle P McIntosh, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.

Hayley Page, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Rachel Woolstencroft, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Monica Slavin, Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia; Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

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Associated Data

Supplementary Materials