Executive summary of consensus clinical practice guidelines for the prevention of infection in patients with multiple myeloma.

Infection remains a significant contributor to morbidity and mortality in patients with myeloma. This guideline was developed by a multidisciplinary group of clinicians who specialise in the management of patients with myeloma and infection from the medical and scientific advisory group from Myeloma Australia and the National Centre for Infections in Cancer. In addition to summarising the current epidemiology and risk factors for infection in patients with myeloma, this guideline provides recommendations that address three key areas in the prevention of infection: screening for latent infection, use of antimicrobial prophylaxis and immunoglobulin replacement and vaccination against leading respiratory infections (severe acute respiratory syndrome coronavirus 2, influenza and Streptococcus pneumoniae) and other preventable infections. This guideline provides a practical approach to the prevention of infection in patients with myeloma and harmonises the clinical approach to screening for infection, use of prophylaxis and vaccination to prevent infectious complications.

Prospective comprehensive profiling of immune responses to COVID-19 vaccination in patients on zanubrutinib therapy.

Zanubrutinib-treated and treatment-naïve patients with chronic lymphocytic leukaemia (CLL) or Waldenstrom's macroglobulinaemia were recruited in this prospective study to comprehensively profile humoral and cellular immune responses to COVID-19 vaccination. Overall, 45 patients (median 72 years old) were recruited; the majority were male (71%), had CLL (76%) and were on zanubrutinib (78%). Seroconversion rates were 65% and 77% following two and three doses, respectively. CD4+ and CD8+ T-cell response rates increased with third dose. In zanubrutinib-treated patients, 86% developed either a humoral or cellular response. Patients on zanubrutinib developed substantial immune responses following two COVID-19 vaccine doses, which further improved following a third dose.

Survey of treatment practices for immunocompromised patients with COVID-19 in Australasia.

Coronavirus disease 2019 (COVID-19) in immunocompromised patients can lead to severe and prolonged illness. Data are limited with regard to management of COVID-19 in this setting, particularly in persistent or recrudescent infection. The authors conducted an online survey among infectious diseases doctors to determine current approaches to treatment across Australasia. There was marked variability in responses relating to the diagnostic modalities and use of antiviral agents in patients with immunocompromise, highlighting the need for high-quality studies to guide treatment decisions in this group.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

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.

Immunogenicity of COVID-19 vaccines in patients with hematologic malignancies: a systematic review and meta-analysis.

The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with hematologic malignancies. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from January 1, 2021, to August 31, 2021, was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL. Primary outcome was the rate of seropositivity after 2 doses of COVID-19 vaccine with rates of seropositivity after 1 dose, rates of positive neutralizing antibodies, cellular responses, and adverse events as secondary outcomes. Rates were pooled from single-arm studies while rates of seropositivity were compared against the rate in healthy controls for comparator studies using a random effects model and expressed as a pooled odds ratios with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 after first dose, 4733 after second dose). Overall seropositivity rates were 62% to 66% after 2 doses of COVID-19 vaccine and 37% to 51% after 1 dose. The lowest seropositivity rate was 51% in patients with chronic lymphocytic leukemia and was highest in patients with acute leukemia (93%). After 2 doses, neutralizing antibody response rates were 57% to 60%, and cellular response rates were 40% to 75%. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months were associated with poor immune responses to COVID-19 vaccine. New approaches to prevention are urgently required to reduce COVID-19 infection morbidity and mortality in high-risk patient groups that respond poorly to COVID-19 vaccination.

Invasive pulmonary aspergillosis in critically ill patients with COVID-19 in Australia: implications for screening and treatment.

We report four cases of invasive pulmonary aspergillus co-infection in patients with coronavirus disease 2019 (COVID-19) infection and acute respiratory distress syndrome requiring intensive care unit (ICU) admission. Aspergillus fumigatus and Aspergillus terreus were isolated, with early infection onset following ICU admission. Clinicians should be aware of invasive pulmonary aspergillosis in ICU patients with COVID-19 infection, particularly those receiving dexamethasone. We propose screening of these high-risk patients with twice-weekly fungal culture from tracheal aspirate and, if feasible, Aspergillus polymerase chain reaction. Diagnosis is challenging and antifungal treatment should be considered in critically ill patients who have new or worsening pulmonary changes on chest imaging and mycological evidence of infection.

Aspergillus Polymerase Chain Reaction-An Update on Technical Recommendations, Clinical Applications, and Justification for Inclusion in the Second Revision of the EORTC/MSGERC Definitions of Invasive Fungal Disease.

Aspergillus polymerase chain reaction testing of blood and respiratory samples has recently been included in the second revision of the EORTC/MSGERC definitions for classifying invasive fungal disease. This is a result of considerable efforts to standardize methodology, the availability of commercial assays and external quality control programs, and additional clinical validation. This supporting article provides both clinical and technical justifications for its inclusion while also summarizing recent advances and likely future developments in the molecular diagnosis of invasive aspergillosis.

Managing low-risk febrile neutropenia in children in the time of COVID-19: What matters to parents and clinicians.

AIM: The Australian 'There is no place like home' project is implementing a paediatric low-risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID-19) pandemic on programme implementation. METHODS: Paediatric oncology, infectious diseases and emergency medicine health-care workers and parent/carers were surveyed to explore the impact of the COVID-19 pandemic on home-based FN care. Online surveys were distributed nationally to health-care workers involved in care of children with FN and to parents or carers of children with cancer. RESULTS: Surveys were completed by 78 health-care workers and 32 parents/carers. Overall, 95% of health-care workers had confidence in the safety of home-based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre-pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home-based FN care. Among both groups, increased telehealth access and acceptance of home-based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re-direction of resources due to COVID-19 and challenges in implementing change during a crisis were potential barriers. CONCLUSION: There is strong clinician and parent/carer support for home-based management of low-risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home-based treatments and opportunities exist to leverage these to refine the low-risk FN programme.

Managing haematology and oncology patients during the COVID-19 pandemic: interim consensus guidance.

INTRODUCTION: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID-19, including other infections and therapy-related pneumonitis. For suspected or confirmed COVID-19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID-19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS-CoV-2 acquisition; support population-wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID-19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID-19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID-19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID-19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.