Drivers and barriers to COVID-19 vaccination in Australians with cancer.

PURPOSE: To understand the drivers and barriers for COVID-19 vaccination in people with cancer in Australia. METHODS: A cross-sectional, online survey, distributed nationally following the establishment of community vaccination programs, wider availability of COVID-19 vaccines and emergence of new variants. Consisting of 21 questions, the survey was designed to determine the behavioural and social drivers of vaccination, participant demographics, underlying disease and treatment, and vaccination status. It was open from the 10th of August 2021 to the 7th of September 2021, recruiting people who had a previous history of cancer (diagnosed or treated in the past 5 years). RESULTS: A total of 1506 responses were included in the final analysis. Overall, 87.8% reported a positive attitude toward vaccination and 83.1% had received at least one dose of a COVID-19 vaccine. Perceived risk of COVID-19 infection (for self and others) and engagement with a trusted health professional were key drivers for vaccination, while concerns about vaccine development, safety and side effects were barriers. Concerns about vaccination mostly stemmed from a place of misinformation, rather than a broader disregard of vaccines. Just over a third (497, 34.3%) of the respondents were concerned that the vaccine would impact their cancer treatment. CONCLUSION: Overall, participants had positive attitudes toward COVID-19 vaccination and thought it was safe. Findings supported the role of health professionals and cancer organisations as trusted information providers and calls for more, credible information to help people with cancer make informed decisions about the COVID-19 vaccine.

Low rates of invasive fungal disease in patients with multiple myeloma managed with new generation therapies: Results from a multi-centre cohort study.

INTRODUCTION: A multi-centre study to determine the outcomes and risks for invasive fungal disease (IFD) in myeloma (MM) patients treated with second-generation immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies was conducted. METHODS: Clinical and microbiology records were reviewed to capture patient demographics, disease characteristics, treatment, IFD episodes and outcomes. Categorical and continuous variables between patients with IFD and without IFD were compared using chi-square test, Fisher's exact test and Mann-Whitney rank sum test, respectively, with P-value < .05 considered statistically significant. RESULTS: Five out of 148 (3.4%) MM patients were diagnosed with five episodes of IFI: 3 were proven, 1 probable and 1 possible. Median time from commencement of new generation therapy to IFD diagnosis was 4.0 months (Interquartile range [IQR]: 3.4-5.7). In patients with IFD, median cumulative steroid dose over 60 days was 1119 mg (IQR: 1066-1333 mg). None of the patients with IFD had prolonged neutropenia (neutrophil count < 0.5 × 109 /L for more than 10 days). Common sites of infection were the respiratory tract (40.0%) and bloodstream (40.0%). Cryptococcus neoformans (n = 2) and Candida krusei (n = 1) were the fungal pathogens isolated in the three proven cases. 30-day mortality rate was 40.0%. Patients with IFD were younger (median 58 versus 68 years, P = .52) and treated with more lines of therapy (median 5 vs 3, P = .04). CONCLUSION: IFD rate is low in heavily treated MM patients treated with second-generation therapy including monoclonal antibodies. Patients do not appear to have traditional risk factors such as prolonged neutropenia.

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.

Evolution of Humoral and Cellular Immunity Post-Breakthrough Coronavirus Disease 2019 in Vaccinated Patients With Hematologic Malignancy Receiving Tixagevimab-Cilgavimab.

Background: In-depth immunogenicity studies of tixagevimab-cilgavimab (T-C) are lacking, including following breakthrough coronavirus disease 2019 (COVID-19) in vaccinated patients with hematologic malignancy (HM) receiving T-C as pre-exposure prophylaxis. Methods: We performed a prospective, observational cohort study and detailed immunological analyses of 93 patients with HM who received T-C from May 2022, with and without breakthrough infection, during a follow-up period of 6 months and dominant Omicron BA.5 variant. Results: In 93 patients who received T-C, there was an increase in Omicron BA.4/5 receptor-binding domain (RBD) immunoglobulin G (IgG) antibody titers that persisted for 6 months and was equivalent to 3-dose-vaccinated uninfected healthy controls at 1 month postinjection. Omicron BA.4/5 neutralizing antibody was lower in patients receiving B-cell-depleting therapy within 12 months despite receipt of T-C. COVID-19 vaccination during T-C treatment did not incrementally improve RBD or neutralizing antibody levels. In 16 patients with predominantly mild breakthrough infection, no change in serum neutralization of Omicron BA.4/5 postinfection was detected. Activation-induced marker assay revealed an increase in CD4+ (but not CD8+) T cells post infection, comparable to previously infected healthy controls. Conclusions: Our study provides proof-of-principle for a pre-exposure prophylaxis strategy and highlights the importance of humoral and cellular immunity post-breakthrough COVID-19 in vaccinated patients with HM.

COVID-19 infection among patients with cancer in Australia from 2020 to 2022: a national multicentre cohort study.

Background: The global COVID-19 pandemic disproportionately affected certain populations and its management differed between countries. This national study describes characteristics and outcomes of COVID-19 in patients with cancer in Australia. Methods: We performed a multicentre cohort study of patients with cancer and COVID-19 from March 2020 to April 2022. Data were analysed to determine varying characteristics between cancer types and changes in outcomes over time. Multivariable analysis was performed to determine risk factors associated with oxygen requirement. Findings: 620 patients with cancer from 15 hospitals had confirmed COVID-19. There were 314/620 (50.6%) male patients, median age 63.5 years (IQR 50-72) and majority had solid organ tumours (392/620, 63.2%). The rate of COVID-19 vaccination (≥1 dose) was 73.4% (455/620). Time from symptom onset to diagnosis was median 1 day (IQR 0-3), patients with haematological malignancy had a longer duration of test positivity. Over the study period, there was a significant decline in COVID-19 severity. Risk factors associated with oxygen requirement included male sex (OR 2.34, 95% CI 1.30-4.20, p = 0.004), age (OR 1.03, 95% CI 1.01-1.06, p = 0.005); not receiving early outpatient therapy (OR 2.78, 95% CI 1.41-5.50, p = 0.003). Diagnosis during the omicron wave was associated with lower odds of oxygen requirement (OR 0.24, 95% CI 0.13-0.43, p < 0.0001). Interpretation: Outcomes from COVID-19 in patients with cancer in Australia over the pandemic have improved, potentially related to changing viral strain and outpatient therapies. Funding: This study was supported by research funding from MSD.

Robust SARS-CoV-2 T cell responses with common TCRαß motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells.

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%-75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.

Epidemiology and Risks of Infections in Patients With Multiple Myeloma Managed With New Generation Therapies.

INTRODUCTION: Treatment for multiple myeloma (MM) has continued to evolve with second generation immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs). This study aims to evaluate the epidemiology and risks of infection in patients with MM managed with these therapies. PATIENTS AND METHODS: Clinical and microbiological records were reviewed to capture patient demographics, disease characteristics, treatment received, episodes of infection, and outcomes. Infections were classified as microbiologically defined (MDI), clinically defined (CDI), and fever of unknown focus (FUF). Univariate and multivariate analyses were performed to determine risk factors for infection, with a P value < .05 considered statistically significant. RESULTS: A total of 148 patients with MM with 345 infection episodes were identified. Of these, 29.0% (100/345), 58.0% (200/345), and 13.0% (45/345) were defined as MDI, CDI, and FUF, respectively. Of 100 MDIs, 50.0% were owing to viruses, whereas 45.0% were owing to bacterial infection. The most common infection site was the respiratory tract (56.8%). Hospital admission occurred in 41.7% of infection episodes, and the 30-day all-cause mortality rate was 5.4%. On multivariate regression, receipt of a PI (odds ratio [OR], 16.80; 95% confidence interval [CI], 2.47-114.52), combination of IMiD and PI (OR, 13.44; 95% CI, 2.39-75.76), mAb-combination (OR, 10.44; 95% CI, 1.99-54.51), and lines of therapy (> 4) (OR, 7.72; 95% CI, 1.25-47.81) were associated with increased risk of infection (all P < .05). CONCLUSION: Viral infections now constitute the majority of infections in patients with MM treated with newer agents. Receipt of a PI and lines of therapy (> 4) were associated with higher risk for infection.