Medicine (St Vincent's) - Research Publications
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ItemLow rates of invasive fungal disease in patients with multiple myeloma managed with new generation therapies: Results from a multi-centre cohort study(WILEY, 2021-01)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.
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ItemSuccessful identification of predictive profiles for infection utilising systems-level immune analysis: a pilot study in patients with relapsed and refractory multiple myeloma(WILEY, 2021)OBJECTIVES: Patients with multiple myeloma (MM) are at increased risk for infection. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapy. A pilot systems-level immune analysis study to identify predictive markers for infection was conducted. METHODS: Patients with relapsed and/or refractory MM (RRMM) who participated in a treatment trial of lenalidomide and dexamethasone were evaluated. Data on patient demographics, disease and episodes of infection were extracted from clinical records. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals were analysed, with or without mitogen re-stimulation, using RNA sequencing and mass cytometry (CyTOF). CyTOF-derived cell subsets and RNAseq gene expression profiles were compared between patients that did and did not develop infection to identify immune signatures that predict infection over a 3-month period. RESULTS: Twenty-three patients participated in the original treatment trial, and we were able to access samples from 17 RRMM patients for further evaluation in our study. Nearly half the patients developed an infection (8/17) within 3 months of sample collection. Infections were mostly clinically diagnosed (62.5%), and the majority involved the respiratory tract (87.5%). We did not detect phenotypic or numerical differences in immune cell populations between patients that did and did not develop infections. Transcriptional profiling of stimulated PBMCs revealed distinct Th2 immune pathway signatures in patients that developed infection. CONCLUSION: Immune cell counts were not useful predictors of infection risk. Functional assessment of stimulated PBMCs has identified potential immune profiles that may predict future infection risk in patients with RRMM.