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Infections cause significant morbidity and mortality in myeloma, contributing to up to 50% of early deaths. The increased risk is attributed to immunoparesis and immunosuppressive therapy. The nature and patterns of infections evolved over time, owing to a changing treatment paradigm, which employs a range of systemic therapies from distinct pharmacological classes, all of which confer differing infection risks, and are used in doublet to quadruplet combinations. The aim of first line therapy in transplant non-eligible (TNE) newly diagnosed myeloma (NDMM) patients is to achieve an optimal disease control whilst maintaining a good quality of life (QoL). As such, the burden of infections can negatively impact QoL, whilst treatment interruptions or discontinuations can lead to a sub-optimal haematological response. We performed a retrospective study of 200 consecutive TNE NDMM patients treated with UK standard of care (2009-2018) to assess infection morbidity and mortality over a 12-month period from diagnosis, and to identify clinical predictors of infective episodes, particularly in elderly co-morbid patients who are largely under-represented in myeloma clinical trials. Data were collected on baseline characteristics of patients and the disease, in addition to treatment. A number of infection outcomes were collected for each patient over a period of 12 months. A detailed method is described in the Online Supplementary Materials and Methods. The median age of the total cohort was 75 years (range: 40-94), of whom 54% had immunoglobulin G (IgG) subtype, and 44% had International Staging System (ISS) 3 staging. According to the Charlson Comorbidity Index (CCI), 76% of patients were moderately to severely comorbid (CCI: 3-4: 48% and CCI: ≥5 =28%). As such, only 5% of patients were enrolled in a clinical trial. Baseline characteristics of the total cohort are fully presented in the Online Supplementary Table S1. Patients received a median of six cycles of therapy (range: 1-39): IMiD-based (69%), PI: proteasome inhibitor-based (20%) and chemo-based (11%). Median follow up was 67.7 months. Median overall survival (OS)

Infection-related morbidity in a large study of transplant non-eligible newly diagnosed myeloma patients treated with UK standard of care