Risks, severity and timing of infections in patients with multiple myeloma: a longitudinal cohort study in the era of immunomodulatory drug therapy

Abstract

We defined the epidemiology and clinical predictors of infection in patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and autologous haematopoietic stem cell transplant (ASCT) in a large longitudinal cohort study. Clinical and microbiology records of patients with MM diagnosed between January 2008 and December 2012 were reviewed to capture patient demographics, characteristics of myeloma and infections (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of infection. One hundred and ninety-nine patients with MM with 771 episodes of infection were identified. 44·6% of infections were clinically defined, 35·5% were microbiologically defined and 19·9% were fever of unknown focus. There was a bimodal peak in incidence of bacterial (4-6 and 70-72 months) and viral infections (7-9 and 52-54 months) following disease diagnosis. Chemotherapy regimens high-dose melphalan [hazard ratio (HR) = 2·07], intravenous cyclophosphamide (HR = 1·96) and intensive combination systemic chemotherapy (HR = 1·86) and cumulative doses of corticosteroid (HR = 3·06 at highest dose) were independently associated with increased risk of infection overall (P < 0·05). IMiDs and PI and other clinical factors were not independently associated with increased risk of infection. New approaches to prevention and treatment of infection should focus upon identified periods of risk and treatment-related risk factors.

How I manage the toxicities of myeloma drugs

“…52 Bacterial infections predominate during the first weeks of first-line therapy, and viral infections are more frequent during PIs and dexamethasone; in very advanced disease, the spectrum of causative microorganisms widens. 53 In 1 study, bacterial cultures revealed gram-negative in 47%, gram-positive in 39%, and multiple organisms in 14% of infections, 54 the most frequent agents being Escherichia coli, Clostridium difficile, pneumococci, Haemophilus, and viruses. 51,54 Viral infections are typically either reactivations of latent herpesviridae infections and, to a lesser extent, latent hepatitis, or newly acquired acute respiratory virus infections.…”

“…53 In 1 study, bacterial cultures revealed gram-negative in 47%, gram-positive in 39%, and multiple organisms in 14% of infections, 54 the most frequent agents being Escherichia coli, Clostridium difficile, pneumococci, Haemophilus, and viruses. 51,54 Viral infections are typically either reactivations of latent herpesviridae infections and, to a lesser extent, latent hepatitis, or newly acquired acute respiratory virus infections. 55 MM predisposes to infections because of the often combined effects of immune dysfunction caused by the disease itself, the immunosuppressive effects of anti-myeloma therapy, and frequent age-and disease-related comorbidities.…”

“…55 MM predisposes to infections because of the often combined effects of immune dysfunction caused by the disease itself, the immunosuppressive effects of anti-myeloma therapy, and frequent age-and disease-related comorbidities. 54 Myeloma affects both the humoral and the cellular immune system, resulting in dysfunction of B and T cells, dendritic cells, and NK cells. 53 The majority of patients are elderly individuals, often with geriatric conditions and disabilities.…”

Predicting Risk of Infection in Patients with Newly Diagnosed Multiple Myeloma: Utility of Immune Profiling

“…Identified clinical risk factors for infection in MM patients range from receipt of intensive combination systemic chemotherapy, cumulative doses of corticosteroids to number of lines of therapy (5). In addition, there is differential infection risk posed by IMiDs and PI with varying treatment periods (3).…”

Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network

“…Bacteria and fungi. The risk for bacterial infections is significantly higher compared to the normal population, 72 and particularly high in patients with active disease after start of initial therapy, 73 and in those with a history of frequent infections and in elderly frail patients. Grade 3 and 4 infections were noted in 29% of patients treated with continuous lenalidomide-dexamethasone 21 and in 16.5% of relapsed/refractory myeloma exposed to carfilzomib-lenalidomide-dexamethasone.…”