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.

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.