Multiple Myeloma and Infections: A Population-Based Study Based On 9,610 Multiple Myeloma Patients
Authors: Blimark Cecilie , Mellqvist Ulf-Henrik , Landgren Ola , Björkholm Magnus , Hultcrantz Malin L , Kjellander Christian , Turesson Ingemar , Holmberg Erik , Kristinsson Sigurdur Y 
Published: October 2019

Abstract
Abstract 945

Background
Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM). No large population-based evaluation has been made to assess the risk of infections in MM patients compared to the normal population. Therefore, we performed a large study, using population-based data from Sweden, to estimate the risk of bacterial and viral infections among 9,610 MM patients compared to 37,718 matched controls.

Methods
We gathered information on all MM patients reported to the nationwide Swedish Cancer Registry from 1988 to 2004, with follow-up to 2007. For each MM patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on occurrence and date of infections was obtained from the centralized Swedish Patient registry that captures information on individual patient-based discharge diagnosis from inpatient (with very high coverage) and outpatient care (since 2000).
Cox proportional hazard models were used to estimate the overall, one- and five-year risk of infections. In addition, the effect of gender, age and calendar period of diagnosis was evaluated. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for the occurrence of different infections.

Results
Overall, MM patients had a 6-fold (HR= 5.9; 95% CI=5.7-6.1) risk of developing any infection compared to matched controls (Figure). The increased risk of developing a bacterial infection was 6-fold (HR=5.9; 95%; CI=5.6-6.1), and for viral infections 9-fold (HR=9.0; 95% CI=8.0-10.1), compared to controls. More specifically, MM patients had an increased risk (p<0.05) of the following bacterial infections: cellulitis (HR=2.6; 95% CI =2.2-3.1), osteomyelitis (HR=3.0; 95% CI 2.0–4.4), endocarditis (HR=4.4; 95% CI 2.9–6.6), meningitis (HR=14.5; 95% CI 9.1–23.0), pneumonia (HR=6.2; 95% CI 5.9–6.5), pyelonephritis (HR=2.5; 95% CI 2.1–3.0), and septicaemia (HR=13.7; 95% CI 12.5–14.9) and for the viral infections influenza (HR=5.4; 95% CI 4.4–6.7) and herpes zoster (HR=12.8; 95% CI 10.5–15.5). The risk of infections was highest during the first year after diagnosis; the risk of bacterial infections was 11-fold (95% CI 10.7–12.9) and the risk of viral infections was 18-fold (95% CI 13.5–24.4) higher compared to controls during the first year after diagnosis.
MM patients diagnosed in the more recent calendar periods had significantly higher risk of infections, reflected in a 1.6-fold (95% CI=1.5-1.7) and 2-fold (95% CI=1.9-2.1) increased risk in patients diagnosed during 1994–1999 and 2000–2004, compared to patients diagnosed 1986–1993. Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001).

Discussion
In this large population-based study including over 9,000 MM patients and 35,000 matched controls, we found that bacterial and viral infections represent a major threat to myeloma patients. We found the risk of specific infections like pneumonia, and septicemia to be over ten times higher in patients than in controls during the first year after MM diagnosis. Importantly, the risk of infections increased in more recent years. The effect on infectious complications due to novel drugs in the treatment of MM needs to be established and trials on prophylactic measures are required.

Disclosures:
Mellqvist: Janssen, Celgene: Honoraria.