Incidence of Infections and Survival Outcomes in Patients with Multiple Myeloma and Chronic Lymphocytic Leukemia in Sweden: A Nationwide Population-Based Study of More Than 15,000 Patients

Background: Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) are characterized by immunodeficiency and the need for multiple treatments. The introduction of modern therapies has led to increased survival, yet patients remain at risk of infection and infection-related death.

Aim: To describe the incidence of secondary care infections over time and outcomes in patients diagnosed with MM and CLL.

Methods: This was a population-based study of patients with MM or CLL identified from the Swedish Cancer Registry (SCR) between January 2010 and December 2021. Longitudinal data were obtained from the National Patient Register, Prescribed Drug Register, National Quality Registry for intensive care, and Cause of Death Register. Patients were followed from the date of first MM or CLL diagnosis (index date) until the end of follow-up (date of death, end of data capture [March 2023 for mortality analyses], or emigration, whichever came first). Descriptive statistics were used to analyze patient demographics. Infection events were captured in the National Patient Register (National Quality Registry for intensive care for coronavirus 2019 [COVID-19] cases) and identified using International Classification of Diseases 10th Revision codes. Diagnosed and coded secondary care infections were defined as those occurring in hospital or during visits to specialized outpatient clinics. Kaplan–Meier methodology was used to assess time to first secondary care infection. Incidence rate (IR) of infections was calculated as the number of infections over the accumulated person-years, and reported as the number per person-year. Overall survival (OS) was assessed as time from first MM or CLL diagnosis to death using Kaplan–Meier methodology. The Fine and Grey competing-risk analysis was performed to estimate the risk of infection-related death. The main event was defined as death from infection (as underlying or contributing cause of death), and competing event was death from all other causes (as underlying or contributing).

Results: 15,766 patients were included in the analysis (MM: 8532; CLL: 7234), and the majority were male (MM: 57.4%; CLL: 62.2%). The median age was 71 (interquartile range [IQR]: 64–78) years in both groups, and the proportion of patients with a high Charlson comorbidity index was 37.4% in the MM group and 25.0% in the CLL group. Patients with MM and CLL were followed up for a mean duration of 3.9 (standard deviation [SD]: 3.0) and 5.2 (SD: 3.3) years, respectively. Overall, 5618 (66%) of patients with MM and 3618 (50%) patients with CLL had at least 1 secondary care infection at follow-up. The median time from diagnosis to first secondary care infection in patients with MM and CLL was 1.7 years and 5.2 years, respectively. There was a significant increase in secondary care infections over time in patients with MM (IR 0.33 to 0.44 per year; P<0.0001 for 2010 versus 2021). The IR for CLL remained stable from 0.14 to 0.13 throughout 2010–2021. Pneumonia was the most common bacterial infection (MM: 21.1%; CLL: 21.3%). Herpes zoster was the most common viral infection (MM: 2.6%; CLL: 1.0%). Median OS (95% confidence interval [CI]) was 4.7 (4.6–4.9) years in the MM group and 9.7 (9.3–10.2) years in the CLL group. Among the patients with MM who died (4822/8532 patients; 56.5%), infection (any type) was the underlying cause of death in 235/4822 patients (4.9%) and the underlying and/or contributing cause of death for 1251/4822 (25.9%) patients. Among the patients with CLL who died (2571/7234 patients; 35.5%), infection (any type) was the underlying cause of death in 249/2571 (9.7%) patients and the underlying and/or contributing cause of death for 835/2571 (32.5%) patients. The 1-, 5-, and 10-year risk of infection-related death was 4.6%, 12.4%, and 18.2% in patients with MM and 2.1%, 7.9%, and 14.5% in patients with CLL.

Conclusion: In this nationwide 12-year study of >15,000 patients diagnosed with MM and CLL, we observed a high incidence of infection. Infection was the underlying cause of death in approximately one quarter of patients with MM and one third of patients with CLL. With the introduction of modern immunotherapies, improved understanding of infection rates and risks is warranted.

This study was funded by Takeda, Sweden. Medical writing support was provided by Parexel and was funded by Takeda.