Differences and Temporal Changes in Risk of Invasive Pneumococcal Disease in Adults with Hematological Malignancies: Results from a Nationwide 16-Year Cohort Study

Abstract

Background: Patients with hematological malignancies (HM) are known to carry an increased risk of invasive pneumococcal disease (IPD). However, temporal variations in IPD risks following a cancer diagnosis remain poorly characterized. To inform vaccine guidelines and patient management, we assessed the IPD incidence among patients with HM and other malignancies.

Methods: The study population included all individuals aged ≥15 years during 2000-2016 in Denmark. Variations in incidences of IPD over time and between different types of hematological malignancies and diagnoses were assessed by Poisson regression.

Results: During 85 002 224 person-years of observation, 13 332 episodes of a first IPD were observed, of which 765 (5.7%) occurred among individuals with HM. Among HM patients, the IPD incidence rate decreased continuously during the study period (rate ratio per year, 0.91; 95% confidence interval, .90-.92). The risk of IPD in patients with HM was up to 39 times higher when compared to the background population and was highest for multiple myeloma, acute lymphoblastic leukemia, and chronic lymphocytic leukemia. Unlike other malignancies, the increased IPD risk did not wane with the time since HM diagnosis. We found a vaccination uptake of only ≤2% in patients with HM and ≤1% for those with other types of malignancies.

Conclusions: Adults with HM in general and patients with lymphoid malignancies in particular have an increased risk for IPD, compared with patients with other types of cancer and with individuals free of cancer. The pneumococcal vaccination uptake is extremely low in this at risk-population. Efforts to prevent IPD in HM patients are continuously warranted.

Keywords: hematological malignancies; invasive pneumococcal disease; mortality; pneumococcal serotypes; risk factors.

Figure 1.

Incidence of invasive pneumococcal disease in the Danish population. The y-axis shows the number of cases per 100 000 PY, and the x-axis shows age stratified by the presence of a hematological malignancy and grouped in 4 calendar periods. Abbreviations: HM, hematological malignancies; PY, person years.

Figure 2.

Incidence rates of invasive pneumococcal disease in the Danish population for individuals with and without a hematological malignancy according to serotypes included in pneumococcal vaccines. The vaccine groups were PCV7 (PCV7 serotypes), additional PCV13 serotypes (serotypes covered by PCV13 but not PCV7), PPV23 non-PCV13 serotypes (serotypes that are covered by PPV23 but not by PCV13), and non-VT (non-VT, defined as all serotypes that are not covered by PCV7, PCV13, or PPV23). Abbreviations: PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPV23, 23-valent pneumococcal polysaccharide vaccine; VT, vaccine serotype.

Figure 3.

Time to invasive pneumococcal disease since time of diagnosis of malignancy. A, Individuals with any nonhematological malignancy. B, Individuals with and without hematological malignancies. RR estimates are adjusted for age, gender, calendar year, comorbidity, and type of malignancy. The y-axis shows the RR, and the x-axis shows the time since malignancy, with 0 being the year of diagnosis. Abbreviations: CI, confidence interval; CLL, chronic lymphocytic leukemia; IPD, invasive pneumococcal disease; RR, rate ratio.