Page 187 - Haematologica Vol. 110 - January 2025

LETTER TO THE EDITOR
Respiratory syncytial virus and other vaccine-preventable infections in multiple myeloma. A population-based study on 8,672 myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry
Infections are a major clinical problem in the management of multiple myeloma (MM) due to both disease- and treat- ment-related factors. Measures to prevent infection, such as vaccinations, are therefore of paramount importance in the clinical care of MM patients. Data on vaccine-pre- ventable infections in MM treated with modern therapy is sparse. Data regarding the burden of Respiratory Syncytial virus (RSV) infection is of particular interest given the re- cent approval of two immunogenic prefusion F-vaccines against RSV in Europe.
The aim of this study was to estimate the risk of vac- cine-preventable infections in myeloma patients compared to a healthy population using real-world data. We used a prospective cohort design with an external comparison population. The study population included all patients with symptomatic MM diagnosed between 2008 and 2021 in Sweden included in the Swedish Myeloma Registry (N=8,672). The coverage in the Swedish Myeloma Registry is high, estimated to be over 95% between 2008-2022. Four controls per MM patient were identified random- ly from the Swedish population database matched for age, sex and county of residence (N=34,567). Diagnoses of infectious diseases were retrieved from the Swedish Patient Registry, with good coverage on diagnostic codes for different infections among mainly inpatient but also outpatient visits.1 Infections must have occurred on sep- arate occasions at least 1 month apart. For COVID-19 this interval was set to 3 months, as prolonged viral replication is common in immunosuppressed patients. Both MM pa- tients and controls were followed until death, permanent emigration or till December 31, 2022. A multi-state Cox proportional hazard model with infection as a time-de- pendent co-variate was used to estimate the overall risk of infections as well as 1- and 5-year risk of infections compared to controls. All models were adjusted for sex, age and year of diagnosis. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Effects of age, sex and autologous stem cell transplantation (auto-SCT) were evaluated separately. When total number of cases with a specific infectious disease was below 10, no sta- tistical analyses were performed. The study was approved by the Swedish Ethical Review Authority (permit number: 2020-01729).
The majority of patients (73 %) were 65 years or older at
diagnosis, 57% were males and 30% were treated with up- front auto-SCT. Patients were treated in accordance with current national MM guidelines at the time,2 importantly the use of immunomodulatory agents (IMiD) increased during this period from low numbers to over 90% of pa- tients receiving these drugs.2 Additional clinical details on the included MM patients are shown in the Online Supplementary Table S1. The median time of follow-up was 3.1 years for patients and 5.7 years for controls (range, 0-15). The risk of acquiring a vaccine-preventable infection was 8-fold in MM patients compared to matched controls (HR=7.5; 95% CI: 7.0-8.0), see Table 1. The risk of acquiring vaccine-preventable infections was higher in males than females (P=0.03) among MM patients. In the group treated with auto-SCT, the risk of vaccine-preventable infections was slightly higher (HR=1.4; 95% CI: 1.2-1.6) compared to patients not treated with auto-SCT. In particular, the risk of herpes zoster was more than two-fold (HR=2.2; 95% CI: 1.7-2.8). The incidence of vaccine-preventable infections was 6-fold higher in MM patients compared to controls in the first year following diagnosis and remained high or increased for certain infections (pneumococcal infection, RSV, influenza and herpes zoster) during follow-up; see Figure 1.
Based on our data, the risk of vaccine-preventable infec- tions was high in MM patients, especially RSV and pneu- mococcal infection where the risk compared to a healthy population was 16- and 17-fold, respectively. The risk of influenza, herpes zoster and Haemophilus influenzae was manyfold in patients with MM and remained high or increased during follow-up. The rates of pneumococcal infection were found to be high in the current study but lower than reported in a Swedish study of invasive pneu- mococcal disease (IPD) between the years 1996-20083 where IPD was shown to be 152-times more common in myeloma patients compared to controls. Pneumococcal vaccination with conjugate vaccines (PCV) was intro- duced in the Swedish National Vaccination Program in 2008 for children, lowering the mortality rates from IPD in the population,4 reducing transmission in the com- munity and protecting immunosuppressed populations. A common misconception is that MM patients do not respond to vaccination. However, clinical effectiveness (i.e., reduction in disease severity, hospitalization and
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