Background The recent development of vaccines for respiratory syncytial virus (RSV) has created a pressing need to better quantify the morbidity and mortality of RSV infection in haematological malignancies (HM). The present study investigated RSV morbidity and mortality in a large, unselected HM population as part of the UNCOVER health data research programme using secondary care data routinely collected by the National Health Service (NHS) in England.

Methods Cancer registry and linked hospital attendance, treatment and survival data were obtained from the NHS England National Cancer Registration Service for all adults with HM diagnosed between 2014 and 2021, alongside a control cohort of patients with non-melanoma skin cancer (NMSC) aged ≥75. Primary outcomes were RSV-related death, hospital admission with RSV as the primary cause, and hospital admission with RSV as a contributory cause. Secondary outcomes included duration of RSV-related hospital admissions, readmission rates, overall survival (OS) and cause-specific survival (CSS) following RSV-related hospitalisation. Baseline variables included comorbidity measured by the Charlson Comorbidity Index and socioeconomic deprivation measured as index of multiple deprivation (IMD) quintiles. Crude incidence rates were reported with incidence rate ratio and P-values calculated using Poisson regression. Within the HM population, propensity score matching (1:4 nearest neighbour) was used to compare outcomes following RSV-related vs matched RSV-unrelated hospitalisations. Admission length was compared using Mann-Whitney U test, while readmission rates were analysed using Anderson-Gill recurrent event models. OS and CSS were analysed using Kaplan-Meier estimates and log-rank tests. Risk factors for severe RSV disease, defined as RSV-related death or hospital admission with RSV as the primary cause, were identified using uni- and multivariable Cox proportional hazards (coxph) models, with cause-specific competing risks regression used to account for RSV-unrelated deaths.

Findings The HM population included 260,029 patients [median age 71 years (IQR 61-80); 56.9% male]. The most common diagnoses were mature B-cell neoplasms (40.7%), plasma cell neoplasms (PCN; 15.1%), myeloproliferative neoplasms (12.9%), myelodysplastic syndrome (MDS; 8.0%), and acute myeloid leukaemia (AML; 6.7%). Over a median follow-up of 39.7 months,131,575 (50.6%) received systemic anti-cancer therapy (SACT) and 10,662 (4.1%) underwent haematopoietic stem cell transplantation (HSCT). Incidence rates for RSV-related death (3.3/100,000 person-years), hospitalisation with RSV as a primary cause (11.7/100,000 person-years) or as a contributory cause (75.2/100,000 person-years) were 2.7- (P=0.017), 5.2- (P<0.001), and 11.4-fold (P<0.001) higher, respectively, than in the control population [n=134,489, median age 82 (IQR 78-86) years]. Compared to matched RSV-unrelated admissions, RSV-related hospitalisations in HM patients were associated with longer admissions (median 7 vs 5 days, P<0.001), higher readmission rates [1.6-fold for first readmission (P<0.001), 1.2-fold for second (P=0.009)]; shorter OS (median 27.4 vs 52.7 months, P=0.003); a 1.7-fold increased risk of infection-related death (P<0.001); and a 1.2-fold increased risk of HM-related death (P=0.005). Multivariable and cause-specific coxph analyses identified acute lymphoblastic leukaemia, AML, MDS, PCN, SACT within 6 months and HSCT within 12 months as independent risk factors for severe RSV. Notably, neither age nor comorbidity were significant predictors of severe RSV, whereas there was a non-linear relationship between severe RSV risk and deprivation. Compared to IMD5 (least deprived), severe RSV risk increased with greater deprivation, reaching significance in IMD2 (P=0.017). However, IMD1 (most deprived) was associated with high RSV-related mortality but low hospitalisation rates with RSV as the primary cause.

Conclusion Given that advanced age is an established risk factor for adverse RSV outcomes, our findings clearly identify HM as an even greater risk factor, providing a strong rationale for prioritising individuals with HM in unfolding RSV vaccination programmes. Among patients with HM, diagnoses including acute leukaemia, MDS and PCN, as well as recent therapy (SACT or HSCT), were associated with a higher risk of severe RSV infections. Such infections may be under-diagnosed and under-treated in patients living in the most deprived areas.

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2025
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