Infection Remains a Major Burden in Blood Cancers

Two-thirds of patients with multiple myeloma (MM) and half of those with chronic lymphocytic leukemia (CLL) experienced at least 1 serious infection during follow-up in a nationwide Swedish study, and infection was a contributing cause of death in roughly a quarter to a third of those who died, according to findings published in eJournal of Haematology.¹

The results, drawn from more than 15,000 patients diagnosed between 2010 and 2021, underscore that infection remains a persistent threat even as treatment for both cancers has advanced.

What Did the Registry Data Show?

The researchers linked these 4 Swedish national registries: the National Patient Register, the Prescribed Drug Register, the Swedish Cancer Register, and the Cause of Death Register. They covered hospital and specialist outpatient visits, prescription drugs, cancer diagnoses, and cause of death to follow 8532 patients with MM (57.4% male patients) and 7234 with CLL (62.2% male patients) from diagnosis until death, emigration, or the end of data capture. The median (IQR) age at diagnosis in both cohorts was identical, at 71 (64-78) years.

A marker of substantial preexisting illness burden, baseline Charlson Comorbidity Index (CCI) score was high (≥ 5) in 37.4% of patients with MM and 25.0% of patients with CLL; moderate (3-4) in 32.1% and 32.2%, respectively; and low (0-2) in 30.5% and 42.8%. Most patients had not reported infection in the decade preceding their diagnosis, at 63.7% of the MM cohort and 69.5% of the CLL cohort.

Over a median follow-up of 3.3 (1.5-5.6) years for MM and 4.8 (2.5-7.6) years for CLL, 66% of patients with MM and 50% of those with CLL developed at least 1 documented infection requiring hospital or specialist care. Bacterial infections were more common than viral infections in both groups: 55.7% vs 12.9% of the MM cohort and 56.3% vs 13.1% of the CLL cohort. Pneumonia was the most frequently specified infection, accounting for 21.1% and 21.3% of cases in each cohort, respectively. Herpes zoster was the most common named viral infection, slightly more frequent in CLL (3.5%) than MM (2.6%).

Why Did Infections Strike Earlier in MM?

One of the study’s more notable findings involved timing: the median time from diagnosis to first infection was 1.7 years in MM vs 5.2 years in CLL. Nearly a third of patients in both cohorts had experienced an infection in the decade before their cancer diagnosis, a pattern the authors say may reflect immune deterioration that begins before the malignancy is clinically apparent.

Median overall survival among patients who developed infection was 4.47 years (95% CI, 4.11-4.85) for MM and 7.97 years (95% CI, 7.61-8.34) for CLL, both notably shorter than survival in patients who remained free of infection, at 4.87 years (95% CI, 4.65-5.05) and not reached, respectively. Infection was the underlying or contributing cause of death in 25.9% of patients with MM and 32.5% of those with CLL, while the malignancy itself remained the leading underlying cause of death in both groups, at 67.3% and 33.1%, respectively.

What Were the Primary Risk Drivers?

In multivariable modeling that accounted for competing mortality risk, higher CCI scores, history of prior infection, and prior prophylactic anti-infective treatment were each independently associated with a greater risk of subsequent infection in both cancers. Conversely, female sex and a more recent year of diagnosis were linked to lower infection risk. Older age was protective in MM but modestly associated with higher risk in CLL. The authors suggest these consistent predictors could help identify patients who would benefit from closer monitoring or earlier prophylactic intervention at the time of diagnosis.

Most patients received at least 1 nonprophylactic anti-infective treatment during follow-up, typically antibiotics (55% of patients with MM, 64.2% of patients with CLL), and 76% of patients with MM but only 39% with CLL received antimicrobial prophylaxis for 3 months or longer. Immunoglobulin replacement therapy, although the authors cautioned that hospital- or clinic-administered immunoglobulins may be underrepresented in prescription registry data.

How Do These Results Fit in With Previous Research?

A previous analysis of more than 8600 patients in the Swedish Myeloma Registry similarly found a roughly 5-fold increased infection risk relative to matched controls, with sepsis and pneumonia as the leading culprits and infection contributing to more than a quarter of deaths within a year of diagnosis.² Also previously reported, secondary immunodeficiency compounds this risk substantially: patients with CLL or small lymphocytic lymphoma who also had a diagnosed secondary immunodeficiency disease were more than twice as likely to develop an infection as those without it.³

Efforts are also underway to move beyond broad risk factors like age and comorbidity toward more precise, data-driven infection prediction models in CLL. A 2026 study found that a machine-learning model trained on combined CLL and lymphoma electronic health records outperformed both a CLL-only model and the standard CLL-International Prognostic Index at flagging patients at high risk of severe posttreatment infection, although the rarity of CLL has made building such tools difficult using CLL data alone.⁴

Infection control cannot be treated as a secondary concern in MM and CLL management, the authors emphasized. With clear predictors identifiable at diagnosis, the authors argue for more systematic risk stratification and infection-prevention planning built into initial treatment pathways, rather than reactive management after infections occur.

“This study confirms that infections represent a significant burden, occurring frequently and early in the disease course,” the authors conclude. “The results emphasize the importance of infection management in hematological malignancies and warrant further investigation into their impact on patient outcomes and healthcare resource utilization.”

References

1. Glimelius I, Tätting L, Freilich J, et al. Infection incidence and survival in patients with multiple myeloma and chronic lymphocytic leukaemia: a growing concern in the era of modern therapies. EJHaem. 2026;7(4):e70363. doi:10.1002/jha2.70363
2. Munz K. High infection risk in MM: insights from the preimmunotherapy era. AJMC^®. January 21, 2025. Accessed August 5, 2026. https://www.ajmc.com/view/high-infection-risk-in-mm-insights-from-the-pre-immunotherapy-era
3. Jacobson-Sive K. Infection rate more than doubles in CLL/SLL accompanied by secondary immunodeficiency disease. AJMC. December 19, 2024. Accessed August 5, 2026. https://www.ajmc.com/view/infection-rate-more-than-double-in-cll-sll-accompanied-by-secondary-immunodeficiency-disease
4. Parviz M, Brieghel C, Werling M, et al. Post-treatment infection prediction in CLL using domain adaptation of lymphoma electronic health records. Acta Oncol. 2026;65:109-118. doi:10.2340/1651-226X.2026.44569