High Infection Risk in MM: Insights From the Pre-Immunotherapy Era

Patients with multiple myeloma (MM) remain exceptionally vulnerable to infections, which greatly increases mortality risk. Although the advent of novel treatments has brought many benefits to this patient population, individuals with multiple myeloma are 5 times more likely to contract infections, according to a recent population-based study published in Haematologica.¹

Infection risk concept; floating viral particles | image credit: ChaoticMind - stock.adobe.com

Chemotherapy, thalidomide, and cortisone have been long-established approaches for the treatment of multiple myeloma. Since the turn of the century, the landscape has shifted to center monoclonal antibodies (MoAb), immunomodulatory drugs (IMiD), and proteasome inhibitors (PI). Prior studies from the “chemotherapy era,” as the present authors outlined, found that infection risks for patients with multiple myeloma could be 7 times higher than healthy individuals.

Furthermore, infections were the underlying cause of mortality for 22% of patients with multiple myeloma within a year of follow-up in a previous study.² Additional studies reveal that upwards of 45% of patients with MM experience early mortality at the hands of infection.^3,4 These results reflect the urgent need for updated data on this patient population for a more comprehensive understanding of the risk factors impacting MM prognoses, the authors added.¹

To explore this further, the researchers conducted a population-based study out of Sweden to evaluate the prevalence of infection and infection-related mortality rates in symptomatic patients with multiple myeloma. Data were collected from the Swedish Myeloma Registry, specifically for individuals who received their diagnosis between 2008 and 2021, with all patients with multiple myeloma being age-matched with health controls.

There were 8672 patients with symptomatic multiple myeloma included in this analysis alongside 34,561 identified controls. Over half of the patients were male (57%) and aged at least 70 years (60%). The rates of patients receiving PI, MoAB or IMiD as first-line therapeutics between 2008-2012, 2013-2017, and 2018-2021 were 68%, 90%, and 97%, respectfully. Patients also had follow-ups at a median time of 3.1 years vs 5.7 years for controls.

Controls exhibited a 32% infection risk during the study period vs 70% for patients with multiple myeloma. The highest infection risk for patients with multiple myeloma were for sepsis (20%) and pneumonia (18%), whereas controls only had a 4% risk of either.

Three months prior to their multiple myeloma diagnosis, those in the patient group carried a significantly higher risk of infection compared with controls (HR, 1.21; 95% CI, 1.16-1.26; P < .05). There was also a significantly greater risk observed for patients 4 years before their diagnosis (HR, 1.16; 95% CI, 1.05-1.28; P < .05).

The clinically significant infection risk associated with symptomatic multiple myeloma was 5 time higher for patients than it was for healthy controls (HR, 5.3; 95% CI, 5.14-5.47). More specifically, there was a 5-fold greater risk of bacterial infections for those with symptomatic multiple myeloma vs controls (HR, 4.88; 95% CI, 4.70-5.07). Additionally, patients with multiple myeloma had a 7-fold greater risk of fungal infections vs controls (HR, 6.77; 95% CI, 6.13-7.47).

Among the infections patients with multiple myeloma were more vulnerable to contracting were Epstein Barr virus, meningitis, cellulitis, endocarditis, influenza, respiratory syncytial virus, endocarditis, herpes simplex, and more. Patients with multiple myeloma were more at risk for developing an infection as they aged (P < .001).

Mortality rates were 8% (n = 678) in patients with multiple myeloma in the first 3 months following their diagnosis compared with 1% (n = 315) of controls. In total, in 32% of patients with multiple myeloma (n = 219) vs 19% (n = 61) of controls had infection-related deaths. The 1-year infection-related mortality rates were 27% for patients with multiple myeloma. Within a 90-day period of contracting a significant infection following a multiple myeloma diagnosis, the 6-month and 1-year all-cause mortality rates were 75% and 56%, vs 56% and 42% in the control group, respectfully.

“The continuous and repeated nature of current MM therapies make it even more important to consider prophylactic measures to prevent morbidity and mortality in infections,” the authors concluded. “Before the advent of immunotherapy in MM with CAR T-cell therapy and T-cell engagers with their specific risks of infections, this study can constitute a baseline of the risk of infections in the pre-immunotherapy era.”

References

1. Blimark CH, Carlson K, Day C, et al. Risk of infections in multiple myeloma. A population-based study on 8,672 multiple myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry. Haematologica. 2025;110(1):163-172. doi:10.3324/haematol.2024.285645

2. Blimark C, Holmberg E, Mellqvist UH, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015;100(1):107-13. doi:10.3324/haematol.2014.107714

3. Augustson BM, Begum G, Dunn JA. Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United Kingdom Medical Research Council trials between 1980 and 2002 - Medical Research Council Adult Leukaemia Working Party. J Clin Oncol. 2005;23(36):9219-9226. doi:10.1200/JCO.2005.03.2086

4. Murakami H, Hayashi K, Hatsumi N. Risk factors for early death in patients undergoing treatment for multiple myeloma. Ann Hematol. 2001;80(8):452-455. doi:10.1007/s002770100330