Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study

Lærke Sloth Andersen; Ricardo Berenguer Navarro; Sara Ekberg; Sæmundur Rögnvaldsson; Marína Rós Levy; Ingigerður Sólveig Sverrisdóttir; Brynjar Viðarsson; Páll Torfi Önundarson; Bjarni A Agnarsson; Margrét Sigurðardóttir; Ingunn Þorsteinsdóttir; Ísleifur Ólafsson; Ásdís Rósa Þórðardóttir; Elías Eyþórsson; Ásbjörn Jónsson; Andri Ólafsson; Brian G M Durie; Stephen Harding; Ola Landgren; Thorvardur Jón Löve; Sigurður Yngvi Kristinsson; Sigrún Thorsteinsdóttir

doi:10.1038/s41375-025-02762-9

Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study

Lærke Sloth Andersen, Ricardo Berenguer Navarro, Sara Ekberg, Sæmundur Rögnvaldsson, Marína Rós Levy, Ingigerður Sólveig Sverrisdóttir, Brynjar Viðarsson, Páll Torfi Önundarson, Bjarni A Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Andri Ólafsson, Brian G M Durie, Stephen Harding, Ola Landgren, Thorvardur Jón LöveSigurður Yngvi Kristinsson, Sigrún Thorsteinsdóttir^*

^*Corresponding author for this work

Department of Haematology

Abstract

Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed with SMM were matched by age and sex with MGUS-free comparators (1:5 ratio) and with individuals with MGUS (1:1 ratio). Infection outcomes were derived from nationwide registries of ICD-10 diagnostic codes and antimicrobial prescriptions. Cox proportional hazards models estimated infection risk, adjusted for immunoparesis. 188 SMM individuals were matched to 188 MGUS individuals and 162 SMM individuals were matched to 810 comparators. Individuals with SMM had significantly more infections (HR 1.36, 95% CI 1.07-1.73) and antibacterial prescriptions (HR 1.24, 95% CI 1.01-1.52) than the comparators. Compared to MGUS, individuals with SMM also had more infections (HR 1.37, 95% CI 1.00-1.87). Adjusting for immunoparesis attenuated the associations, suggesting it may partially mediate infection risk. This first screened cohort of SMM shows a significantly increased infection risk, compared to both MGUS and to individuals without MM precursors, suggesting an underrecognized infection burden in SMM.

Original language	English
Journal	Leukemia
Volume	39
Issue number	12
Pages (from-to)	2997-3003
Number of pages	7
ISSN	0887-6924
DOIs	https://doi.org/10.1038/s41375-025-02762-9
Publication status	Published - Dec 2025

Keywords

Humans
Male
Female
Middle Aged
Aged
Smoldering Multiple Myeloma/complications
Infections/etiology
Adult
Risk Factors
Iceland/epidemiology
Monoclonal Gammopathy of Undetermined Significance/complications
Aged, 80 and over
Follow-Up Studies
Multiple Myeloma/complications

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Andersen, L. S., Navarro, R. B., Ekberg, S., Rögnvaldsson, S., Levy, M. R., Sverrisdóttir, I. S., Viðarsson, B., Önundarson, P. T., Agnarsson, B. A., Sigurðardóttir, M., Þorsteinsdóttir, I., Ólafsson, Í., Þórðardóttir, Á. R., Eyþórsson, E., Jónsson, Á., Ólafsson, A., Durie, B. G. M., Harding, S., Landgren, O., ... Thorsteinsdóttir, S. (2025). Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study. Leukemia, 39(12), 2997-3003. https://doi.org/10.1038/s41375-025-02762-9

Andersen, LS, Navarro, RB, Ekberg, S, Rögnvaldsson, S, Levy, MR, Sverrisdóttir, IS, Viðarsson, B, Önundarson, PT, Agnarsson, BA, Sigurðardóttir, M, Þorsteinsdóttir, I, Ólafsson, Í, Þórðardóttir, ÁR, Eyþórsson, E, Jónsson, Á, Ólafsson, A, Durie, BGM, Harding, S, Landgren, O, Löve, TJ, Kristinsson, SY & Thorsteinsdóttir, S 2025, 'Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study', Leukemia, vol. 39, no. 12, pp. 2997-3003. https://doi.org/10.1038/s41375-025-02762-9

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title = "Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study",

abstract = "Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed with SMM were matched by age and sex with MGUS-free comparators (1:5 ratio) and with individuals with MGUS (1:1 ratio). Infection outcomes were derived from nationwide registries of ICD-10 diagnostic codes and antimicrobial prescriptions. Cox proportional hazards models estimated infection risk, adjusted for immunoparesis. 188 SMM individuals were matched to 188 MGUS individuals and 162 SMM individuals were matched to 810 comparators. Individuals with SMM had significantly more infections (HR 1.36, 95\% CI 1.07-1.73) and antibacterial prescriptions (HR 1.24, 95\% CI 1.01-1.52) than the comparators. Compared to MGUS, individuals with SMM also had more infections (HR 1.37, 95\% CI 1.00-1.87). Adjusting for immunoparesis attenuated the associations, suggesting it may partially mediate infection risk. This first screened cohort of SMM shows a significantly increased infection risk, compared to both MGUS and to individuals without MM precursors, suggesting an underrecognized infection burden in SMM.",

keywords = "Humans, Male, Female, Middle Aged, Aged, Smoldering Multiple Myeloma/complications, Infections/etiology, Adult, Risk Factors, Iceland/epidemiology, Monoclonal Gammopathy of Undetermined Significance/complications, Aged, 80 and over, Follow-Up Studies, Multiple Myeloma/complications",

author = "Andersen, \{L{\ae}rke Sloth\} and Navarro, \{Ricardo Berenguer\} and Sara Ekberg and S{\ae}mundur R{\"o}gnvaldsson and Levy, \{Mar{\'i}na R{\'o}s\} and Sverrisd{\'o}ttir, \{Ingiger{\dh}ur S{\'o}lveig\} and Brynjar Vi{\dh}arsson and {\"O}nundarson, \{P{\'a}ll Torfi\} and Agnarsson, \{Bjarni A\} and Margr{\'e}t Sigur{\dh}ard{\'o}ttir and Ingunn {\TH}orsteinsd{\'o}ttir and {\'I}sleifur {\'O}lafsson and {\TH}{\'o}r{\dh}ard{\'o}ttir, \{{\'A}sd{\'i}s R{\'o}sa\} and El{\'i}as Ey{\th}{\'o}rsson and {\'A}sbj{\"o}rn J{\'o}nsson and Andri {\'O}lafsson and Durie, \{Brian G M\} and Stephen Harding and Ola Landgren and L{\"o}ve, \{Thorvardur J{\'o}n\} and Kristinsson, \{Sigur{\dh}ur Yngvi\} and Sigr{\'u}n Thorsteinsd{\'o}ttir",

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year = "2025",

month = dec,

doi = "10.1038/s41375-025-02762-9",

language = "English",

volume = "39",

pages = "2997--3003",

journal = "Leukemia",

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TY - JOUR

T1 - Increased risk of infections in smoldering multiple myeloma

T2 - results from the screened iStopMM study

AU - Andersen, Lærke Sloth

AU - Navarro, Ricardo Berenguer

AU - Ekberg, Sara

AU - Rögnvaldsson, Sæmundur

AU - Levy, Marína Rós

AU - Sverrisdóttir, Ingigerður Sólveig

AU - Viðarsson, Brynjar

AU - Önundarson, Páll Torfi

AU - Agnarsson, Bjarni A

AU - Sigurðardóttir, Margrét

AU - Þorsteinsdóttir, Ingunn

AU - Ólafsson, Ísleifur

AU - Þórðardóttir, Ásdís Rósa

AU - Eyþórsson, Elías

AU - Jónsson, Ásbjörn

AU - Ólafsson, Andri

AU - Durie, Brian G M

AU - Harding, Stephen

AU - Landgren, Ola

AU - Löve, Thorvardur Jón

AU - Kristinsson, Sigurður Yngvi

AU - Thorsteinsdóttir, Sigrún

PY - 2025/12

Y1 - 2025/12

N2 - Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed with SMM were matched by age and sex with MGUS-free comparators (1:5 ratio) and with individuals with MGUS (1:1 ratio). Infection outcomes were derived from nationwide registries of ICD-10 diagnostic codes and antimicrobial prescriptions. Cox proportional hazards models estimated infection risk, adjusted for immunoparesis. 188 SMM individuals were matched to 188 MGUS individuals and 162 SMM individuals were matched to 810 comparators. Individuals with SMM had significantly more infections (HR 1.36, 95% CI 1.07-1.73) and antibacterial prescriptions (HR 1.24, 95% CI 1.01-1.52) than the comparators. Compared to MGUS, individuals with SMM also had more infections (HR 1.37, 95% CI 1.00-1.87). Adjusting for immunoparesis attenuated the associations, suggesting it may partially mediate infection risk. This first screened cohort of SMM shows a significantly increased infection risk, compared to both MGUS and to individuals without MM precursors, suggesting an underrecognized infection burden in SMM.

AB - Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed with SMM were matched by age and sex with MGUS-free comparators (1:5 ratio) and with individuals with MGUS (1:1 ratio). Infection outcomes were derived from nationwide registries of ICD-10 diagnostic codes and antimicrobial prescriptions. Cox proportional hazards models estimated infection risk, adjusted for immunoparesis. 188 SMM individuals were matched to 188 MGUS individuals and 162 SMM individuals were matched to 810 comparators. Individuals with SMM had significantly more infections (HR 1.36, 95% CI 1.07-1.73) and antibacterial prescriptions (HR 1.24, 95% CI 1.01-1.52) than the comparators. Compared to MGUS, individuals with SMM also had more infections (HR 1.37, 95% CI 1.00-1.87). Adjusting for immunoparesis attenuated the associations, suggesting it may partially mediate infection risk. This first screened cohort of SMM shows a significantly increased infection risk, compared to both MGUS and to individuals without MM precursors, suggesting an underrecognized infection burden in SMM.

KW - Humans

KW - Male

KW - Female

KW - Middle Aged

KW - Aged

KW - Smoldering Multiple Myeloma/complications

KW - Infections/etiology

KW - Adult

KW - Risk Factors

KW - Iceland/epidemiology

KW - Monoclonal Gammopathy of Undetermined Significance/complications

KW - Aged, 80 and over

KW - Follow-Up Studies

KW - Multiple Myeloma/complications

UR - https://www.scopus.com/pages/publications/105015792793

U2 - 10.1038/s41375-025-02762-9

DO - 10.1038/s41375-025-02762-9

M3 - Journal article

C2 - 40940581

SN - 0887-6924

VL - 39

SP - 2997

EP - 3003

JO - Leukemia

JF - Leukemia

IS - 12

ER -

Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study

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Keywords

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