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Letters to the Editor
Table 2. Baseline characteristics, rates and incidence of progression, and risk of progression to MM, WM, and AL as well as death for study participants with MGUS with and without PN as assessed by Cox proportional hazard regression with PN as a time dependent covari- ate.
1Faculty of Medicine, University of Iceland, Reykjavík, Iceland; 2Skåne University Hospital, Malmö/Lund, Sweden; 3Department of Medicine, Karolinska University Hospital Solna and Institutet, Stockholm, Sweden and 4Myeloma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Correspondence:
SAEMUNDUR ROGNVALDSSON - saer2@hi.is
doi:10.3324/haematol.2019.239632
Funding: this research was supported by grants from the University of Iceland Research Fund, Icelandic Centre for Research (RANNIS), Landspitali University Hospital Research Fund, and Karolinska Institutet Foundations. Funding support for this publication was provid- ed by the Memorial Sloan Kettering Core Grant (P30 CA008748) and the Perelman Family Foundation in collaboration with the Multiple Myeloma Research Foundation (MMRF) for OL. SR is a PhD candi- date at the University of Iceland and this work is submitted in partial fulfilment of the requirement for a PhD.
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N
Male
Median age
Median follow-up (years) Progressed to MM (incidence1)
HR (95%CI)2
Progressed to WM (incidence1)
HR (95%CI)2
Progressed to AL (incidence1)
HR (95%CI)2
Death (mortality rate1)
HR (95%CI)3
1,328 (1.6)
MGUS without PN
14,355
51%
73
4.0
MGUS and PN
996
63%
69
3.0
40 (1.0)
0.7 (0.5-0.9)*
27 (0.7)
1.2 (0.8-1.8)
21 (0.5)
2.3 (1.5-3.7)***
315 (8.0)
1.3 (1.2-1.5)***
-
422 (0.5)
-
153 (0.2)
-
5,522 (6.8)
-
1Incidence per 100 person-years. 2Adjusted for sex, age, and year of inclusion. 3Adjusted for sex, age, year of inclusion, and diabetes mellitus (DM). ***P<0.001, MGUS: monoclonal gammopathy of undetermined significance; PN: peripheral neuropathy; MM: multiple myeloma; WM: Waldenström’s macroglobulinemia; AL: amyloid light-chain amyloidosis; HR: hazard ratio; 95%CI: 95% confidence interval.
assessing risk of PN. Thirdly, and unfortunately, immunoglobulin isotype data are not available for this cohort, and some isotypes, especially IgM, might be asso- ciated with higher risk of PN and skew the average risk for the whole cohort so that it might not be representa- tive for each isotype. Furthermore, this limits the inter- pretation of analyses of progression to MM and WM. Prospective studies including screening for MGUS and PN are needed to validate these findings. We are current- ly conducting a population-based screening study for MGUS (clinincaltrials.gov identifier: NCT03327597). A sub- study is ongoing assessing the prevalence, symptoms, clinical impact, and associated disease factors of MGUS- associated PN.
In conclusion, in this large population-based study, including 15,351 MGUS individuals and 58,619 matched controls, we found that a significant proportion of indi- viduals with MGUS have clinically evident PN (6.5%) and that PN is truly associated with MGUS. In addition, our findings suggest under-recognition of PN in the real- world care of individuals with MGUS. Interestingly, we found PN to be associated with a 2.9-fold risk of AL and that PN is not associated with increased risk of MM or WM. PN was associated with increased risk of death, but multiple confounders make it impossible to establish a causal relationship. When associated with other disor- ders, PN leads to falls, fractures,11-13 and lower quality of life.14 It is, therefore, reasonable to assume that PN causes considerable morbidity in MGUS that may go unrecog- nized. Our findings should help increase awareness of MGUS as a cause of PN among all clinicians and promote closer monitoring of individuals with MGUS for symp- toms of PN.
Sæmundur Rögnvaldsson,1 Vilhjálmur Steingrímsson,1 Ingemar Turesson,2 Magnus Björkholm,3 Ola Landgren4 and Sigurður Yngvi Kristinsson1,3
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