P950: prior cancer and risk of monoclonal gammopathy of undetermined significance (mgus): a population-based study in iceland and sweden

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Second primary malignancies (SPM) can be a complication of cancer therapy or be due to shared genetic or environmental risk factors. SPM are well known after multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM), but MM and WM are rarely considered as SPM after other cancers. There is some, but limited, evidence that prior cancers may affect the risk of MM. If that is the case, prior cancers should affect the risk of developing monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and WM, or the risk of MGUS progression. Aims: To evaluate whether a prior cancer diagnosis was associated with the risk of MGUS and/or the risk of progression from MGUS to more advanced disease Methods: We performed a two-part population-based study in Iceland and Sweden. In the first part, we included participants in the Iceland screens, treats, or prevents MM study (iStopMM). The study is a nationwide screening study for MGUS and a randomized trial of follow-up strategies. Prior cancer diagnoses were acquired from the validated Icelandic Cancer Registry (founded in 1955). The risk of MGUS at screening for those with a prior cancer diagnosis was assessed using logistic regression, adjusting for age at screening and sex. In the second part of the study, we included a population-based cohort of individuals diagnosed with MGUS in Sweden between 1987-2013. Prior cancer diagnoses and MGUS progression were acquired from the validated Swedish Cancer Registry (founded in 1958) and in the case of amyloidosis, from the Swedish Patient Registry. To exclude preliminary diagnoses of MGUS, we performed a landmark analysis at 3 months after MGUS diagnosis and followed participants until death, progression to active disease, or to the end of 2013. A Fine-Grey survival model was used to estimate hazard ratios (HRs) for MGUS progression, adjusting for the competing risk of death and for age at MGUS diagnosis and sex. Results: Of the 75,422 individuals screened in the iStopMM study, 3,669 had MGUS based on the screening samples. A total of 10,616 (14%) of these had a prior history of cancer at screening. A prior cancer diagnosis was associated with an increased risk of MGUS at screening (odds ratio(OR)=1.23; 95% confidence interval (CI): 1.13-1.33). No specific cancer subtypes were associated with MGUS risk (Figure). A total of 13,790 individuals with MGUS were included in the second part of the study. Of those, 1,658 participants progressed to MM, WM, and related disorders over a median follow-up time of 5.3 years. A prior cancer diagnosis was not associated with an increased risk of MGUS progression (HR=1.14; 95% CI: 0.97-1.34). However, a statistically significant decreased risk of progression was observed for those with a prior history of myeloproliferative disorders (HR=0.37; 95% CI: 0.16-0.89; events in the exposed group=5). Summary/Conclusion: This is the first comprehensive study assessing whether prior cancer affects the risk of MGUS or its progression to active malignancy. The findings indicate prior cancers are associated with a modestly increased risk of having MGUS later in life but not with an increased risk of progression from MGUS to active malignancy. Myeloproliferative disorders were associated with a lower risk of MGUS progression, but the events were few and this finding may have been due to multiple testing. The results not warrant surveillance of cancer patients for MGUS but indicate that cancer therapy or shared genetic or environmental factors of prior cancers may lead to the development of MGUS. Alternatively, there could be reverse causality where MGUS is a risk factor for other cancers than MM, WM, and related disorders. Further studies are necessary to better understand the causative mechanisms of MGUS and MGUS progression to malignancy.Keywords: Epidemiology, Multiple myeloma, Second malignancy, MGUS