Study Suggests Need For Long Term Follow Up Of Monoclonal Gammopathy

Prof. Sigurdur Y Kristinsson Professor of Hematology University of Interview with:
Prof. Sigurdur Y Kristinsson
Professor of Hematology
University of Iceland

MedicalResearch: What is the background for this study? What are the main findings?

Prof. Kristinsson: Multiple myeloma is always preceded by a precursor condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS is characterized by a detectable monoclonal protein in persons without evidence for end-organ damage or other related plasma cell or lymphoproliferative disorders. MGUS is very common and is detected in approximately 5 percent of persons 70 years or older. However, only a small proportion of MGUS progresses to a malignant disorder, in fact the annual risk of progression to multiple myeloma or other related disorders is on average 1 percent, with varying risks according to risk groups. Current guidelines suggest, depending on the individual patient’s clinical risk score, life-long monitoring of MGUS individuals to detect progression to multiple myeloma or related disorders. At this time, the impact of annual monitoring on the outcome of patients who eventually develop multiple myeloma is unclear.

Using high-quality population-based data from Sweden, we estimated the impact of prior knowledge of MGUS diagnosis and comorbidities on multiple myeloma survival, by performing a large population-based study using data on more than 14,000 multiple myeloma patients diagnosed in Sweden 1976-2005, with follow-up through 2007. The hypothesis that detection and follow-up of MGUS may influence survival in multiple myeloma is unlikely to ever be tested in a prospective clinical study due to the large sample size required with long follow-up time, and consequent extreme costs.

We found that multiple myeloma patients with prior knowledge of MGUS had significantly 15% better survival, despite having significantly more comorbidities. Interestingly, low-risk MGUS (with very low M-protein) had highest risk of death. The observation that low M-protein concentration at MGUS diagnosis was associated with poorer multiple myeloma survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in MGUS, regardless of risk stratification.

MedicalResearch: What should clinicians and patients take away from your report?

Prof. Kristinsson: Our results reflect the importance of life-long follow-up for individuals diagnosed with MGUS, independent of risk score and highlight the need for better risk models based on the biology of the disease. Patients should receive balanced information stressing both the overall very low risk of progression to malignant disease but also what symptoms could signal such development and the need of consulting their physician. The higher prevalence of comorbid conditions in multiple myeloma patients with prior MGUS knowledge supports that MGUS most often is diagnosed during follow-up for unrelated conditions. Our findings raise the question whether screening for MGUS in the general population could translate into earlier detection and treatment of multiple myeloma and lead to better multiple myeloma survival.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Prof. Kristinsson: Our results highlight the need for better risk models based on the biology of multiple myeloma and MGUS. Also the impact of screening needs to be studied and discussed and importantly, the impact of comorbidity on outcome in multiple myeloma should be studied.


Sigurdardottir E, Turesson I, Lund S, et al. The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma. JAMA Oncol. Published online March 05, 2015. doi:10.1001/jamaoncol.2015.23. Interview with: Prof. Sigurdur Y Kristinsson (2015). Study Suggests Need For Long Term Follow Up Of Monoclonal Gammopathy 


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