Elin Edda Sigurdardottir1, Ingemar Turesson2, Sigrun Helga Lund1, Ebba K Lindqvist3, Sham Mailankody4, Neha Korde4, Magnus Björkholm3, Ola Landgren5, Sigurdur Y Kristinsson6. 1. Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2. Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmö, Sweden. 3. Division of Hematology, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. 4. Multiple Myeloma Section, Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, Maryland. 5. Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, New York. 6. Faculty of Medicine, University of Iceland, Reykjavik, Iceland3Division of Hematology, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Abstract
IMPORTANCE: Multiple myeloma (MM) is consistently preceded by the precursor state, monoclonal gammopathy of undetermined significance (MGUS). The average annual risk of progression from MGUS to multiple myeloma is 0.5% to 1.0%. Current guidelines suggest life-long clinical follow-up of individuals diagnosed as having MGUS depending on risk stratification. The impact of diagnosing and conducting clinical follow-up of MGUS on MM survival is unclear. OBJECTIVE: To estimate the impact of prior knowledge of MGUS diagnosis and comorbidities on MM survival. DESIGN, SETTING, AND PARTICIPANTS: We conducted a population-based study including all patients with MM (MM patients) diagnosed in Sweden (n = 14,798) from 1976 to 2005 (with follow-up until 2007); 394 (2.7%) had previously been diagnosed as having MGUS. Information on comorbidities was gathered for all patients. We calculated survival rates from the time of MM diagnosis, comparing patients with vs those without prior knowledge of MGUS. Using Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% CIs for risk factors for death. χ2 Tests were used to evaluate differences in comorbidities. EXPOSURES: Prior knowledge of MGUS among MM patients. In a subanalysis, monoclonal (M)-protein concentration and type were used as exposure. MAIN OUTCOMES AND MEASURES: Risk of death and comorbidities. RESULTS: Patients with MM with prior knowledge of MGUS had significantly (HR, 0.86; 95% CI, 0.77-0.96; P < .01) better overall survival (median survival, 2.8 years) than MM patients without prior knowledge of MGUS (median survival, 2.1 years), although MM patients with (vs without) prior knowledge of MGUS had more comorbidities (P < .001). Among MM patients with prior knowledge of MGUS, low M-protein concentration (<0.5 g/dL) at MGUS diagnosis was associated with poorer MM survival (HR, 1.86; 95% CI, 1.13-3.04; P = .01). CONCLUSIONS AND RELEVANCE: Patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. The observation that a low M-protein concentration at MGUS diagnosis was associated with poorer MM survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in patients with MGUS, regardless of risk stratification.
IMPORTANCE: Multiple myeloma (MM) is consistently preceded by the precursor state, monoclonal gammopathy of undetermined significance (MGUS). The average annual risk of progression from MGUS to multiple myeloma is 0.5% to 1.0%. Current guidelines suggest life-long clinical follow-up of individuals diagnosed as having MGUS depending on risk stratification. The impact of diagnosing and conducting clinical follow-up of MGUS on MM survival is unclear. OBJECTIVE: To estimate the impact of prior knowledge of MGUS diagnosis and comorbidities on MM survival. DESIGN, SETTING, AND PARTICIPANTS: We conducted a population-based study including all patients with MM (MM patients) diagnosed in Sweden (n = 14,798) from 1976 to 2005 (with follow-up until 2007); 394 (2.7%) had previously been diagnosed as having MGUS. Information on comorbidities was gathered for all patients. We calculated survival rates from the time of MM diagnosis, comparing patients with vs those without prior knowledge of MGUS. Using Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% CIs for risk factors for death. χ2 Tests were used to evaluate differences in comorbidities. EXPOSURES: Prior knowledge of MGUS among MM patients. In a subanalysis, monoclonal (M)-protein concentration and type were used as exposure. MAIN OUTCOMES AND MEASURES: Risk of death and comorbidities. RESULTS:Patients with MM with prior knowledge of MGUS had significantly (HR, 0.86; 95% CI, 0.77-0.96; P < .01) better overall survival (median survival, 2.8 years) than MM patients without prior knowledge of MGUS (median survival, 2.1 years), although MM patients with (vs without) prior knowledge of MGUS had more comorbidities (P < .001). Among MM patients with prior knowledge of MGUS, low M-protein concentration (<0.5 g/dL) at MGUS diagnosis was associated with poorer MM survival (HR, 1.86; 95% CI, 1.13-3.04; P = .01). CONCLUSIONS AND RELEVANCE: Patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. The observation that a low M-protein concentration at MGUS diagnosis was associated with poorer MM survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in patients with MGUS, regardless of risk stratification.
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