Causal relationship between prior MGUS knowledge and better outcomes is unclear
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MGUS awareness linked to better survival in patients with multiple myeloma

A large, population-based Swedish study found that patients with multiple myeloma who had prior knowledge of monoclonal gammopathy of undetermined significance had better overall survival than patients without prior knowledge, according to a report published online March 5 in JAMA Oncology.

Despite having a higher prevalence of comorbidities, those with prior knowledge of monoclonal gammopathy of undetermined significance (MGUS) had significantly higher median survival than patients without prior knowledge (hazard ratio, 0.86; 95% confidence interval 0.77-0.96; P < .01), Ms. Elin Edda Sigurdardottir of the University of Iceland, Reykjavik, and her associates report.

“We speculate that the reason for the prolonged survival observed in our study most likely reflects the fact that MGUS patients are evaluated more often for signs of MM [multiple myeloma] progression and may be diagnosed and started on antimyeloma therapy at an earlier stage. This argues for early treatment approaches in MM and raises the question of whether systematic screening for MGUS should be initiated,” they said (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.23]).

Virtually all cases of MM are preceded by MGUS, characterized by detectable serum M protein and the absence of end-organ damage. Most MGUS cases go undiagnosed, and only a fraction progress to malignant disease, with absolute risk of progression 0.5%-1% per year. Studies show MGUS is present in 2%-3% of adults aged 50 years and older and about 5% of adults aged 70 years and older.

The population-based study analyzed Swedish national health registry data from 1976 to 2005 and included 14,798 MM patients, 394 (2.7%) of whom had previously been diagnosed with MGUS. MGUS was typically detected as part of a medical work-up for another cause, and patients with prior MGUS knowledge had significantly more comorbidities, including autoimmune diseases, infections, ischemic heart disease, heart failure, cerebrovascular diseases, and renal diseases (P < .001 for all comparisons).

Among the subset of patients with prior knowledge of MGUS, the median M-protein concentration at diagnosis was 1.2 g/dL. Surprisingly, those with M-protein concentrations less than 0.5 g/dL had poorer survival than did those with greater M-protein concentrations (HR, 1.86; 95% CI, 1.13-3.04; P = .01). The authors speculate this may be due to current guidelines that suggest less frequent monitoring of individuals with lower M-protein concentrations.

“Our findings raise the question whether screening for MGUS in the general population could translate into earlier detection and treatment of MM and lead to better MM survival,” Ms. Sigurdardottir and her associates wrote.

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Sigurdardottir et al. report an important finding that patients who had multiple myeloma and previously recognized MGUS had better overall survival than those with no prior knowledge of MGUS. The authors postulate that better outcomes are due to frequent follow up and timely diagnosis of multiple myeloma; however, the study did not determine whether the patients with prior MGUS knowledge had more follow-up care, making it difficult to attribute a causal relationship between prior MGUS knowledge and outcomes. Furthermore, the mechanisms by which knowledge of prior MGUS may lead to better survival are not clear.

Other factors may play a role in the association. First, the timing of the clinical diagnosis of multiple myeloma is subject to lead time bias in patients known to have MGUS. Second, the patients with prior knowledge of MGUS had comorbidities that made it likely they would seek more frequent medical care regardless of MGUS diagnosis. Third, the multiple myeloma cohort in the study had a median survival of less than 3 years, whereas current median survival is more than 5 years. Finally, to reliably assert a link between better follow-up and changes in outcome, randomized clinical trial data are needed.

The IMWG [International Myeloma Working Group] recommends a risk-adapted approach to follow-up of MGUS, based on data that indicate absolute risk of progression over 20 years to be 2% for low-risk MGUS (M-protein cutoff 1.5 g/dL). Data from the Sigurdardottir et al. paper should not be used to dismiss these recommendations. The possible merits of screening for MGUS in a normal, older population, given the cost, inconvenience, anxiety generated, and low absolute risk of progression, would require further research to justify.

Dr. Robert A. Kyle and Dr. S. Vincent Rajkumar are professors of medicine in the division of hematology, department of internal medicine, Mayo Clinic, Rochester, Minn. The remarks were taken from an accompanying editorial (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.33]).

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Sigurdardottir et al. report an important finding that patients who had multiple myeloma and previously recognized MGUS had better overall survival than those with no prior knowledge of MGUS. The authors postulate that better outcomes are due to frequent follow up and timely diagnosis of multiple myeloma; however, the study did not determine whether the patients with prior MGUS knowledge had more follow-up care, making it difficult to attribute a causal relationship between prior MGUS knowledge and outcomes. Furthermore, the mechanisms by which knowledge of prior MGUS may lead to better survival are not clear.

Other factors may play a role in the association. First, the timing of the clinical diagnosis of multiple myeloma is subject to lead time bias in patients known to have MGUS. Second, the patients with prior knowledge of MGUS had comorbidities that made it likely they would seek more frequent medical care regardless of MGUS diagnosis. Third, the multiple myeloma cohort in the study had a median survival of less than 3 years, whereas current median survival is more than 5 years. Finally, to reliably assert a link between better follow-up and changes in outcome, randomized clinical trial data are needed.

The IMWG [International Myeloma Working Group] recommends a risk-adapted approach to follow-up of MGUS, based on data that indicate absolute risk of progression over 20 years to be 2% for low-risk MGUS (M-protein cutoff 1.5 g/dL). Data from the Sigurdardottir et al. paper should not be used to dismiss these recommendations. The possible merits of screening for MGUS in a normal, older population, given the cost, inconvenience, anxiety generated, and low absolute risk of progression, would require further research to justify.

Dr. Robert A. Kyle and Dr. S. Vincent Rajkumar are professors of medicine in the division of hematology, department of internal medicine, Mayo Clinic, Rochester, Minn. The remarks were taken from an accompanying editorial (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.33]).

Body

Sigurdardottir et al. report an important finding that patients who had multiple myeloma and previously recognized MGUS had better overall survival than those with no prior knowledge of MGUS. The authors postulate that better outcomes are due to frequent follow up and timely diagnosis of multiple myeloma; however, the study did not determine whether the patients with prior MGUS knowledge had more follow-up care, making it difficult to attribute a causal relationship between prior MGUS knowledge and outcomes. Furthermore, the mechanisms by which knowledge of prior MGUS may lead to better survival are not clear.

Other factors may play a role in the association. First, the timing of the clinical diagnosis of multiple myeloma is subject to lead time bias in patients known to have MGUS. Second, the patients with prior knowledge of MGUS had comorbidities that made it likely they would seek more frequent medical care regardless of MGUS diagnosis. Third, the multiple myeloma cohort in the study had a median survival of less than 3 years, whereas current median survival is more than 5 years. Finally, to reliably assert a link between better follow-up and changes in outcome, randomized clinical trial data are needed.

The IMWG [International Myeloma Working Group] recommends a risk-adapted approach to follow-up of MGUS, based on data that indicate absolute risk of progression over 20 years to be 2% for low-risk MGUS (M-protein cutoff 1.5 g/dL). Data from the Sigurdardottir et al. paper should not be used to dismiss these recommendations. The possible merits of screening for MGUS in a normal, older population, given the cost, inconvenience, anxiety generated, and low absolute risk of progression, would require further research to justify.

Dr. Robert A. Kyle and Dr. S. Vincent Rajkumar are professors of medicine in the division of hematology, department of internal medicine, Mayo Clinic, Rochester, Minn. The remarks were taken from an accompanying editorial (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.33]).

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Causal relationship between prior MGUS knowledge and better outcomes is unclear
Causal relationship between prior MGUS knowledge and better outcomes is unclear

A large, population-based Swedish study found that patients with multiple myeloma who had prior knowledge of monoclonal gammopathy of undetermined significance had better overall survival than patients without prior knowledge, according to a report published online March 5 in JAMA Oncology.

Despite having a higher prevalence of comorbidities, those with prior knowledge of monoclonal gammopathy of undetermined significance (MGUS) had significantly higher median survival than patients without prior knowledge (hazard ratio, 0.86; 95% confidence interval 0.77-0.96; P < .01), Ms. Elin Edda Sigurdardottir of the University of Iceland, Reykjavik, and her associates report.

“We speculate that the reason for the prolonged survival observed in our study most likely reflects the fact that MGUS patients are evaluated more often for signs of MM [multiple myeloma] progression and may be diagnosed and started on antimyeloma therapy at an earlier stage. This argues for early treatment approaches in MM and raises the question of whether systematic screening for MGUS should be initiated,” they said (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.23]).

Virtually all cases of MM are preceded by MGUS, characterized by detectable serum M protein and the absence of end-organ damage. Most MGUS cases go undiagnosed, and only a fraction progress to malignant disease, with absolute risk of progression 0.5%-1% per year. Studies show MGUS is present in 2%-3% of adults aged 50 years and older and about 5% of adults aged 70 years and older.

The population-based study analyzed Swedish national health registry data from 1976 to 2005 and included 14,798 MM patients, 394 (2.7%) of whom had previously been diagnosed with MGUS. MGUS was typically detected as part of a medical work-up for another cause, and patients with prior MGUS knowledge had significantly more comorbidities, including autoimmune diseases, infections, ischemic heart disease, heart failure, cerebrovascular diseases, and renal diseases (P < .001 for all comparisons).

Among the subset of patients with prior knowledge of MGUS, the median M-protein concentration at diagnosis was 1.2 g/dL. Surprisingly, those with M-protein concentrations less than 0.5 g/dL had poorer survival than did those with greater M-protein concentrations (HR, 1.86; 95% CI, 1.13-3.04; P = .01). The authors speculate this may be due to current guidelines that suggest less frequent monitoring of individuals with lower M-protein concentrations.

“Our findings raise the question whether screening for MGUS in the general population could translate into earlier detection and treatment of MM and lead to better MM survival,” Ms. Sigurdardottir and her associates wrote.

A large, population-based Swedish study found that patients with multiple myeloma who had prior knowledge of monoclonal gammopathy of undetermined significance had better overall survival than patients without prior knowledge, according to a report published online March 5 in JAMA Oncology.

Despite having a higher prevalence of comorbidities, those with prior knowledge of monoclonal gammopathy of undetermined significance (MGUS) had significantly higher median survival than patients without prior knowledge (hazard ratio, 0.86; 95% confidence interval 0.77-0.96; P < .01), Ms. Elin Edda Sigurdardottir of the University of Iceland, Reykjavik, and her associates report.

“We speculate that the reason for the prolonged survival observed in our study most likely reflects the fact that MGUS patients are evaluated more often for signs of MM [multiple myeloma] progression and may be diagnosed and started on antimyeloma therapy at an earlier stage. This argues for early treatment approaches in MM and raises the question of whether systematic screening for MGUS should be initiated,” they said (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.23]).

Virtually all cases of MM are preceded by MGUS, characterized by detectable serum M protein and the absence of end-organ damage. Most MGUS cases go undiagnosed, and only a fraction progress to malignant disease, with absolute risk of progression 0.5%-1% per year. Studies show MGUS is present in 2%-3% of adults aged 50 years and older and about 5% of adults aged 70 years and older.

The population-based study analyzed Swedish national health registry data from 1976 to 2005 and included 14,798 MM patients, 394 (2.7%) of whom had previously been diagnosed with MGUS. MGUS was typically detected as part of a medical work-up for another cause, and patients with prior MGUS knowledge had significantly more comorbidities, including autoimmune diseases, infections, ischemic heart disease, heart failure, cerebrovascular diseases, and renal diseases (P < .001 for all comparisons).

Among the subset of patients with prior knowledge of MGUS, the median M-protein concentration at diagnosis was 1.2 g/dL. Surprisingly, those with M-protein concentrations less than 0.5 g/dL had poorer survival than did those with greater M-protein concentrations (HR, 1.86; 95% CI, 1.13-3.04; P = .01). The authors speculate this may be due to current guidelines that suggest less frequent monitoring of individuals with lower M-protein concentrations.

“Our findings raise the question whether screening for MGUS in the general population could translate into earlier detection and treatment of MM and lead to better MM survival,” Ms. Sigurdardottir and her associates wrote.

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MGUS awareness linked to better survival in patients with multiple myeloma
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MGUS awareness linked to better survival in patients with multiple myeloma
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multiple myeloma, MGUS
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FROM JAMA ONCOLOGY

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Key clinical point: Patients with multiple myeloma who had prior knowledge of monoclonal gammopathy of undetermined significance (MGUS) survived significantly longer than did patients with no prior knowledge of MGUS.

Major finding: The median survival for patients with MGUS knowledge was 2.8 years (95% CI, 2.6-3.3) compared with 2.1 years (2.1-2.2) for those without knowledge (P < .01).

Data source: The population-based study included data from 1976 to 2005 of 14,798 patients with multiple myeloma, 394 (2.7%) of whom were previously diagnosed with MGUS.

Disclosures: The authors reported having no financial disclosures.