Compared with the general population, patients with newly diagnosed symptomatic epilepsy have reduced life expectancy, according to an investigation published in the November 2017 issue of Epilepsia. Patients with newly diagnosed idiopathic or cryptogenic epilepsy, however, have a normal or prolonged life expectancy. The year of diagnosis and the type of epilepsy appear to influence life expectancy.

Previous Estimates Had Weaknesses

Many studies have suggested increased mortality among patients with epilepsy. Two previous investigations have reported the more specific measure of life expectancy in epilepsy, but both had methodologic weaknesses and were prone to substantial bias, said Claudia A. Granbichler, MD, PhD, a neurology resident in Tel-Aviv.

Dr. Granbichler and colleagues examined data for all patients visiting the epilepsy outpatient clinic of Innsbruck Medical University in Austria to calculate their life expectancy. They included 1,112 adults who presented between January 1, 1970, and December 31, 2010, in their analysis. Patient data were recorded and updated continuously over time. Dr. Granbichler and colleagues compared patients’ life expectancies at the year of diagnosis and at five, 10, 15, and 20 years following diagnosis to those of the general population.

The authors classified patients’ epilepsies as symptomatic, idiopathic, or cryptogenic. They defined symptomatic epilepsy as the result of a known or suspected CNS disorder. Epilepsies not preceded by another disorder were considered idiopathic. The authors defined epilepsies of unknown cause as cryptogenic.

Life Expectancy Improved With Time

The difference in life expectancy between patients with epilepsy and the general population depended on the type of epilepsy and the time of diagnosis. Between 1970 and 1980, patients diagnosed with symptomatic epilepsy had a substantially greater reduction in life expectancy (–7.4 years in women and –7.2 years in men) than people diagnosed with idiopathic epilepsy (–5.5 years in women and –5.2 years in men) and people diagnosed with cryptogenic epilepsy (–1.8 years in women and –1.4 years in men).

Regardless of the type of epilepsy, patients diagnosed in subsequent decades had progressively smaller reductions in life expectancy, relative to the general population, or prolonged life expectancy. For all three groups, life expectancy increased with increasing duration of epilepsy.

Participants diagnosed with cryptogenic epilepsy between 2001 and 2010 had increased life expectancy, compared with the general population (2.5 years in women and 3.4 years in men). This increased life expectancy could be explained by lower mortality resulting from decreased engagement in risky activities such as driving motorcycles, skiing, and mountain climbing, said Dr. Granbichler. People with epilepsy also may benefit from more frequent medical follow-ups and laboratory testing.

A potential limitation of the study is that patients had different follow-up durations because of their varying dates of entry and the investigation’s fixed end date. The comparatively short follow-up duration may have introduced positive bias into the estimates of life expectancy for patients diagnosed after 2000, said Dr. Granbichler.

—Erik Greb

Suggested Reading

Granbichler CA, Zimmermann G, Oberaigner W, et al. Potential years lost and life expectancy in adults with newly diagnosed epilepsy. Epilepsia. 2017;58(11):1939-1945.

Compared with the general population, patients with newly diagnosed symptomatic epilepsy have reduced life expectancy, according to an investigation published in the November 2017 issue of Epilepsia. Patients with newly diagnosed idiopathic or cryptogenic epilepsy, however, have a normal or prolonged life expectancy. The year of diagnosis and the type of epilepsy appear to influence life expectancy.

Previous Estimates Had Weaknesses

Many studies have suggested increased mortality among patients with epilepsy. Two previous investigations have reported the more specific measure of life expectancy in epilepsy, but both had methodologic weaknesses and were prone to substantial bias, said Claudia A. Granbichler, MD, PhD, a neurology resident in Tel-Aviv.

Dr. Granbichler and colleagues examined data for all patients visiting the epilepsy outpatient clinic of Innsbruck Medical University in Austria to calculate their life expectancy. They included 1,112 adults who presented between January 1, 1970, and December 31, 2010, in their analysis. Patient data were recorded and updated continuously over time. Dr. Granbichler and colleagues compared patients’ life expectancies at the year of diagnosis and at five, 10, 15, and 20 years following diagnosis to those of the general population.

The authors classified patients’ epilepsies as symptomatic, idiopathic, or cryptogenic. They defined symptomatic epilepsy as the result of a known or suspected CNS disorder. Epilepsies not preceded by another disorder were considered idiopathic. The authors defined epilepsies of unknown cause as cryptogenic.

Life Expectancy Improved With Time

The difference in life expectancy between patients with epilepsy and the general population depended on the type of epilepsy and the time of diagnosis. Between 1970 and 1980, patients diagnosed with symptomatic epilepsy had a substantially greater reduction in life expectancy (–7.4 years in women and –7.2 years in men) than people diagnosed with idiopathic epilepsy (–5.5 years in women and –5.2 years in men) and people diagnosed with cryptogenic epilepsy (–1.8 years in women and –1.4 years in men).

Regardless of the type of epilepsy, patients diagnosed in subsequent decades had progressively smaller reductions in life expectancy, relative to the general population, or prolonged life expectancy. For all three groups, life expectancy increased with increasing duration of epilepsy.

Participants diagnosed with cryptogenic epilepsy between 2001 and 2010 had increased life expectancy, compared with the general population (2.5 years in women and 3.4 years in men). This increased life expectancy could be explained by lower mortality resulting from decreased engagement in risky activities such as driving motorcycles, skiing, and mountain climbing, said Dr. Granbichler. People with epilepsy also may benefit from more frequent medical follow-ups and laboratory testing.

A potential limitation of the study is that patients had different follow-up durations because of their varying dates of entry and the investigation’s fixed end date. The comparatively short follow-up duration may have introduced positive bias into the estimates of life expectancy for patients diagnosed after 2000, said Dr. Granbichler.

—Erik Greb

Suggested Reading

Granbichler CA, Zimmermann G, Oberaigner W, et al. Potential years lost and life expectancy in adults with newly diagnosed epilepsy. Epilepsia. 2017;58(11):1939-1945.

Compared with the general population, patients with newly diagnosed symptomatic epilepsy have reduced life expectancy, according to an investigation published in the November 2017 issue of Epilepsia. Patients with newly diagnosed idiopathic or cryptogenic epilepsy, however, have a normal or prolonged life expectancy. The year of diagnosis and the type of epilepsy appear to influence life expectancy.

Previous Estimates Had Weaknesses

Many studies have suggested increased mortality among patients with epilepsy. Two previous investigations have reported the more specific measure of life expectancy in epilepsy, but both had methodologic weaknesses and were prone to substantial bias, said Claudia A. Granbichler, MD, PhD, a neurology resident in Tel-Aviv.

Dr. Granbichler and colleagues examined data for all patients visiting the epilepsy outpatient clinic of Innsbruck Medical University in Austria to calculate their life expectancy. They included 1,112 adults who presented between January 1, 1970, and December 31, 2010, in their analysis. Patient data were recorded and updated continuously over time. Dr. Granbichler and colleagues compared patients’ life expectancies at the year of diagnosis and at five, 10, 15, and 20 years following diagnosis to those of the general population.

The authors classified patients’ epilepsies as symptomatic, idiopathic, or cryptogenic. They defined symptomatic epilepsy as the result of a known or suspected CNS disorder. Epilepsies not preceded by another disorder were considered idiopathic. The authors defined epilepsies of unknown cause as cryptogenic.

Life Expectancy Improved With Time

The difference in life expectancy between patients with epilepsy and the general population depended on the type of epilepsy and the time of diagnosis. Between 1970 and 1980, patients diagnosed with symptomatic epilepsy had a substantially greater reduction in life expectancy (–7.4 years in women and –7.2 years in men) than people diagnosed with idiopathic epilepsy (–5.5 years in women and –5.2 years in men) and people diagnosed with cryptogenic epilepsy (–1.8 years in women and –1.4 years in men).

Regardless of the type of epilepsy, patients diagnosed in subsequent decades had progressively smaller reductions in life expectancy, relative to the general population, or prolonged life expectancy. For all three groups, life expectancy increased with increasing duration of epilepsy.

Participants diagnosed with cryptogenic epilepsy between 2001 and 2010 had increased life expectancy, compared with the general population (2.5 years in women and 3.4 years in men). This increased life expectancy could be explained by lower mortality resulting from decreased engagement in risky activities such as driving motorcycles, skiing, and mountain climbing, said Dr. Granbichler. People with epilepsy also may benefit from more frequent medical follow-ups and laboratory testing.

A potential limitation of the study is that patients had different follow-up durations because of their varying dates of entry and the investigation’s fixed end date. The comparatively short follow-up duration may have introduced positive bias into the estimates of life expectancy for patients diagnosed after 2000, said Dr. Granbichler.

—Erik Greb

Suggested Reading

Granbichler CA, Zimmermann G, Oberaigner W, et al. Potential years lost and life expectancy in adults with newly diagnosed epilepsy. Epilepsia. 2017;58(11):1939-1945.

Registration is now open for the Vascular Research Initiatives Conference, to be held May 9 at the Hilton San Francisco Union Square. The one-day meeting emphasizes emerging vascular science and is held the day before the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions.

VRIC registration fees are $275 for members; $300, nonmembers; and $150 for residents, students, candidates and nonmember residents and students.

Registration is now open for the Vascular Research Initiatives Conference, to be held May 9 at the Hilton San Francisco Union Square. The one-day meeting emphasizes emerging vascular science and is held the day before the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions.

VRIC registration fees are $275 for members; $300, nonmembers; and $150 for residents, students, candidates and nonmember residents and students.

Registration is now open for the Vascular Research Initiatives Conference, to be held May 9 at the Hilton San Francisco Union Square. The one-day meeting emphasizes emerging vascular science and is held the day before the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions.

VRIC registration fees are $275 for members; $300, nonmembers; and $150 for residents, students, candidates and nonmember residents and students.

To improve access, efficiency and service to existing and future SVS members, the Society is now reviewing and approving membership applications quarterly, instead of yearly. The first deadline for 2018 is March 1.

Learn more at vsweb.org/JoinSVS and apply today.

The SVS is also the management home for the Society for Vascular Nursing. SVN welcomes nurses and nurse practitioners in the vascular setting at many levels and ranges of expertise. For more information, visit svnnet.org.

To improve access, efficiency and service to existing and future SVS members, the Society is now reviewing and approving membership applications quarterly, instead of yearly. The first deadline for 2018 is March 1.

Learn more at vsweb.org/JoinSVS and apply today.

The SVS is also the management home for the Society for Vascular Nursing. SVN welcomes nurses and nurse practitioners in the vascular setting at many levels and ranges of expertise. For more information, visit svnnet.org.

To improve access, efficiency and service to existing and future SVS members, the Society is now reviewing and approving membership applications quarterly, instead of yearly. The first deadline for 2018 is March 1.

Learn more at vsweb.org/JoinSVS and apply today.

The SVS is also the management home for the Society for Vascular Nursing. SVN welcomes nurses and nurse practitioners in the vascular setting at many levels and ranges of expertise. For more information, visit svnnet.org.

SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarships to attend the 2018 Vascular Annual Meeting. Scholarship applications are due by Feb. 1.

The awards are the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.

VAM will be held June 20 to 23, 2018, in Boston, with scientific sessions on June 21-23 and exhibits open June 21-22). 

The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada. Urge students you know with an interest in research to apply today.

SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarships to attend the 2018 Vascular Annual Meeting. Scholarship applications are due by Feb. 1.

The awards are the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.

VAM will be held June 20 to 23, 2018, in Boston, with scientific sessions on June 21-23 and exhibits open June 21-22). 

The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada. Urge students you know with an interest in research to apply today.

SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarships to attend the 2018 Vascular Annual Meeting. Scholarship applications are due by Feb. 1.

The awards are the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.

VAM will be held June 20 to 23, 2018, in Boston, with scientific sessions on June 21-23 and exhibits open June 21-22). 

The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada. Urge students you know with an interest in research to apply today.

More than 17 years ago, I published an article that was largely ignored, predicating that patient benefit from the sentinel node biopsy procedure was unlikely.

I asserted that the lymph nodes are not a reliable filter for melanoma cells, lymphatic drainage is capricious, and many individuals (especially younger ones) have benign neval rests in their lymph nodes that cannot be distinguished from melanoma deposits, since they are both positive for the S100 protein (Int J Dermatol. 2000 Nov;39[11]:807-11). In addition, multiple uncontrolled studies had shown that locating sentinel nodes, followed by a complete lymph node dissection, had no survival benefit. At the time, I argued that sentinel node biopsy should be performed only if the patient was going to be enrolled in a clinical study.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Dr. Coldiron has no financial or other conflicts of interest with Castle Biosciences, the manufacturer of the DecisionDx-Melanoma genetic expression profile test. Email him at [email protected].

More than 17 years ago, I published an article that was largely ignored, predicating that patient benefit from the sentinel node biopsy procedure was unlikely.

I asserted that the lymph nodes are not a reliable filter for melanoma cells, lymphatic drainage is capricious, and many individuals (especially younger ones) have benign neval rests in their lymph nodes that cannot be distinguished from melanoma deposits, since they are both positive for the S100 protein (Int J Dermatol. 2000 Nov;39[11]:807-11). In addition, multiple uncontrolled studies had shown that locating sentinel nodes, followed by a complete lymph node dissection, had no survival benefit. At the time, I argued that sentinel node biopsy should be performed only if the patient was going to be enrolled in a clinical study.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Dr. Coldiron has no financial or other conflicts of interest with Castle Biosciences, the manufacturer of the DecisionDx-Melanoma genetic expression profile test. Email him at [email protected].

More than 17 years ago, I published an article that was largely ignored, predicating that patient benefit from the sentinel node biopsy procedure was unlikely.

I asserted that the lymph nodes are not a reliable filter for melanoma cells, lymphatic drainage is capricious, and many individuals (especially younger ones) have benign neval rests in their lymph nodes that cannot be distinguished from melanoma deposits, since they are both positive for the S100 protein (Int J Dermatol. 2000 Nov;39[11]:807-11). In addition, multiple uncontrolled studies had shown that locating sentinel nodes, followed by a complete lymph node dissection, had no survival benefit. At the time, I argued that sentinel node biopsy should be performed only if the patient was going to be enrolled in a clinical study.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Dr. Coldiron has no financial or other conflicts of interest with Castle Biosciences, the manufacturer of the DecisionDx-Melanoma genetic expression profile test. Email him at [email protected].

The mode and risk of disease progression significantly differs for patients with IgM monoclonal gammopathy of undetermined significance (MGUS) and those with non-IgM MGUS, Robert A. Kyle, MD, and his colleagues reported in the New England Journal of Medicine.

The risk for progression among IgM MGUS patients was 1.1 events/100 person-years, compared with 0.8 events among those with non-IgM MGUS – a significant difference. The researchers also found that risk is related to monoclonal (M) protein level and abnormal serum-free, light-chain assay results for both forms of MGUS.

Further, risk of progression varied with duration of follow-up in IgM MGUS, unlike non-IgM MGUS. However, for MGUS in general, “the risk of progression to myeloma or a related disorder is much less than the competing risk of death due to other causes,” Dr. Kyle, of the Mayo Clinic, Rochester, Minn., and his associates wrote.

The findings should help to determine the appropriate type of monitoring for MGUS patients, the researchers concluded.

The researchers reported results of the longest-yet follow-up study of MGUS patients. The team described median 34-year follow-up data on 1,384 patients with MGUS –70% with IgG type, 12% with IgA type, 15% with IgM type, and 3% with a biclonal gammopathy. (The patients formed the basis of an initial 2002 report.) They were diagnosed during 1960-1994, at a mean age of 72 years. Of these patients, 1,300 (94%) have died.

Among the 210 patients with IgM MGUS, the risk of progression was 2%/year in the first 10 years after diagnosis and 1%/year thereafter. Risk of progression did not vary during the follow-up of patients with non-IgM MGUS.

“The initial concentration of the serum M protein and the serum-free, light-chain ratio were the most important univariate risk factors for progression to a plasma cell disorder among patients with IgM or non-IgM MGUS. Combined, these two variables provided prognostic value in both IgM MGUS and non-IgM types of MGUS,” the authors wrote.

They explained that the difference may lie in the origins of MGUS. “IgM MGUS typically arises from a CD20+ lymphoplasmacytic cell that has not undergone switch recombination. … In contrast, non-IgM MGUS typically arises from mature plasma cells that have undergone switch recombination.”

During follow-up, 11% of the group (147) developed an MGUS-related disorder, including multiple myeloma, lymphoma with an IgM serum M protein, AL amyloidosis, macroglobulinemia, chronic lymphocytic leukemia, or plasmacytoma. This represents a 6.5-fold increased risk compared to the age- and sex-matched background population. Patients with IgM MGUS had a higher risk of progression than did those with non-IgM MGUS (relative risk, 10.8 vs. 5.7).

The overall risk of progression to a plasma cell–related disorder was 10% at 10 years; 18% at 20 years; 28% at 30 years; 36% at 35 years, and 36% at 40 years.

Among patients with IgM MGUS, the presence of high serum M protein (at least 1.5 g/dL) and an abnormal serum-free, light-chain ratio increased the risk of progression to 55% at 20 years, compared with a 41% risk among those patients with one risk factor and 19% among those with neither factor.

Among patients with non-IgM MGUS, the presence of both factors conferred a 30% risk of progression by 20 years. The risk was 20% among those with one factor and 7% among those with neither.

Compared with a control population, patients experienced about a 4-year shorter median survival time (8.1 vs. 12 years). Patients with IgM MGUS had worse 30-year overall survival than those with non-IgM MGUS (4% vs. 7%).

“There were 474 excess deaths in the cohort and 142 persons who had progression to multiple myeloma or a related disorder – findings that indicate that many additional deaths cannot be attributed to disease progression,” the authors noted.

The majority of deceased patients had died from non-plasma cell disorders (87%), including cardiovascular and cerebrovascular events, and nonplasma cell cancers. “In addition to the risk of malignant progression, this finding may be related to potentially serious disorders that led to the initial unexpected diagnosis of MGUS.”

The study was funded in part by the National Cancer Institute.

Dr. Kyle disclosed financial relationships with Celgene, Bristol-Myers Squibb, Amgen, Pharmacyclics, and Pfizer.

[email protected]

SOURCE: Kyle RA et al. N Engl J Med. 2018;378:241-9.

The mode and risk of disease progression significantly differs for patients with IgM monoclonal gammopathy of undetermined significance (MGUS) and those with non-IgM MGUS, Robert A. Kyle, MD, and his colleagues reported in the New England Journal of Medicine.

The risk for progression among IgM MGUS patients was 1.1 events/100 person-years, compared with 0.8 events among those with non-IgM MGUS – a significant difference. The researchers also found that risk is related to monoclonal (M) protein level and abnormal serum-free, light-chain assay results for both forms of MGUS.

Further, risk of progression varied with duration of follow-up in IgM MGUS, unlike non-IgM MGUS. However, for MGUS in general, “the risk of progression to myeloma or a related disorder is much less than the competing risk of death due to other causes,” Dr. Kyle, of the Mayo Clinic, Rochester, Minn., and his associates wrote.

The findings should help to determine the appropriate type of monitoring for MGUS patients, the researchers concluded.

The researchers reported results of the longest-yet follow-up study of MGUS patients. The team described median 34-year follow-up data on 1,384 patients with MGUS –70% with IgG type, 12% with IgA type, 15% with IgM type, and 3% with a biclonal gammopathy. (The patients formed the basis of an initial 2002 report.) They were diagnosed during 1960-1994, at a mean age of 72 years. Of these patients, 1,300 (94%) have died.

Among the 210 patients with IgM MGUS, the risk of progression was 2%/year in the first 10 years after diagnosis and 1%/year thereafter. Risk of progression did not vary during the follow-up of patients with non-IgM MGUS.

“The initial concentration of the serum M protein and the serum-free, light-chain ratio were the most important univariate risk factors for progression to a plasma cell disorder among patients with IgM or non-IgM MGUS. Combined, these two variables provided prognostic value in both IgM MGUS and non-IgM types of MGUS,” the authors wrote.

They explained that the difference may lie in the origins of MGUS. “IgM MGUS typically arises from a CD20+ lymphoplasmacytic cell that has not undergone switch recombination. … In contrast, non-IgM MGUS typically arises from mature plasma cells that have undergone switch recombination.”

During follow-up, 11% of the group (147) developed an MGUS-related disorder, including multiple myeloma, lymphoma with an IgM serum M protein, AL amyloidosis, macroglobulinemia, chronic lymphocytic leukemia, or plasmacytoma. This represents a 6.5-fold increased risk compared to the age- and sex-matched background population. Patients with IgM MGUS had a higher risk of progression than did those with non-IgM MGUS (relative risk, 10.8 vs. 5.7).

The overall risk of progression to a plasma cell–related disorder was 10% at 10 years; 18% at 20 years; 28% at 30 years; 36% at 35 years, and 36% at 40 years.

Among patients with IgM MGUS, the presence of high serum M protein (at least 1.5 g/dL) and an abnormal serum-free, light-chain ratio increased the risk of progression to 55% at 20 years, compared with a 41% risk among those patients with one risk factor and 19% among those with neither factor.

Among patients with non-IgM MGUS, the presence of both factors conferred a 30% risk of progression by 20 years. The risk was 20% among those with one factor and 7% among those with neither.

Compared with a control population, patients experienced about a 4-year shorter median survival time (8.1 vs. 12 years). Patients with IgM MGUS had worse 30-year overall survival than those with non-IgM MGUS (4% vs. 7%).

“There were 474 excess deaths in the cohort and 142 persons who had progression to multiple myeloma or a related disorder – findings that indicate that many additional deaths cannot be attributed to disease progression,” the authors noted.

The majority of deceased patients had died from non-plasma cell disorders (87%), including cardiovascular and cerebrovascular events, and nonplasma cell cancers. “In addition to the risk of malignant progression, this finding may be related to potentially serious disorders that led to the initial unexpected diagnosis of MGUS.”

The study was funded in part by the National Cancer Institute.

Dr. Kyle disclosed financial relationships with Celgene, Bristol-Myers Squibb, Amgen, Pharmacyclics, and Pfizer.

[email protected]

SOURCE: Kyle RA et al. N Engl J Med. 2018;378:241-9.

The mode and risk of disease progression significantly differs for patients with IgM monoclonal gammopathy of undetermined significance (MGUS) and those with non-IgM MGUS, Robert A. Kyle, MD, and his colleagues reported in the New England Journal of Medicine.

The risk for progression among IgM MGUS patients was 1.1 events/100 person-years, compared with 0.8 events among those with non-IgM MGUS – a significant difference. The researchers also found that risk is related to monoclonal (M) protein level and abnormal serum-free, light-chain assay results for both forms of MGUS.

Further, risk of progression varied with duration of follow-up in IgM MGUS, unlike non-IgM MGUS. However, for MGUS in general, “the risk of progression to myeloma or a related disorder is much less than the competing risk of death due to other causes,” Dr. Kyle, of the Mayo Clinic, Rochester, Minn., and his associates wrote.

The findings should help to determine the appropriate type of monitoring for MGUS patients, the researchers concluded.

The researchers reported results of the longest-yet follow-up study of MGUS patients. The team described median 34-year follow-up data on 1,384 patients with MGUS –70% with IgG type, 12% with IgA type, 15% with IgM type, and 3% with a biclonal gammopathy. (The patients formed the basis of an initial 2002 report.) They were diagnosed during 1960-1994, at a mean age of 72 years. Of these patients, 1,300 (94%) have died.

Among the 210 patients with IgM MGUS, the risk of progression was 2%/year in the first 10 years after diagnosis and 1%/year thereafter. Risk of progression did not vary during the follow-up of patients with non-IgM MGUS.

“The initial concentration of the serum M protein and the serum-free, light-chain ratio were the most important univariate risk factors for progression to a plasma cell disorder among patients with IgM or non-IgM MGUS. Combined, these two variables provided prognostic value in both IgM MGUS and non-IgM types of MGUS,” the authors wrote.

They explained that the difference may lie in the origins of MGUS. “IgM MGUS typically arises from a CD20+ lymphoplasmacytic cell that has not undergone switch recombination. … In contrast, non-IgM MGUS typically arises from mature plasma cells that have undergone switch recombination.”

During follow-up, 11% of the group (147) developed an MGUS-related disorder, including multiple myeloma, lymphoma with an IgM serum M protein, AL amyloidosis, macroglobulinemia, chronic lymphocytic leukemia, or plasmacytoma. This represents a 6.5-fold increased risk compared to the age- and sex-matched background population. Patients with IgM MGUS had a higher risk of progression than did those with non-IgM MGUS (relative risk, 10.8 vs. 5.7).

The overall risk of progression to a plasma cell–related disorder was 10% at 10 years; 18% at 20 years; 28% at 30 years; 36% at 35 years, and 36% at 40 years.

Among patients with IgM MGUS, the presence of high serum M protein (at least 1.5 g/dL) and an abnormal serum-free, light-chain ratio increased the risk of progression to 55% at 20 years, compared with a 41% risk among those patients with one risk factor and 19% among those with neither factor.

Among patients with non-IgM MGUS, the presence of both factors conferred a 30% risk of progression by 20 years. The risk was 20% among those with one factor and 7% among those with neither.

Compared with a control population, patients experienced about a 4-year shorter median survival time (8.1 vs. 12 years). Patients with IgM MGUS had worse 30-year overall survival than those with non-IgM MGUS (4% vs. 7%).

“There were 474 excess deaths in the cohort and 142 persons who had progression to multiple myeloma or a related disorder – findings that indicate that many additional deaths cannot be attributed to disease progression,” the authors noted.

The majority of deceased patients had died from non-plasma cell disorders (87%), including cardiovascular and cerebrovascular events, and nonplasma cell cancers. “In addition to the risk of malignant progression, this finding may be related to potentially serious disorders that led to the initial unexpected diagnosis of MGUS.”

The study was funded in part by the National Cancer Institute.

Dr. Kyle disclosed financial relationships with Celgene, Bristol-Myers Squibb, Amgen, Pharmacyclics, and Pfizer.

[email protected]

SOURCE: Kyle RA et al. N Engl J Med. 2018;378:241-9.

No shocker here: > 90% of American homes have ≥ 3 detectable allergens, and 73% have at least 1 allergen at elevated levels, acceding to the largest U.S. indoor allergen study to date.

Using data from National Institute of Environmental Health Sciences  (NHANES) 2005-2006, researchers studied levels of 8 common allergens (cat, dog, cockroach, mouse, rat, mold, and 2 types of dust mite allergens) in nearly 7,000 homes.

Mobile homes, older homes, rental homes, and rural homes were more likely to have higher amounts of indoor allergens, as were homes with pets and pests.

Elevated levels of dust mites were more common in the South and Northeast and humid regions. Cat and dust mite allergens were more common in rural settings compared with urban.

The NHANES 2005-2006 data allowed national comparisons for the first time of exposure and sensitization. Men and non-Hispanic blacks were less likely to be exposed to multiple allergens, and sensitization was more common in those groups compared with women and other racial groups, respectively. Exposure to several elevated allergens was most prevalent in rural areas. Sensitization rates were higher in urban areas.

The researchers emphasize that the relationships between allergen exposures, allergic sensitization, and disease are complex. They also note that studies are still investigating how allergen exposures interact with other environmental and genetic factors in asthma and allergies. However, among the tips they offer: vacuum every week, wash sheets and blankets in hot water every week, and lower indoor humidity levels below 50%.

No shocker here: > 90% of American homes have ≥ 3 detectable allergens, and 73% have at least 1 allergen at elevated levels, acceding to the largest U.S. indoor allergen study to date.

Using data from National Institute of Environmental Health Sciences  (NHANES) 2005-2006, researchers studied levels of 8 common allergens (cat, dog, cockroach, mouse, rat, mold, and 2 types of dust mite allergens) in nearly 7,000 homes.

Mobile homes, older homes, rental homes, and rural homes were more likely to have higher amounts of indoor allergens, as were homes with pets and pests.

Elevated levels of dust mites were more common in the South and Northeast and humid regions. Cat and dust mite allergens were more common in rural settings compared with urban.

The NHANES 2005-2006 data allowed national comparisons for the first time of exposure and sensitization. Men and non-Hispanic blacks were less likely to be exposed to multiple allergens, and sensitization was more common in those groups compared with women and other racial groups, respectively. Exposure to several elevated allergens was most prevalent in rural areas. Sensitization rates were higher in urban areas.

The researchers emphasize that the relationships between allergen exposures, allergic sensitization, and disease are complex. They also note that studies are still investigating how allergen exposures interact with other environmental and genetic factors in asthma and allergies. However, among the tips they offer: vacuum every week, wash sheets and blankets in hot water every week, and lower indoor humidity levels below 50%.

No shocker here: > 90% of American homes have ≥ 3 detectable allergens, and 73% have at least 1 allergen at elevated levels, acceding to the largest U.S. indoor allergen study to date.

Using data from National Institute of Environmental Health Sciences  (NHANES) 2005-2006, researchers studied levels of 8 common allergens (cat, dog, cockroach, mouse, rat, mold, and 2 types of dust mite allergens) in nearly 7,000 homes.

Mobile homes, older homes, rental homes, and rural homes were more likely to have higher amounts of indoor allergens, as were homes with pets and pests.

Elevated levels of dust mites were more common in the South and Northeast and humid regions. Cat and dust mite allergens were more common in rural settings compared with urban.

The NHANES 2005-2006 data allowed national comparisons for the first time of exposure and sensitization. Men and non-Hispanic blacks were less likely to be exposed to multiple allergens, and sensitization was more common in those groups compared with women and other racial groups, respectively. Exposure to several elevated allergens was most prevalent in rural areas. Sensitization rates were higher in urban areas.

The researchers emphasize that the relationships between allergen exposures, allergic sensitization, and disease are complex. They also note that studies are still investigating how allergen exposures interact with other environmental and genetic factors in asthma and allergies. However, among the tips they offer: vacuum every week, wash sheets and blankets in hot water every week, and lower indoor humidity levels below 50%.

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).

This sBLA is for daratumumab (D) to be used in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

The FDA expects to make a decision on the sBLA by May 21, 2018.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The priority review for this sBLA is based on data from the phase 3 ALCYONE study, which were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this study, researchers compared VMP to D-VMP in 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

D-VMP produced deeper responses than VMP. The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The rate of complete response was 24% and 43%, respectively (P<0.0001).

D-VMP also prolonged progression-free survival (PFS) compared to VMP.

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

The median overall survival was not reached in either treatment arm.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

There were 6 deaths due to treatment-emergent adverse events in the D-VMP arm and 5 in the VMP arm.

About daratumumab

Daratumumab is a CD38-directed cytolytic antibody that is FDA approved for the following indications:

• In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of MM patients who have received at least 1 prior therapy
• In combination with pomalidomide and dexamethasone for the treatment of MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI)
• As monotherapy for MM patients who have received at least 3 prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
  

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).

This sBLA is for daratumumab (D) to be used in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

The FDA expects to make a decision on the sBLA by May 21, 2018.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The priority review for this sBLA is based on data from the phase 3 ALCYONE study, which were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this study, researchers compared VMP to D-VMP in 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

D-VMP produced deeper responses than VMP. The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The rate of complete response was 24% and 43%, respectively (P<0.0001).

D-VMP also prolonged progression-free survival (PFS) compared to VMP.

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

The median overall survival was not reached in either treatment arm.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

There were 6 deaths due to treatment-emergent adverse events in the D-VMP arm and 5 in the VMP arm.

About daratumumab

Daratumumab is a CD38-directed cytolytic antibody that is FDA approved for the following indications:

• In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of MM patients who have received at least 1 prior therapy
• In combination with pomalidomide and dexamethasone for the treatment of MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI)
• As monotherapy for MM patients who have received at least 3 prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
  

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).

This sBLA is for daratumumab (D) to be used in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.

The FDA expects to make a decision on the sBLA by May 21, 2018.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The priority review for this sBLA is based on data from the phase 3 ALCYONE study, which were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this study, researchers compared VMP to D-VMP in 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.

D-VMP produced deeper responses than VMP. The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The rate of complete response was 24% and 43%, respectively (P<0.0001).

D-VMP also prolonged progression-free survival (PFS) compared to VMP.

The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.

The median overall survival was not reached in either treatment arm.

The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).

The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.

There were 6 deaths due to treatment-emergent adverse events in the D-VMP arm and 5 in the VMP arm.

About daratumumab

Daratumumab is a CD38-directed cytolytic antibody that is FDA approved for the following indications:

• In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of MM patients who have received at least 1 prior therapy
• In combination with pomalidomide and dexamethasone for the treatment of MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor (PI)
• As monotherapy for MM patients who have received at least 3 prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
  

Clinical question: Does cost messaging at the time of ordering reduce prescriber use of high-cost medications?

Background: Overprescribing expensive medications contributes to inpatient health care expenditures and may be avoidable when low-cost alternatives are available.

Dr. Lublin is a hospitalist at the University of Colorado School of Medicine.

Clinical question: Does cost messaging at the time of ordering reduce prescriber use of high-cost medications?

Background: Overprescribing expensive medications contributes to inpatient health care expenditures and may be avoidable when low-cost alternatives are available.

Dr. Lublin is a hospitalist at the University of Colorado School of Medicine.

Clinical question: Does cost messaging at the time of ordering reduce prescriber use of high-cost medications?

Background: Overprescribing expensive medications contributes to inpatient health care expenditures and may be avoidable when low-cost alternatives are available.

Dr. Lublin is a hospitalist at the University of Colorado School of Medicine.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.