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First 2018 Membership Application Deadline is March 1
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.
Applications due Feb. 1 for VAM Scholarships, Research Fellowship
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.
Sentinel node biopsy: Who needs it?
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.
Many surgical oncologists have built their careers around the flawed premise that removing the draining nodes would cure melanoma. It doesn’t. It is past time to admit it and move on.
So, if completion node dissection does not save lives, why do a sentinel node biopsy? I recently asked a dermatologist friend, who is a committed acolyte of the sentinel node biopsy school, why he continues to recommend sentinel node biopsy if there is no benefit from complete node dissection. His quick response was that patients want to know if they are at higher risk of metastatic disease so that they can be followed closely with high-resolution ultrasound at a major cancer center and can be eligible for clinical trials. His reply gave me pause, so I asked why completion node dissection was still being recommended. I was told that some patients with positive sentinel nodes lived far away, and if they would not make regular follow-up visits for high-resolution ultrasound, the surgical oncologists do completion node dissection to ensure “local nodal control.” Yipes! You’re going to rip my groin out because I like quiet county living?
I doubt that patients would be enthusiastic if told beforehand that sentinel node biopsies costs $14,000-$18,000, and has a 9% complication rate, and one-third of those patients who have complications end up with permanent lymphedema. I wondered if the patients were told they could have a genetic test done on their already excised melanoma tissue that would tell them if they were in a high-risk group without having an additional invasive surgical procedure. I wondered if they were told that 10%-30% of people with negative sentinel nodes go on to develop metastatic disease. I also wondered if they had been told they would have to walk around with their melanoma, which could spread at any time, for several additional weeks, while waiting for the results of their sentinel node biopsy, instead of having the melanoma immediately removed by their dermatologist. I also wondered if they had been told that high-resolution ultrasound has not definitively been shown to be superior to clinical palpation of the lymph nodes.
I looked into the possibility of clinical trials for patients with positive sentinel nodes, as well. Based on my search of clinical trials.gov in January, there are 33 trials in the United States studying patients with stage 3 (positive sentinel node) or greater disease. If I had a positive sentinel node, I would look for a study in which I had a chance of getting nivolumab, which recently has been shown to be superior to ipilimumab in the phase 3 Checkmate 238 trial published in 2017 (N Engl J Med 2017 Nov 9; 377:1824-35).
But I am getting ahead of myself.
As a thinking man, if I had a thick melanoma (that was less than 2 mm), I would opt for a genetic test of my already excised melanoma tissue. If the results of that genetic test (which has near identical sensitivity and specificity for developing metastatic disease as a sentinel node) put me in the low-risk group, I would pass on the sentinel node biopsy. This would eliminate a lot of unnecessary surgery. If I fell into the high-risk group, I would consider a sentinel node biopsy so I could get into a study, or determine if I needed to find a way to get my insurance to pay, or if I could personally afford nivolumab. Even if I opted not to take the drug, because of the potential risk of high-grade side effects, the high-risk genetic profile tells me I would still need more frequent follow-up.
These are exciting times. I am looking forward to clinical trials that allow a patient with a high-risk genetic profile to go directly into a trial. We are moving into the realm of individualized genomic medicine in which metastatic melanoma truly becomes a curable disease.
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.
Many surgical oncologists have built their careers around the flawed premise that removing the draining nodes would cure melanoma. It doesn’t. It is past time to admit it and move on.
So, if completion node dissection does not save lives, why do a sentinel node biopsy? I recently asked a dermatologist friend, who is a committed acolyte of the sentinel node biopsy school, why he continues to recommend sentinel node biopsy if there is no benefit from complete node dissection. His quick response was that patients want to know if they are at higher risk of metastatic disease so that they can be followed closely with high-resolution ultrasound at a major cancer center and can be eligible for clinical trials. His reply gave me pause, so I asked why completion node dissection was still being recommended. I was told that some patients with positive sentinel nodes lived far away, and if they would not make regular follow-up visits for high-resolution ultrasound, the surgical oncologists do completion node dissection to ensure “local nodal control.” Yipes! You’re going to rip my groin out because I like quiet county living?
I doubt that patients would be enthusiastic if told beforehand that sentinel node biopsies costs $14,000-$18,000, and has a 9% complication rate, and one-third of those patients who have complications end up with permanent lymphedema. I wondered if the patients were told they could have a genetic test done on their already excised melanoma tissue that would tell them if they were in a high-risk group without having an additional invasive surgical procedure. I wondered if they were told that 10%-30% of people with negative sentinel nodes go on to develop metastatic disease. I also wondered if they had been told they would have to walk around with their melanoma, which could spread at any time, for several additional weeks, while waiting for the results of their sentinel node biopsy, instead of having the melanoma immediately removed by their dermatologist. I also wondered if they had been told that high-resolution ultrasound has not definitively been shown to be superior to clinical palpation of the lymph nodes.
I looked into the possibility of clinical trials for patients with positive sentinel nodes, as well. Based on my search of clinical trials.gov in January, there are 33 trials in the United States studying patients with stage 3 (positive sentinel node) or greater disease. If I had a positive sentinel node, I would look for a study in which I had a chance of getting nivolumab, which recently has been shown to be superior to ipilimumab in the phase 3 Checkmate 238 trial published in 2017 (N Engl J Med 2017 Nov 9; 377:1824-35).
But I am getting ahead of myself.
As a thinking man, if I had a thick melanoma (that was less than 2 mm), I would opt for a genetic test of my already excised melanoma tissue. If the results of that genetic test (which has near identical sensitivity and specificity for developing metastatic disease as a sentinel node) put me in the low-risk group, I would pass on the sentinel node biopsy. This would eliminate a lot of unnecessary surgery. If I fell into the high-risk group, I would consider a sentinel node biopsy so I could get into a study, or determine if I needed to find a way to get my insurance to pay, or if I could personally afford nivolumab. Even if I opted not to take the drug, because of the potential risk of high-grade side effects, the high-risk genetic profile tells me I would still need more frequent follow-up.
These are exciting times. I am looking forward to clinical trials that allow a patient with a high-risk genetic profile to go directly into a trial. We are moving into the realm of individualized genomic medicine in which metastatic melanoma truly becomes a curable disease.
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.
Many surgical oncologists have built their careers around the flawed premise that removing the draining nodes would cure melanoma. It doesn’t. It is past time to admit it and move on.
So, if completion node dissection does not save lives, why do a sentinel node biopsy? I recently asked a dermatologist friend, who is a committed acolyte of the sentinel node biopsy school, why he continues to recommend sentinel node biopsy if there is no benefit from complete node dissection. His quick response was that patients want to know if they are at higher risk of metastatic disease so that they can be followed closely with high-resolution ultrasound at a major cancer center and can be eligible for clinical trials. His reply gave me pause, so I asked why completion node dissection was still being recommended. I was told that some patients with positive sentinel nodes lived far away, and if they would not make regular follow-up visits for high-resolution ultrasound, the surgical oncologists do completion node dissection to ensure “local nodal control.” Yipes! You’re going to rip my groin out because I like quiet county living?
I doubt that patients would be enthusiastic if told beforehand that sentinel node biopsies costs $14,000-$18,000, and has a 9% complication rate, and one-third of those patients who have complications end up with permanent lymphedema. I wondered if the patients were told they could have a genetic test done on their already excised melanoma tissue that would tell them if they were in a high-risk group without having an additional invasive surgical procedure. I wondered if they were told that 10%-30% of people with negative sentinel nodes go on to develop metastatic disease. I also wondered if they had been told they would have to walk around with their melanoma, which could spread at any time, for several additional weeks, while waiting for the results of their sentinel node biopsy, instead of having the melanoma immediately removed by their dermatologist. I also wondered if they had been told that high-resolution ultrasound has not definitively been shown to be superior to clinical palpation of the lymph nodes.
I looked into the possibility of clinical trials for patients with positive sentinel nodes, as well. Based on my search of clinical trials.gov in January, there are 33 trials in the United States studying patients with stage 3 (positive sentinel node) or greater disease. If I had a positive sentinel node, I would look for a study in which I had a chance of getting nivolumab, which recently has been shown to be superior to ipilimumab in the phase 3 Checkmate 238 trial published in 2017 (N Engl J Med 2017 Nov 9; 377:1824-35).
But I am getting ahead of myself.
As a thinking man, if I had a thick melanoma (that was less than 2 mm), I would opt for a genetic test of my already excised melanoma tissue. If the results of that genetic test (which has near identical sensitivity and specificity for developing metastatic disease as a sentinel node) put me in the low-risk group, I would pass on the sentinel node biopsy. This would eliminate a lot of unnecessary surgery. If I fell into the high-risk group, I would consider a sentinel node biopsy so I could get into a study, or determine if I needed to find a way to get my insurance to pay, or if I could personally afford nivolumab. Even if I opted not to take the drug, because of the potential risk of high-grade side effects, the high-risk genetic profile tells me I would still need more frequent follow-up.
These are exciting times. I am looking forward to clinical trials that allow a patient with a high-risk genetic profile to go directly into a trial. We are moving into the realm of individualized genomic medicine in which metastatic melanoma truly becomes a curable disease.
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].
MGUS progression risk linked to IgM status
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.
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.
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.
SOURCE: Kyle RA et al. N Engl J Med. 2018;378:241-9.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Survival is shorter in MGUS patients, but most die of causes unrelated to the disorder.
Major finding: Patients have an overall progression risk of 10% by 10 years, and experience a 4-year shortening of median survival time.
Study details: The 34-year follow-up study comprised 1,384 patients.Disclosures: The study was funded in part by the National Cancer Institute. Dr. Kyle disclosed relationships with several pharmaceutical companies.
Source: Kyle RA et al. N Engl J Med. 2018 Jan 18;378:241-9.
Sharing Our Homes With Allergens
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%.
FDA grants priority review to daratumumab sBLA
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.
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.
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.
Cost transparency fails to affect high-cost medication utilization rates
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.
Setting: Single center, 1,145-bed, tertiary-care academic medical center.
Synopsis: Nine medications were chosen by committee to be targeted for intervention: intravenous voriconazole, IV levetiracetam, IV levothyroxine, IV linezolid, IV eculizumab, IV pantoprazole, IV calcitonin, inhaled ribavirin, and IV mycophenolate. The costs for these nine medications plus lower-cost alternatives were displayed for providers in the order entry system after about 2 years of baseline data had been collected. There was no change in the number of orders or ordering trends for eight of the nine high-cost medications after the intervention. Only ribavirin was ordered less after cost messaging was implemented (16.3 fewer orders per 10,000 patient-days). Lower IV pantoprazole use (73% reduction), correlated with a national shortage unrelated to the study intervention, a potential confounder. Data on dosing frequency and duration were not collected.
Bottom line: Displaying medication costs and alternatives did not alter the use of these nine high-cost medications.
Citation: Conway SJ et al. Impact of displaying inpatient pharmaceutical costs at the time of order entry: Lessons from a tertiary care center. J Hosp Med. 2017 Aug;12(8):639-45.
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.
Setting: Single center, 1,145-bed, tertiary-care academic medical center.
Synopsis: Nine medications were chosen by committee to be targeted for intervention: intravenous voriconazole, IV levetiracetam, IV levothyroxine, IV linezolid, IV eculizumab, IV pantoprazole, IV calcitonin, inhaled ribavirin, and IV mycophenolate. The costs for these nine medications plus lower-cost alternatives were displayed for providers in the order entry system after about 2 years of baseline data had been collected. There was no change in the number of orders or ordering trends for eight of the nine high-cost medications after the intervention. Only ribavirin was ordered less after cost messaging was implemented (16.3 fewer orders per 10,000 patient-days). Lower IV pantoprazole use (73% reduction), correlated with a national shortage unrelated to the study intervention, a potential confounder. Data on dosing frequency and duration were not collected.
Bottom line: Displaying medication costs and alternatives did not alter the use of these nine high-cost medications.
Citation: Conway SJ et al. Impact of displaying inpatient pharmaceutical costs at the time of order entry: Lessons from a tertiary care center. J Hosp Med. 2017 Aug;12(8):639-45.
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.
Setting: Single center, 1,145-bed, tertiary-care academic medical center.
Synopsis: Nine medications were chosen by committee to be targeted for intervention: intravenous voriconazole, IV levetiracetam, IV levothyroxine, IV linezolid, IV eculizumab, IV pantoprazole, IV calcitonin, inhaled ribavirin, and IV mycophenolate. The costs for these nine medications plus lower-cost alternatives were displayed for providers in the order entry system after about 2 years of baseline data had been collected. There was no change in the number of orders or ordering trends for eight of the nine high-cost medications after the intervention. Only ribavirin was ordered less after cost messaging was implemented (16.3 fewer orders per 10,000 patient-days). Lower IV pantoprazole use (73% reduction), correlated with a national shortage unrelated to the study intervention, a potential confounder. Data on dosing frequency and duration were not collected.
Bottom line: Displaying medication costs and alternatives did not alter the use of these nine high-cost medications.
Citation: Conway SJ et al. Impact of displaying inpatient pharmaceutical costs at the time of order entry: Lessons from a tertiary care center. J Hosp Med. 2017 Aug;12(8):639-45.
Dr. Lublin is a hospitalist at the University of Colorado School of Medicine.
Managing the "Hot" Mess of Thyroiditis
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.
Recurrent serious infection risk captured in real world RA study
according to findings from a study of the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis.
Sujith Subesinghe, MBBS, from the academic department of rheumatology at King’s College London and his coauthors identified 5,289 individuals from the registry who had experienced at least one episode of serious infection. All patients were also on either conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs at the time of their index infection.
Serious infections were more likely to occur in individuals who were older, male, seropositive, steroid users, or who had higher baseline Health Assessment Questionnaire scores. The most common type of serious infection was respiratory, which accounted for 44% of all events.
Overall, recurrent infections tended to occur in the same organ as index infections. Patients who experienced sepsis as the index infection had the highest risk of recurrent serious infection of 19.7% per annum, representing a 32% increased risk for recurrent serious infection, compared with individuals whose index infection was in the respiratory tract. Patients whose initial infection was musculoskeletal or gastrointestinal had a recurrence rate below 10%.
“It has been shown previously that a history of SI [serious infection] is a strong predictor of subsequent SI, but what has not been shown before is that the organ class of the index event has a large impact on the likelihood of recurrent SI,” the authors wrote.
Each decade of increased age was associated with a 34% increase in risk of recurrent infection. Noting that multiple drug use was a surrogate measure of comorbidity at baseline, researchers found that individuals taking 6-10 drugs at baseline had a 26% increased risk for recurrent infection, while those treated with 11 or more drugs had a 74% increased risk.
The authors observed that baseline steroid use was higher among patients suffering sepsis, compared with other types of serious infection.
They observed that, although a strong association between serious infection and steroid use has been reported, no firm conclusions have been reached by systematic reviews or meta-analyses “Steroids are more likely to be prescribed to patients with more aggressive, recalcitrant disease; this group has a higher baseline infection risk, and therefore, there is potential for confounding by indication.”
However, baseline disease activity score, disease duration, seropositivity, and smoking did not significantly predict the likelihood of infection recurrence, despite the fact that these are traditional predictors of infection. The authors suggested this may be the result of a form of selection bias.
“Patients readmitted with SI were from an already at-risk group and therefore lack of association between traditional predictors of infection and recurrent SI may be spurious.”
Commenting on their findings, the authors observed that individuals with rheumatoid arthritis and a history of infection were a complex group to manage, and even small differences in relative infection risk with different biologics may become significant.
“Further research needs to be undertaken to understand the patterns of recurrent infection and to appreciate the nuances in differential infection profiles of immunosuppressive drugs, to promote safe therapeutic decisions and promote personalization of care.”
The study was supported by the British Society for Rheumatology. Two authors declared speaking fees or honoraria from the pharmaceutical industry.
SOURCE: Subesinghe S et al. Rheumatology [Oxford]. 2018 Jan 10. doi: 10.1093/rheumatology/kex469.
according to findings from a study of the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis.
Sujith Subesinghe, MBBS, from the academic department of rheumatology at King’s College London and his coauthors identified 5,289 individuals from the registry who had experienced at least one episode of serious infection. All patients were also on either conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs at the time of their index infection.
Serious infections were more likely to occur in individuals who were older, male, seropositive, steroid users, or who had higher baseline Health Assessment Questionnaire scores. The most common type of serious infection was respiratory, which accounted for 44% of all events.
Overall, recurrent infections tended to occur in the same organ as index infections. Patients who experienced sepsis as the index infection had the highest risk of recurrent serious infection of 19.7% per annum, representing a 32% increased risk for recurrent serious infection, compared with individuals whose index infection was in the respiratory tract. Patients whose initial infection was musculoskeletal or gastrointestinal had a recurrence rate below 10%.
“It has been shown previously that a history of SI [serious infection] is a strong predictor of subsequent SI, but what has not been shown before is that the organ class of the index event has a large impact on the likelihood of recurrent SI,” the authors wrote.
Each decade of increased age was associated with a 34% increase in risk of recurrent infection. Noting that multiple drug use was a surrogate measure of comorbidity at baseline, researchers found that individuals taking 6-10 drugs at baseline had a 26% increased risk for recurrent infection, while those treated with 11 or more drugs had a 74% increased risk.
The authors observed that baseline steroid use was higher among patients suffering sepsis, compared with other types of serious infection.
They observed that, although a strong association between serious infection and steroid use has been reported, no firm conclusions have been reached by systematic reviews or meta-analyses “Steroids are more likely to be prescribed to patients with more aggressive, recalcitrant disease; this group has a higher baseline infection risk, and therefore, there is potential for confounding by indication.”
However, baseline disease activity score, disease duration, seropositivity, and smoking did not significantly predict the likelihood of infection recurrence, despite the fact that these are traditional predictors of infection. The authors suggested this may be the result of a form of selection bias.
“Patients readmitted with SI were from an already at-risk group and therefore lack of association between traditional predictors of infection and recurrent SI may be spurious.”
Commenting on their findings, the authors observed that individuals with rheumatoid arthritis and a history of infection were a complex group to manage, and even small differences in relative infection risk with different biologics may become significant.
“Further research needs to be undertaken to understand the patterns of recurrent infection and to appreciate the nuances in differential infection profiles of immunosuppressive drugs, to promote safe therapeutic decisions and promote personalization of care.”
The study was supported by the British Society for Rheumatology. Two authors declared speaking fees or honoraria from the pharmaceutical industry.
SOURCE: Subesinghe S et al. Rheumatology [Oxford]. 2018 Jan 10. doi: 10.1093/rheumatology/kex469.
according to findings from a study of the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis.
Sujith Subesinghe, MBBS, from the academic department of rheumatology at King’s College London and his coauthors identified 5,289 individuals from the registry who had experienced at least one episode of serious infection. All patients were also on either conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs at the time of their index infection.
Serious infections were more likely to occur in individuals who were older, male, seropositive, steroid users, or who had higher baseline Health Assessment Questionnaire scores. The most common type of serious infection was respiratory, which accounted for 44% of all events.
Overall, recurrent infections tended to occur in the same organ as index infections. Patients who experienced sepsis as the index infection had the highest risk of recurrent serious infection of 19.7% per annum, representing a 32% increased risk for recurrent serious infection, compared with individuals whose index infection was in the respiratory tract. Patients whose initial infection was musculoskeletal or gastrointestinal had a recurrence rate below 10%.
“It has been shown previously that a history of SI [serious infection] is a strong predictor of subsequent SI, but what has not been shown before is that the organ class of the index event has a large impact on the likelihood of recurrent SI,” the authors wrote.
Each decade of increased age was associated with a 34% increase in risk of recurrent infection. Noting that multiple drug use was a surrogate measure of comorbidity at baseline, researchers found that individuals taking 6-10 drugs at baseline had a 26% increased risk for recurrent infection, while those treated with 11 or more drugs had a 74% increased risk.
The authors observed that baseline steroid use was higher among patients suffering sepsis, compared with other types of serious infection.
They observed that, although a strong association between serious infection and steroid use has been reported, no firm conclusions have been reached by systematic reviews or meta-analyses “Steroids are more likely to be prescribed to patients with more aggressive, recalcitrant disease; this group has a higher baseline infection risk, and therefore, there is potential for confounding by indication.”
However, baseline disease activity score, disease duration, seropositivity, and smoking did not significantly predict the likelihood of infection recurrence, despite the fact that these are traditional predictors of infection. The authors suggested this may be the result of a form of selection bias.
“Patients readmitted with SI were from an already at-risk group and therefore lack of association between traditional predictors of infection and recurrent SI may be spurious.”
Commenting on their findings, the authors observed that individuals with rheumatoid arthritis and a history of infection were a complex group to manage, and even small differences in relative infection risk with different biologics may become significant.
“Further research needs to be undertaken to understand the patterns of recurrent infection and to appreciate the nuances in differential infection profiles of immunosuppressive drugs, to promote safe therapeutic decisions and promote personalization of care.”
The study was supported by the British Society for Rheumatology. Two authors declared speaking fees or honoraria from the pharmaceutical industry.
SOURCE: Subesinghe S et al. Rheumatology [Oxford]. 2018 Jan 10. doi: 10.1093/rheumatology/kex469.
FROM RHEUMATOLOGY
Key clinical point: Recurrent serious infections are relatively common among individuals with RA, particularly in the first year after an initial serious infection.
Major finding: The baseline annual rate of serious infections in patients with RA increased to 14.1% after having infection.
Data source: Analysis of data from 5,289 individuals from the British Society for Rheumatology Biologics Register–Rheumatoid Arthritis cohort.
Disclosures: The study was supported by the British Society for Rheumatology. Two authors declared speaking fees or honoraria from the pharmaceutical industry.
Source: Subesinghe S et al. Rheumatology [Oxford]. 2018 Jan 10. doi: 10.1093/rheumatology/kex469.
Immunotherapy with less intense chemotherapy safe and effective for older patients with ALL
according to the results of a single-arm phase 2 study.
After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.
Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.
They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.
Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.
Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.
“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.
Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.
They suggested that modifications to the regimen could further improve safety and that such modifications required further research.
For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.
The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.
SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.
The efficacy and safety of inotuzumab ozogamicin reported by Hagop Kantarjian, MD, and his colleagues are an encouraging building block for older patents with acute lymphoblastic leukemia, according to Carmelo Rizzari, MD.
“The authors have upgraded the valuable premises available from early inotuzumab ozogamicin studies into more concrete promises by rationally integrating the drug in a reduced-intensity chemotherapy regimen,” wrote Dr. Rizzari in an accompanying editorial published Lancet Oncology.
Adding inotuzumab ozogamicin to chemotherapy has shown efficacy and safety for both pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia and therefore deserves more investigation in the “neglected” subgroup of older patients, according to Dr. Rizzari.
“Monoclonal antibodies represent, in the wider settings of immunotherapy, viable options to improve the results obtained in different subsets of patients with acute lymphoblastic leukemia,” wrote Dr. Rizzari.
Echoing the researchers, Dr. Rizzari mentioned the importance of the next step – a phase 3 trial comparing inotuzumab ozogamicin with the current standard of care – but also mentioned that a specific, widely recognized standard of care for this patient subgroup is difficult to pin down.
Dr. Rizzari is with the Pediatric Hematology-Oncology Unit of the University of Milano-Bicocca in Milan. These comments are based on an accompanying editorial published online in Lancet Oncology (2018 Jan 15. doi: 10.1016/S1470-2045[18]30013-5 ). Dr. Rizzari declared no competing interests.
The efficacy and safety of inotuzumab ozogamicin reported by Hagop Kantarjian, MD, and his colleagues are an encouraging building block for older patents with acute lymphoblastic leukemia, according to Carmelo Rizzari, MD.
“The authors have upgraded the valuable premises available from early inotuzumab ozogamicin studies into more concrete promises by rationally integrating the drug in a reduced-intensity chemotherapy regimen,” wrote Dr. Rizzari in an accompanying editorial published Lancet Oncology.
Adding inotuzumab ozogamicin to chemotherapy has shown efficacy and safety for both pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia and therefore deserves more investigation in the “neglected” subgroup of older patients, according to Dr. Rizzari.
“Monoclonal antibodies represent, in the wider settings of immunotherapy, viable options to improve the results obtained in different subsets of patients with acute lymphoblastic leukemia,” wrote Dr. Rizzari.
Echoing the researchers, Dr. Rizzari mentioned the importance of the next step – a phase 3 trial comparing inotuzumab ozogamicin with the current standard of care – but also mentioned that a specific, widely recognized standard of care for this patient subgroup is difficult to pin down.
Dr. Rizzari is with the Pediatric Hematology-Oncology Unit of the University of Milano-Bicocca in Milan. These comments are based on an accompanying editorial published online in Lancet Oncology (2018 Jan 15. doi: 10.1016/S1470-2045[18]30013-5 ). Dr. Rizzari declared no competing interests.
The efficacy and safety of inotuzumab ozogamicin reported by Hagop Kantarjian, MD, and his colleagues are an encouraging building block for older patents with acute lymphoblastic leukemia, according to Carmelo Rizzari, MD.
“The authors have upgraded the valuable premises available from early inotuzumab ozogamicin studies into more concrete promises by rationally integrating the drug in a reduced-intensity chemotherapy regimen,” wrote Dr. Rizzari in an accompanying editorial published Lancet Oncology.
Adding inotuzumab ozogamicin to chemotherapy has shown efficacy and safety for both pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia and therefore deserves more investigation in the “neglected” subgroup of older patients, according to Dr. Rizzari.
“Monoclonal antibodies represent, in the wider settings of immunotherapy, viable options to improve the results obtained in different subsets of patients with acute lymphoblastic leukemia,” wrote Dr. Rizzari.
Echoing the researchers, Dr. Rizzari mentioned the importance of the next step – a phase 3 trial comparing inotuzumab ozogamicin with the current standard of care – but also mentioned that a specific, widely recognized standard of care for this patient subgroup is difficult to pin down.
Dr. Rizzari is with the Pediatric Hematology-Oncology Unit of the University of Milano-Bicocca in Milan. These comments are based on an accompanying editorial published online in Lancet Oncology (2018 Jan 15. doi: 10.1016/S1470-2045[18]30013-5 ). Dr. Rizzari declared no competing interests.
according to the results of a single-arm phase 2 study.
After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.
Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.
They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.
Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.
Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.
“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.
Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.
They suggested that modifications to the regimen could further improve safety and that such modifications required further research.
For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.
The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.
SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.
according to the results of a single-arm phase 2 study.
After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD, and his associates reported online in the Lancet Oncology.
Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.
They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.
Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.
Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.
“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.
Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.
They suggested that modifications to the regimen could further improve safety and that such modifications required further research.
For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.
The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.
SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.
FROM LANCET ONCOLOGY
Key clinical point: Inotuzumab ozogamicin with less intense chemotherapy is safe and effective for older patients with ALL.
Major finding: After a median follow-up of 29 months, 59% of patients experienced 2-year recurrence-free survival, 56% experienced 3-year overall survival and only four patients died within four weeks of treatment.
Data source: Single-arm phase 2 study of 52 patients aged 60 years or older with newly diagnosed Philadelphia chromosome–negative ALL.
Disclosures: The study was funded by a grant from the MD Anderson Cancer Center. Pfizer provided inotuzumab ozogamicin free of charge. Dr. Kantarjian and two other researchers reported receiving grants from Pfizer.
Source: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1.