Andrew D. Bowser

Chronic use of prescription opioid drugs correlated with support for the Republican candidate in the 2016 U.S. presidential election, according to a cross-sectional analysis published in JAMA Network Open.

The mean Republican presidential vote was 60% in U.S. counties with significantly higher-than-average rates of prescriptions for prolonged opioid use, versus 39% for counties with significantly lower rates, according to the study, which was based on prescription data for Medicare Part D enrollees (JAMA Network Open. 2018;1(2):e180450).

Those findings suggest the importance of economic, cultural, and environmental factors in the opioid epidemic, according to study author James S. Goodwin, MD, of the University of Texas Medical Branch, Galveston, and co-authors.

“Public health policy directed at stemming the opioid epidemic must go beyond the medical model and incorporate socioenvironmental disadvantage factors and health behaviors into policy planning and implementation,” Dr. Goodwin and co-authors wrote.

The cross-sectional analysis included data for 3.76 million Medicare Part D enrollees. They looked specifically at the proportion of enrollees with chronic opioid use, which they defined as receipt of at least a 90-day supply in 1 year.

After adjusting for age, disability, and other factors, they found 693 out of 3,100 counties (22.4%) had rates of chronic opioid use higher than the mean, and 638 (20.6%) had rates lower than the mean. The correlation between opioid use rates and the presidential vote was 0.42 (P < .001), according to investigators.

They also published two county maps that they said shared some similar patterns. The first shows the proportion of older chronic opioid users by quintile, and the second shows Republican vote percentages, also by quintile. The correlation coefficient between those two rates was 0.32 (P < .001).

This study adds to the emerging literature on the relationships between health status and support of Donald Trump in the 2016 election, according to authors.

However, there were limitations to the study, they added. Of note, the presidential vote data was from 2016, but the information on prolonged opioid prescriptions was from 2015. Moreover, the voting data included all voters, while the opioid data came only from Medicare Part D enrollees, which represent about 72% of the full Medicare population.

One study author reported grants from the National Institute on Drug Abuse and Agency for Healthcare Research and Quality. Another reported membership in Physicians for Responsible Opioid Prescribing

SOURCE: Goodwin JS, et al. JAMA Network Open. 2018;1(2):e180450.

This article was updated 6/26/18.

Chronic use of prescription opioid drugs correlated with support for the Republican candidate in the 2016 U.S. presidential election, according to a cross-sectional analysis published in JAMA Network Open.

The mean Republican presidential vote was 60% in U.S. counties with significantly higher-than-average rates of prescriptions for prolonged opioid use, versus 39% for counties with significantly lower rates, according to the study, which was based on prescription data for Medicare Part D enrollees (JAMA Network Open. 2018;1(2):e180450).

Those findings suggest the importance of economic, cultural, and environmental factors in the opioid epidemic, according to study author James S. Goodwin, MD, of the University of Texas Medical Branch, Galveston, and co-authors.

“Public health policy directed at stemming the opioid epidemic must go beyond the medical model and incorporate socioenvironmental disadvantage factors and health behaviors into policy planning and implementation,” Dr. Goodwin and co-authors wrote.

The cross-sectional analysis included data for 3.76 million Medicare Part D enrollees. They looked specifically at the proportion of enrollees with chronic opioid use, which they defined as receipt of at least a 90-day supply in 1 year.

After adjusting for age, disability, and other factors, they found 693 out of 3,100 counties (22.4%) had rates of chronic opioid use higher than the mean, and 638 (20.6%) had rates lower than the mean. The correlation between opioid use rates and the presidential vote was 0.42 (P < .001), according to investigators.

They also published two county maps that they said shared some similar patterns. The first shows the proportion of older chronic opioid users by quintile, and the second shows Republican vote percentages, also by quintile. The correlation coefficient between those two rates was 0.32 (P < .001).

This study adds to the emerging literature on the relationships between health status and support of Donald Trump in the 2016 election, according to authors.

However, there were limitations to the study, they added. Of note, the presidential vote data was from 2016, but the information on prolonged opioid prescriptions was from 2015. Moreover, the voting data included all voters, while the opioid data came only from Medicare Part D enrollees, which represent about 72% of the full Medicare population.

One study author reported grants from the National Institute on Drug Abuse and Agency for Healthcare Research and Quality. Another reported membership in Physicians for Responsible Opioid Prescribing

SOURCE: Goodwin JS, et al. JAMA Network Open. 2018;1(2):e180450.

This article was updated 6/26/18.

Chronic use of prescription opioid drugs correlated with support for the Republican candidate in the 2016 U.S. presidential election, according to a cross-sectional analysis published in JAMA Network Open.

The mean Republican presidential vote was 60% in U.S. counties with significantly higher-than-average rates of prescriptions for prolonged opioid use, versus 39% for counties with significantly lower rates, according to the study, which was based on prescription data for Medicare Part D enrollees (JAMA Network Open. 2018;1(2):e180450).

Those findings suggest the importance of economic, cultural, and environmental factors in the opioid epidemic, according to study author James S. Goodwin, MD, of the University of Texas Medical Branch, Galveston, and co-authors.

“Public health policy directed at stemming the opioid epidemic must go beyond the medical model and incorporate socioenvironmental disadvantage factors and health behaviors into policy planning and implementation,” Dr. Goodwin and co-authors wrote.

The cross-sectional analysis included data for 3.76 million Medicare Part D enrollees. They looked specifically at the proportion of enrollees with chronic opioid use, which they defined as receipt of at least a 90-day supply in 1 year.

After adjusting for age, disability, and other factors, they found 693 out of 3,100 counties (22.4%) had rates of chronic opioid use higher than the mean, and 638 (20.6%) had rates lower than the mean. The correlation between opioid use rates and the presidential vote was 0.42 (P < .001), according to investigators.

They also published two county maps that they said shared some similar patterns. The first shows the proportion of older chronic opioid users by quintile, and the second shows Republican vote percentages, also by quintile. The correlation coefficient between those two rates was 0.32 (P < .001).

This study adds to the emerging literature on the relationships between health status and support of Donald Trump in the 2016 election, according to authors.

However, there were limitations to the study, they added. Of note, the presidential vote data was from 2016, but the information on prolonged opioid prescriptions was from 2015. Moreover, the voting data included all voters, while the opioid data came only from Medicare Part D enrollees, which represent about 72% of the full Medicare population.

One study author reported grants from the National Institute on Drug Abuse and Agency for Healthcare Research and Quality. Another reported membership in Physicians for Responsible Opioid Prescribing

SOURCE: Goodwin JS, et al. JAMA Network Open. 2018;1(2):e180450.

This article was updated 6/26/18.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

CHICAGO – Are today’s myeloma drugs affordable? Two Mayo Clinic researchers agreed that costs are high but not whether the price is offset by the value.

“I don’t think there is any debate here. It’s like debating whether the Earth is flat or not,” S. Vincent Rajkumar, MD, of Mayo Clinic, Rochester, Minn., said during a debate at the annual meeting of the American Society of Clinical Oncology. “These drugs are expensive.”

“I would trust Dr. Rajkumar with my life if I were diagnosed with myeloma,” countered Rafael Fonseca, MD, of Mayo Clinic in Phoenix, Ariz., “But I think he’s wrong on drug economics.”

Dr. Rajkumar said the total lifetime costs to treat all patients diagnosed with multiple myeloma in 2017 were $22.4 billion, a “conservative estimate” that excluded hospital, infusion, laboratory, imaging, physician, nursing, and ancillary costs.

“Every single drug is expensive,” he said, referring to newer approved myeloma therapies that cost up to $192,000/year individually, and up to $590,000/year in triplet or quadruplet combination regimens, according to estimates he included in a related article he wrote for the 2018 ASCO Educational Book.

Of $50 billion spent in 2017 on cancer drugs, 80% of that spending was based on just 35 drugs, of which 6 were myeloma drugs – and myeloma is just 1% of all cancers. “Maybe it’s because of all the progress we’ve made in myeloma, but unless you think none of the other cancers should have the type of progress we have, this is not going to be affordable,” Dr. Rajkumar said.

Drugs approved by the Food and Drug Administration (FDA) in 2017 cost $100,000/year or more, with an average of $150,000/year, according to Dr. Rajkumar. He compared that with the average U.S. annual gross household income of $52,000, saying that the high price of drugs has contributed to compliance problems and medical bankruptcy.

While Dr. Fonseca agreed that drug prices are “skyrocketing,” he challenged the notion that the increases were not affordable in his presentation and an associated ASCO Educational Book article.

In his talk, Dr. Fonseca said the availability of new myeloma drugs has led to “astounding” improvements in overall survival, but today’s best drugs are still not good enough. “We cannot afford to stop innovation and the move forward as we are ever so close to curing a large fraction of myeloma patients,” he said.

The increasing cost of drugs has been offset by societal and health effects, Dr. Fonseca argued.

The war on cancer from 1988 to 2000 added 23 million additional life-years, which has equated to $1.9 trillion in social value for Americans, according to one analysis he cited. In one myeloma-specific study, investigators found myeloma drug costs increased from $36,607 in 2004 to $109,544 in 2009, but those increases were balanced out by $67,900 in health benefits.

Although the financial impact of myeloma on the individual patient can be significant, it’s not bankruptcies, but out-of-pocket costs such as copayments, that have the most direct effect on patients, Dr. Fonseca said. Research shows medical bankruptcies are not associated with drug copayments, he added, but rather other medical expenses, such as hospital and physician bills, along with loss of income and limited savings.

Dr. Rajkumar – unconvinced that myeloma drugs are currently affordable – urged action on several fronts, including value-based pricing or tying the price of a drug to how much value it produces.

The Medicare program has to be able to negotiate prices, he added, and patients should be allowed to reimport cancer drugs from other countries for personal use. He also pushed for more to be done to facilitate the entry of generics and biosimilars into the marketplace.

He also called for a relaxation of FDA regulations to lower drug development costs. “We have so many regulations so that every T is crossed and every I is dotted, to the point that it costs $30,000, $40,000 per patient to do a trial,” he said.

But Dr. Fonseca opposed market interference, saying that price controls would kill innovation.

“The patented drugs of today are the generics of the future, and absent innovation, we won’t have future generics,” he said in his presentation. “Price fixing kills innovation. ... So if we engage in that, today’s best is simply the best there is going to be.”

Dr. Rajkumar reported having no conflicts of interest. Dr. Fonseca reported consulting work with Amgen, Bristol-Myers Squibb, Celgene, Takeda Pharmaceutical, Bayer, Janssen, AbbVie, Pharmacyclics, Sanofi, Kite Pharma, and Juno Therapeutics, and scientific advisory board work with Adaptive Biotechnologies.

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

Offspring of obese mothers should be regarded as a high-risk population for endothelial cell dysfunction and, therefore, for cardiovascular events later in life, authors of a thematic literature review concluded.

Maternal obesity has been tied to the development of cardiovascular disease (CVD) and premature death in epidemiologic studies, the authors noted in the review.

anopdesignstock/Thinkstock

“Raised leptin levels, secreted by the adipose tissue, inhibit the in vitro proliferation of smooth muscle cells and could impede the angiogenesis process in vivo, but this assumption needs scientific validation in humans,” they said in their review.

However, human studies are lacking, aside from the epidemiologic reports that “cannot be used to confirm or contradict” the fetal programming hypothesis, they said.

Meanwhile, an increasing body of evidence has suggested that stressors in critical periods of fetal development may lead to epigenetic alterations that could play a role in either up-regulating atherogenic genes or down-regulating enzymatic activities that guard against oxidative stress.

For example, cohort studies have shown differences in DNA methylation among offspring born before and after bariatric surgery in the mother, which has lent credence to the hypothesis that maternal obesity in pregnancy alters methylation patterns for those offspring, Ms. Van De Maele and her colleagues wrote.

Lifestyle changes in obese pregnant women may have an effect on adverse metabolic or cardiovascular outcomes in offspring, although results to date are inconclusive, they added.

Diet, exercise, or both during pregnancy may lower the risk of macrosomia, respiratory distress syndrome, or other neonatal outcomes, particularly in high-risk women, according to the conclusions of a 2015 Cochrane review that Ms. Van De Maele and her coauthors cited.

However, follow-up studies on offspring are scarce and have shown no clear effects on long-term metabolic profiles in offspring, likely because of insufficient follow-up time, they said in their review.

Ms. Van De Maele and her coauthors said they had no conflict of interest disclosures related to their manuscript.

SOURCE: Van De Maele K et al. Atherosclerosis. 2018 Jun. doi: 10.1016/j.atherosclerosis.2018.06.016.

Among the reasons health care providers give for adolescent human papillomavirus (HPV) vaccination, U.S. parents ranked cancer prevention as the best, according to an analysis of a national survey.

Preventing a common infection also ranked highly as a reason for giving the vaccine, as did appeals to the vaccine’s lasting benefits and safety, the analysis showed.

Choreograph/Thinkstock

SOURCE: Gilkey MB et al. Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):762-7.

Among the reasons health care providers give for adolescent human papillomavirus (HPV) vaccination, U.S. parents ranked cancer prevention as the best, according to an analysis of a national survey.

Preventing a common infection also ranked highly as a reason for giving the vaccine, as did appeals to the vaccine’s lasting benefits and safety, the analysis showed.

Choreograph/Thinkstock

SOURCE: Gilkey MB et al. Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):762-7.

Among the reasons health care providers give for adolescent human papillomavirus (HPV) vaccination, U.S. parents ranked cancer prevention as the best, according to an analysis of a national survey.

Preventing a common infection also ranked highly as a reason for giving the vaccine, as did appeals to the vaccine’s lasting benefits and safety, the analysis showed.

Choreograph/Thinkstock

SOURCE: Gilkey MB et al. Cancer Epidemiol Biomarkers Prev. 2018 Jul;27(7):762-7.

Nearly half of patients with Parkinson’s disease who were taking dopamine agonist treatment experienced impulse control disorders over a follow-up of 5 years, according to recently published results of a longitudinal study.

The 5-year cumulative incidence of impulse control disorders was approximately 45% in the study, which included 411 patients with a high prevalence of dopamine agonist use and disease duration of 5 years or less at baseline.

There was a strong association between dopamine agonist use and impulse control disorders in the study, which was conducted by Jean-Christophe Corvol, MD, of Publique Hôpitaux de Paris and his coinvestigators.

Impulse disorders increased in incidence with both duration and dose of dopamine agonists and resolved progressively after discontinuation of those agents, the investigators reported online June 20 in Neurology. The investigators used item 1.6 of part I of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale to determine the presence of an impulse control disorder.

“Given the high cumulative incidence of impulse control disorders in patients with Parkinson’s disease, these adverse effects should be carefully monitored in patients ever treated with dopamine agonists,” Dr. Corvol and his coauthors wrote.

The results came from the ongoing Drug Interaction With Genes in Parkinson’s Disease (DIGPD) study, a longitudinal cohort study including Parkinson’s disease patients consecutively recruited between 2009 and 2013 at eight French hospitals. All patients had no more than 5 years of disease duration at recruitment, and follow-up included annual evaluations by movement disorder specialists.

At baseline, the majority of patients (302, or 73.5%) had taken dopamine agonists within the past 12 months.

Over the course of 5 years, the prevalence of impulse control disorders increased from 19.7% at baseline to 32.8%, Dr. Corvol and his colleagues reported.

Among 306 patients with no impulse control disorders at baseline, 94 developed one, for a 5-year cumulative incidence of 46.1%, they added. Only 4 of the 94 new cases occurred in patients who never used dopamine agonists.

Dopamine agonist use in the previous 12 months was associated with a 2.23-fold higher prevalence of impulse control disorders (P less than .001), with prevalence increasing along with average daily dose and cumulative dose duration over that time period, according to the investigators.

These findings suggests tools are needed to screen for impulse control disorders and identify high-risk patients, they said.

“Further studies are needed to understand the mechanisms involved in the relation between [dopamine agonists] and [impulse control disorders], in particular the role of apathy, anxiety, and depression,” they added.

The study was funded by grants from the French Ministry of Health and from the French Drug Agency. Dr. Corvol and many of his colleagues reported financial disclosures with many pharmaceutical companies.

SOURCE: Corvol J-C et al. Neurology. 2018 Jun 20. doi: 10.1212/WNL.0000000000005816.

Nearly half of patients with Parkinson’s disease who were taking dopamine agonist treatment experienced impulse control disorders over a follow-up of 5 years, according to recently published results of a longitudinal study.

The 5-year cumulative incidence of impulse control disorders was approximately 45% in the study, which included 411 patients with a high prevalence of dopamine agonist use and disease duration of 5 years or less at baseline.

There was a strong association between dopamine agonist use and impulse control disorders in the study, which was conducted by Jean-Christophe Corvol, MD, of Publique Hôpitaux de Paris and his coinvestigators.

Impulse disorders increased in incidence with both duration and dose of dopamine agonists and resolved progressively after discontinuation of those agents, the investigators reported online June 20 in Neurology. The investigators used item 1.6 of part I of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale to determine the presence of an impulse control disorder.

“Given the high cumulative incidence of impulse control disorders in patients with Parkinson’s disease, these adverse effects should be carefully monitored in patients ever treated with dopamine agonists,” Dr. Corvol and his coauthors wrote.

The results came from the ongoing Drug Interaction With Genes in Parkinson’s Disease (DIGPD) study, a longitudinal cohort study including Parkinson’s disease patients consecutively recruited between 2009 and 2013 at eight French hospitals. All patients had no more than 5 years of disease duration at recruitment, and follow-up included annual evaluations by movement disorder specialists.

At baseline, the majority of patients (302, or 73.5%) had taken dopamine agonists within the past 12 months.

Over the course of 5 years, the prevalence of impulse control disorders increased from 19.7% at baseline to 32.8%, Dr. Corvol and his colleagues reported.

Among 306 patients with no impulse control disorders at baseline, 94 developed one, for a 5-year cumulative incidence of 46.1%, they added. Only 4 of the 94 new cases occurred in patients who never used dopamine agonists.

Dopamine agonist use in the previous 12 months was associated with a 2.23-fold higher prevalence of impulse control disorders (P less than .001), with prevalence increasing along with average daily dose and cumulative dose duration over that time period, according to the investigators.

These findings suggests tools are needed to screen for impulse control disorders and identify high-risk patients, they said.

“Further studies are needed to understand the mechanisms involved in the relation between [dopamine agonists] and [impulse control disorders], in particular the role of apathy, anxiety, and depression,” they added.

The study was funded by grants from the French Ministry of Health and from the French Drug Agency. Dr. Corvol and many of his colleagues reported financial disclosures with many pharmaceutical companies.

SOURCE: Corvol J-C et al. Neurology. 2018 Jun 20. doi: 10.1212/WNL.0000000000005816.

Nearly half of patients with Parkinson’s disease who were taking dopamine agonist treatment experienced impulse control disorders over a follow-up of 5 years, according to recently published results of a longitudinal study.

The 5-year cumulative incidence of impulse control disorders was approximately 45% in the study, which included 411 patients with a high prevalence of dopamine agonist use and disease duration of 5 years or less at baseline.

There was a strong association between dopamine agonist use and impulse control disorders in the study, which was conducted by Jean-Christophe Corvol, MD, of Publique Hôpitaux de Paris and his coinvestigators.

Impulse disorders increased in incidence with both duration and dose of dopamine agonists and resolved progressively after discontinuation of those agents, the investigators reported online June 20 in Neurology. The investigators used item 1.6 of part I of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale to determine the presence of an impulse control disorder.

“Given the high cumulative incidence of impulse control disorders in patients with Parkinson’s disease, these adverse effects should be carefully monitored in patients ever treated with dopamine agonists,” Dr. Corvol and his coauthors wrote.

The results came from the ongoing Drug Interaction With Genes in Parkinson’s Disease (DIGPD) study, a longitudinal cohort study including Parkinson’s disease patients consecutively recruited between 2009 and 2013 at eight French hospitals. All patients had no more than 5 years of disease duration at recruitment, and follow-up included annual evaluations by movement disorder specialists.

At baseline, the majority of patients (302, or 73.5%) had taken dopamine agonists within the past 12 months.

Over the course of 5 years, the prevalence of impulse control disorders increased from 19.7% at baseline to 32.8%, Dr. Corvol and his colleagues reported.

Among 306 patients with no impulse control disorders at baseline, 94 developed one, for a 5-year cumulative incidence of 46.1%, they added. Only 4 of the 94 new cases occurred in patients who never used dopamine agonists.

Dopamine agonist use in the previous 12 months was associated with a 2.23-fold higher prevalence of impulse control disorders (P less than .001), with prevalence increasing along with average daily dose and cumulative dose duration over that time period, according to the investigators.

These findings suggests tools are needed to screen for impulse control disorders and identify high-risk patients, they said.

“Further studies are needed to understand the mechanisms involved in the relation between [dopamine agonists] and [impulse control disorders], in particular the role of apathy, anxiety, and depression,” they added.

The study was funded by grants from the French Ministry of Health and from the French Drug Agency. Dr. Corvol and many of his colleagues reported financial disclosures with many pharmaceutical companies.

SOURCE: Corvol J-C et al. Neurology. 2018 Jun 20. doi: 10.1212/WNL.0000000000005816.

CHICAGO – Chemoimmunotherapy for chronic lymphocytic leukemia is on the way out, but there’s one scenario where it still plays a key role, according to one leukemia expert.

That scenario is not in relapsed or refractory chronic lymphocytic leukemia (CLL), where the use of fludarabine, cyclophosphamide, and rituximab (FCR) may be hard to justify today. Data supporting use of FCR in relapsed CLL show a median progression-free survival (PFS) of about 21 months, Susan M. O’Brien, MD, of the University of California, Irvine, said at the annual meeting of the American Society of Clinical Oncology. There is also data for bendamustine-rituximab retreatment showing a median event-free survival of about 15 months, she added.

By contrast, the 5-year follow-up data for the Bruton tyrosine kinase inhibitor ibrutinib in the relapsed/refractory setting shows a median PFS of 52 months, which is “extraordinary,” given that the patients had a median of four prior regimens, Dr. O’Brien said.

Similarly, recently published results from the randomized, phase 3 MURANO study of venetoclax plus rituximab in relapsed/refractory CLL showed that median PFS was not reached at a median follow-up of 23.8 months, versus a median of 17 months for the bendamustine-rituximab comparison arm (N Engl J Med. 2018;378[12]:1107-20).

“Thanks to the MURANO study, we likely will have an expanded label for venetoclax that includes the combination of venetoclax and rituximab,” Dr. O’Brien said. “I think it’s quite clear that either of these is dramatically better than what you get with retreatment with chemotherapy, so I personally don’t think there is a role for chemoimmunotherapy in the relapsed patient.”

On June 8, 2018, the Food and Drug Administration granted regular approval for venetoclax for patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who have received at least one prior therapy. The FDA also approved its use in combination with rituximab.*

But frontline CLL treatment is currently a little bit more complicated, Dr. O’Brien said.

Recent studies show favorable long-term outcomes with FCR frontline therapy in the immunoglobulin heavy chain variable gene (IgHV) –mutated subgroup of patients, she noted.

The longest follow-up comes from a study from investigators at the University of Texas MD Anderson Cancer Center, Houston, published in 2016. In that study, the 12.8-year PFS was 53.9% for IgHV-mutated patients, versus just 8.7% for patients with unmutated IgHV. Of the IgHV-mutated group, more than half achieved minimal residual disease (MRD) negativity after treatment (Blood. 2016 Jan 21; 127[3]: 303-9).

“I’m going to go out on a limb and I’m going to suggest that I think there is a cure fraction here,” Dr. O’Brien said. “On the other hand, if there’s not a cure fraction and they’re going to relapse after 17 years, that’s a pretty attractive endpoint, even if it’s not a cure fraction.”

Clinical practice guidelines now recognize IgHV mutation status as an important marker that should be obtained when deciding on treatment, Dr. O’Brien noted.

For unmutated patients, the RESONATE-2 trial showed that ibrutinib was superior to chlorambucil in older patients, many of whom had comorbid conditions. In the 3-year update, median PFS was approximately 15 months for chlorambucil, while for ibrutinib the median PFS was “nowhere near” being reached, Dr. O’Brien said.

Those data may not be so relevant for fit, unmutated patients, and two randomized trials comparing FCR with bendamustine and rituximab have yet to report data. However, one recent cross-trial comparison found fairly overlapping survival curves for the two chemoimmunotherapy approaches.

Dr. O’Brien said she would put older patients with comorbidities on ibrutinib if a clinical trial was not available, and for fit, unmutated patients, while more data are needed, she would also use ibrutinib. However, patient preference sometimes tips the scale in favor of FCR.

“The discussions sometimes are quite long about whether the patient should opt to take ibrutinib or FCR,” Dr. O’Brien said. “The last patient I had that discussion with elected to take FCR. When I asked him why, he said because he liked the idea of being finished in six cycles, off all therapy, and hopefully in remission.”

While Dr. O’Brien said she views chemoimmunotherapy as still relevant in IgHV-mutated patients, eventually it will go away, she concluded. Toward that end, there is considerable interest in venetoclax plus ibrutinib, a combination that, in early reports, has yielded very encouraging MRD results in first-line CLL.

“We have no long-term data, but very, very exciting MRD negativity data,” Dr. O’Brien said.

Dr. O’Brien reported relationships with Abbvie, Amgen, Celgene, Gilead Sciences, Janssen, Pfizer, Pharmacyclics, Sunesis Pharmaceuticals, and others.

*This story was updated 6/25/2018.

CHICAGO – Chemoimmunotherapy for chronic lymphocytic leukemia is on the way out, but there’s one scenario where it still plays a key role, according to one leukemia expert.

That scenario is not in relapsed or refractory chronic lymphocytic leukemia (CLL), where the use of fludarabine, cyclophosphamide, and rituximab (FCR) may be hard to justify today. Data supporting use of FCR in relapsed CLL show a median progression-free survival (PFS) of about 21 months, Susan M. O’Brien, MD, of the University of California, Irvine, said at the annual meeting of the American Society of Clinical Oncology. There is also data for bendamustine-rituximab retreatment showing a median event-free survival of about 15 months, she added.

By contrast, the 5-year follow-up data for the Bruton tyrosine kinase inhibitor ibrutinib in the relapsed/refractory setting shows a median PFS of 52 months, which is “extraordinary,” given that the patients had a median of four prior regimens, Dr. O’Brien said.

Similarly, recently published results from the randomized, phase 3 MURANO study of venetoclax plus rituximab in relapsed/refractory CLL showed that median PFS was not reached at a median follow-up of 23.8 months, versus a median of 17 months for the bendamustine-rituximab comparison arm (N Engl J Med. 2018;378[12]:1107-20).

“Thanks to the MURANO study, we likely will have an expanded label for venetoclax that includes the combination of venetoclax and rituximab,” Dr. O’Brien said. “I think it’s quite clear that either of these is dramatically better than what you get with retreatment with chemotherapy, so I personally don’t think there is a role for chemoimmunotherapy in the relapsed patient.”

On June 8, 2018, the Food and Drug Administration granted regular approval for venetoclax for patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who have received at least one prior therapy. The FDA also approved its use in combination with rituximab.*

But frontline CLL treatment is currently a little bit more complicated, Dr. O’Brien said.

Recent studies show favorable long-term outcomes with FCR frontline therapy in the immunoglobulin heavy chain variable gene (IgHV) –mutated subgroup of patients, she noted.

The longest follow-up comes from a study from investigators at the University of Texas MD Anderson Cancer Center, Houston, published in 2016. In that study, the 12.8-year PFS was 53.9% for IgHV-mutated patients, versus just 8.7% for patients with unmutated IgHV. Of the IgHV-mutated group, more than half achieved minimal residual disease (MRD) negativity after treatment (Blood. 2016 Jan 21; 127[3]: 303-9).

“I’m going to go out on a limb and I’m going to suggest that I think there is a cure fraction here,” Dr. O’Brien said. “On the other hand, if there’s not a cure fraction and they’re going to relapse after 17 years, that’s a pretty attractive endpoint, even if it’s not a cure fraction.”

Clinical practice guidelines now recognize IgHV mutation status as an important marker that should be obtained when deciding on treatment, Dr. O’Brien noted.

For unmutated patients, the RESONATE-2 trial showed that ibrutinib was superior to chlorambucil in older patients, many of whom had comorbid conditions. In the 3-year update, median PFS was approximately 15 months for chlorambucil, while for ibrutinib the median PFS was “nowhere near” being reached, Dr. O’Brien said.

Those data may not be so relevant for fit, unmutated patients, and two randomized trials comparing FCR with bendamustine and rituximab have yet to report data. However, one recent cross-trial comparison found fairly overlapping survival curves for the two chemoimmunotherapy approaches.

Dr. O’Brien said she would put older patients with comorbidities on ibrutinib if a clinical trial was not available, and for fit, unmutated patients, while more data are needed, she would also use ibrutinib. However, patient preference sometimes tips the scale in favor of FCR.

“The discussions sometimes are quite long about whether the patient should opt to take ibrutinib or FCR,” Dr. O’Brien said. “The last patient I had that discussion with elected to take FCR. When I asked him why, he said because he liked the idea of being finished in six cycles, off all therapy, and hopefully in remission.”

While Dr. O’Brien said she views chemoimmunotherapy as still relevant in IgHV-mutated patients, eventually it will go away, she concluded. Toward that end, there is considerable interest in venetoclax plus ibrutinib, a combination that, in early reports, has yielded very encouraging MRD results in first-line CLL.

“We have no long-term data, but very, very exciting MRD negativity data,” Dr. O’Brien said.

Dr. O’Brien reported relationships with Abbvie, Amgen, Celgene, Gilead Sciences, Janssen, Pfizer, Pharmacyclics, Sunesis Pharmaceuticals, and others.

*This story was updated 6/25/2018.

CHICAGO – Chemoimmunotherapy for chronic lymphocytic leukemia is on the way out, but there’s one scenario where it still plays a key role, according to one leukemia expert.

That scenario is not in relapsed or refractory chronic lymphocytic leukemia (CLL), where the use of fludarabine, cyclophosphamide, and rituximab (FCR) may be hard to justify today. Data supporting use of FCR in relapsed CLL show a median progression-free survival (PFS) of about 21 months, Susan M. O’Brien, MD, of the University of California, Irvine, said at the annual meeting of the American Society of Clinical Oncology. There is also data for bendamustine-rituximab retreatment showing a median event-free survival of about 15 months, she added.

By contrast, the 5-year follow-up data for the Bruton tyrosine kinase inhibitor ibrutinib in the relapsed/refractory setting shows a median PFS of 52 months, which is “extraordinary,” given that the patients had a median of four prior regimens, Dr. O’Brien said.

Similarly, recently published results from the randomized, phase 3 MURANO study of venetoclax plus rituximab in relapsed/refractory CLL showed that median PFS was not reached at a median follow-up of 23.8 months, versus a median of 17 months for the bendamustine-rituximab comparison arm (N Engl J Med. 2018;378[12]:1107-20).

“Thanks to the MURANO study, we likely will have an expanded label for venetoclax that includes the combination of venetoclax and rituximab,” Dr. O’Brien said. “I think it’s quite clear that either of these is dramatically better than what you get with retreatment with chemotherapy, so I personally don’t think there is a role for chemoimmunotherapy in the relapsed patient.”

On June 8, 2018, the Food and Drug Administration granted regular approval for venetoclax for patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who have received at least one prior therapy. The FDA also approved its use in combination with rituximab.*

But frontline CLL treatment is currently a little bit more complicated, Dr. O’Brien said.

Recent studies show favorable long-term outcomes with FCR frontline therapy in the immunoglobulin heavy chain variable gene (IgHV) –mutated subgroup of patients, she noted.

The longest follow-up comes from a study from investigators at the University of Texas MD Anderson Cancer Center, Houston, published in 2016. In that study, the 12.8-year PFS was 53.9% for IgHV-mutated patients, versus just 8.7% for patients with unmutated IgHV. Of the IgHV-mutated group, more than half achieved minimal residual disease (MRD) negativity after treatment (Blood. 2016 Jan 21; 127[3]: 303-9).

“I’m going to go out on a limb and I’m going to suggest that I think there is a cure fraction here,” Dr. O’Brien said. “On the other hand, if there’s not a cure fraction and they’re going to relapse after 17 years, that’s a pretty attractive endpoint, even if it’s not a cure fraction.”

Clinical practice guidelines now recognize IgHV mutation status as an important marker that should be obtained when deciding on treatment, Dr. O’Brien noted.

For unmutated patients, the RESONATE-2 trial showed that ibrutinib was superior to chlorambucil in older patients, many of whom had comorbid conditions. In the 3-year update, median PFS was approximately 15 months for chlorambucil, while for ibrutinib the median PFS was “nowhere near” being reached, Dr. O’Brien said.

Those data may not be so relevant for fit, unmutated patients, and two randomized trials comparing FCR with bendamustine and rituximab have yet to report data. However, one recent cross-trial comparison found fairly overlapping survival curves for the two chemoimmunotherapy approaches.

Dr. O’Brien said she would put older patients with comorbidities on ibrutinib if a clinical trial was not available, and for fit, unmutated patients, while more data are needed, she would also use ibrutinib. However, patient preference sometimes tips the scale in favor of FCR.

“The discussions sometimes are quite long about whether the patient should opt to take ibrutinib or FCR,” Dr. O’Brien said. “The last patient I had that discussion with elected to take FCR. When I asked him why, he said because he liked the idea of being finished in six cycles, off all therapy, and hopefully in remission.”

While Dr. O’Brien said she views chemoimmunotherapy as still relevant in IgHV-mutated patients, eventually it will go away, she concluded. Toward that end, there is considerable interest in venetoclax plus ibrutinib, a combination that, in early reports, has yielded very encouraging MRD results in first-line CLL.

“We have no long-term data, but very, very exciting MRD negativity data,” Dr. O’Brien said.

Dr. O’Brien reported relationships with Abbvie, Amgen, Celgene, Gilead Sciences, Janssen, Pfizer, Pharmacyclics, Sunesis Pharmaceuticals, and others.

*This story was updated 6/25/2018.

Unnecessary testing for group A streptococcal (GAS) pharyngitis was less common in one ambulatory pediatrics practice after a collaborative interprofessional quality improvement (QI) initiative, results of a study found.

The average monthly frequency of unnecessary testing in that practice fell from 64% before the intervention to 41% afterward. Although the initiative did not appear to improve appropriate antibiotic use for GAS pharyngitis, most of the providers (88%) perceived an improvement in their ability to communicate with families about appropriate antibiotic use and the need for testing, Laura E. Norton, MD, of the University of Minnesota, Minneapolis, and her associates wrote.

CDC/ Melissa Brower

SOURCE: Norton LE, et al. Pediatrics. 2018;142(1):e20172033.

Unnecessary testing for group A streptococcal (GAS) pharyngitis was less common in one ambulatory pediatrics practice after a collaborative interprofessional quality improvement (QI) initiative, results of a study found.

The average monthly frequency of unnecessary testing in that practice fell from 64% before the intervention to 41% afterward. Although the initiative did not appear to improve appropriate antibiotic use for GAS pharyngitis, most of the providers (88%) perceived an improvement in their ability to communicate with families about appropriate antibiotic use and the need for testing, Laura E. Norton, MD, of the University of Minnesota, Minneapolis, and her associates wrote.

CDC/ Melissa Brower

SOURCE: Norton LE, et al. Pediatrics. 2018;142(1):e20172033.

Unnecessary testing for group A streptococcal (GAS) pharyngitis was less common in one ambulatory pediatrics practice after a collaborative interprofessional quality improvement (QI) initiative, results of a study found.

The average monthly frequency of unnecessary testing in that practice fell from 64% before the intervention to 41% afterward. Although the initiative did not appear to improve appropriate antibiotic use for GAS pharyngitis, most of the providers (88%) perceived an improvement in their ability to communicate with families about appropriate antibiotic use and the need for testing, Laura E. Norton, MD, of the University of Minnesota, Minneapolis, and her associates wrote.

CDC/ Melissa Brower

SOURCE: Norton LE, et al. Pediatrics. 2018;142(1):e20172033.

©ASCO/Zach Boyden-Holmes 2018

CHICAGO—A specific gene signature might be able to identify patients at risk of CD19 CAR T-cell associated neurotoxicity, according to results of an exploratory analysis presented at the 2018 ASCO Annual Meeting.

The analysis, based on bone marrow samples from patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated with JCAR015 in the ROCKET trial, helped identify a set of neurotoxicity-associated genes that separated patients based on molecular subtype.

“These findings suggest that patient risk stratification by molecular subtype of disease or gene expression signature may play a role in identifying patients at elevated risk of neurotoxicity,” said Jae Park, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, in a presentation of the findings (abstract 7007).

The phase 2 ROCKET study included adult patients with relapsed or refractory morphological (>5% blasts in bone marrow) CD-19 positive disease in first salvage or greater, including post allogeneic hematopoietic stem cell transplantation (HSCT). Prior blinatumomab was allowed.

The tumor gene expression study presented at ASCO was based on sequenced RNA from pre-apheresis bone marrow samples available for 31 patients in the ROCKET study.

Investigators identified a set of 10 genes expressed more frequently in bone marrow samples from patients in ROCKET with low (grade 0-1) neurotoxicity, and 7 that were more frequent in those who had severe (grade 4-5) neurotoxicity.

Looking at B-cell ALL samples in public datasets by molecular subtype, they found genes highly expressed in the low neurotoxicity ROCKET patients were also highly expressed in Philadelphia chromosome-positive (Ph+) and Ph-like subtypes.

Conversely, the genes highly expressed in the severe neurotoxicity patients were also highly expressed in non-Ph-like samples.

A total of 16 ROCKET patients were classified as having Ph-like gene expression and 15 as having non-Ph-like expression.

There were no grade 4-5 neurotoxicity events in the Ph-like patients, while both grade 3+ and grade 4+ neurotoxicity were significantly more prevalent in the non-Ph-like patients, investigators reported.

One of the most differentially expressed genes in the set was CCL17, which was higher in the low-neurotoxicity tumor samples, and likewise highly expressed in Ph-like B-cell ALL, according to the report.

“[CCL17] may serve as an early biomarker for differentiating severe neurotoxicity,” Dr Park said.

These findings are now being validated in the previously mentioned data set, as well as other studies to see if the findings can be replicated, according to Dr Park.

Juno Therapeutics, a Celgene company, shut down the phase 2 ROCKET trial of JCAR015 in 2017 after 2 clinical holds in 2016 and 5 patient deaths. 

©ASCO/Zach Boyden-Holmes 2018

CHICAGO—A specific gene signature might be able to identify patients at risk of CD19 CAR T-cell associated neurotoxicity, according to results of an exploratory analysis presented at the 2018 ASCO Annual Meeting.

The analysis, based on bone marrow samples from patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated with JCAR015 in the ROCKET trial, helped identify a set of neurotoxicity-associated genes that separated patients based on molecular subtype.

“These findings suggest that patient risk stratification by molecular subtype of disease or gene expression signature may play a role in identifying patients at elevated risk of neurotoxicity,” said Jae Park, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, in a presentation of the findings (abstract 7007).

The phase 2 ROCKET study included adult patients with relapsed or refractory morphological (>5% blasts in bone marrow) CD-19 positive disease in first salvage or greater, including post allogeneic hematopoietic stem cell transplantation (HSCT). Prior blinatumomab was allowed.

The tumor gene expression study presented at ASCO was based on sequenced RNA from pre-apheresis bone marrow samples available for 31 patients in the ROCKET study.

Investigators identified a set of 10 genes expressed more frequently in bone marrow samples from patients in ROCKET with low (grade 0-1) neurotoxicity, and 7 that were more frequent in those who had severe (grade 4-5) neurotoxicity.

Looking at B-cell ALL samples in public datasets by molecular subtype, they found genes highly expressed in the low neurotoxicity ROCKET patients were also highly expressed in Philadelphia chromosome-positive (Ph+) and Ph-like subtypes.

Conversely, the genes highly expressed in the severe neurotoxicity patients were also highly expressed in non-Ph-like samples.

A total of 16 ROCKET patients were classified as having Ph-like gene expression and 15 as having non-Ph-like expression.

There were no grade 4-5 neurotoxicity events in the Ph-like patients, while both grade 3+ and grade 4+ neurotoxicity were significantly more prevalent in the non-Ph-like patients, investigators reported.

One of the most differentially expressed genes in the set was CCL17, which was higher in the low-neurotoxicity tumor samples, and likewise highly expressed in Ph-like B-cell ALL, according to the report.

“[CCL17] may serve as an early biomarker for differentiating severe neurotoxicity,” Dr Park said.

These findings are now being validated in the previously mentioned data set, as well as other studies to see if the findings can be replicated, according to Dr Park.

Juno Therapeutics, a Celgene company, shut down the phase 2 ROCKET trial of JCAR015 in 2017 after 2 clinical holds in 2016 and 5 patient deaths. 

©ASCO/Zach Boyden-Holmes 2018

CHICAGO—A specific gene signature might be able to identify patients at risk of CD19 CAR T-cell associated neurotoxicity, according to results of an exploratory analysis presented at the 2018 ASCO Annual Meeting.

The analysis, based on bone marrow samples from patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated with JCAR015 in the ROCKET trial, helped identify a set of neurotoxicity-associated genes that separated patients based on molecular subtype.

“These findings suggest that patient risk stratification by molecular subtype of disease or gene expression signature may play a role in identifying patients at elevated risk of neurotoxicity,” said Jae Park, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, in a presentation of the findings (abstract 7007).

The phase 2 ROCKET study included adult patients with relapsed or refractory morphological (>5% blasts in bone marrow) CD-19 positive disease in first salvage or greater, including post allogeneic hematopoietic stem cell transplantation (HSCT). Prior blinatumomab was allowed.

The tumor gene expression study presented at ASCO was based on sequenced RNA from pre-apheresis bone marrow samples available for 31 patients in the ROCKET study.

Investigators identified a set of 10 genes expressed more frequently in bone marrow samples from patients in ROCKET with low (grade 0-1) neurotoxicity, and 7 that were more frequent in those who had severe (grade 4-5) neurotoxicity.

Looking at B-cell ALL samples in public datasets by molecular subtype, they found genes highly expressed in the low neurotoxicity ROCKET patients were also highly expressed in Philadelphia chromosome-positive (Ph+) and Ph-like subtypes.

Conversely, the genes highly expressed in the severe neurotoxicity patients were also highly expressed in non-Ph-like samples.

A total of 16 ROCKET patients were classified as having Ph-like gene expression and 15 as having non-Ph-like expression.

There were no grade 4-5 neurotoxicity events in the Ph-like patients, while both grade 3+ and grade 4+ neurotoxicity were significantly more prevalent in the non-Ph-like patients, investigators reported.

One of the most differentially expressed genes in the set was CCL17, which was higher in the low-neurotoxicity tumor samples, and likewise highly expressed in Ph-like B-cell ALL, according to the report.

“[CCL17] may serve as an early biomarker for differentiating severe neurotoxicity,” Dr Park said.

These findings are now being validated in the previously mentioned data set, as well as other studies to see if the findings can be replicated, according to Dr Park.

Juno Therapeutics, a Celgene company, shut down the phase 2 ROCKET trial of JCAR015 in 2017 after 2 clinical holds in 2016 and 5 patient deaths. 

©ASCO/Rodney White 2018

CHICAGO—Prior exposure to blinatumomab does not appear to affect the successful manufacture of KTE-C19 or its efficacy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), an investigator reported at the 2018 ASCO Annual Meeting.

The clinical benefit of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was preserved regardless of whether patients were exposed to blinatumomab, said Bijal D. Shah, MD, of Moffitt Cancer Center in Tampa, Florida.

High rates of complete response and undetectable minimal residual disease (MRD) were independent of exposure to blinatumomab, a CD19/CD3 bispecific T-cell engager.

“We feel the results of these data support KTE-C19 as an effective option for adults with refractory leukemia, regardless of prior exposure to CD19-directed therapy,” Dr Shah reported at the meeting (abstract 7006*).

The current standard of care for adults with relapsed/refractory ALL includes blinatumomab, raising the question of whether prior exposure to this CD19-directed treatment could influence the manufacture or efficacy of KTE-C19.

Sara Cooley, MD, of Masonic Medical Center, University of Minnesota in Minneapolis, said results of this analysis suggest prior blinatumomab should not be a contraindication or concern in the context of KTE-C19.

“This remains to be shown with other CAR T-cell therapies,” she said in a presentation at ASCO on cellular therapy in leukemia.

The analysis by Dr Shah and co-investigators was based on ZUMA-3 (NCT02614066), a phase 1 study including adults with relapsed/refractory ALL who received KTE-C19 at doses of 0.5, 1, or 2 x 10⁶ cells/kg.

They excluded patients in the highest dose cohort, who were required to be blinatumomab naïve, per protocol. That left 23 patients who received 0.5 or 1 x 10⁶ cells/kg, of whom 11 had prior blinatumomab exposure and 12 did not.

Best overall response appeared to be independent of prior blinatumomab treatment, with a CR rate of 72% overall, and 63% and 80% for blinatumomab-exposed and blinatumomab-naïve patients, respectively.

The rate of undetectable MRD was likewise high at 88% in the prior blinatumomab group and 100% in the no-blinatumomab group.

Product characteristics did not vary according to blinatumomab exposure, though there was a trend toward a more differentiated phenotype in those patients who had received prior CD19-directed treatment, he said.

There were no significant differences between groups in the rate of grade 3 or greater cytokine release syndrome. Neurologic events were higher in the blinatumomab-naïve patients, though a higher percentage of those patients received the 1 x 10⁶ cells/kg dose, Dr Shah reported.

Investigators also looked at CAR T levels by treatment.

“We cannot appreciate any significant differences between the blinatumomab-naïve and the blinatumomab-exposed groups,” Dr Shah told ASCO attendees.

The ZUMA-3 trial was sponsored by Kite, a Gilead Company. 

*Data in the abstract differ from the presentation.

©ASCO/Rodney White 2018

CHICAGO—Prior exposure to blinatumomab does not appear to affect the successful manufacture of KTE-C19 or its efficacy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), an investigator reported at the 2018 ASCO Annual Meeting.

The clinical benefit of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was preserved regardless of whether patients were exposed to blinatumomab, said Bijal D. Shah, MD, of Moffitt Cancer Center in Tampa, Florida.

High rates of complete response and undetectable minimal residual disease (MRD) were independent of exposure to blinatumomab, a CD19/CD3 bispecific T-cell engager.

“We feel the results of these data support KTE-C19 as an effective option for adults with refractory leukemia, regardless of prior exposure to CD19-directed therapy,” Dr Shah reported at the meeting (abstract 7006*).

The current standard of care for adults with relapsed/refractory ALL includes blinatumomab, raising the question of whether prior exposure to this CD19-directed treatment could influence the manufacture or efficacy of KTE-C19.

Sara Cooley, MD, of Masonic Medical Center, University of Minnesota in Minneapolis, said results of this analysis suggest prior blinatumomab should not be a contraindication or concern in the context of KTE-C19.

“This remains to be shown with other CAR T-cell therapies,” she said in a presentation at ASCO on cellular therapy in leukemia.

The analysis by Dr Shah and co-investigators was based on ZUMA-3 (NCT02614066), a phase 1 study including adults with relapsed/refractory ALL who received KTE-C19 at doses of 0.5, 1, or 2 x 10⁶ cells/kg.

They excluded patients in the highest dose cohort, who were required to be blinatumomab naïve, per protocol. That left 23 patients who received 0.5 or 1 x 10⁶ cells/kg, of whom 11 had prior blinatumomab exposure and 12 did not.

Best overall response appeared to be independent of prior blinatumomab treatment, with a CR rate of 72% overall, and 63% and 80% for blinatumomab-exposed and blinatumomab-naïve patients, respectively.

The rate of undetectable MRD was likewise high at 88% in the prior blinatumomab group and 100% in the no-blinatumomab group.

Product characteristics did not vary according to blinatumomab exposure, though there was a trend toward a more differentiated phenotype in those patients who had received prior CD19-directed treatment, he said.

There were no significant differences between groups in the rate of grade 3 or greater cytokine release syndrome. Neurologic events were higher in the blinatumomab-naïve patients, though a higher percentage of those patients received the 1 x 10⁶ cells/kg dose, Dr Shah reported.

Investigators also looked at CAR T levels by treatment.

“We cannot appreciate any significant differences between the blinatumomab-naïve and the blinatumomab-exposed groups,” Dr Shah told ASCO attendees.

The ZUMA-3 trial was sponsored by Kite, a Gilead Company. 

*Data in the abstract differ from the presentation.

©ASCO/Rodney White 2018

CHICAGO—Prior exposure to blinatumomab does not appear to affect the successful manufacture of KTE-C19 or its efficacy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), an investigator reported at the 2018 ASCO Annual Meeting.

The clinical benefit of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was preserved regardless of whether patients were exposed to blinatumomab, said Bijal D. Shah, MD, of Moffitt Cancer Center in Tampa, Florida.

High rates of complete response and undetectable minimal residual disease (MRD) were independent of exposure to blinatumomab, a CD19/CD3 bispecific T-cell engager.

“We feel the results of these data support KTE-C19 as an effective option for adults with refractory leukemia, regardless of prior exposure to CD19-directed therapy,” Dr Shah reported at the meeting (abstract 7006*).

The current standard of care for adults with relapsed/refractory ALL includes blinatumomab, raising the question of whether prior exposure to this CD19-directed treatment could influence the manufacture or efficacy of KTE-C19.

Sara Cooley, MD, of Masonic Medical Center, University of Minnesota in Minneapolis, said results of this analysis suggest prior blinatumomab should not be a contraindication or concern in the context of KTE-C19.

“This remains to be shown with other CAR T-cell therapies,” she said in a presentation at ASCO on cellular therapy in leukemia.

The analysis by Dr Shah and co-investigators was based on ZUMA-3 (NCT02614066), a phase 1 study including adults with relapsed/refractory ALL who received KTE-C19 at doses of 0.5, 1, or 2 x 10⁶ cells/kg.

They excluded patients in the highest dose cohort, who were required to be blinatumomab naïve, per protocol. That left 23 patients who received 0.5 or 1 x 10⁶ cells/kg, of whom 11 had prior blinatumomab exposure and 12 did not.

Best overall response appeared to be independent of prior blinatumomab treatment, with a CR rate of 72% overall, and 63% and 80% for blinatumomab-exposed and blinatumomab-naïve patients, respectively.

The rate of undetectable MRD was likewise high at 88% in the prior blinatumomab group and 100% in the no-blinatumomab group.

Product characteristics did not vary according to blinatumomab exposure, though there was a trend toward a more differentiated phenotype in those patients who had received prior CD19-directed treatment, he said.

There were no significant differences between groups in the rate of grade 3 or greater cytokine release syndrome. Neurologic events were higher in the blinatumomab-naïve patients, though a higher percentage of those patients received the 1 x 10⁶ cells/kg dose, Dr Shah reported.

Investigators also looked at CAR T levels by treatment.

“We cannot appreciate any significant differences between the blinatumomab-naïve and the blinatumomab-exposed groups,” Dr Shah told ASCO attendees.

The ZUMA-3 trial was sponsored by Kite, a Gilead Company. 

*Data in the abstract differ from the presentation.

Twelve weeks of treatment with three different antipsychotics commonly used in children and adolescents with disruptive behavioral disorders was associated with rapid-onset adverse changes in adiposity and insulin sensitivity, results of a randomized clinical trial show.

The adverse effect on adiposity was greatest for children aged 6-18 years who received olanzapine, but was also seen in study participants randomized to receive risperidone or aripiprazole, according to results of the study published in JAMA Psychiatry.

These findings inform the risk-benefit analysis for off-label pediatric use of antipsychotics for disruptive behavior disorders, Ginger E. Nicol, MD, of Washington University, St. Louis, and colleagues wrote.

“The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that – compared with adult onset – further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions,” the researchers wrote.

This randomized, prospective clinical trial included 144 antipsychotic-naive children and adolescents aged 6-18 years who had been diagnosed with one or more psychiatric disorders and clinically significant aggression. They were randomly and evenly assigned to 12 weeks of treatment with oral olanzapine, risperidone, or aripiprazole.

Those who received olanzapine had a 4.12% increase in percentage total body fat from baseline to week 12, as measured by dual-energy x-ray absorptiometry (DXA). That increase was significantly greater than the total body fat increases of 1.18% for risperidone and 1.66% for aripiprazole seen over that same time period (P less than .001 for time-by-treatment interaction), the researchers reported.

Insulin sensitivity decreased over time in the pooled study sample, with significant changes reported in insulin-stimulated glucose rate of disappearance, glucose rate of appearance, and glycerol rate of appearance. The changes did not differ significantly across the three treatment groups.

The lack of a placebo group in this study makes it unclear how much of the body fat and insulin sensitivity changes were attributable to antipsychotic medication. Psychiatric symptoms did improve significantly with treatment, the researchers noted.

Dr. Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical, Alkermes PLC, The Sidney R. Baer Jr. Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Co-authors reported financial ties to Reviva Pharmaceuticals, Sunovion Pharmaceuticals, Indivior, Amgen, and other companies.

SOURCE: Nicol GE et al. JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1088.

Twelve weeks of treatment with three different antipsychotics commonly used in children and adolescents with disruptive behavioral disorders was associated with rapid-onset adverse changes in adiposity and insulin sensitivity, results of a randomized clinical trial show.

The adverse effect on adiposity was greatest for children aged 6-18 years who received olanzapine, but was also seen in study participants randomized to receive risperidone or aripiprazole, according to results of the study published in JAMA Psychiatry.

These findings inform the risk-benefit analysis for off-label pediatric use of antipsychotics for disruptive behavior disorders, Ginger E. Nicol, MD, of Washington University, St. Louis, and colleagues wrote.

“The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that – compared with adult onset – further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions,” the researchers wrote.

This randomized, prospective clinical trial included 144 antipsychotic-naive children and adolescents aged 6-18 years who had been diagnosed with one or more psychiatric disorders and clinically significant aggression. They were randomly and evenly assigned to 12 weeks of treatment with oral olanzapine, risperidone, or aripiprazole.

Those who received olanzapine had a 4.12% increase in percentage total body fat from baseline to week 12, as measured by dual-energy x-ray absorptiometry (DXA). That increase was significantly greater than the total body fat increases of 1.18% for risperidone and 1.66% for aripiprazole seen over that same time period (P less than .001 for time-by-treatment interaction), the researchers reported.

Insulin sensitivity decreased over time in the pooled study sample, with significant changes reported in insulin-stimulated glucose rate of disappearance, glucose rate of appearance, and glycerol rate of appearance. The changes did not differ significantly across the three treatment groups.

The lack of a placebo group in this study makes it unclear how much of the body fat and insulin sensitivity changes were attributable to antipsychotic medication. Psychiatric symptoms did improve significantly with treatment, the researchers noted.

Dr. Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical, Alkermes PLC, The Sidney R. Baer Jr. Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Co-authors reported financial ties to Reviva Pharmaceuticals, Sunovion Pharmaceuticals, Indivior, Amgen, and other companies.

SOURCE: Nicol GE et al. JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1088.

Twelve weeks of treatment with three different antipsychotics commonly used in children and adolescents with disruptive behavioral disorders was associated with rapid-onset adverse changes in adiposity and insulin sensitivity, results of a randomized clinical trial show.

The adverse effect on adiposity was greatest for children aged 6-18 years who received olanzapine, but was also seen in study participants randomized to receive risperidone or aripiprazole, according to results of the study published in JAMA Psychiatry.

These findings inform the risk-benefit analysis for off-label pediatric use of antipsychotics for disruptive behavior disorders, Ginger E. Nicol, MD, of Washington University, St. Louis, and colleagues wrote.

“The potential psychiatric benefits of antipsychotic use in this population, evident in this trial and others, should be carefully weighed against the potential for childhood onset of abdominal obesity and insulin resistance that – compared with adult onset – further increases long-term risk for [type 2 diabetes], cardiovascular disease, and related conditions,” the researchers wrote.

This randomized, prospective clinical trial included 144 antipsychotic-naive children and adolescents aged 6-18 years who had been diagnosed with one or more psychiatric disorders and clinically significant aggression. They were randomly and evenly assigned to 12 weeks of treatment with oral olanzapine, risperidone, or aripiprazole.

Those who received olanzapine had a 4.12% increase in percentage total body fat from baseline to week 12, as measured by dual-energy x-ray absorptiometry (DXA). That increase was significantly greater than the total body fat increases of 1.18% for risperidone and 1.66% for aripiprazole seen over that same time period (P less than .001 for time-by-treatment interaction), the researchers reported.

Insulin sensitivity decreased over time in the pooled study sample, with significant changes reported in insulin-stimulated glucose rate of disappearance, glucose rate of appearance, and glycerol rate of appearance. The changes did not differ significantly across the three treatment groups.

The lack of a placebo group in this study makes it unclear how much of the body fat and insulin sensitivity changes were attributable to antipsychotic medication. Psychiatric symptoms did improve significantly with treatment, the researchers noted.

Dr. Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical, Alkermes PLC, The Sidney R. Baer Jr. Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Co-authors reported financial ties to Reviva Pharmaceuticals, Sunovion Pharmaceuticals, Indivior, Amgen, and other companies.

SOURCE: Nicol GE et al. JAMA Psychiatry. 2018 Jun 13. doi: 10.1001/jamapsychiatry.2018.1088.