CAR T-cell trial in adult ALL shut down

Article Type
Changed
Fri, 03/03/2017 - 06:00
Display Headline
CAR T-cell trial in adult ALL shut down

Image from NIAID
T cells

After 2 clinical holds in 2016 and 5 patient deaths, the Seattle biotech Juno Therapeutics is shutting down the phase 2 ROCKET trial of JCAR015.

The chimeric antigen receptor (CAR) T-cell therapy JCAR015 was being tested in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

“We have decided not to move forward . . . at this time,” CEO Hans Bishop said in a statement, “even though it generated important learnings for us and the immunotherapy field.”

He said the company remains “committed to developing better treatment for patients battling ALL.”

The first clinical hold of the ROCKET trial occurred in July after 2 patients died. The company attributed the deaths primarily to the addition of fludarabine to the regimen.

Juno removed fludarabine from the treatment protocol, the clinical hold was lifted, and the trial resumed.

Then, in November, 2 more patients died from cerebral edema, and the trial was put on hold once again.

One patient had died earlier in 2016, totaling 5 patient deaths from cerebral edema, although the earliest death was not necessarily related to treatment, the company stated.

Juno attributed the deaths to multiple factors, including the patients’ treatment history and treatment received at the beginning of the trial.

Juno plans to start a new adult ALL trial in 2018. The therapy, they say, is more similar to JCAR017, which is being tested in pediatric patients.

ROCKET is not the first trial of JCAR015 to be placed on hold.

In 2014, after 2 patients died of cytokine release syndrome, the phase 1 trial was placed on clinical hold.

Juno made changes to the enrollment criteria and dosing, and the hold was lifted. Results from this trial were presented at ASCO 2015 and ASCO 2016.

Publications
Topics

Image from NIAID
T cells

After 2 clinical holds in 2016 and 5 patient deaths, the Seattle biotech Juno Therapeutics is shutting down the phase 2 ROCKET trial of JCAR015.

The chimeric antigen receptor (CAR) T-cell therapy JCAR015 was being tested in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

“We have decided not to move forward . . . at this time,” CEO Hans Bishop said in a statement, “even though it generated important learnings for us and the immunotherapy field.”

He said the company remains “committed to developing better treatment for patients battling ALL.”

The first clinical hold of the ROCKET trial occurred in July after 2 patients died. The company attributed the deaths primarily to the addition of fludarabine to the regimen.

Juno removed fludarabine from the treatment protocol, the clinical hold was lifted, and the trial resumed.

Then, in November, 2 more patients died from cerebral edema, and the trial was put on hold once again.

One patient had died earlier in 2016, totaling 5 patient deaths from cerebral edema, although the earliest death was not necessarily related to treatment, the company stated.

Juno attributed the deaths to multiple factors, including the patients’ treatment history and treatment received at the beginning of the trial.

Juno plans to start a new adult ALL trial in 2018. The therapy, they say, is more similar to JCAR017, which is being tested in pediatric patients.

ROCKET is not the first trial of JCAR015 to be placed on hold.

In 2014, after 2 patients died of cytokine release syndrome, the phase 1 trial was placed on clinical hold.

Juno made changes to the enrollment criteria and dosing, and the hold was lifted. Results from this trial were presented at ASCO 2015 and ASCO 2016.

Image from NIAID
T cells

After 2 clinical holds in 2016 and 5 patient deaths, the Seattle biotech Juno Therapeutics is shutting down the phase 2 ROCKET trial of JCAR015.

The chimeric antigen receptor (CAR) T-cell therapy JCAR015 was being tested in adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

“We have decided not to move forward . . . at this time,” CEO Hans Bishop said in a statement, “even though it generated important learnings for us and the immunotherapy field.”

He said the company remains “committed to developing better treatment for patients battling ALL.”

The first clinical hold of the ROCKET trial occurred in July after 2 patients died. The company attributed the deaths primarily to the addition of fludarabine to the regimen.

Juno removed fludarabine from the treatment protocol, the clinical hold was lifted, and the trial resumed.

Then, in November, 2 more patients died from cerebral edema, and the trial was put on hold once again.

One patient had died earlier in 2016, totaling 5 patient deaths from cerebral edema, although the earliest death was not necessarily related to treatment, the company stated.

Juno attributed the deaths to multiple factors, including the patients’ treatment history and treatment received at the beginning of the trial.

Juno plans to start a new adult ALL trial in 2018. The therapy, they say, is more similar to JCAR017, which is being tested in pediatric patients.

ROCKET is not the first trial of JCAR015 to be placed on hold.

In 2014, after 2 patients died of cytokine release syndrome, the phase 1 trial was placed on clinical hold.

Juno made changes to the enrollment criteria and dosing, and the hold was lifted. Results from this trial were presented at ASCO 2015 and ASCO 2016.

Publications
Publications
Topics
Article Type
Display Headline
CAR T-cell trial in adult ALL shut down
Display Headline
CAR T-cell trial in adult ALL shut down
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica

Exercise better than meds to reduce fatigue in cancer patients

Article Type
Changed
Fri, 03/03/2017 - 05:30
Display Headline
Exercise better than meds to reduce fatigue in cancer patients

Photo by Petr Kratochvil
Woman in yoga pose

Exercise and/or psychological therapy work better than medications to reduce cancer-related fatigue, according to research published in JAMA Oncology.

Researchers conducted a review and meta-analysis of more than 113 studies and found that exercise and psychological interventions, as well as a combination of both, were associated with reduced fatigue during and after cancer treatment.

However, pharmaceutical interventions were not associated with the same magnitude of improvement.

The researchers therefore concluded that exercise and psychological therapy should be recommended over medications.

“If a cancer patient is having trouble with fatigue, rather than looking for extra cups of coffee, a nap, or a pharmaceutical solution, consider a 15-minute walk,” said study author Karen Mustian, PhD, of the University of Rochester Medical Center in Rochester, New York.

“It’s a really simple concept, but it’s very hard for patients and the medical community to wrap their heads around it because these interventions have not been front-and-center in the past. Our research gives clinicians a valuable asset to alleviate cancer-related fatigue.”

Dr Mustian and her colleagues reached their conclusions after analyzing data from 113 randomized clinical trials testing various treatments for cancer-related fatigue.

There were 11,525 patients enrolled in these studies. Nearly half (46.9%) were women with breast cancer. Ten studies focused on other types of cancer and enrolled only men.

Dr Mustian and her colleagues performed a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the fatigue treatments.

The team found that exercise alone—whether aerobic or anaerobic—reduced cancer-related fatigue most significantly. The WES was 0.30 (95% CI, 0.25-0.36; P<0.001).

Psychological interventions—such as therapy designed to provide education, change personal behavior, and adapt the way a person thinks about his or her circumstances—also improved fatigue. The WES was 0.27 (95% CI, 0.21-0.330.30; P<0.001).

A combination of psychological interventions and exercise had a significant improvement on fatigue as well. The WES was 0.26 (95% CI, 0.13-0.38; P<0.001).

However, the drugs tested for treating cancer-related fatigue—paroxetine hydrochloride, modafinil, armodafinil, methylphenidate hydrochloride, dexymethylphenidate, dexamphetamine, and methylprednisolone—were not as effective as the other interventions. The WES was 0.09 (95% CI, 0.00-0.19; P=0.05).

“The literature bears out that these drugs don’t work very well, although they are continually prescribed,” Dr Mustian said. “Cancer patients already take a lot of medications, and they all come with risks and side effects. So any time you can subtract a pharmaceutical from the picture it usually benefits patients.”

Publications
Topics

Photo by Petr Kratochvil
Woman in yoga pose

Exercise and/or psychological therapy work better than medications to reduce cancer-related fatigue, according to research published in JAMA Oncology.

Researchers conducted a review and meta-analysis of more than 113 studies and found that exercise and psychological interventions, as well as a combination of both, were associated with reduced fatigue during and after cancer treatment.

However, pharmaceutical interventions were not associated with the same magnitude of improvement.

The researchers therefore concluded that exercise and psychological therapy should be recommended over medications.

“If a cancer patient is having trouble with fatigue, rather than looking for extra cups of coffee, a nap, or a pharmaceutical solution, consider a 15-minute walk,” said study author Karen Mustian, PhD, of the University of Rochester Medical Center in Rochester, New York.

“It’s a really simple concept, but it’s very hard for patients and the medical community to wrap their heads around it because these interventions have not been front-and-center in the past. Our research gives clinicians a valuable asset to alleviate cancer-related fatigue.”

Dr Mustian and her colleagues reached their conclusions after analyzing data from 113 randomized clinical trials testing various treatments for cancer-related fatigue.

There were 11,525 patients enrolled in these studies. Nearly half (46.9%) were women with breast cancer. Ten studies focused on other types of cancer and enrolled only men.

Dr Mustian and her colleagues performed a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the fatigue treatments.

The team found that exercise alone—whether aerobic or anaerobic—reduced cancer-related fatigue most significantly. The WES was 0.30 (95% CI, 0.25-0.36; P<0.001).

Psychological interventions—such as therapy designed to provide education, change personal behavior, and adapt the way a person thinks about his or her circumstances—also improved fatigue. The WES was 0.27 (95% CI, 0.21-0.330.30; P<0.001).

A combination of psychological interventions and exercise had a significant improvement on fatigue as well. The WES was 0.26 (95% CI, 0.13-0.38; P<0.001).

However, the drugs tested for treating cancer-related fatigue—paroxetine hydrochloride, modafinil, armodafinil, methylphenidate hydrochloride, dexymethylphenidate, dexamphetamine, and methylprednisolone—were not as effective as the other interventions. The WES was 0.09 (95% CI, 0.00-0.19; P=0.05).

“The literature bears out that these drugs don’t work very well, although they are continually prescribed,” Dr Mustian said. “Cancer patients already take a lot of medications, and they all come with risks and side effects. So any time you can subtract a pharmaceutical from the picture it usually benefits patients.”

Photo by Petr Kratochvil
Woman in yoga pose

Exercise and/or psychological therapy work better than medications to reduce cancer-related fatigue, according to research published in JAMA Oncology.

Researchers conducted a review and meta-analysis of more than 113 studies and found that exercise and psychological interventions, as well as a combination of both, were associated with reduced fatigue during and after cancer treatment.

However, pharmaceutical interventions were not associated with the same magnitude of improvement.

The researchers therefore concluded that exercise and psychological therapy should be recommended over medications.

“If a cancer patient is having trouble with fatigue, rather than looking for extra cups of coffee, a nap, or a pharmaceutical solution, consider a 15-minute walk,” said study author Karen Mustian, PhD, of the University of Rochester Medical Center in Rochester, New York.

“It’s a really simple concept, but it’s very hard for patients and the medical community to wrap their heads around it because these interventions have not been front-and-center in the past. Our research gives clinicians a valuable asset to alleviate cancer-related fatigue.”

Dr Mustian and her colleagues reached their conclusions after analyzing data from 113 randomized clinical trials testing various treatments for cancer-related fatigue.

There were 11,525 patients enrolled in these studies. Nearly half (46.9%) were women with breast cancer. Ten studies focused on other types of cancer and enrolled only men.

Dr Mustian and her colleagues performed a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the fatigue treatments.

The team found that exercise alone—whether aerobic or anaerobic—reduced cancer-related fatigue most significantly. The WES was 0.30 (95% CI, 0.25-0.36; P<0.001).

Psychological interventions—such as therapy designed to provide education, change personal behavior, and adapt the way a person thinks about his or her circumstances—also improved fatigue. The WES was 0.27 (95% CI, 0.21-0.330.30; P<0.001).

A combination of psychological interventions and exercise had a significant improvement on fatigue as well. The WES was 0.26 (95% CI, 0.13-0.38; P<0.001).

However, the drugs tested for treating cancer-related fatigue—paroxetine hydrochloride, modafinil, armodafinil, methylphenidate hydrochloride, dexymethylphenidate, dexamphetamine, and methylprednisolone—were not as effective as the other interventions. The WES was 0.09 (95% CI, 0.00-0.19; P=0.05).

“The literature bears out that these drugs don’t work very well, although they are continually prescribed,” Dr Mustian said. “Cancer patients already take a lot of medications, and they all come with risks and side effects. So any time you can subtract a pharmaceutical from the picture it usually benefits patients.”

Publications
Publications
Topics
Article Type
Display Headline
Exercise better than meds to reduce fatigue in cancer patients
Display Headline
Exercise better than meds to reduce fatigue in cancer patients
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica

More Than “Teen Angst”: What to Watch For

Article Type
Changed
Fri, 03/03/2017 - 01:10
Display Headline
More Than “Teen Angst”: What to Watch For
 

The incidence of high-risk behavior among teenagers has attracted increased media attention lately. It feels like a new report surfaces every day detailing the death of one or more teens as a result of alcohol, illicit drug use, or speeding. These risky behaviors grab our attention; they are overt and somewhat public. But behaviors that correlate with anxiety and depression, which can in turn lead to suicide or suicidal ideation, are more subtle—and that is what concerns me.

The data on suicide is staggering. On a daily basis, almost 3,000 people worldwide complete suicide, and approximately 20 times as many survive a suicide attempt.1 Annually, deaths resulting from suicide exceed deaths from homicide and war combined.2 In 2013, there were 41,149 suicides in the US—that translates to a rate of 113 suicides each day, or one every 13 minutes.3 Suicide has surpassed homicide to become the second leading cause of death among 10- to 29-year-olds; in 2012, suicide claimed the lives of more than 5,000 people within this age bracket.4,5 In the 2013 Youth Risk Behavior Survey (YRBS), 17.7% of high school students reported seriously considering suicide during the prior 12 months, and nearly 9% of those students had attempted suicide during that same period.6 I wonder how many of those students exhibited telling behaviors that went unnoticed.

What are these subtle signs that are so easily overlooked? Behaviors most might consider “within the norm” of today’s youth—hours playing video games, sending hundreds of texts every day, lack of exercise, and lack of sleep. Research has demonstrated that moderate-to-vigorous physical activity reduces the incidence of depression in adolescents.7 A 2014 study of European teens published in World Psychiatry found that the adolescents most at risk for symptoms of depression and anxiety are those who are fixated on media, don’t get enough sleep, and have a sedentary lifestyle.8 Hmm... sounds like many US teenagers today. While that doesn’t mean that every teen who lacks sleep, plays video games, or isn’t active is at risk, we do need to pay closer attention to them, because this combination exacerbates risk.

There’s another unhealthy habit that contributes to the risk for teen suicidality: smoking and use of electronic vapor products (EVPs). The 2015 YRBS, which surveyed more than 15,000 high school students, noted that 3.2% smoked cigarettes only, 15.8% used EVPs only, and 7.5% were dual users. Analysis of that data identified associations between health-risk behaviors and both cigarette smoking and EVP use.9 Teens who smoked or used EVPs were more likely to engage in violence, substance abuse, and other high-risk behaviors, compared with nonusers. Moreover, compared with nonusers, cigarette-only, EVP-only, and dual smokers were significantly more likely to attempt suicide; cigarette-only smokers were more likely than EVP-only users to attempt suicide.9

Smoking, inactivity, sleep deprivation, and social isolation (because texting or face-timing with your friends is not being social) are a recipe for depression and anxiety in an adolescent. Sleep deprivation alone has been linked to depression and may be associated with a decreased ability to control, inhibit, or change emotional responses.10 Far too often, teens view suicide as the only relief from these feelings.

Awareness of this problem has grown in the past 30 years. The YRBS was developed in 1990 to monitor priority health risk behaviors that contribute to the leading causes of death, disability, and social problems among youth in the US—one of which is suicide.11 In 2001, the Department of Health and Human Services introduced the National Strategy for Suicide Prevention, the first national program of its kind, and released an evidence-based practice guide for school-based suicide prevention plans.12 The 2002 Institute of Medicine report Reducing Suicide: A National Imperative recognized the need for early recognition and prevention of suicidality.13 And yet, we still have the staggering statistics I cited earlier.

Because of their proximity to children and adolescents, schools are frequently viewed as an integral setting for youth suicide prevention efforts. It is encouraging that suicide prevention programs exist in more than 77% of US public schools—but disheartening that it is not 100%.

 

 

 

And what about the rest of us? What can we, as health care providers, do to stem this tide of teen suicide? The importance of early prevention strategies to reduce onset of suicidal thoughts and help identify persons who are at risk for or are currently contemplating suicide cannot be overemphasized. We need more health care practitioners who are trained to assess suicide plans and to intervene with young persons. This involves education in recognizing risk factors and making appropriate referrals, expanding access to social services, reducing stigma and other barriers to seeking help, and providing awareness that suicide prevention is paramount.

It is incumbent on us as health care providers to screen for and ask our teenaged patients about those subtle behaviors. As adults, it is our responsibility to support and watch over our youth. In the words of former Surgeon General David Satcher, “We must act now. We cannot change the past, but together we can shape a different future.”14

References

1. World Health Organization. World Suicide Prevention Day. www.who.int/mediacentre/news/statements/2007/s16/en/. Accessed February 2, 2017
2. World Health Organization. Suicide huge but preventable public health problem, says WHO. www.who.int/mediacentre/news/releases/2004/pr61/en. Accessed February 2, 2017.
3. CDC. Web-based Injury Statistics Query and Reporting System (WISQARS). www.cdc.gov/injury/wisqars/index.html. Accessed February 2, 2017.
4. World Health Organization. Suicide. www.who.int/mediacentre/factsheets/fs398/en. Accessed February 2, 2017.
5. CDC. Suicide trends among persons aged 10-24 years—United States, 1994-2012. www.cdc.gov/mmwr/pdf/wk/mm6408.pdf. Accessed February 2, 2017.
6. CDC. Trends in the prevalence of suicide-related behavior. National Youth Risk Behavior Survey: 1991-2013. www.cdc.gov/healthyyouth/data/yrbs/pdf/trends/us_suicide_trend_yrbs.pdf. Accessed February 2, 2017.
7. Zahl T, Steinsbekk S, Wichstrøm L. Physical activity, sedentary behavior, and symptoms of major depression in middle childhood. Pediatrics. 2017;139(2):e20161711.
8. Carli V, Hoven CW, Wasserman C, et al. A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study. World Psychiatry. 2014;13(1):78-86.
9. Demissie Z, Everett Jones S, Clayton HB, King BA. Adolescent risk behaviors and use of electronic vapor products and cigarettes. Pediatrics. 2017;139(2):e20162921.
10. National Sleep Foundation. Adolescent sleep needs and patterns. https://sleepfoundation.org/sites/default/files/sleep_and_teens_report1.pdf. Accessed February 2, 2017.
11. CDC. Youth Risk Behavior Surveillance System (YRBSS) overview. www.cdc.gov/healthyyouth/data/yrbs/overview.htm. Accessed February 2, 2017.
12. Cooper GD, Clements PT, Holt K. A review and application of suicide prevention programs in high school settings. Issues Ment Health Nurs. 2011;32(11):696-702.
13. Goldsmith SK, Pellmar TC, Kleinman AM, Bunney WE. Reducing Suicide: A National Imperative. Washington, DC: National Academics Press; 2002.
14. US Public Health Service. The Surgeon General’s Call to Action to Prevent Suicide. Washington, DC: 1999.

Article PDF
Author and Disclosure Information

Issue
Clinician Reviews - 27(3)
Publications
Topics
Page Number
14,28
Sections
Author and Disclosure Information

Author and Disclosure Information

Article PDF
Article PDF
Related Articles
 

The incidence of high-risk behavior among teenagers has attracted increased media attention lately. It feels like a new report surfaces every day detailing the death of one or more teens as a result of alcohol, illicit drug use, or speeding. These risky behaviors grab our attention; they are overt and somewhat public. But behaviors that correlate with anxiety and depression, which can in turn lead to suicide or suicidal ideation, are more subtle—and that is what concerns me.

The data on suicide is staggering. On a daily basis, almost 3,000 people worldwide complete suicide, and approximately 20 times as many survive a suicide attempt.1 Annually, deaths resulting from suicide exceed deaths from homicide and war combined.2 In 2013, there were 41,149 suicides in the US—that translates to a rate of 113 suicides each day, or one every 13 minutes.3 Suicide has surpassed homicide to become the second leading cause of death among 10- to 29-year-olds; in 2012, suicide claimed the lives of more than 5,000 people within this age bracket.4,5 In the 2013 Youth Risk Behavior Survey (YRBS), 17.7% of high school students reported seriously considering suicide during the prior 12 months, and nearly 9% of those students had attempted suicide during that same period.6 I wonder how many of those students exhibited telling behaviors that went unnoticed.

What are these subtle signs that are so easily overlooked? Behaviors most might consider “within the norm” of today’s youth—hours playing video games, sending hundreds of texts every day, lack of exercise, and lack of sleep. Research has demonstrated that moderate-to-vigorous physical activity reduces the incidence of depression in adolescents.7 A 2014 study of European teens published in World Psychiatry found that the adolescents most at risk for symptoms of depression and anxiety are those who are fixated on media, don’t get enough sleep, and have a sedentary lifestyle.8 Hmm... sounds like many US teenagers today. While that doesn’t mean that every teen who lacks sleep, plays video games, or isn’t active is at risk, we do need to pay closer attention to them, because this combination exacerbates risk.

There’s another unhealthy habit that contributes to the risk for teen suicidality: smoking and use of electronic vapor products (EVPs). The 2015 YRBS, which surveyed more than 15,000 high school students, noted that 3.2% smoked cigarettes only, 15.8% used EVPs only, and 7.5% were dual users. Analysis of that data identified associations between health-risk behaviors and both cigarette smoking and EVP use.9 Teens who smoked or used EVPs were more likely to engage in violence, substance abuse, and other high-risk behaviors, compared with nonusers. Moreover, compared with nonusers, cigarette-only, EVP-only, and dual smokers were significantly more likely to attempt suicide; cigarette-only smokers were more likely than EVP-only users to attempt suicide.9

Smoking, inactivity, sleep deprivation, and social isolation (because texting or face-timing with your friends is not being social) are a recipe for depression and anxiety in an adolescent. Sleep deprivation alone has been linked to depression and may be associated with a decreased ability to control, inhibit, or change emotional responses.10 Far too often, teens view suicide as the only relief from these feelings.

Awareness of this problem has grown in the past 30 years. The YRBS was developed in 1990 to monitor priority health risk behaviors that contribute to the leading causes of death, disability, and social problems among youth in the US—one of which is suicide.11 In 2001, the Department of Health and Human Services introduced the National Strategy for Suicide Prevention, the first national program of its kind, and released an evidence-based practice guide for school-based suicide prevention plans.12 The 2002 Institute of Medicine report Reducing Suicide: A National Imperative recognized the need for early recognition and prevention of suicidality.13 And yet, we still have the staggering statistics I cited earlier.

Because of their proximity to children and adolescents, schools are frequently viewed as an integral setting for youth suicide prevention efforts. It is encouraging that suicide prevention programs exist in more than 77% of US public schools—but disheartening that it is not 100%.

 

 

 

And what about the rest of us? What can we, as health care providers, do to stem this tide of teen suicide? The importance of early prevention strategies to reduce onset of suicidal thoughts and help identify persons who are at risk for or are currently contemplating suicide cannot be overemphasized. We need more health care practitioners who are trained to assess suicide plans and to intervene with young persons. This involves education in recognizing risk factors and making appropriate referrals, expanding access to social services, reducing stigma and other barriers to seeking help, and providing awareness that suicide prevention is paramount.

It is incumbent on us as health care providers to screen for and ask our teenaged patients about those subtle behaviors. As adults, it is our responsibility to support and watch over our youth. In the words of former Surgeon General David Satcher, “We must act now. We cannot change the past, but together we can shape a different future.”14

 

The incidence of high-risk behavior among teenagers has attracted increased media attention lately. It feels like a new report surfaces every day detailing the death of one or more teens as a result of alcohol, illicit drug use, or speeding. These risky behaviors grab our attention; they are overt and somewhat public. But behaviors that correlate with anxiety and depression, which can in turn lead to suicide or suicidal ideation, are more subtle—and that is what concerns me.

The data on suicide is staggering. On a daily basis, almost 3,000 people worldwide complete suicide, and approximately 20 times as many survive a suicide attempt.1 Annually, deaths resulting from suicide exceed deaths from homicide and war combined.2 In 2013, there were 41,149 suicides in the US—that translates to a rate of 113 suicides each day, or one every 13 minutes.3 Suicide has surpassed homicide to become the second leading cause of death among 10- to 29-year-olds; in 2012, suicide claimed the lives of more than 5,000 people within this age bracket.4,5 In the 2013 Youth Risk Behavior Survey (YRBS), 17.7% of high school students reported seriously considering suicide during the prior 12 months, and nearly 9% of those students had attempted suicide during that same period.6 I wonder how many of those students exhibited telling behaviors that went unnoticed.

What are these subtle signs that are so easily overlooked? Behaviors most might consider “within the norm” of today’s youth—hours playing video games, sending hundreds of texts every day, lack of exercise, and lack of sleep. Research has demonstrated that moderate-to-vigorous physical activity reduces the incidence of depression in adolescents.7 A 2014 study of European teens published in World Psychiatry found that the adolescents most at risk for symptoms of depression and anxiety are those who are fixated on media, don’t get enough sleep, and have a sedentary lifestyle.8 Hmm... sounds like many US teenagers today. While that doesn’t mean that every teen who lacks sleep, plays video games, or isn’t active is at risk, we do need to pay closer attention to them, because this combination exacerbates risk.

There’s another unhealthy habit that contributes to the risk for teen suicidality: smoking and use of electronic vapor products (EVPs). The 2015 YRBS, which surveyed more than 15,000 high school students, noted that 3.2% smoked cigarettes only, 15.8% used EVPs only, and 7.5% were dual users. Analysis of that data identified associations between health-risk behaviors and both cigarette smoking and EVP use.9 Teens who smoked or used EVPs were more likely to engage in violence, substance abuse, and other high-risk behaviors, compared with nonusers. Moreover, compared with nonusers, cigarette-only, EVP-only, and dual smokers were significantly more likely to attempt suicide; cigarette-only smokers were more likely than EVP-only users to attempt suicide.9

Smoking, inactivity, sleep deprivation, and social isolation (because texting or face-timing with your friends is not being social) are a recipe for depression and anxiety in an adolescent. Sleep deprivation alone has been linked to depression and may be associated with a decreased ability to control, inhibit, or change emotional responses.10 Far too often, teens view suicide as the only relief from these feelings.

Awareness of this problem has grown in the past 30 years. The YRBS was developed in 1990 to monitor priority health risk behaviors that contribute to the leading causes of death, disability, and social problems among youth in the US—one of which is suicide.11 In 2001, the Department of Health and Human Services introduced the National Strategy for Suicide Prevention, the first national program of its kind, and released an evidence-based practice guide for school-based suicide prevention plans.12 The 2002 Institute of Medicine report Reducing Suicide: A National Imperative recognized the need for early recognition and prevention of suicidality.13 And yet, we still have the staggering statistics I cited earlier.

Because of their proximity to children and adolescents, schools are frequently viewed as an integral setting for youth suicide prevention efforts. It is encouraging that suicide prevention programs exist in more than 77% of US public schools—but disheartening that it is not 100%.

 

 

 

And what about the rest of us? What can we, as health care providers, do to stem this tide of teen suicide? The importance of early prevention strategies to reduce onset of suicidal thoughts and help identify persons who are at risk for or are currently contemplating suicide cannot be overemphasized. We need more health care practitioners who are trained to assess suicide plans and to intervene with young persons. This involves education in recognizing risk factors and making appropriate referrals, expanding access to social services, reducing stigma and other barriers to seeking help, and providing awareness that suicide prevention is paramount.

It is incumbent on us as health care providers to screen for and ask our teenaged patients about those subtle behaviors. As adults, it is our responsibility to support and watch over our youth. In the words of former Surgeon General David Satcher, “We must act now. We cannot change the past, but together we can shape a different future.”14

References

1. World Health Organization. World Suicide Prevention Day. www.who.int/mediacentre/news/statements/2007/s16/en/. Accessed February 2, 2017
2. World Health Organization. Suicide huge but preventable public health problem, says WHO. www.who.int/mediacentre/news/releases/2004/pr61/en. Accessed February 2, 2017.
3. CDC. Web-based Injury Statistics Query and Reporting System (WISQARS). www.cdc.gov/injury/wisqars/index.html. Accessed February 2, 2017.
4. World Health Organization. Suicide. www.who.int/mediacentre/factsheets/fs398/en. Accessed February 2, 2017.
5. CDC. Suicide trends among persons aged 10-24 years—United States, 1994-2012. www.cdc.gov/mmwr/pdf/wk/mm6408.pdf. Accessed February 2, 2017.
6. CDC. Trends in the prevalence of suicide-related behavior. National Youth Risk Behavior Survey: 1991-2013. www.cdc.gov/healthyyouth/data/yrbs/pdf/trends/us_suicide_trend_yrbs.pdf. Accessed February 2, 2017.
7. Zahl T, Steinsbekk S, Wichstrøm L. Physical activity, sedentary behavior, and symptoms of major depression in middle childhood. Pediatrics. 2017;139(2):e20161711.
8. Carli V, Hoven CW, Wasserman C, et al. A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study. World Psychiatry. 2014;13(1):78-86.
9. Demissie Z, Everett Jones S, Clayton HB, King BA. Adolescent risk behaviors and use of electronic vapor products and cigarettes. Pediatrics. 2017;139(2):e20162921.
10. National Sleep Foundation. Adolescent sleep needs and patterns. https://sleepfoundation.org/sites/default/files/sleep_and_teens_report1.pdf. Accessed February 2, 2017.
11. CDC. Youth Risk Behavior Surveillance System (YRBSS) overview. www.cdc.gov/healthyyouth/data/yrbs/overview.htm. Accessed February 2, 2017.
12. Cooper GD, Clements PT, Holt K. A review and application of suicide prevention programs in high school settings. Issues Ment Health Nurs. 2011;32(11):696-702.
13. Goldsmith SK, Pellmar TC, Kleinman AM, Bunney WE. Reducing Suicide: A National Imperative. Washington, DC: National Academics Press; 2002.
14. US Public Health Service. The Surgeon General’s Call to Action to Prevent Suicide. Washington, DC: 1999.

References

1. World Health Organization. World Suicide Prevention Day. www.who.int/mediacentre/news/statements/2007/s16/en/. Accessed February 2, 2017
2. World Health Organization. Suicide huge but preventable public health problem, says WHO. www.who.int/mediacentre/news/releases/2004/pr61/en. Accessed February 2, 2017.
3. CDC. Web-based Injury Statistics Query and Reporting System (WISQARS). www.cdc.gov/injury/wisqars/index.html. Accessed February 2, 2017.
4. World Health Organization. Suicide. www.who.int/mediacentre/factsheets/fs398/en. Accessed February 2, 2017.
5. CDC. Suicide trends among persons aged 10-24 years—United States, 1994-2012. www.cdc.gov/mmwr/pdf/wk/mm6408.pdf. Accessed February 2, 2017.
6. CDC. Trends in the prevalence of suicide-related behavior. National Youth Risk Behavior Survey: 1991-2013. www.cdc.gov/healthyyouth/data/yrbs/pdf/trends/us_suicide_trend_yrbs.pdf. Accessed February 2, 2017.
7. Zahl T, Steinsbekk S, Wichstrøm L. Physical activity, sedentary behavior, and symptoms of major depression in middle childhood. Pediatrics. 2017;139(2):e20161711.
8. Carli V, Hoven CW, Wasserman C, et al. A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study. World Psychiatry. 2014;13(1):78-86.
9. Demissie Z, Everett Jones S, Clayton HB, King BA. Adolescent risk behaviors and use of electronic vapor products and cigarettes. Pediatrics. 2017;139(2):e20162921.
10. National Sleep Foundation. Adolescent sleep needs and patterns. https://sleepfoundation.org/sites/default/files/sleep_and_teens_report1.pdf. Accessed February 2, 2017.
11. CDC. Youth Risk Behavior Surveillance System (YRBSS) overview. www.cdc.gov/healthyyouth/data/yrbs/overview.htm. Accessed February 2, 2017.
12. Cooper GD, Clements PT, Holt K. A review and application of suicide prevention programs in high school settings. Issues Ment Health Nurs. 2011;32(11):696-702.
13. Goldsmith SK, Pellmar TC, Kleinman AM, Bunney WE. Reducing Suicide: A National Imperative. Washington, DC: National Academics Press; 2002.
14. US Public Health Service. The Surgeon General’s Call to Action to Prevent Suicide. Washington, DC: 1999.

Issue
Clinician Reviews - 27(3)
Issue
Clinician Reviews - 27(3)
Page Number
14,28
Page Number
14,28
Publications
Publications
Topics
Article Type
Display Headline
More Than “Teen Angst”: What to Watch For
Display Headline
More Than “Teen Angst”: What to Watch For
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Article PDF Media

Ecofriendly surfactant is allergen of the year

Article Type
Changed
Fri, 01/18/2019 - 16:35


– Alkyl glucosides, mild surfactants derived from natural, sustainable sources, have been named allergen of the year by the American Contact Dermatitis Society.

The ecofriendly nature of these compounds has led to their inclusion in more personal care products in the last decade and a half. Alkyl glucosides are derived from coconut, palm, or rapeseed oil with glucose supplied by corn, wheat starch, or potatoes. They can be found in rinse-off products such as shampoos, shower gels, and liquid cleansers but also in leave-on products such as deodorants, sunscreens, and moisturizers, investigators said at the annual meeting of the American Contact Dermatitis Society, held just prior to the start of the American Academy of Dermatology’s annual meeting.

Camille Loranger, MD, of the department of dermatology, McGill University Health Center, Montreal, presented her institution’s experience with allergic contact dermatitis caused by alkyl glucosides. A total of 3,095 patients were patch tested at the clinic between January 2009 and June 2016. Researchers used the North American Contact Dermatitis Group 65-allergen series, which includes decyl glucoside (5% in petrolatum). Slightly more than half of patients (1,628) also were tested for reactions to lauryl glucoside (3% in petrolatum) as part of an additional cosmetic series. Twenty patients in the larger series reacted to decyl glucoside, while 15 of those who tested for lauryl glucoside reacted. Of those 15 patients, 6 were found to be allergic to decyl glucoside as well (Dermatitis. 2017 Jan/Feb;28[1]:5-13).

Allergy to alkyl glucosides became more common over time in the McGill series. The rate of positivity was low in the early years of the series, but increased from 1.37% of 437 patients in 2014 to 2.2% of 227 patients tested in the first half of 2016, Dr. Loranger said.

“Most of our patients were women with an average age of 48 years,” she added. “Body sites most commonly affected were the head and the hands. Only one case could be attributed to occupational exposure.”

Most patients – 86% – also were atopic (asthma, eczema, and rhinitis).

Products identified as most commonly causing a positive reaction were leave-on moisturizers and hand creams.

Donald V. Belsito, MD, professor of dermatology at Columbia University, N.Y., introduced the allergen of the year, pointing out that the compounds selected are not necessarily “bad actors.”

“The allergen of the year is really chosen to educate dermatologists about allergens that may be of low prevalence but a high relevance,” Dr. Belsito said. The allergens selected “are difficult to test for because they are tested for at irritant concentrations. It doesn’t mean they are these horrible substances that are damaging the world necessarily.”

The ACDS has been naming an allergen of the year since 2004.
 

Meeting/Event
Publications
Topics
Sections
Meeting/Event
Meeting/Event


– Alkyl glucosides, mild surfactants derived from natural, sustainable sources, have been named allergen of the year by the American Contact Dermatitis Society.

The ecofriendly nature of these compounds has led to their inclusion in more personal care products in the last decade and a half. Alkyl glucosides are derived from coconut, palm, or rapeseed oil with glucose supplied by corn, wheat starch, or potatoes. They can be found in rinse-off products such as shampoos, shower gels, and liquid cleansers but also in leave-on products such as deodorants, sunscreens, and moisturizers, investigators said at the annual meeting of the American Contact Dermatitis Society, held just prior to the start of the American Academy of Dermatology’s annual meeting.

Camille Loranger, MD, of the department of dermatology, McGill University Health Center, Montreal, presented her institution’s experience with allergic contact dermatitis caused by alkyl glucosides. A total of 3,095 patients were patch tested at the clinic between January 2009 and June 2016. Researchers used the North American Contact Dermatitis Group 65-allergen series, which includes decyl glucoside (5% in petrolatum). Slightly more than half of patients (1,628) also were tested for reactions to lauryl glucoside (3% in petrolatum) as part of an additional cosmetic series. Twenty patients in the larger series reacted to decyl glucoside, while 15 of those who tested for lauryl glucoside reacted. Of those 15 patients, 6 were found to be allergic to decyl glucoside as well (Dermatitis. 2017 Jan/Feb;28[1]:5-13).

Allergy to alkyl glucosides became more common over time in the McGill series. The rate of positivity was low in the early years of the series, but increased from 1.37% of 437 patients in 2014 to 2.2% of 227 patients tested in the first half of 2016, Dr. Loranger said.

“Most of our patients were women with an average age of 48 years,” she added. “Body sites most commonly affected were the head and the hands. Only one case could be attributed to occupational exposure.”

Most patients – 86% – also were atopic (asthma, eczema, and rhinitis).

Products identified as most commonly causing a positive reaction were leave-on moisturizers and hand creams.

Donald V. Belsito, MD, professor of dermatology at Columbia University, N.Y., introduced the allergen of the year, pointing out that the compounds selected are not necessarily “bad actors.”

“The allergen of the year is really chosen to educate dermatologists about allergens that may be of low prevalence but a high relevance,” Dr. Belsito said. The allergens selected “are difficult to test for because they are tested for at irritant concentrations. It doesn’t mean they are these horrible substances that are damaging the world necessarily.”

The ACDS has been naming an allergen of the year since 2004.
 


– Alkyl glucosides, mild surfactants derived from natural, sustainable sources, have been named allergen of the year by the American Contact Dermatitis Society.

The ecofriendly nature of these compounds has led to their inclusion in more personal care products in the last decade and a half. Alkyl glucosides are derived from coconut, palm, or rapeseed oil with glucose supplied by corn, wheat starch, or potatoes. They can be found in rinse-off products such as shampoos, shower gels, and liquid cleansers but also in leave-on products such as deodorants, sunscreens, and moisturizers, investigators said at the annual meeting of the American Contact Dermatitis Society, held just prior to the start of the American Academy of Dermatology’s annual meeting.

Camille Loranger, MD, of the department of dermatology, McGill University Health Center, Montreal, presented her institution’s experience with allergic contact dermatitis caused by alkyl glucosides. A total of 3,095 patients were patch tested at the clinic between January 2009 and June 2016. Researchers used the North American Contact Dermatitis Group 65-allergen series, which includes decyl glucoside (5% in petrolatum). Slightly more than half of patients (1,628) also were tested for reactions to lauryl glucoside (3% in petrolatum) as part of an additional cosmetic series. Twenty patients in the larger series reacted to decyl glucoside, while 15 of those who tested for lauryl glucoside reacted. Of those 15 patients, 6 were found to be allergic to decyl glucoside as well (Dermatitis. 2017 Jan/Feb;28[1]:5-13).

Allergy to alkyl glucosides became more common over time in the McGill series. The rate of positivity was low in the early years of the series, but increased from 1.37% of 437 patients in 2014 to 2.2% of 227 patients tested in the first half of 2016, Dr. Loranger said.

“Most of our patients were women with an average age of 48 years,” she added. “Body sites most commonly affected were the head and the hands. Only one case could be attributed to occupational exposure.”

Most patients – 86% – also were atopic (asthma, eczema, and rhinitis).

Products identified as most commonly causing a positive reaction were leave-on moisturizers and hand creams.

Donald V. Belsito, MD, professor of dermatology at Columbia University, N.Y., introduced the allergen of the year, pointing out that the compounds selected are not necessarily “bad actors.”

“The allergen of the year is really chosen to educate dermatologists about allergens that may be of low prevalence but a high relevance,” Dr. Belsito said. The allergens selected “are difficult to test for because they are tested for at irritant concentrations. It doesn’t mean they are these horrible substances that are damaging the world necessarily.”

The ACDS has been naming an allergen of the year since 2004.
 

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME

CAR designers report high B-cell cancer response rates

Article Type
Changed
Tue, 01/17/2023 - 11:17

 

– Patients with advanced hematologic malignancies of B-cell lineage had robust immune responses following infusion of a chimeric antigen receptor (CAR)–T-cell construct designed to deliver a specific balance of antigens, investigators reported.

Adults with relapsed or refractory B-lineage acute myeloid leukemia (ALL), non–Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) who received a CAR-T cell construct consisting of autologous CD4-positive and CD-8-positive T cells that were transduced separately, recombined, and then delivered in a single infusion had comparatively high overall response and complete response rates, reported Cameron Turtle, MBBS, PhD, from the Fred Hutchinson Cancer Research Center in Seattle.

“We know that patients have a highly variable CD4 to CD8 ratio, so by actually controlling this and separately transducing, expanding, and then reformulating in this defined composition, we’re able to eliminate one source of variability in CAR-T cell products,” Dr. Turtle said at the ASCO-SITC Clinical Immuno-Oncology Symposium.

In preclinical studies, an even balance of CD4-positive and CD8-positive central memory T cells or naive T cells evoked more potent immune responses against B-cell malignancies in mice than CD19-positive cells, he explained

To see whether this would also hold true in humans, the investigators enrolled into a phase I/II trial adults with relapsed/refractory B-cell malignancies, including ALL (36 patients), NHL (41), and CLL (24). No patients were excluded on the basis of either absolute lymphocyte, circulating tumors cells, history of stem cell transplant, or results of in vitro test expansions.

All patients underwent leukapheresis for harvesting of T-cells, and populations of CD4- and CD8-positive cells were separated and transduced with a lentiviral vector to express a CD19 CAR and a truncated human epidermal growth factor receptor that allowed tracing of the transduced cells via flow cytometry. The patients underwent lymphodepleting chemotherapy with cyclophosphamide (for the earliest patients), or cyclophosphamide plus fludarabine. Fifteen days after leukapheresis, the separated, transduced, and expanded cells were combined and delivered back to patients in a single infusion at one of three dose levels: 2 x 105, 2 x 106, or 2 x 107 CAR-T cells/kg.
 

ALL results

Two of the 36 patients with ALL died from complications of the CAR-T cell infusion process prior to evaluation. The 34 remaining patients all had morphologic bone marrow complete responses (CR). Of this group, 32 also had bone marrow CR on flow cytometry.

Using immunoglobulin H (IgH) deep sequencing in a subset of 20 patients 3 weeks after CAR-T cell infusion, the investigators could not detect the malignant IgH index clone in 13 of the patients, and found fewer than 10 copies in the bone marrow of 5 patients.

Six of seven patients with extramedullary disease at baseline had a complete response. The remaining patient in this group had an equivocal PET scan result, and experienced a relapse 2 months after assessment.

The investigators also determined that the lymphodepletion regimen may affect overall results, based on the finding that 10 of 12 patients who received cyclophosphamide alone achieved a CR, but seven of these 10 patients had a relapse within a few months. Of these seven patients. five received a second T-cell infusion, but none had significant T-cell expansion. The investigators traced the failure of the second attempt to a CD8-mediated transgene immune response to a murine single-chain variable fragment used in the construct.

For subsequent patients, they altered the lymphodepletion regimen to include fludarabine to prevent priming of the anti-CAR transgenic immune response. This modification resulted in improved progression-free survival and overall survival for subsequent patients receiving a second infusion, Dr. Turtle said.
 

NHL results

Of the 41 patients with NHL, 30 (73%) had aggressive histologies, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich large B-cell, and Burkitt lymphomas, and 11 (27%) had indolent histologies, including mantle cell and follicular lymphomas. Most of the patients had received multiple prior lines of therapy, and 19 (46%) had undergone either an autologous or allogeneic stem cell transplant.

Of the 39 evaluable patients who completed therapy, the overall response rate was 67%, including 13 (39%) with CR. Dr. Turtle noted that the CR rate was substantially higher among patients who received cyclophosphamide and fludarabine lymphodepletion, compared with cyclophosphamide alone.

There were also a few responses, including two CRs, among patients with indolent histologies, he said.

CLL, safety results

All 24 patients with CLL had previously received ibrutinib (Imbruvica). Of this group, 19 either had no significant responses to the drug, inactivating mutations, or intolerable toxicities. All but 1 of the 24 patients also had high-risk cytogenetics.

Of the 16 ibrutinib-refractory patients who were evaluable for restaging, 14 had no evidence of disease in bone marrow by flow cytometry at 4 weeks. The overall response rate in this group was 69%, which included four CRs.

Among a majority of all patients, toxicity with the CAR-T cell therapy was mild to moderate. Early cytokine changes appeared to be predictive of serious adverse events such as the cytokine release syndrome, a finding that may allow clinicians to intervene early to prevent complications, Dr. Turtle said.

In the CAR-T cell therapy, “multiple things affect the response and toxicity, including CAR T-cell dose, disease burden, the anti-CAR transgene immune response and the lymphodepletion regimen, not to mention other patient factors that we’re still sorting out,” he commented.

The trial was funded by the National Institutes of Health, Life Science Development Fund, Juno Therapeutics and the Bezos Family Foundation. Dr. Turtle disclosed consultancy, honoraria, and/or research funding from Juno Therapeutics and Seattle Genetics.

Meeting/Event
Publications
Topics
Sections
Meeting/Event
Meeting/Event

 

– Patients with advanced hematologic malignancies of B-cell lineage had robust immune responses following infusion of a chimeric antigen receptor (CAR)–T-cell construct designed to deliver a specific balance of antigens, investigators reported.

Adults with relapsed or refractory B-lineage acute myeloid leukemia (ALL), non–Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) who received a CAR-T cell construct consisting of autologous CD4-positive and CD-8-positive T cells that were transduced separately, recombined, and then delivered in a single infusion had comparatively high overall response and complete response rates, reported Cameron Turtle, MBBS, PhD, from the Fred Hutchinson Cancer Research Center in Seattle.

“We know that patients have a highly variable CD4 to CD8 ratio, so by actually controlling this and separately transducing, expanding, and then reformulating in this defined composition, we’re able to eliminate one source of variability in CAR-T cell products,” Dr. Turtle said at the ASCO-SITC Clinical Immuno-Oncology Symposium.

In preclinical studies, an even balance of CD4-positive and CD8-positive central memory T cells or naive T cells evoked more potent immune responses against B-cell malignancies in mice than CD19-positive cells, he explained

To see whether this would also hold true in humans, the investigators enrolled into a phase I/II trial adults with relapsed/refractory B-cell malignancies, including ALL (36 patients), NHL (41), and CLL (24). No patients were excluded on the basis of either absolute lymphocyte, circulating tumors cells, history of stem cell transplant, or results of in vitro test expansions.

All patients underwent leukapheresis for harvesting of T-cells, and populations of CD4- and CD8-positive cells were separated and transduced with a lentiviral vector to express a CD19 CAR and a truncated human epidermal growth factor receptor that allowed tracing of the transduced cells via flow cytometry. The patients underwent lymphodepleting chemotherapy with cyclophosphamide (for the earliest patients), or cyclophosphamide plus fludarabine. Fifteen days after leukapheresis, the separated, transduced, and expanded cells were combined and delivered back to patients in a single infusion at one of three dose levels: 2 x 105, 2 x 106, or 2 x 107 CAR-T cells/kg.
 

ALL results

Two of the 36 patients with ALL died from complications of the CAR-T cell infusion process prior to evaluation. The 34 remaining patients all had morphologic bone marrow complete responses (CR). Of this group, 32 also had bone marrow CR on flow cytometry.

Using immunoglobulin H (IgH) deep sequencing in a subset of 20 patients 3 weeks after CAR-T cell infusion, the investigators could not detect the malignant IgH index clone in 13 of the patients, and found fewer than 10 copies in the bone marrow of 5 patients.

Six of seven patients with extramedullary disease at baseline had a complete response. The remaining patient in this group had an equivocal PET scan result, and experienced a relapse 2 months after assessment.

The investigators also determined that the lymphodepletion regimen may affect overall results, based on the finding that 10 of 12 patients who received cyclophosphamide alone achieved a CR, but seven of these 10 patients had a relapse within a few months. Of these seven patients. five received a second T-cell infusion, but none had significant T-cell expansion. The investigators traced the failure of the second attempt to a CD8-mediated transgene immune response to a murine single-chain variable fragment used in the construct.

For subsequent patients, they altered the lymphodepletion regimen to include fludarabine to prevent priming of the anti-CAR transgenic immune response. This modification resulted in improved progression-free survival and overall survival for subsequent patients receiving a second infusion, Dr. Turtle said.
 

NHL results

Of the 41 patients with NHL, 30 (73%) had aggressive histologies, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich large B-cell, and Burkitt lymphomas, and 11 (27%) had indolent histologies, including mantle cell and follicular lymphomas. Most of the patients had received multiple prior lines of therapy, and 19 (46%) had undergone either an autologous or allogeneic stem cell transplant.

Of the 39 evaluable patients who completed therapy, the overall response rate was 67%, including 13 (39%) with CR. Dr. Turtle noted that the CR rate was substantially higher among patients who received cyclophosphamide and fludarabine lymphodepletion, compared with cyclophosphamide alone.

There were also a few responses, including two CRs, among patients with indolent histologies, he said.

CLL, safety results

All 24 patients with CLL had previously received ibrutinib (Imbruvica). Of this group, 19 either had no significant responses to the drug, inactivating mutations, or intolerable toxicities. All but 1 of the 24 patients also had high-risk cytogenetics.

Of the 16 ibrutinib-refractory patients who were evaluable for restaging, 14 had no evidence of disease in bone marrow by flow cytometry at 4 weeks. The overall response rate in this group was 69%, which included four CRs.

Among a majority of all patients, toxicity with the CAR-T cell therapy was mild to moderate. Early cytokine changes appeared to be predictive of serious adverse events such as the cytokine release syndrome, a finding that may allow clinicians to intervene early to prevent complications, Dr. Turtle said.

In the CAR-T cell therapy, “multiple things affect the response and toxicity, including CAR T-cell dose, disease burden, the anti-CAR transgene immune response and the lymphodepletion regimen, not to mention other patient factors that we’re still sorting out,” he commented.

The trial was funded by the National Institutes of Health, Life Science Development Fund, Juno Therapeutics and the Bezos Family Foundation. Dr. Turtle disclosed consultancy, honoraria, and/or research funding from Juno Therapeutics and Seattle Genetics.

 

– Patients with advanced hematologic malignancies of B-cell lineage had robust immune responses following infusion of a chimeric antigen receptor (CAR)–T-cell construct designed to deliver a specific balance of antigens, investigators reported.

Adults with relapsed or refractory B-lineage acute myeloid leukemia (ALL), non–Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) who received a CAR-T cell construct consisting of autologous CD4-positive and CD-8-positive T cells that were transduced separately, recombined, and then delivered in a single infusion had comparatively high overall response and complete response rates, reported Cameron Turtle, MBBS, PhD, from the Fred Hutchinson Cancer Research Center in Seattle.

“We know that patients have a highly variable CD4 to CD8 ratio, so by actually controlling this and separately transducing, expanding, and then reformulating in this defined composition, we’re able to eliminate one source of variability in CAR-T cell products,” Dr. Turtle said at the ASCO-SITC Clinical Immuno-Oncology Symposium.

In preclinical studies, an even balance of CD4-positive and CD8-positive central memory T cells or naive T cells evoked more potent immune responses against B-cell malignancies in mice than CD19-positive cells, he explained

To see whether this would also hold true in humans, the investigators enrolled into a phase I/II trial adults with relapsed/refractory B-cell malignancies, including ALL (36 patients), NHL (41), and CLL (24). No patients were excluded on the basis of either absolute lymphocyte, circulating tumors cells, history of stem cell transplant, or results of in vitro test expansions.

All patients underwent leukapheresis for harvesting of T-cells, and populations of CD4- and CD8-positive cells were separated and transduced with a lentiviral vector to express a CD19 CAR and a truncated human epidermal growth factor receptor that allowed tracing of the transduced cells via flow cytometry. The patients underwent lymphodepleting chemotherapy with cyclophosphamide (for the earliest patients), or cyclophosphamide plus fludarabine. Fifteen days after leukapheresis, the separated, transduced, and expanded cells were combined and delivered back to patients in a single infusion at one of three dose levels: 2 x 105, 2 x 106, or 2 x 107 CAR-T cells/kg.
 

ALL results

Two of the 36 patients with ALL died from complications of the CAR-T cell infusion process prior to evaluation. The 34 remaining patients all had morphologic bone marrow complete responses (CR). Of this group, 32 also had bone marrow CR on flow cytometry.

Using immunoglobulin H (IgH) deep sequencing in a subset of 20 patients 3 weeks after CAR-T cell infusion, the investigators could not detect the malignant IgH index clone in 13 of the patients, and found fewer than 10 copies in the bone marrow of 5 patients.

Six of seven patients with extramedullary disease at baseline had a complete response. The remaining patient in this group had an equivocal PET scan result, and experienced a relapse 2 months after assessment.

The investigators also determined that the lymphodepletion regimen may affect overall results, based on the finding that 10 of 12 patients who received cyclophosphamide alone achieved a CR, but seven of these 10 patients had a relapse within a few months. Of these seven patients. five received a second T-cell infusion, but none had significant T-cell expansion. The investigators traced the failure of the second attempt to a CD8-mediated transgene immune response to a murine single-chain variable fragment used in the construct.

For subsequent patients, they altered the lymphodepletion regimen to include fludarabine to prevent priming of the anti-CAR transgenic immune response. This modification resulted in improved progression-free survival and overall survival for subsequent patients receiving a second infusion, Dr. Turtle said.
 

NHL results

Of the 41 patients with NHL, 30 (73%) had aggressive histologies, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich large B-cell, and Burkitt lymphomas, and 11 (27%) had indolent histologies, including mantle cell and follicular lymphomas. Most of the patients had received multiple prior lines of therapy, and 19 (46%) had undergone either an autologous or allogeneic stem cell transplant.

Of the 39 evaluable patients who completed therapy, the overall response rate was 67%, including 13 (39%) with CR. Dr. Turtle noted that the CR rate was substantially higher among patients who received cyclophosphamide and fludarabine lymphodepletion, compared with cyclophosphamide alone.

There were also a few responses, including two CRs, among patients with indolent histologies, he said.

CLL, safety results

All 24 patients with CLL had previously received ibrutinib (Imbruvica). Of this group, 19 either had no significant responses to the drug, inactivating mutations, or intolerable toxicities. All but 1 of the 24 patients also had high-risk cytogenetics.

Of the 16 ibrutinib-refractory patients who were evaluable for restaging, 14 had no evidence of disease in bone marrow by flow cytometry at 4 weeks. The overall response rate in this group was 69%, which included four CRs.

Among a majority of all patients, toxicity with the CAR-T cell therapy was mild to moderate. Early cytokine changes appeared to be predictive of serious adverse events such as the cytokine release syndrome, a finding that may allow clinicians to intervene early to prevent complications, Dr. Turtle said.

In the CAR-T cell therapy, “multiple things affect the response and toxicity, including CAR T-cell dose, disease burden, the anti-CAR transgene immune response and the lymphodepletion regimen, not to mention other patient factors that we’re still sorting out,” he commented.

The trial was funded by the National Institutes of Health, Life Science Development Fund, Juno Therapeutics and the Bezos Family Foundation. Dr. Turtle disclosed consultancy, honoraria, and/or research funding from Juno Therapeutics and Seattle Genetics.

Publications
Publications
Topics
Article Type
Sections
Article Source

AT THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Vitals

 

Key clinical point: A defined CAR-T cell construct was associated with high response rates in patients with B-cell malignancies.

Major finding: The overall response rate among patients with ibrutinib-refractory chronic lymphocytic leukemia was 69%, including four complete responses.

Data source: Phase I/II dose-finding, safety and efficacy study in patients with B-lineage hematologic malignancies

Disclosures: The trial was funded by the National Institutes of Health, Life Science Development Fund, Juno Therapeutics and the Bezos Family Foundation. Dr. Turtle disclosed consultancy, honoraria, and/or research funding from Juno Therapeutics and Seattle Genetics.

Use ProPublica

CMS nominee Verma clears Senate Finance hurdle

Article Type
Changed
Wed, 04/03/2019 - 10:28

 

Seema Verma has moved one step closer to becoming the administrator of the Centers for Medicare & Medicaid Services.

The Senate Finance Committee voted 13-12 on March 2 to approve Ms. Verma’s nomination after a delayed vote the day before. The vote, conducted during a meeting off the floor, was a straight party-line vote, with 13 Republicans voting for Ms. Verma and 12 Democrats voting against. One proxy vote was not counted into the final tally per Senate rules.

Her nomination will now be considered by the full Senate.

Senate Finance Committee Chairman Orrin Hatch (R-Utah) praised Ms. Verma as a qualified leader who will help improve CMS.

Wikimedia
Sen. Orrin Hatch (R-Utah)
“We need experienced and responsible leadership at the helm of our federal agencies and CMS is no exception,” Sen. Hatch said in a statement. “The challenges plaguing both Medicare and Medicaid require a strong partnership between the administration and Congress to improve these programs and help enact the necessary reforms to ensure their solvency for future generations. Ms. Verma will help facilitate that partnership and as we work to repeal and replace Obamacare; she will play a vital role in realigning the focus on patient-centered solutions. I look forward to her nomination being considered by the full Senate.”

Senate Finance Committee Ranking Member Ron Wyden, (D-Ore.) denounced Ms. Verma, stressing that she failed to adequately answer questions during her nomination hearing and has presented no clear vision of her plans as the next CMS administrator.

Sen. Ron Wyden (D-Ore.)
“Without any clear indication what her own views are, what I’m left to conclude is that Ms. Verma shares the views of many in her party, including her new boss if she is confirmed, Secretary Tom Price,” Sen. Wyden said in a statement. “Their proposals say that Medicare’s guarantee of defined health benefits should be ended, that Medicaid should be cut to the bone, and that insurance companies should be put in charge and allowed to use loopholes to once again discriminate against people with expensive preexisting conditions.”

During her nomination hearing on Feb. 16, Ms. Verma came under fire for past consulting agreements with states while working for Hewlett Packard, a company that had financial interests in the health programs she designed. The issue was raised again during a preliminary vote by the Finance Committee on March 1.

“Ms. Verma was on both sides of the deal, helping manage the state’s health programs while being paid by vendors to those same programs,” Sen. Wyden said during the hearing. “I am concerned that if Ms. Verma is confirmed to lead CMS, where many of the companies she worked for are major vendors, there will not be adequate scrutiny of her past relationships with them, just as there wasn’t in Indiana.”

Ms. Verma previously said she never negotiated on behalf of Hewlett Packard and that the work she conducted for the states did not overlap with work she completed for HP.

“I hold honesty and integrity and adherence to a high ethical standard as part of my personal philosophy. That’s for me, I demand that from my employees, and I set that example for my own children,” she said during the Feb. 16 hearing. “We were never in a position where we were negotiating on behalf of HP or any other contractor with the state that we had a relationship with. If there was the potential [for a conflict], we would recuse ourselves.”

Ms. Verma’s nomination will now move to the full Senate. No date has yet been set for the vote.

Publications
Topics
Sections

 

Seema Verma has moved one step closer to becoming the administrator of the Centers for Medicare & Medicaid Services.

The Senate Finance Committee voted 13-12 on March 2 to approve Ms. Verma’s nomination after a delayed vote the day before. The vote, conducted during a meeting off the floor, was a straight party-line vote, with 13 Republicans voting for Ms. Verma and 12 Democrats voting against. One proxy vote was not counted into the final tally per Senate rules.

Her nomination will now be considered by the full Senate.

Senate Finance Committee Chairman Orrin Hatch (R-Utah) praised Ms. Verma as a qualified leader who will help improve CMS.

Wikimedia
Sen. Orrin Hatch (R-Utah)
“We need experienced and responsible leadership at the helm of our federal agencies and CMS is no exception,” Sen. Hatch said in a statement. “The challenges plaguing both Medicare and Medicaid require a strong partnership between the administration and Congress to improve these programs and help enact the necessary reforms to ensure their solvency for future generations. Ms. Verma will help facilitate that partnership and as we work to repeal and replace Obamacare; she will play a vital role in realigning the focus on patient-centered solutions. I look forward to her nomination being considered by the full Senate.”

Senate Finance Committee Ranking Member Ron Wyden, (D-Ore.) denounced Ms. Verma, stressing that she failed to adequately answer questions during her nomination hearing and has presented no clear vision of her plans as the next CMS administrator.

Sen. Ron Wyden (D-Ore.)
“Without any clear indication what her own views are, what I’m left to conclude is that Ms. Verma shares the views of many in her party, including her new boss if she is confirmed, Secretary Tom Price,” Sen. Wyden said in a statement. “Their proposals say that Medicare’s guarantee of defined health benefits should be ended, that Medicaid should be cut to the bone, and that insurance companies should be put in charge and allowed to use loopholes to once again discriminate against people with expensive preexisting conditions.”

During her nomination hearing on Feb. 16, Ms. Verma came under fire for past consulting agreements with states while working for Hewlett Packard, a company that had financial interests in the health programs she designed. The issue was raised again during a preliminary vote by the Finance Committee on March 1.

“Ms. Verma was on both sides of the deal, helping manage the state’s health programs while being paid by vendors to those same programs,” Sen. Wyden said during the hearing. “I am concerned that if Ms. Verma is confirmed to lead CMS, where many of the companies she worked for are major vendors, there will not be adequate scrutiny of her past relationships with them, just as there wasn’t in Indiana.”

Ms. Verma previously said she never negotiated on behalf of Hewlett Packard and that the work she conducted for the states did not overlap with work she completed for HP.

“I hold honesty and integrity and adherence to a high ethical standard as part of my personal philosophy. That’s for me, I demand that from my employees, and I set that example for my own children,” she said during the Feb. 16 hearing. “We were never in a position where we were negotiating on behalf of HP or any other contractor with the state that we had a relationship with. If there was the potential [for a conflict], we would recuse ourselves.”

Ms. Verma’s nomination will now move to the full Senate. No date has yet been set for the vote.

 

Seema Verma has moved one step closer to becoming the administrator of the Centers for Medicare & Medicaid Services.

The Senate Finance Committee voted 13-12 on March 2 to approve Ms. Verma’s nomination after a delayed vote the day before. The vote, conducted during a meeting off the floor, was a straight party-line vote, with 13 Republicans voting for Ms. Verma and 12 Democrats voting against. One proxy vote was not counted into the final tally per Senate rules.

Her nomination will now be considered by the full Senate.

Senate Finance Committee Chairman Orrin Hatch (R-Utah) praised Ms. Verma as a qualified leader who will help improve CMS.

Wikimedia
Sen. Orrin Hatch (R-Utah)
“We need experienced and responsible leadership at the helm of our federal agencies and CMS is no exception,” Sen. Hatch said in a statement. “The challenges plaguing both Medicare and Medicaid require a strong partnership between the administration and Congress to improve these programs and help enact the necessary reforms to ensure their solvency for future generations. Ms. Verma will help facilitate that partnership and as we work to repeal and replace Obamacare; she will play a vital role in realigning the focus on patient-centered solutions. I look forward to her nomination being considered by the full Senate.”

Senate Finance Committee Ranking Member Ron Wyden, (D-Ore.) denounced Ms. Verma, stressing that she failed to adequately answer questions during her nomination hearing and has presented no clear vision of her plans as the next CMS administrator.

Sen. Ron Wyden (D-Ore.)
“Without any clear indication what her own views are, what I’m left to conclude is that Ms. Verma shares the views of many in her party, including her new boss if she is confirmed, Secretary Tom Price,” Sen. Wyden said in a statement. “Their proposals say that Medicare’s guarantee of defined health benefits should be ended, that Medicaid should be cut to the bone, and that insurance companies should be put in charge and allowed to use loopholes to once again discriminate against people with expensive preexisting conditions.”

During her nomination hearing on Feb. 16, Ms. Verma came under fire for past consulting agreements with states while working for Hewlett Packard, a company that had financial interests in the health programs she designed. The issue was raised again during a preliminary vote by the Finance Committee on March 1.

“Ms. Verma was on both sides of the deal, helping manage the state’s health programs while being paid by vendors to those same programs,” Sen. Wyden said during the hearing. “I am concerned that if Ms. Verma is confirmed to lead CMS, where many of the companies she worked for are major vendors, there will not be adequate scrutiny of her past relationships with them, just as there wasn’t in Indiana.”

Ms. Verma previously said she never negotiated on behalf of Hewlett Packard and that the work she conducted for the states did not overlap with work she completed for HP.

“I hold honesty and integrity and adherence to a high ethical standard as part of my personal philosophy. That’s for me, I demand that from my employees, and I set that example for my own children,” she said during the Feb. 16 hearing. “We were never in a position where we were negotiating on behalf of HP or any other contractor with the state that we had a relationship with. If there was the potential [for a conflict], we would recuse ourselves.”

Ms. Verma’s nomination will now move to the full Senate. No date has yet been set for the vote.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME

Children with chronic conditions have poor influenza vaccination coverage

Article Type
Changed
Fri, 01/18/2019 - 16:35

 

Poor influenza vaccination rates in children with chronic diseases is primarily due to poor parental understanding of influenza risk and vaccination benefits, according to Janita Pak Chun Chau, PhD, of the Chinese University of Hong Kong, and associates.

Studies show that children with chronic conditions “are at a disproportionately higher risk for severe influenza-associated complications, causing increased visits to outpatient or emergency departments, longer hospital stays, and higher mortality,” the researchers said.

A total of 623 parents of children with chronic conditions in Hong Kong were included in the study. The most common chronic condition was asthma, followed by chronic respiratory disease and cardiomyopathy. Only 33% of children had received an influenza vaccination in the previous 12 months, and 57% of children had ever received one.

Just under 40% of parents indicated intent to have their children vaccinated in the next 12 months. Parents who had their children vaccinated were more aware of vaccination benefits and considered vaccination a social norm, compared with parents who had not had their children vaccinated. Television was by far the most common source of information about influenza, followed by health professionals, and newspapers and magazines.

“Development of community-based influenza vaccination programs by health care professionals targeted to promote awareness and communicate the benefits and effectiveness of the vaccines in children with chronic conditions, as well as clarifying safety issues concerning the vaccination, may be able to promote the uptake of influenza vaccination,” the investigators wrote.

Find the study in the Pediatric Infectious Disease Journal (doi: INF.0000000000001550).

Publications
Topics
Sections

 

Poor influenza vaccination rates in children with chronic diseases is primarily due to poor parental understanding of influenza risk and vaccination benefits, according to Janita Pak Chun Chau, PhD, of the Chinese University of Hong Kong, and associates.

Studies show that children with chronic conditions “are at a disproportionately higher risk for severe influenza-associated complications, causing increased visits to outpatient or emergency departments, longer hospital stays, and higher mortality,” the researchers said.

A total of 623 parents of children with chronic conditions in Hong Kong were included in the study. The most common chronic condition was asthma, followed by chronic respiratory disease and cardiomyopathy. Only 33% of children had received an influenza vaccination in the previous 12 months, and 57% of children had ever received one.

Just under 40% of parents indicated intent to have their children vaccinated in the next 12 months. Parents who had their children vaccinated were more aware of vaccination benefits and considered vaccination a social norm, compared with parents who had not had their children vaccinated. Television was by far the most common source of information about influenza, followed by health professionals, and newspapers and magazines.

“Development of community-based influenza vaccination programs by health care professionals targeted to promote awareness and communicate the benefits and effectiveness of the vaccines in children with chronic conditions, as well as clarifying safety issues concerning the vaccination, may be able to promote the uptake of influenza vaccination,” the investigators wrote.

Find the study in the Pediatric Infectious Disease Journal (doi: INF.0000000000001550).

 

Poor influenza vaccination rates in children with chronic diseases is primarily due to poor parental understanding of influenza risk and vaccination benefits, according to Janita Pak Chun Chau, PhD, of the Chinese University of Hong Kong, and associates.

Studies show that children with chronic conditions “are at a disproportionately higher risk for severe influenza-associated complications, causing increased visits to outpatient or emergency departments, longer hospital stays, and higher mortality,” the researchers said.

A total of 623 parents of children with chronic conditions in Hong Kong were included in the study. The most common chronic condition was asthma, followed by chronic respiratory disease and cardiomyopathy. Only 33% of children had received an influenza vaccination in the previous 12 months, and 57% of children had ever received one.

Just under 40% of parents indicated intent to have their children vaccinated in the next 12 months. Parents who had their children vaccinated were more aware of vaccination benefits and considered vaccination a social norm, compared with parents who had not had their children vaccinated. Television was by far the most common source of information about influenza, followed by health professionals, and newspapers and magazines.

“Development of community-based influenza vaccination programs by health care professionals targeted to promote awareness and communicate the benefits and effectiveness of the vaccines in children with chronic conditions, as well as clarifying safety issues concerning the vaccination, may be able to promote the uptake of influenza vaccination,” the investigators wrote.

Find the study in the Pediatric Infectious Disease Journal (doi: INF.0000000000001550).

Publications
Publications
Topics
Article Type
Sections
Article Source

FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME

Pigmented skin lesions lightened during melanoma immunotherapy

Article Type
Changed
Mon, 01/14/2019 - 09:57

 

Treatment with pembrolizumab, a humanized antibody used in cancer immunotherapy, may affect the pigmentation of some benign skin lesions, according to a case study in British Journal of Dermatology.

Pembrolizumab works by targeting the programmed cell death-1 (PD-1) receptor and is used in the treatment of metastatic melanoma and some other cancers.

The case report, by Zachary J. Wolner, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, describes a male patient in his 60s with HRAS mutant metastatic melanoma who was treated with pembrolizumab 2 mg/kg every 3 weeks for 13 months, and had received no previous systematic treatment. At 4 months after starting pembrolizumab, the patient experienced whitening of eyebrows and eyelashes, along with scalp and body hair, followed by lighter overall skin pigmentation and the fading of pigmented skin lesions. Baseline (pre-pembrolizumab) and 1-year follow-up skin photography confirmed lightening or disappearance of solar lentigines, seborrheic keratoses, and melanocytic nevi along with overall lightening of the skin (Br J. Dermatol. 2017 doi: 10.1111/bjd.15354).

Dr. Wolner and his colleagues noted that while changing skin lesions have not been reported in clinical trials of anti-PD-1 therapies, one study in patients treated with an anti-PD-1 therapy for metastatic melanoma found changes to nevi in 6 of 34 (18%) patients. Patients using a melanoma website also have self-reported disappearing nevi after immunotherapy treatment, the authors noted.

Expression of the coinhibitory molecule PD-L1 “is not limited to malignant tumors,” the researchers wrote, adding that previous studies have identified PD-L1 expression in melanocytes of benign melanocytic nevi. “Therefore it is biologically plausible that PD-1 inhibition may affect the natural history of benign melanocytic neoplasms.”

Also, they wrote, “the co-occurrence of vitiligo and poliosis in our patient suggests a role for autoimmunity in the fading/disappearance of his pigmented lesions.” The investigators cited a recent study in 67 patients with metastatic melanoma receiving pembrolizumab, which found that 25% developed vitiligo. Response to treatment also was significantly associated with occurrence of vitiligo (JAMA Dermatol. 2016;152[1]:45-51).

Dr. Wolner and his colleagues cautioned that their findings were limited to a single case report, and also by “lack of histological sampling and molecular characterization of fading/disappearing nevi.” An alternative explanation for the observed changes “includes fading/disappearance not related to PD-1 inhibition or due to chance alone.”

A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.

Publications
Topics
Sections

 

Treatment with pembrolizumab, a humanized antibody used in cancer immunotherapy, may affect the pigmentation of some benign skin lesions, according to a case study in British Journal of Dermatology.

Pembrolizumab works by targeting the programmed cell death-1 (PD-1) receptor and is used in the treatment of metastatic melanoma and some other cancers.

The case report, by Zachary J. Wolner, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, describes a male patient in his 60s with HRAS mutant metastatic melanoma who was treated with pembrolizumab 2 mg/kg every 3 weeks for 13 months, and had received no previous systematic treatment. At 4 months after starting pembrolizumab, the patient experienced whitening of eyebrows and eyelashes, along with scalp and body hair, followed by lighter overall skin pigmentation and the fading of pigmented skin lesions. Baseline (pre-pembrolizumab) and 1-year follow-up skin photography confirmed lightening or disappearance of solar lentigines, seborrheic keratoses, and melanocytic nevi along with overall lightening of the skin (Br J. Dermatol. 2017 doi: 10.1111/bjd.15354).

Dr. Wolner and his colleagues noted that while changing skin lesions have not been reported in clinical trials of anti-PD-1 therapies, one study in patients treated with an anti-PD-1 therapy for metastatic melanoma found changes to nevi in 6 of 34 (18%) patients. Patients using a melanoma website also have self-reported disappearing nevi after immunotherapy treatment, the authors noted.

Expression of the coinhibitory molecule PD-L1 “is not limited to malignant tumors,” the researchers wrote, adding that previous studies have identified PD-L1 expression in melanocytes of benign melanocytic nevi. “Therefore it is biologically plausible that PD-1 inhibition may affect the natural history of benign melanocytic neoplasms.”

Also, they wrote, “the co-occurrence of vitiligo and poliosis in our patient suggests a role for autoimmunity in the fading/disappearance of his pigmented lesions.” The investigators cited a recent study in 67 patients with metastatic melanoma receiving pembrolizumab, which found that 25% developed vitiligo. Response to treatment also was significantly associated with occurrence of vitiligo (JAMA Dermatol. 2016;152[1]:45-51).

Dr. Wolner and his colleagues cautioned that their findings were limited to a single case report, and also by “lack of histological sampling and molecular characterization of fading/disappearing nevi.” An alternative explanation for the observed changes “includes fading/disappearance not related to PD-1 inhibition or due to chance alone.”

A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.

 

Treatment with pembrolizumab, a humanized antibody used in cancer immunotherapy, may affect the pigmentation of some benign skin lesions, according to a case study in British Journal of Dermatology.

Pembrolizumab works by targeting the programmed cell death-1 (PD-1) receptor and is used in the treatment of metastatic melanoma and some other cancers.

The case report, by Zachary J. Wolner, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, describes a male patient in his 60s with HRAS mutant metastatic melanoma who was treated with pembrolizumab 2 mg/kg every 3 weeks for 13 months, and had received no previous systematic treatment. At 4 months after starting pembrolizumab, the patient experienced whitening of eyebrows and eyelashes, along with scalp and body hair, followed by lighter overall skin pigmentation and the fading of pigmented skin lesions. Baseline (pre-pembrolizumab) and 1-year follow-up skin photography confirmed lightening or disappearance of solar lentigines, seborrheic keratoses, and melanocytic nevi along with overall lightening of the skin (Br J. Dermatol. 2017 doi: 10.1111/bjd.15354).

Dr. Wolner and his colleagues noted that while changing skin lesions have not been reported in clinical trials of anti-PD-1 therapies, one study in patients treated with an anti-PD-1 therapy for metastatic melanoma found changes to nevi in 6 of 34 (18%) patients. Patients using a melanoma website also have self-reported disappearing nevi after immunotherapy treatment, the authors noted.

Expression of the coinhibitory molecule PD-L1 “is not limited to malignant tumors,” the researchers wrote, adding that previous studies have identified PD-L1 expression in melanocytes of benign melanocytic nevi. “Therefore it is biologically plausible that PD-1 inhibition may affect the natural history of benign melanocytic neoplasms.”

Also, they wrote, “the co-occurrence of vitiligo and poliosis in our patient suggests a role for autoimmunity in the fading/disappearance of his pigmented lesions.” The investigators cited a recent study in 67 patients with metastatic melanoma receiving pembrolizumab, which found that 25% developed vitiligo. Response to treatment also was significantly associated with occurrence of vitiligo (JAMA Dermatol. 2016;152[1]:45-51).

Dr. Wolner and his colleagues cautioned that their findings were limited to a single case report, and also by “lack of histological sampling and molecular characterization of fading/disappearing nevi.” An alternative explanation for the observed changes “includes fading/disappearance not related to PD-1 inhibition or due to chance alone.”

A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.

Publications
Publications
Topics
Article Type
Click for Credit Status
Active
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
CME ID
132598
Vitals

 

Key clinical point: A melanoma patient treated with pembrolizumab saw lightening of pigmented benign skin lesions.

Major finding: Pembrolizumab and other PD-1 inhibitors may affect benign pigmented lesions.

Data source: A single-center, single-patient case report.

Disclosures: A National Institutes of Health/National Cancer Institute Cancer Center grant was used to help fund the study. Two of Dr. Wolner’s coauthors disclosed consultant or advisory board relationships with Merck and other pharmaceutical manufacturers.

How Can Neurologists Manage Pediatric Migraine?

Article Type
Changed
Mon, 01/07/2019 - 10:27
Forty percent of pediatric and adolescent patients with migraine do not get better following first-line treatment.

OJAI, CA—Migraine headaches can be debilitating in children and adolescents and result in more missed days of school and poorer performance in the classroom, compared with children without migraine, according to an overview presented at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific.

Amy Gelfand, MD
 “The estimate is that 130,000 school days are missed every two weeks due to pediatric migraine…. It is really a remarkable amount of disability coming from migraine in kids,” said Amy Gelfand, MD, Assistant Professor of Clinical Neurology and Pediatrics at the University of California, San Francisco School of Medicine. Taking a proper headache history and helping children maintain a regular lifestyle that includes regular sleep and exercise, as well as adequate water intake, in addition to providing optimal acute treatments that are well tolerated, are key components to managing pediatric migraine.

Understanding Pediatric Migraine

Pediatric migraine is defined as at least five attacks that fulfill the following criteria: headache attack lasting for two to 72 hours (untreated or unsuccessfully treated), headache with at least two of four characteristics (ie, unilateral location [though in children it is often bilateral], pulsating quality, moderate or severe intensity, and aggravation by or causing avoidance of routine physical activity), and headache accompanied by either nausea and vomiting or phonophobia and photophobia. It affects approximately 5% of children by age 10, making migraine five to 10 times more common than epilepsy in children. Chronic migraine, which entails headache on at least 15 days per month for at least three months, affects 0.6% of children between ages 5 and 12.

Pediatric migraine can have a different phenotype than adult migraine. The shortest duration for untreated or unsuccessfully treated attacks in adults is four hours, compared with two hours in children. In addition, migraines in children and adolescents tend to be bilateral.

Following puberty, there is a higher prevalence of migraine among young women and girls than among boys and young men, said Dr. Gelfand. Also, children with low socioeconomic status are nearly fourfold more likely to have chronic migraine than children from affluent backgrounds.

How to Take a Pediatric Headache History

A systematic approach to taking a headache history can be helpful, said Dr. Gelfand. When neurologists take a headache history, seating the child or adolescent in a central position near the clinican can help signal that the patient is going to be the primary person to provide the history. In addition, neurologists should set expectations for pediatric patients by explaining the questions they are going to ask about the child’s headaches.

Children are encouraged to share additional information about their headaches and to ask parents for help when necessary. Also, neurologists should hesitate to consider “not really” an answer to questions about the presence of symptoms such as nausea or movement sensitivity, because it often means “yes, but it is mild, and I can handle it and do not want to complain.”

Finally, when querying for sensitivity to light or sound, neurologists are advised to ask the following questions: During your headaches, do lights ever bother you? Do lights ever seem brighter than usual? Do lights ever make the headache worse? “For younger kids who might not be able to articulate sensitivity to light or sensitivity to sound, we may be able to infer those sensitivity symptoms from their behavior. Are they pulling the blankets up over their head or are they asking for the TV to be turned off? These are behaviors that their caregivers can report,” said Dr. Gelfand.

Acute Migraine Treatment

Acetaminophen and ibuprofen have been examined in randomized controlled trials that included children as young as 4. These drugs appear to be efficacious. In addition, the FDA has approved four triptans for acute treatment of pediatric migraine. Almotriptan was approved in 2009 for adolescents ages 12 to 17. In 2012, the FDA approved rizatriptan for children and adolescents ages 6 to 17. Finally, in 2015, zolmitriptan, a nasal spray, was approved for adolescents ages 12 to 17, as was a combination including naproxen and sumatriptan. Children with a history of peripheral vascular disease, stroke, and uncontrolled hypertension should not use triptans for the treatment of pediatric migraine.

In addition, Powers et al observed that amitriptyline and topiramate were no different from placebo for reducing headache frequency; approximately 60% of participants in all three study arms improved. The 361 children and adolescents involved in the study received a lot of headache education and counseling about medication overuse, and also received optimally dosed acute migraine medications, which may have contributed to the high rate of excellent outcomes, said Dr. Gelfand.

 

 

Preventative Strategies and Diet

A key component to preventive care in pediatric migraine is maintaining a healthy lifestyle. Neurologists should encourage patients to eat regular meals, get regular exercise and sleep, and stay consistently hydrated. Additionally, daily preventive treatment may include medications or supplements that are well tolerated. Cognitive behavioral therapy can also be beneficial.

Children and adolescents with migraine should avoid fasting, alcohol, or nitrate-containing meats such as hot dogs, some lunch meats, salami, and beef jerky. Chocolate, cheese, citrus, gluten, sugar, or dairy might not need to be avoided. Also, proper hydration can help control or prevent migraines. Pilot studies have shown that increased water intake decreases headache hours and severity. Spigt et al found that greater water intake resulted in a statically significant improvement in quality of life.

The Future of Pediatric Migraine Research

Sixty percent of patients will improve following treatment, but 40% of patients do not get better. In addition, “children who have continous headache and medication overuse have not been well studied, so we do not know what treatments might be most effective for them,” said Dr. Gelfand. “These are the kids that our future trials should be focusing on. That is where we need to spend our time, money, and attention.”

Erica Tricarico

Suggested Reading

Qubty W, Gelfand AA. Psychological and behavioral issues in the management of migraine in children and adolescents. Curr Pain Headache Rep. 2016;20(12):69.

Spigt MG, Kuijper EC, Schayck CP, et al. Increasing the daily water intake for the prophylactic treatment of headache: a pilot trial. Eur J Neurol. 2005;12(9):715-718.

Issue
Neurology Reviews - 25(3)
Publications
Topics
Page Number
29
Sections
Related Articles
Forty percent of pediatric and adolescent patients with migraine do not get better following first-line treatment.
Forty percent of pediatric and adolescent patients with migraine do not get better following first-line treatment.

OJAI, CA—Migraine headaches can be debilitating in children and adolescents and result in more missed days of school and poorer performance in the classroom, compared with children without migraine, according to an overview presented at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific.

Amy Gelfand, MD
 “The estimate is that 130,000 school days are missed every two weeks due to pediatric migraine…. It is really a remarkable amount of disability coming from migraine in kids,” said Amy Gelfand, MD, Assistant Professor of Clinical Neurology and Pediatrics at the University of California, San Francisco School of Medicine. Taking a proper headache history and helping children maintain a regular lifestyle that includes regular sleep and exercise, as well as adequate water intake, in addition to providing optimal acute treatments that are well tolerated, are key components to managing pediatric migraine.

Understanding Pediatric Migraine

Pediatric migraine is defined as at least five attacks that fulfill the following criteria: headache attack lasting for two to 72 hours (untreated or unsuccessfully treated), headache with at least two of four characteristics (ie, unilateral location [though in children it is often bilateral], pulsating quality, moderate or severe intensity, and aggravation by or causing avoidance of routine physical activity), and headache accompanied by either nausea and vomiting or phonophobia and photophobia. It affects approximately 5% of children by age 10, making migraine five to 10 times more common than epilepsy in children. Chronic migraine, which entails headache on at least 15 days per month for at least three months, affects 0.6% of children between ages 5 and 12.

Pediatric migraine can have a different phenotype than adult migraine. The shortest duration for untreated or unsuccessfully treated attacks in adults is four hours, compared with two hours in children. In addition, migraines in children and adolescents tend to be bilateral.

Following puberty, there is a higher prevalence of migraine among young women and girls than among boys and young men, said Dr. Gelfand. Also, children with low socioeconomic status are nearly fourfold more likely to have chronic migraine than children from affluent backgrounds.

How to Take a Pediatric Headache History

A systematic approach to taking a headache history can be helpful, said Dr. Gelfand. When neurologists take a headache history, seating the child or adolescent in a central position near the clinican can help signal that the patient is going to be the primary person to provide the history. In addition, neurologists should set expectations for pediatric patients by explaining the questions they are going to ask about the child’s headaches.

Children are encouraged to share additional information about their headaches and to ask parents for help when necessary. Also, neurologists should hesitate to consider “not really” an answer to questions about the presence of symptoms such as nausea or movement sensitivity, because it often means “yes, but it is mild, and I can handle it and do not want to complain.”

Finally, when querying for sensitivity to light or sound, neurologists are advised to ask the following questions: During your headaches, do lights ever bother you? Do lights ever seem brighter than usual? Do lights ever make the headache worse? “For younger kids who might not be able to articulate sensitivity to light or sensitivity to sound, we may be able to infer those sensitivity symptoms from their behavior. Are they pulling the blankets up over their head or are they asking for the TV to be turned off? These are behaviors that their caregivers can report,” said Dr. Gelfand.

Acute Migraine Treatment

Acetaminophen and ibuprofen have been examined in randomized controlled trials that included children as young as 4. These drugs appear to be efficacious. In addition, the FDA has approved four triptans for acute treatment of pediatric migraine. Almotriptan was approved in 2009 for adolescents ages 12 to 17. In 2012, the FDA approved rizatriptan for children and adolescents ages 6 to 17. Finally, in 2015, zolmitriptan, a nasal spray, was approved for adolescents ages 12 to 17, as was a combination including naproxen and sumatriptan. Children with a history of peripheral vascular disease, stroke, and uncontrolled hypertension should not use triptans for the treatment of pediatric migraine.

In addition, Powers et al observed that amitriptyline and topiramate were no different from placebo for reducing headache frequency; approximately 60% of participants in all three study arms improved. The 361 children and adolescents involved in the study received a lot of headache education and counseling about medication overuse, and also received optimally dosed acute migraine medications, which may have contributed to the high rate of excellent outcomes, said Dr. Gelfand.

 

 

Preventative Strategies and Diet

A key component to preventive care in pediatric migraine is maintaining a healthy lifestyle. Neurologists should encourage patients to eat regular meals, get regular exercise and sleep, and stay consistently hydrated. Additionally, daily preventive treatment may include medications or supplements that are well tolerated. Cognitive behavioral therapy can also be beneficial.

Children and adolescents with migraine should avoid fasting, alcohol, or nitrate-containing meats such as hot dogs, some lunch meats, salami, and beef jerky. Chocolate, cheese, citrus, gluten, sugar, or dairy might not need to be avoided. Also, proper hydration can help control or prevent migraines. Pilot studies have shown that increased water intake decreases headache hours and severity. Spigt et al found that greater water intake resulted in a statically significant improvement in quality of life.

The Future of Pediatric Migraine Research

Sixty percent of patients will improve following treatment, but 40% of patients do not get better. In addition, “children who have continous headache and medication overuse have not been well studied, so we do not know what treatments might be most effective for them,” said Dr. Gelfand. “These are the kids that our future trials should be focusing on. That is where we need to spend our time, money, and attention.”

Erica Tricarico

Suggested Reading

Qubty W, Gelfand AA. Psychological and behavioral issues in the management of migraine in children and adolescents. Curr Pain Headache Rep. 2016;20(12):69.

Spigt MG, Kuijper EC, Schayck CP, et al. Increasing the daily water intake for the prophylactic treatment of headache: a pilot trial. Eur J Neurol. 2005;12(9):715-718.

OJAI, CA—Migraine headaches can be debilitating in children and adolescents and result in more missed days of school and poorer performance in the classroom, compared with children without migraine, according to an overview presented at the 10th Annual Winter Conference of the Headache Cooperative of the Pacific.

Amy Gelfand, MD
 “The estimate is that 130,000 school days are missed every two weeks due to pediatric migraine…. It is really a remarkable amount of disability coming from migraine in kids,” said Amy Gelfand, MD, Assistant Professor of Clinical Neurology and Pediatrics at the University of California, San Francisco School of Medicine. Taking a proper headache history and helping children maintain a regular lifestyle that includes regular sleep and exercise, as well as adequate water intake, in addition to providing optimal acute treatments that are well tolerated, are key components to managing pediatric migraine.

Understanding Pediatric Migraine

Pediatric migraine is defined as at least five attacks that fulfill the following criteria: headache attack lasting for two to 72 hours (untreated or unsuccessfully treated), headache with at least two of four characteristics (ie, unilateral location [though in children it is often bilateral], pulsating quality, moderate or severe intensity, and aggravation by or causing avoidance of routine physical activity), and headache accompanied by either nausea and vomiting or phonophobia and photophobia. It affects approximately 5% of children by age 10, making migraine five to 10 times more common than epilepsy in children. Chronic migraine, which entails headache on at least 15 days per month for at least three months, affects 0.6% of children between ages 5 and 12.

Pediatric migraine can have a different phenotype than adult migraine. The shortest duration for untreated or unsuccessfully treated attacks in adults is four hours, compared with two hours in children. In addition, migraines in children and adolescents tend to be bilateral.

Following puberty, there is a higher prevalence of migraine among young women and girls than among boys and young men, said Dr. Gelfand. Also, children with low socioeconomic status are nearly fourfold more likely to have chronic migraine than children from affluent backgrounds.

How to Take a Pediatric Headache History

A systematic approach to taking a headache history can be helpful, said Dr. Gelfand. When neurologists take a headache history, seating the child or adolescent in a central position near the clinican can help signal that the patient is going to be the primary person to provide the history. In addition, neurologists should set expectations for pediatric patients by explaining the questions they are going to ask about the child’s headaches.

Children are encouraged to share additional information about their headaches and to ask parents for help when necessary. Also, neurologists should hesitate to consider “not really” an answer to questions about the presence of symptoms such as nausea or movement sensitivity, because it often means “yes, but it is mild, and I can handle it and do not want to complain.”

Finally, when querying for sensitivity to light or sound, neurologists are advised to ask the following questions: During your headaches, do lights ever bother you? Do lights ever seem brighter than usual? Do lights ever make the headache worse? “For younger kids who might not be able to articulate sensitivity to light or sensitivity to sound, we may be able to infer those sensitivity symptoms from their behavior. Are they pulling the blankets up over their head or are they asking for the TV to be turned off? These are behaviors that their caregivers can report,” said Dr. Gelfand.

Acute Migraine Treatment

Acetaminophen and ibuprofen have been examined in randomized controlled trials that included children as young as 4. These drugs appear to be efficacious. In addition, the FDA has approved four triptans for acute treatment of pediatric migraine. Almotriptan was approved in 2009 for adolescents ages 12 to 17. In 2012, the FDA approved rizatriptan for children and adolescents ages 6 to 17. Finally, in 2015, zolmitriptan, a nasal spray, was approved for adolescents ages 12 to 17, as was a combination including naproxen and sumatriptan. Children with a history of peripheral vascular disease, stroke, and uncontrolled hypertension should not use triptans for the treatment of pediatric migraine.

In addition, Powers et al observed that amitriptyline and topiramate were no different from placebo for reducing headache frequency; approximately 60% of participants in all three study arms improved. The 361 children and adolescents involved in the study received a lot of headache education and counseling about medication overuse, and also received optimally dosed acute migraine medications, which may have contributed to the high rate of excellent outcomes, said Dr. Gelfand.

 

 

Preventative Strategies and Diet

A key component to preventive care in pediatric migraine is maintaining a healthy lifestyle. Neurologists should encourage patients to eat regular meals, get regular exercise and sleep, and stay consistently hydrated. Additionally, daily preventive treatment may include medications or supplements that are well tolerated. Cognitive behavioral therapy can also be beneficial.

Children and adolescents with migraine should avoid fasting, alcohol, or nitrate-containing meats such as hot dogs, some lunch meats, salami, and beef jerky. Chocolate, cheese, citrus, gluten, sugar, or dairy might not need to be avoided. Also, proper hydration can help control or prevent migraines. Pilot studies have shown that increased water intake decreases headache hours and severity. Spigt et al found that greater water intake resulted in a statically significant improvement in quality of life.

The Future of Pediatric Migraine Research

Sixty percent of patients will improve following treatment, but 40% of patients do not get better. In addition, “children who have continous headache and medication overuse have not been well studied, so we do not know what treatments might be most effective for them,” said Dr. Gelfand. “These are the kids that our future trials should be focusing on. That is where we need to spend our time, money, and attention.”

Erica Tricarico

Suggested Reading

Qubty W, Gelfand AA. Psychological and behavioral issues in the management of migraine in children and adolescents. Curr Pain Headache Rep. 2016;20(12):69.

Spigt MG, Kuijper EC, Schayck CP, et al. Increasing the daily water intake for the prophylactic treatment of headache: a pilot trial. Eur J Neurol. 2005;12(9):715-718.

Issue
Neurology Reviews - 25(3)
Issue
Neurology Reviews - 25(3)
Page Number
29
Page Number
29
Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME

FDA approves sublingual immunotherapy for dust mite allergies

Article Type
Changed
Fri, 01/18/2019 - 16:35

 

The Food and Drug administration has approved a sublingual immunotherapy to treat nasal inflammation caused by dust mite allergy.



The sublingual tablets are intended to be taken daily, year-round, and the first dose must be taken under physician supervision to monitor for adverse reactions, according to the FDA. As with other sublingual immunotherapies, patients using the tablets should be simultaneously prescribed autoinjectable epinephrine.

The approval was based on results from randomized trials enrolling about 2,500 patients in Europe and the United States, according to the FDA. Patients taking the tablets saw a 16%-18% reduction in symptoms across studies, compared with placebo. Clinical benefit may be delayed by 8-14 weeks after starting the therapy, the agency said. Common adverse reactions reported in the studies included nausea, itching of the ears and mouth, and swelling of the lips and tongue.

Odactra is the fourth sublingual immunotherapy to be approved in the United States since 2014. Other approved therapies target grass and ragweed allergies.

Publications
Topics
Sections

 

The Food and Drug administration has approved a sublingual immunotherapy to treat nasal inflammation caused by dust mite allergy.



The sublingual tablets are intended to be taken daily, year-round, and the first dose must be taken under physician supervision to monitor for adverse reactions, according to the FDA. As with other sublingual immunotherapies, patients using the tablets should be simultaneously prescribed autoinjectable epinephrine.

The approval was based on results from randomized trials enrolling about 2,500 patients in Europe and the United States, according to the FDA. Patients taking the tablets saw a 16%-18% reduction in symptoms across studies, compared with placebo. Clinical benefit may be delayed by 8-14 weeks after starting the therapy, the agency said. Common adverse reactions reported in the studies included nausea, itching of the ears and mouth, and swelling of the lips and tongue.

Odactra is the fourth sublingual immunotherapy to be approved in the United States since 2014. Other approved therapies target grass and ragweed allergies.

 

The Food and Drug administration has approved a sublingual immunotherapy to treat nasal inflammation caused by dust mite allergy.



The sublingual tablets are intended to be taken daily, year-round, and the first dose must be taken under physician supervision to monitor for adverse reactions, according to the FDA. As with other sublingual immunotherapies, patients using the tablets should be simultaneously prescribed autoinjectable epinephrine.

The approval was based on results from randomized trials enrolling about 2,500 patients in Europe and the United States, according to the FDA. Patients taking the tablets saw a 16%-18% reduction in symptoms across studies, compared with placebo. Clinical benefit may be delayed by 8-14 weeks after starting the therapy, the agency said. Common adverse reactions reported in the studies included nausea, itching of the ears and mouth, and swelling of the lips and tongue.

Odactra is the fourth sublingual immunotherapy to be approved in the United States since 2014. Other approved therapies target grass and ragweed allergies.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME