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Cutting-edge nasal tech could usher in a new era of medicine
Noses are like caverns – twisting, turning, no two exactly the same. But if you nose past anyone’s nostrils, you’ll discover a surprisingly sprawling space.
“The size of the nasal cavity is about the same as a large handkerchief,” said Hugh Smyth, PhD, a professor of molecular pharmaceutics and drug delivery at the University of Texas at Austin.
“It’s very accessible tissue, and it has a lot of blood flow,” said Dr. Smyth. “The speed of onset can often be as fast as injections, sometimes even faster.”
It’s nothing new to get medicines via your nose. For decades, we’ve squirted various sprays into our nostrils to treat local maladies like allergies or infections. Even the ancients saw wisdom in the nasal route.
But recently, the nose has gained scientific attention as a gateway to the rest of the body – even the brain, a notoriously difficult target.
The upshot: Someday, inhaling therapies could be as routine as swallowing pills.
The nasal route is quick, needle free, and user friendly, and it often requires a smaller dose than other methods, since the drug doesn’t have to pass through the digestive tract, losing potency during digestion.
But there are challenges.
How hard can it be?
Old-school nasal sprayers, mostly unchanged since the 1800s, aren’t cut out for deep-nose delivery. “The technology is relatively limited because you’ve just got a single spray nozzle,” said Michael Hindle, PhD, a professor of pharmaceutics at Virginia Commonwealth University, Richmond.
These traditional devices (similar to perfume sprayers) don’t consistently push meds past the lower to middle sections inside the nose, called the nasal valve – if they do so at all: In a 2020 Rhinology study (doi: 10.4193/Rhin18.304) conventional nasal sprays only reached this first segment of the nose, a less-than-ideal spot to land.
Inside the nasal valve, the surface is skin-like and doesn’t absorb very well. Its narrow design slows airflow, preventing particles from moving to deeper regions, where tissue is vascular and porous like the lungs. And even if this structural roadblock is surpassed, other hurdles remain.
The nose is designed to keep stuff out. Nose hair, cilia, mucus, sneezing, coughing – all make “distributing drugs evenly across the nasal cavity difficult,” said Dr. Smyth. “The spray gets filtered out before it reaches those deeper zones,” potentially dripping out of the nostrils instead of being absorbed.
Complicating matters is how every person’s nose is different. In a 2018 study, Dr. Smyth and a research team created three dimensional–printed models of people’s nasal cavities. They varied widely. “Nasal cavities are very different in size, length, and internal geometry,” he said. “This makes it challenging to target specific areas.”
Although carefully positioning the spray nozzle can help, even something as minor as sniffing too hard (constricting the nostrils) can keep sprays from reaching the absorptive deeper regions.
Still, the benefits are enough to compel researchers to find a way in.
“This really is a drug delivery challenge we’ve been wrestling with,” said Dr. Hindle. “It’s not new formulations we hear about. It’s new devices and delivery methods trying to target the different nasal regions.”
Delivering the goods
In the late aughts, John Hoekman was a graduate student in the University of Washington’s pharmaceutics program, studying nasal drug delivery. In his experiments, he noticed that drugs distributed differently, depending on the region targeted – aiming for the upper nasal cavity led to a spike in absorption.
The results convinced Mr. Hoekman to stake his future on nasal drug delivery.
In 2008, while still in graduate school, he started his own company, now known as Impel Pharmaceuticals. In 2021, Impel released its first product: Trudhesa, a nasal spray for migraines. Although the drug itself – dihydroergotamine mesylate – was hardly novel, used for migraine relief since 1946 (Headache. 2020 Jan;60[1]:40-57), it was usually delivered through an intravenous line, often in the ED.
But with Mr. Hoekman’s POD device – short for precision olfactory delivery – the drug can be given by the patient, via the nose. This generally means faster, more reliable relief, with fewer side effects. “We were able to lower the dose and improve the overall absorption,” said Mr. Hoekman.
The POD’s nozzle is engineered to spray a soft, narrow plume. It’s gas propelled, so patients don’t have to breathe in any special way to ensure delivery. The drug can zip right through the nasal valve into the upper nasal cavity.
Another company – OptiNose – has a “bidirectional” delivery method that propels drugs, either liquid or dry powder, deep into the nose.
“You insert the nozzle into your nose, and as you blow through the mouthpiece, your soft palate closes,” said Dr. Hindle. With the throat sealed off, “the only place for the drug to go is into one nostril and out the other, coating both sides of the nasal passageways.”
The device is only available for Onzetra Xsail, a powder for migraines. But another application is on its way.
In May, OptiNose announced that the FDA is reviewing Xhance, which uses the system to direct a steroid to the sinuses. In a clinical trial, patients with chronic sinusitis who tried the drug-device combo saw a decline in congestion, facial pain, and inflammation.
Targeting the brain
Both of those migraine drugs – Trudhesa and Onzetra Xsail – are thought to penetrate the upper nasal cavity. That’s where you’ll find the olfactory zone, a sheet of neurons that connects to the olfactory bulb. Located behind the eyes, these two nerve bundles detect odors.
“The olfactory region is almost like a back door to the brain,” said Mr. Hoekman.
By bypassing the blood-brain barrier, it offers a direct pathway – the only direct pathway, actually – between an exposed area of the body and the brain. Meaning it can ferry drugs straight from the nasal cavity to the central nervous system.
Nose-to-brain treatments could be game-changing for central nervous system disorders, such as Parkinson’s disease, Alzheimer’s, or anxiety.
But reaching the olfactory zone is notoriously hard. “The vasculature in your nose is like a big freeway, and the olfactory tract is like a side alley,” explained Mr. Hoekman. “It’s very limiting in what it will allow through.” The region is also small, occupying only 3%-10% of the nasal cavity’s surface area.
Again, POD means “precision olfactory delivery.” But the device isn’t quite as laser focused on the region as its name implies. “We’re not at the stage where we’re able to exclusively deliver to one target site in the nose,” said Dr. Hindle.
While wending its way toward the olfactory zone, some of the drug will be absorbed by other regions, then circulate throughout the body.
“About 59% of the drug that we put into the upper nasal space gets absorbed into the bloodstream,” said Mr. Hoekman.
Janssen Pharmaceuticals’ Spravato – a nasal spray for drug-resistant depression – is thought to work similarly: Some goes straight to the brain via the olfactory nerves, while the rest takes a more roundabout route, passing through the blood vessels to circulate in your system.
A needle-free option
Sometimes, the bloodstream is the main target. Because the nose’s middle and upper stretches are so vascular, drugs can be rapidly absorbed.
This is especially valuable for time-sensitive conditions. “If you give something nasally, you can have peak uptake in 15-30 minutes,” said Mr. Hoekman.
Take Narcan nasal spray, which delivers a burst of naloxone to quickly reverse the effects of opioid an overdose. Or Noctiva nasal spray. Taken just half an hour before bed, it can prevent frequent nighttime urination.
There’s also a group of seizure-stopping sprays, known as “rescue treatments.” One works by temporarily loosening the space between nasal cells, allowing the seizure drug to be quickly absorbed through the vessels.
This systemic access also has potential for drugs that would otherwise have to be injected, such as biologics.
The same goes for vaccines. Mucosal tissue inside the nasal cavity offers direct access to the infection-fighting lymphatic system, making the nose a prime target for inoculation against certain viruses.
Inhaling protection against viruses
Despite the recent surge of interest, nasal vaccines faced a rocky start. After the first nasal flu vaccine hit the market in 2001, it was pulled due to potential toxicity and reports of Bell’s palsy, a type of facial paralysis.
FluMist came in 2003 and has been plagued by problems ever since. Because it contains a weakened live virus, flu-like side effects can occur. And it doesn’t always work. During the 2016-2017 flu season, FluMist protected only 3% of kids, prompting the Centers for Disease Control and Prevention to advise against the nasal route that year.
Why FluMist can be so hit-or-miss is poorly understood. But generally, the nose can pose an effectiveness challenge. “The nose is highly cycling,” said Dr. Hindle. “Anything we deposit usually gets transported out within 15-20 minutes.”
For kids – big fans of not using needles – chronically runny noses can be an issue. “You squirt it in the nose, and it will probably just come back out in their snot,” said Jay Kolls, MD, a professor of medicine and pediatrics at Tulane University, New Orleans, who is developing an intranasal pneumonia vaccine.
Even so, nasal vaccines became a hot topic among researchers after the world was shut down by a virus that invades through the nose.
“We realized that intramuscular vaccines were effective at preventing severe disease, but they weren’t that effective at preventing transmission,” said Michael Diamond, MD, PhD, an immunologist at Washington University in St. Louis.
Nasal vaccines could solve that problem by putting an immune barrier at the point of entry, denying access to the rest of the body. “You squash the infection early enough that it not only prevents disease,” said Dr. Kolls, “but potentially prevents transmission.”
And yes, a nasal COVID vaccine is on the way
In March 2020, Dr. Diamond’s team began exploring a nasal COVID vaccine. Promising results in animals prompted a vaccine development company to license the technology. The resulting nasal vaccine – the first for COVID – has been approved in India, both as a primary vaccine and a booster.
It works by stimulating an influx of IgA, a type of antibody found in the nasal passages, and production of resident memory T cells, immune cells on standby just beneath the surface tissue in the nose.
By contrast, injected vaccines generate mostly IgG antibodies, which struggle to enter the respiratory tract. Only a tiny fraction – an estimated 1% – typically reach the nose.
Nasal vaccines could also be used along with shots. The latter could prime the whole body to fight back, while a nasal spritz could pull that immune protection to the mucosal surfaces.
Nasal technology could yield more effective vaccines for infections like tuberculosis or malaria, or even safeguard against new – sometimes surprising – conditions.
In a 2021 Nature study, an intranasal vaccine derived from fentanyl was better at preventing overdose than an injected vaccine. “Through some clever chemistry, the drug [in the vaccine] isn’t fentanyl anymore,” said study author Elizabeth Norton, PhD, an assistant professor of microbiology and immunology at Tulane University. “But the immune system still has an antibody response to it.”
Novel applications like this represent the future of nasal drug delivery.
“We’re not going to innovate in asthma or COPD. We’re not going to innovate in local delivery to the nose,” said Dr. Hindle. “Innovation will only come if we look to treat new conditions.”
A version of this article originally appeared on WebMD.com.
Noses are like caverns – twisting, turning, no two exactly the same. But if you nose past anyone’s nostrils, you’ll discover a surprisingly sprawling space.
“The size of the nasal cavity is about the same as a large handkerchief,” said Hugh Smyth, PhD, a professor of molecular pharmaceutics and drug delivery at the University of Texas at Austin.
“It’s very accessible tissue, and it has a lot of blood flow,” said Dr. Smyth. “The speed of onset can often be as fast as injections, sometimes even faster.”
It’s nothing new to get medicines via your nose. For decades, we’ve squirted various sprays into our nostrils to treat local maladies like allergies or infections. Even the ancients saw wisdom in the nasal route.
But recently, the nose has gained scientific attention as a gateway to the rest of the body – even the brain, a notoriously difficult target.
The upshot: Someday, inhaling therapies could be as routine as swallowing pills.
The nasal route is quick, needle free, and user friendly, and it often requires a smaller dose than other methods, since the drug doesn’t have to pass through the digestive tract, losing potency during digestion.
But there are challenges.
How hard can it be?
Old-school nasal sprayers, mostly unchanged since the 1800s, aren’t cut out for deep-nose delivery. “The technology is relatively limited because you’ve just got a single spray nozzle,” said Michael Hindle, PhD, a professor of pharmaceutics at Virginia Commonwealth University, Richmond.
These traditional devices (similar to perfume sprayers) don’t consistently push meds past the lower to middle sections inside the nose, called the nasal valve – if they do so at all: In a 2020 Rhinology study (doi: 10.4193/Rhin18.304) conventional nasal sprays only reached this first segment of the nose, a less-than-ideal spot to land.
Inside the nasal valve, the surface is skin-like and doesn’t absorb very well. Its narrow design slows airflow, preventing particles from moving to deeper regions, where tissue is vascular and porous like the lungs. And even if this structural roadblock is surpassed, other hurdles remain.
The nose is designed to keep stuff out. Nose hair, cilia, mucus, sneezing, coughing – all make “distributing drugs evenly across the nasal cavity difficult,” said Dr. Smyth. “The spray gets filtered out before it reaches those deeper zones,” potentially dripping out of the nostrils instead of being absorbed.
Complicating matters is how every person’s nose is different. In a 2018 study, Dr. Smyth and a research team created three dimensional–printed models of people’s nasal cavities. They varied widely. “Nasal cavities are very different in size, length, and internal geometry,” he said. “This makes it challenging to target specific areas.”
Although carefully positioning the spray nozzle can help, even something as minor as sniffing too hard (constricting the nostrils) can keep sprays from reaching the absorptive deeper regions.
Still, the benefits are enough to compel researchers to find a way in.
“This really is a drug delivery challenge we’ve been wrestling with,” said Dr. Hindle. “It’s not new formulations we hear about. It’s new devices and delivery methods trying to target the different nasal regions.”
Delivering the goods
In the late aughts, John Hoekman was a graduate student in the University of Washington’s pharmaceutics program, studying nasal drug delivery. In his experiments, he noticed that drugs distributed differently, depending on the region targeted – aiming for the upper nasal cavity led to a spike in absorption.
The results convinced Mr. Hoekman to stake his future on nasal drug delivery.
In 2008, while still in graduate school, he started his own company, now known as Impel Pharmaceuticals. In 2021, Impel released its first product: Trudhesa, a nasal spray for migraines. Although the drug itself – dihydroergotamine mesylate – was hardly novel, used for migraine relief since 1946 (Headache. 2020 Jan;60[1]:40-57), it was usually delivered through an intravenous line, often in the ED.
But with Mr. Hoekman’s POD device – short for precision olfactory delivery – the drug can be given by the patient, via the nose. This generally means faster, more reliable relief, with fewer side effects. “We were able to lower the dose and improve the overall absorption,” said Mr. Hoekman.
The POD’s nozzle is engineered to spray a soft, narrow plume. It’s gas propelled, so patients don’t have to breathe in any special way to ensure delivery. The drug can zip right through the nasal valve into the upper nasal cavity.
Another company – OptiNose – has a “bidirectional” delivery method that propels drugs, either liquid or dry powder, deep into the nose.
“You insert the nozzle into your nose, and as you blow through the mouthpiece, your soft palate closes,” said Dr. Hindle. With the throat sealed off, “the only place for the drug to go is into one nostril and out the other, coating both sides of the nasal passageways.”
The device is only available for Onzetra Xsail, a powder for migraines. But another application is on its way.
In May, OptiNose announced that the FDA is reviewing Xhance, which uses the system to direct a steroid to the sinuses. In a clinical trial, patients with chronic sinusitis who tried the drug-device combo saw a decline in congestion, facial pain, and inflammation.
Targeting the brain
Both of those migraine drugs – Trudhesa and Onzetra Xsail – are thought to penetrate the upper nasal cavity. That’s where you’ll find the olfactory zone, a sheet of neurons that connects to the olfactory bulb. Located behind the eyes, these two nerve bundles detect odors.
“The olfactory region is almost like a back door to the brain,” said Mr. Hoekman.
By bypassing the blood-brain barrier, it offers a direct pathway – the only direct pathway, actually – between an exposed area of the body and the brain. Meaning it can ferry drugs straight from the nasal cavity to the central nervous system.
Nose-to-brain treatments could be game-changing for central nervous system disorders, such as Parkinson’s disease, Alzheimer’s, or anxiety.
But reaching the olfactory zone is notoriously hard. “The vasculature in your nose is like a big freeway, and the olfactory tract is like a side alley,” explained Mr. Hoekman. “It’s very limiting in what it will allow through.” The region is also small, occupying only 3%-10% of the nasal cavity’s surface area.
Again, POD means “precision olfactory delivery.” But the device isn’t quite as laser focused on the region as its name implies. “We’re not at the stage where we’re able to exclusively deliver to one target site in the nose,” said Dr. Hindle.
While wending its way toward the olfactory zone, some of the drug will be absorbed by other regions, then circulate throughout the body.
“About 59% of the drug that we put into the upper nasal space gets absorbed into the bloodstream,” said Mr. Hoekman.
Janssen Pharmaceuticals’ Spravato – a nasal spray for drug-resistant depression – is thought to work similarly: Some goes straight to the brain via the olfactory nerves, while the rest takes a more roundabout route, passing through the blood vessels to circulate in your system.
A needle-free option
Sometimes, the bloodstream is the main target. Because the nose’s middle and upper stretches are so vascular, drugs can be rapidly absorbed.
This is especially valuable for time-sensitive conditions. “If you give something nasally, you can have peak uptake in 15-30 minutes,” said Mr. Hoekman.
Take Narcan nasal spray, which delivers a burst of naloxone to quickly reverse the effects of opioid an overdose. Or Noctiva nasal spray. Taken just half an hour before bed, it can prevent frequent nighttime urination.
There’s also a group of seizure-stopping sprays, known as “rescue treatments.” One works by temporarily loosening the space between nasal cells, allowing the seizure drug to be quickly absorbed through the vessels.
This systemic access also has potential for drugs that would otherwise have to be injected, such as biologics.
The same goes for vaccines. Mucosal tissue inside the nasal cavity offers direct access to the infection-fighting lymphatic system, making the nose a prime target for inoculation against certain viruses.
Inhaling protection against viruses
Despite the recent surge of interest, nasal vaccines faced a rocky start. After the first nasal flu vaccine hit the market in 2001, it was pulled due to potential toxicity and reports of Bell’s palsy, a type of facial paralysis.
FluMist came in 2003 and has been plagued by problems ever since. Because it contains a weakened live virus, flu-like side effects can occur. And it doesn’t always work. During the 2016-2017 flu season, FluMist protected only 3% of kids, prompting the Centers for Disease Control and Prevention to advise against the nasal route that year.
Why FluMist can be so hit-or-miss is poorly understood. But generally, the nose can pose an effectiveness challenge. “The nose is highly cycling,” said Dr. Hindle. “Anything we deposit usually gets transported out within 15-20 minutes.”
For kids – big fans of not using needles – chronically runny noses can be an issue. “You squirt it in the nose, and it will probably just come back out in their snot,” said Jay Kolls, MD, a professor of medicine and pediatrics at Tulane University, New Orleans, who is developing an intranasal pneumonia vaccine.
Even so, nasal vaccines became a hot topic among researchers after the world was shut down by a virus that invades through the nose.
“We realized that intramuscular vaccines were effective at preventing severe disease, but they weren’t that effective at preventing transmission,” said Michael Diamond, MD, PhD, an immunologist at Washington University in St. Louis.
Nasal vaccines could solve that problem by putting an immune barrier at the point of entry, denying access to the rest of the body. “You squash the infection early enough that it not only prevents disease,” said Dr. Kolls, “but potentially prevents transmission.”
And yes, a nasal COVID vaccine is on the way
In March 2020, Dr. Diamond’s team began exploring a nasal COVID vaccine. Promising results in animals prompted a vaccine development company to license the technology. The resulting nasal vaccine – the first for COVID – has been approved in India, both as a primary vaccine and a booster.
It works by stimulating an influx of IgA, a type of antibody found in the nasal passages, and production of resident memory T cells, immune cells on standby just beneath the surface tissue in the nose.
By contrast, injected vaccines generate mostly IgG antibodies, which struggle to enter the respiratory tract. Only a tiny fraction – an estimated 1% – typically reach the nose.
Nasal vaccines could also be used along with shots. The latter could prime the whole body to fight back, while a nasal spritz could pull that immune protection to the mucosal surfaces.
Nasal technology could yield more effective vaccines for infections like tuberculosis or malaria, or even safeguard against new – sometimes surprising – conditions.
In a 2021 Nature study, an intranasal vaccine derived from fentanyl was better at preventing overdose than an injected vaccine. “Through some clever chemistry, the drug [in the vaccine] isn’t fentanyl anymore,” said study author Elizabeth Norton, PhD, an assistant professor of microbiology and immunology at Tulane University. “But the immune system still has an antibody response to it.”
Novel applications like this represent the future of nasal drug delivery.
“We’re not going to innovate in asthma or COPD. We’re not going to innovate in local delivery to the nose,” said Dr. Hindle. “Innovation will only come if we look to treat new conditions.”
A version of this article originally appeared on WebMD.com.
Noses are like caverns – twisting, turning, no two exactly the same. But if you nose past anyone’s nostrils, you’ll discover a surprisingly sprawling space.
“The size of the nasal cavity is about the same as a large handkerchief,” said Hugh Smyth, PhD, a professor of molecular pharmaceutics and drug delivery at the University of Texas at Austin.
“It’s very accessible tissue, and it has a lot of blood flow,” said Dr. Smyth. “The speed of onset can often be as fast as injections, sometimes even faster.”
It’s nothing new to get medicines via your nose. For decades, we’ve squirted various sprays into our nostrils to treat local maladies like allergies or infections. Even the ancients saw wisdom in the nasal route.
But recently, the nose has gained scientific attention as a gateway to the rest of the body – even the brain, a notoriously difficult target.
The upshot: Someday, inhaling therapies could be as routine as swallowing pills.
The nasal route is quick, needle free, and user friendly, and it often requires a smaller dose than other methods, since the drug doesn’t have to pass through the digestive tract, losing potency during digestion.
But there are challenges.
How hard can it be?
Old-school nasal sprayers, mostly unchanged since the 1800s, aren’t cut out for deep-nose delivery. “The technology is relatively limited because you’ve just got a single spray nozzle,” said Michael Hindle, PhD, a professor of pharmaceutics at Virginia Commonwealth University, Richmond.
These traditional devices (similar to perfume sprayers) don’t consistently push meds past the lower to middle sections inside the nose, called the nasal valve – if they do so at all: In a 2020 Rhinology study (doi: 10.4193/Rhin18.304) conventional nasal sprays only reached this first segment of the nose, a less-than-ideal spot to land.
Inside the nasal valve, the surface is skin-like and doesn’t absorb very well. Its narrow design slows airflow, preventing particles from moving to deeper regions, where tissue is vascular and porous like the lungs. And even if this structural roadblock is surpassed, other hurdles remain.
The nose is designed to keep stuff out. Nose hair, cilia, mucus, sneezing, coughing – all make “distributing drugs evenly across the nasal cavity difficult,” said Dr. Smyth. “The spray gets filtered out before it reaches those deeper zones,” potentially dripping out of the nostrils instead of being absorbed.
Complicating matters is how every person’s nose is different. In a 2018 study, Dr. Smyth and a research team created three dimensional–printed models of people’s nasal cavities. They varied widely. “Nasal cavities are very different in size, length, and internal geometry,” he said. “This makes it challenging to target specific areas.”
Although carefully positioning the spray nozzle can help, even something as minor as sniffing too hard (constricting the nostrils) can keep sprays from reaching the absorptive deeper regions.
Still, the benefits are enough to compel researchers to find a way in.
“This really is a drug delivery challenge we’ve been wrestling with,” said Dr. Hindle. “It’s not new formulations we hear about. It’s new devices and delivery methods trying to target the different nasal regions.”
Delivering the goods
In the late aughts, John Hoekman was a graduate student in the University of Washington’s pharmaceutics program, studying nasal drug delivery. In his experiments, he noticed that drugs distributed differently, depending on the region targeted – aiming for the upper nasal cavity led to a spike in absorption.
The results convinced Mr. Hoekman to stake his future on nasal drug delivery.
In 2008, while still in graduate school, he started his own company, now known as Impel Pharmaceuticals. In 2021, Impel released its first product: Trudhesa, a nasal spray for migraines. Although the drug itself – dihydroergotamine mesylate – was hardly novel, used for migraine relief since 1946 (Headache. 2020 Jan;60[1]:40-57), it was usually delivered through an intravenous line, often in the ED.
But with Mr. Hoekman’s POD device – short for precision olfactory delivery – the drug can be given by the patient, via the nose. This generally means faster, more reliable relief, with fewer side effects. “We were able to lower the dose and improve the overall absorption,” said Mr. Hoekman.
The POD’s nozzle is engineered to spray a soft, narrow plume. It’s gas propelled, so patients don’t have to breathe in any special way to ensure delivery. The drug can zip right through the nasal valve into the upper nasal cavity.
Another company – OptiNose – has a “bidirectional” delivery method that propels drugs, either liquid or dry powder, deep into the nose.
“You insert the nozzle into your nose, and as you blow through the mouthpiece, your soft palate closes,” said Dr. Hindle. With the throat sealed off, “the only place for the drug to go is into one nostril and out the other, coating both sides of the nasal passageways.”
The device is only available for Onzetra Xsail, a powder for migraines. But another application is on its way.
In May, OptiNose announced that the FDA is reviewing Xhance, which uses the system to direct a steroid to the sinuses. In a clinical trial, patients with chronic sinusitis who tried the drug-device combo saw a decline in congestion, facial pain, and inflammation.
Targeting the brain
Both of those migraine drugs – Trudhesa and Onzetra Xsail – are thought to penetrate the upper nasal cavity. That’s where you’ll find the olfactory zone, a sheet of neurons that connects to the olfactory bulb. Located behind the eyes, these two nerve bundles detect odors.
“The olfactory region is almost like a back door to the brain,” said Mr. Hoekman.
By bypassing the blood-brain barrier, it offers a direct pathway – the only direct pathway, actually – between an exposed area of the body and the brain. Meaning it can ferry drugs straight from the nasal cavity to the central nervous system.
Nose-to-brain treatments could be game-changing for central nervous system disorders, such as Parkinson’s disease, Alzheimer’s, or anxiety.
But reaching the olfactory zone is notoriously hard. “The vasculature in your nose is like a big freeway, and the olfactory tract is like a side alley,” explained Mr. Hoekman. “It’s very limiting in what it will allow through.” The region is also small, occupying only 3%-10% of the nasal cavity’s surface area.
Again, POD means “precision olfactory delivery.” But the device isn’t quite as laser focused on the region as its name implies. “We’re not at the stage where we’re able to exclusively deliver to one target site in the nose,” said Dr. Hindle.
While wending its way toward the olfactory zone, some of the drug will be absorbed by other regions, then circulate throughout the body.
“About 59% of the drug that we put into the upper nasal space gets absorbed into the bloodstream,” said Mr. Hoekman.
Janssen Pharmaceuticals’ Spravato – a nasal spray for drug-resistant depression – is thought to work similarly: Some goes straight to the brain via the olfactory nerves, while the rest takes a more roundabout route, passing through the blood vessels to circulate in your system.
A needle-free option
Sometimes, the bloodstream is the main target. Because the nose’s middle and upper stretches are so vascular, drugs can be rapidly absorbed.
This is especially valuable for time-sensitive conditions. “If you give something nasally, you can have peak uptake in 15-30 minutes,” said Mr. Hoekman.
Take Narcan nasal spray, which delivers a burst of naloxone to quickly reverse the effects of opioid an overdose. Or Noctiva nasal spray. Taken just half an hour before bed, it can prevent frequent nighttime urination.
There’s also a group of seizure-stopping sprays, known as “rescue treatments.” One works by temporarily loosening the space between nasal cells, allowing the seizure drug to be quickly absorbed through the vessels.
This systemic access also has potential for drugs that would otherwise have to be injected, such as biologics.
The same goes for vaccines. Mucosal tissue inside the nasal cavity offers direct access to the infection-fighting lymphatic system, making the nose a prime target for inoculation against certain viruses.
Inhaling protection against viruses
Despite the recent surge of interest, nasal vaccines faced a rocky start. After the first nasal flu vaccine hit the market in 2001, it was pulled due to potential toxicity and reports of Bell’s palsy, a type of facial paralysis.
FluMist came in 2003 and has been plagued by problems ever since. Because it contains a weakened live virus, flu-like side effects can occur. And it doesn’t always work. During the 2016-2017 flu season, FluMist protected only 3% of kids, prompting the Centers for Disease Control and Prevention to advise against the nasal route that year.
Why FluMist can be so hit-or-miss is poorly understood. But generally, the nose can pose an effectiveness challenge. “The nose is highly cycling,” said Dr. Hindle. “Anything we deposit usually gets transported out within 15-20 minutes.”
For kids – big fans of not using needles – chronically runny noses can be an issue. “You squirt it in the nose, and it will probably just come back out in their snot,” said Jay Kolls, MD, a professor of medicine and pediatrics at Tulane University, New Orleans, who is developing an intranasal pneumonia vaccine.
Even so, nasal vaccines became a hot topic among researchers after the world was shut down by a virus that invades through the nose.
“We realized that intramuscular vaccines were effective at preventing severe disease, but they weren’t that effective at preventing transmission,” said Michael Diamond, MD, PhD, an immunologist at Washington University in St. Louis.
Nasal vaccines could solve that problem by putting an immune barrier at the point of entry, denying access to the rest of the body. “You squash the infection early enough that it not only prevents disease,” said Dr. Kolls, “but potentially prevents transmission.”
And yes, a nasal COVID vaccine is on the way
In March 2020, Dr. Diamond’s team began exploring a nasal COVID vaccine. Promising results in animals prompted a vaccine development company to license the technology. The resulting nasal vaccine – the first for COVID – has been approved in India, both as a primary vaccine and a booster.
It works by stimulating an influx of IgA, a type of antibody found in the nasal passages, and production of resident memory T cells, immune cells on standby just beneath the surface tissue in the nose.
By contrast, injected vaccines generate mostly IgG antibodies, which struggle to enter the respiratory tract. Only a tiny fraction – an estimated 1% – typically reach the nose.
Nasal vaccines could also be used along with shots. The latter could prime the whole body to fight back, while a nasal spritz could pull that immune protection to the mucosal surfaces.
Nasal technology could yield more effective vaccines for infections like tuberculosis or malaria, or even safeguard against new – sometimes surprising – conditions.
In a 2021 Nature study, an intranasal vaccine derived from fentanyl was better at preventing overdose than an injected vaccine. “Through some clever chemistry, the drug [in the vaccine] isn’t fentanyl anymore,” said study author Elizabeth Norton, PhD, an assistant professor of microbiology and immunology at Tulane University. “But the immune system still has an antibody response to it.”
Novel applications like this represent the future of nasal drug delivery.
“We’re not going to innovate in asthma or COPD. We’re not going to innovate in local delivery to the nose,” said Dr. Hindle. “Innovation will only come if we look to treat new conditions.”
A version of this article originally appeared on WebMD.com.
Time to prescribe sauna bathing for cardiovascular health?
Is it time to start recommending regular sauna bathing to improve heart health?
While a post-workout sauna can compound the benefits of exercise, the hormetic effects of heat therapy alone can produce significant gains for microvascular and endothelial function, no workout required.
“There’s enough evidence to say that regular sauna use improves cardiovascular health,” Matthew S. Ganio, PhD, a professor of exercise science at the University of Arkansas in Fayetteville, who studies thermoregulatory responses and cardiovascular health, said.
“The more they used it, the greater the reduction in cardiovascular events like heart attack. But you don’t need to be in there more than 20-30 minutes. That’s where it seemed to have the best effect,” Dr. Ganio said, adding that studies have shown a dose-response.
A prospective cohort study published in 2015 in JAMA Internal Medicine included 20 years of data on more than 2,300 Finnish men who regularly sauna bathed. The researchers found that among participants who sat in saunas more frequently, rates of death from heart disease and stroke were lower than among those who did so less often.
Cutaneous vasodilation
The body experiences several physiologic changes when exposed to heat therapy of any kind, including sauna, hot water submerging, shortwave diathermy, and heat wrapping. Many of these changes involve elements of the cardiovascular system, said Earric Lee, PhD, an exercise physiologist and postdoctoral researcher at the University of Jyväskylä in Finland, who has studied the effects of sauna on cardiovascular health.
The mechanisms by which heat therapy improves cardiovascular fitness have not been determined, as few studies of sauna bathing have been conducted to this degree. One driver appears to be cutaneous vasodilation. To cool the body when exposed to extreme external heat, cutaneous vessels dilate and push blood to the skin, which lowers body temperature, increases heart rate, and delivers oxygen to muscles in the limbs in a way similar to aerobic exercise.
Sauna bathing has similar effects on heart rate and cardiac output. Studies have shown it can improve the circulation of blood through the body, as well as vascular endothelial function, which is closely tied to vascular tone.
“Increased cardiac output is one of the physiologic reasons sauna is good for heart health,” Dr. Ganio said.
During a sauna session, cardiac output can increase by as much as 70% in relation to elevated heart rate. And while heart rate and cardiac output rise, stroke volume remains stable. As stroke volume increases, the effort that muscle must exert increases. When heart rate rises, stroke volume often falls, which subjects the heart to less of a workout and reduces the amount of oxygen and blood circulating throughout the body.
Heat therapy also temporarily increases blood pressure, but in a way similar to exercise, which supports better long-term heart health, said Christopher Minson, PhD, the Kenneth M. and Kenda H. Singer Endowed Professor of Human Physiology at the University of Oregon in Eugene.
A small study of 19 healthy adults that was published in Complementary Therapies in Medicine in 2019 found that blood pressure and heart rate rose during a 25-minute sauna session as they might during moderate exercise, equivalent to an exercise load of about 60-100 watts. These parameters then steadily decreased for 30 minutes after the sauna. An earlier study found that in the long term, blood pressure was lower after a sauna than before a sauna.
Upregulated heat shock proteins
Both aerobic exercise and heat stress from sauna bathing increase the activity of heat shock proteins. A 2021 review published in Experimental Gerontology found that heat shock proteins become elevated in cells within 30 minutes of exposure to heat and remain elevated over time – an effect similar to exercise.
“Saunas increase heat shock proteins that break down old, dysfunctional proteins and then protect new proteins from becoming dysfunctional,” Hunter S. Waldman, PhD, an assistant professor of exercise science at the University of North Alabama in Florence, said. This effect is one way sauna bathing may quell systemic inflammation, Dr. Waldman said.
According to a 2018 review published in BioMed Research International, an abundance of heat shock proteins may increase exercise tolerance. The researchers concluded that the positive stress associated with elevated body temperature could help people be physically active for longer periods.
Added stress, especially heat-related strain, is not good for everyone, however. Dr. Waldman cautioned that heat exposure, be it through a sauna, hot tub, or other source, can be harmful for pregnant women and children and can be dangerous for people who have low blood pressure, since blood pressure often drops to rates that are lower than before taking a sauna. It also can impair semen quality for months after exposure, so people who are trying to conceive should avoid sauna bathing.
Anyone who has been diagnosed with a heart condition, including cardiac arrhythmia, coronary artery disease, and congestive heart failure, should always consult their physician prior to using sauna for the first time or before using it habitually, Dr. Lee said.
Effects compounded by exercise
Dr. Minson stressed that any type of heat therapy should be part of a lifestyle that includes mostly healthy habits overall, especially a regular exercise regime when possible.
“You have to have everything else working as well: finding time to relax, not being overly stressed, staying hydrated – all those things are critical with any exercise training and heat therapy program,” he said.
Dr. Lee said it’s easy to overhype the benefits of sauna bathing and agreed the practice should be used in tandem with other therapies, not as a replacement. So far, stacking research has shown it to be an effective extension of aerobic exercise.
A June 2023 review published in Mayo Clinic Proceedings found that while sauna bathing can produce benefits on its own, a post-workout sauna can extend the benefits of exercise. As a result, the researchers concluded, saunas likely provide the most benefit when combined with aerobic and strength training.
While some of the benefits of exercise overlap those associated with sauna bathing, “you’re going to get some benefits with exercise that you’re never going to get with sauna,” Dr. Ganio said.
For instance, strength training or aerobic exercise usually results in muscle contractions, which sauna bathing does not produce.
If a person is impaired in a way that makes exercise difficult, taking a sauna after aerobic activity can extend the cardiovascular benefits of the workout, even if muscle-building does not occur, Dr. Lee said.
“All other things considered, especially with aerobic exercise, it is very comparable, so we can look at adding sauna bathing post exercise as a way to lengthen the aerobic exercise workout,” he said. “It’s not to the same degree, but you can get many of the ranging benefits of exercising simply by going into the sauna.”
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Is it time to start recommending regular sauna bathing to improve heart health?
While a post-workout sauna can compound the benefits of exercise, the hormetic effects of heat therapy alone can produce significant gains for microvascular and endothelial function, no workout required.
“There’s enough evidence to say that regular sauna use improves cardiovascular health,” Matthew S. Ganio, PhD, a professor of exercise science at the University of Arkansas in Fayetteville, who studies thermoregulatory responses and cardiovascular health, said.
“The more they used it, the greater the reduction in cardiovascular events like heart attack. But you don’t need to be in there more than 20-30 minutes. That’s where it seemed to have the best effect,” Dr. Ganio said, adding that studies have shown a dose-response.
A prospective cohort study published in 2015 in JAMA Internal Medicine included 20 years of data on more than 2,300 Finnish men who regularly sauna bathed. The researchers found that among participants who sat in saunas more frequently, rates of death from heart disease and stroke were lower than among those who did so less often.
Cutaneous vasodilation
The body experiences several physiologic changes when exposed to heat therapy of any kind, including sauna, hot water submerging, shortwave diathermy, and heat wrapping. Many of these changes involve elements of the cardiovascular system, said Earric Lee, PhD, an exercise physiologist and postdoctoral researcher at the University of Jyväskylä in Finland, who has studied the effects of sauna on cardiovascular health.
The mechanisms by which heat therapy improves cardiovascular fitness have not been determined, as few studies of sauna bathing have been conducted to this degree. One driver appears to be cutaneous vasodilation. To cool the body when exposed to extreme external heat, cutaneous vessels dilate and push blood to the skin, which lowers body temperature, increases heart rate, and delivers oxygen to muscles in the limbs in a way similar to aerobic exercise.
Sauna bathing has similar effects on heart rate and cardiac output. Studies have shown it can improve the circulation of blood through the body, as well as vascular endothelial function, which is closely tied to vascular tone.
“Increased cardiac output is one of the physiologic reasons sauna is good for heart health,” Dr. Ganio said.
During a sauna session, cardiac output can increase by as much as 70% in relation to elevated heart rate. And while heart rate and cardiac output rise, stroke volume remains stable. As stroke volume increases, the effort that muscle must exert increases. When heart rate rises, stroke volume often falls, which subjects the heart to less of a workout and reduces the amount of oxygen and blood circulating throughout the body.
Heat therapy also temporarily increases blood pressure, but in a way similar to exercise, which supports better long-term heart health, said Christopher Minson, PhD, the Kenneth M. and Kenda H. Singer Endowed Professor of Human Physiology at the University of Oregon in Eugene.
A small study of 19 healthy adults that was published in Complementary Therapies in Medicine in 2019 found that blood pressure and heart rate rose during a 25-minute sauna session as they might during moderate exercise, equivalent to an exercise load of about 60-100 watts. These parameters then steadily decreased for 30 minutes after the sauna. An earlier study found that in the long term, blood pressure was lower after a sauna than before a sauna.
Upregulated heat shock proteins
Both aerobic exercise and heat stress from sauna bathing increase the activity of heat shock proteins. A 2021 review published in Experimental Gerontology found that heat shock proteins become elevated in cells within 30 minutes of exposure to heat and remain elevated over time – an effect similar to exercise.
“Saunas increase heat shock proteins that break down old, dysfunctional proteins and then protect new proteins from becoming dysfunctional,” Hunter S. Waldman, PhD, an assistant professor of exercise science at the University of North Alabama in Florence, said. This effect is one way sauna bathing may quell systemic inflammation, Dr. Waldman said.
According to a 2018 review published in BioMed Research International, an abundance of heat shock proteins may increase exercise tolerance. The researchers concluded that the positive stress associated with elevated body temperature could help people be physically active for longer periods.
Added stress, especially heat-related strain, is not good for everyone, however. Dr. Waldman cautioned that heat exposure, be it through a sauna, hot tub, or other source, can be harmful for pregnant women and children and can be dangerous for people who have low blood pressure, since blood pressure often drops to rates that are lower than before taking a sauna. It also can impair semen quality for months after exposure, so people who are trying to conceive should avoid sauna bathing.
Anyone who has been diagnosed with a heart condition, including cardiac arrhythmia, coronary artery disease, and congestive heart failure, should always consult their physician prior to using sauna for the first time or before using it habitually, Dr. Lee said.
Effects compounded by exercise
Dr. Minson stressed that any type of heat therapy should be part of a lifestyle that includes mostly healthy habits overall, especially a regular exercise regime when possible.
“You have to have everything else working as well: finding time to relax, not being overly stressed, staying hydrated – all those things are critical with any exercise training and heat therapy program,” he said.
Dr. Lee said it’s easy to overhype the benefits of sauna bathing and agreed the practice should be used in tandem with other therapies, not as a replacement. So far, stacking research has shown it to be an effective extension of aerobic exercise.
A June 2023 review published in Mayo Clinic Proceedings found that while sauna bathing can produce benefits on its own, a post-workout sauna can extend the benefits of exercise. As a result, the researchers concluded, saunas likely provide the most benefit when combined with aerobic and strength training.
While some of the benefits of exercise overlap those associated with sauna bathing, “you’re going to get some benefits with exercise that you’re never going to get with sauna,” Dr. Ganio said.
For instance, strength training or aerobic exercise usually results in muscle contractions, which sauna bathing does not produce.
If a person is impaired in a way that makes exercise difficult, taking a sauna after aerobic activity can extend the cardiovascular benefits of the workout, even if muscle-building does not occur, Dr. Lee said.
“All other things considered, especially with aerobic exercise, it is very comparable, so we can look at adding sauna bathing post exercise as a way to lengthen the aerobic exercise workout,” he said. “It’s not to the same degree, but you can get many of the ranging benefits of exercising simply by going into the sauna.”
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Is it time to start recommending regular sauna bathing to improve heart health?
While a post-workout sauna can compound the benefits of exercise, the hormetic effects of heat therapy alone can produce significant gains for microvascular and endothelial function, no workout required.
“There’s enough evidence to say that regular sauna use improves cardiovascular health,” Matthew S. Ganio, PhD, a professor of exercise science at the University of Arkansas in Fayetteville, who studies thermoregulatory responses and cardiovascular health, said.
“The more they used it, the greater the reduction in cardiovascular events like heart attack. But you don’t need to be in there more than 20-30 minutes. That’s where it seemed to have the best effect,” Dr. Ganio said, adding that studies have shown a dose-response.
A prospective cohort study published in 2015 in JAMA Internal Medicine included 20 years of data on more than 2,300 Finnish men who regularly sauna bathed. The researchers found that among participants who sat in saunas more frequently, rates of death from heart disease and stroke were lower than among those who did so less often.
Cutaneous vasodilation
The body experiences several physiologic changes when exposed to heat therapy of any kind, including sauna, hot water submerging, shortwave diathermy, and heat wrapping. Many of these changes involve elements of the cardiovascular system, said Earric Lee, PhD, an exercise physiologist and postdoctoral researcher at the University of Jyväskylä in Finland, who has studied the effects of sauna on cardiovascular health.
The mechanisms by which heat therapy improves cardiovascular fitness have not been determined, as few studies of sauna bathing have been conducted to this degree. One driver appears to be cutaneous vasodilation. To cool the body when exposed to extreme external heat, cutaneous vessels dilate and push blood to the skin, which lowers body temperature, increases heart rate, and delivers oxygen to muscles in the limbs in a way similar to aerobic exercise.
Sauna bathing has similar effects on heart rate and cardiac output. Studies have shown it can improve the circulation of blood through the body, as well as vascular endothelial function, which is closely tied to vascular tone.
“Increased cardiac output is one of the physiologic reasons sauna is good for heart health,” Dr. Ganio said.
During a sauna session, cardiac output can increase by as much as 70% in relation to elevated heart rate. And while heart rate and cardiac output rise, stroke volume remains stable. As stroke volume increases, the effort that muscle must exert increases. When heart rate rises, stroke volume often falls, which subjects the heart to less of a workout and reduces the amount of oxygen and blood circulating throughout the body.
Heat therapy also temporarily increases blood pressure, but in a way similar to exercise, which supports better long-term heart health, said Christopher Minson, PhD, the Kenneth M. and Kenda H. Singer Endowed Professor of Human Physiology at the University of Oregon in Eugene.
A small study of 19 healthy adults that was published in Complementary Therapies in Medicine in 2019 found that blood pressure and heart rate rose during a 25-minute sauna session as they might during moderate exercise, equivalent to an exercise load of about 60-100 watts. These parameters then steadily decreased for 30 minutes after the sauna. An earlier study found that in the long term, blood pressure was lower after a sauna than before a sauna.
Upregulated heat shock proteins
Both aerobic exercise and heat stress from sauna bathing increase the activity of heat shock proteins. A 2021 review published in Experimental Gerontology found that heat shock proteins become elevated in cells within 30 minutes of exposure to heat and remain elevated over time – an effect similar to exercise.
“Saunas increase heat shock proteins that break down old, dysfunctional proteins and then protect new proteins from becoming dysfunctional,” Hunter S. Waldman, PhD, an assistant professor of exercise science at the University of North Alabama in Florence, said. This effect is one way sauna bathing may quell systemic inflammation, Dr. Waldman said.
According to a 2018 review published in BioMed Research International, an abundance of heat shock proteins may increase exercise tolerance. The researchers concluded that the positive stress associated with elevated body temperature could help people be physically active for longer periods.
Added stress, especially heat-related strain, is not good for everyone, however. Dr. Waldman cautioned that heat exposure, be it through a sauna, hot tub, or other source, can be harmful for pregnant women and children and can be dangerous for people who have low blood pressure, since blood pressure often drops to rates that are lower than before taking a sauna. It also can impair semen quality for months after exposure, so people who are trying to conceive should avoid sauna bathing.
Anyone who has been diagnosed with a heart condition, including cardiac arrhythmia, coronary artery disease, and congestive heart failure, should always consult their physician prior to using sauna for the first time or before using it habitually, Dr. Lee said.
Effects compounded by exercise
Dr. Minson stressed that any type of heat therapy should be part of a lifestyle that includes mostly healthy habits overall, especially a regular exercise regime when possible.
“You have to have everything else working as well: finding time to relax, not being overly stressed, staying hydrated – all those things are critical with any exercise training and heat therapy program,” he said.
Dr. Lee said it’s easy to overhype the benefits of sauna bathing and agreed the practice should be used in tandem with other therapies, not as a replacement. So far, stacking research has shown it to be an effective extension of aerobic exercise.
A June 2023 review published in Mayo Clinic Proceedings found that while sauna bathing can produce benefits on its own, a post-workout sauna can extend the benefits of exercise. As a result, the researchers concluded, saunas likely provide the most benefit when combined with aerobic and strength training.
While some of the benefits of exercise overlap those associated with sauna bathing, “you’re going to get some benefits with exercise that you’re never going to get with sauna,” Dr. Ganio said.
For instance, strength training or aerobic exercise usually results in muscle contractions, which sauna bathing does not produce.
If a person is impaired in a way that makes exercise difficult, taking a sauna after aerobic activity can extend the cardiovascular benefits of the workout, even if muscle-building does not occur, Dr. Lee said.
“All other things considered, especially with aerobic exercise, it is very comparable, so we can look at adding sauna bathing post exercise as a way to lengthen the aerobic exercise workout,” he said. “It’s not to the same degree, but you can get many of the ranging benefits of exercising simply by going into the sauna.”
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
West Nile virus cases rising nationwide amid mosquito season
In the past 2 weeks, new cases have been reported in Iowa and Nebraska, adding to previous 2023 reports from Arizona, Georgia, Illinois, Louisiana, Oregon, Pennsylvania, and Wyoming. A mosquito at a monitoring site near Houston tested positive last week for the potentially fatal virus, prompting local health officials to begin evening spray operations in the area where the mosquito was found, according to an announcement from Harris County Public Health.
According to the CDC, which compiles local reports, there have been 13 human cases of West Nile virus in 2023. In 2022, there were 1,126 cases, including 90 deaths.
Among this year’s 13 cases reported to the CDC so far, eight people add severe neuroinvasive disease, which means the disease spread to the nervous system. Such severe symptoms typically occur in 1 in every 150 cases of West Nile virus and can include encephalitis, which is inflammation of the brain, or meningitis, which is inflammation of the membranes that surround the brain and spinal cord. Three of the neuroinvasive cases occurred earlier this year amid an outbreak in Maricopa County, Arizona, where the disease is considered endemic, according to an April 28 report from the CDC.
The CDC says West Nile virus is the most common disease spread by mosquitoes in the continental United States. Local health officials sample mosquitoes to guide mosquito control strategies. So far this year, the CDC has received 28 reports of mosquitoes testing positive. Those mosquito testing reports came from Arizona, California, Florida, Indiana, Louisiana, and Texas.
West Nile virus is transmitted to people by the bite of an infected mosquito, but it can also be spread to humans if they handle a dead bird that is infected. The CDC says there are no medications to treat the virus in people. Most people who are infected do not feel sick, and 1 in 5 people infected develop a fever and other symptoms like headache, body ache, or a rash.
Prevention strategies are to wear insect repellent and to wear long-sleeved shirts and long pants to avoid mosquito bites.
A version of this article originally appeared on WebMD.com.
In the past 2 weeks, new cases have been reported in Iowa and Nebraska, adding to previous 2023 reports from Arizona, Georgia, Illinois, Louisiana, Oregon, Pennsylvania, and Wyoming. A mosquito at a monitoring site near Houston tested positive last week for the potentially fatal virus, prompting local health officials to begin evening spray operations in the area where the mosquito was found, according to an announcement from Harris County Public Health.
According to the CDC, which compiles local reports, there have been 13 human cases of West Nile virus in 2023. In 2022, there were 1,126 cases, including 90 deaths.
Among this year’s 13 cases reported to the CDC so far, eight people add severe neuroinvasive disease, which means the disease spread to the nervous system. Such severe symptoms typically occur in 1 in every 150 cases of West Nile virus and can include encephalitis, which is inflammation of the brain, or meningitis, which is inflammation of the membranes that surround the brain and spinal cord. Three of the neuroinvasive cases occurred earlier this year amid an outbreak in Maricopa County, Arizona, where the disease is considered endemic, according to an April 28 report from the CDC.
The CDC says West Nile virus is the most common disease spread by mosquitoes in the continental United States. Local health officials sample mosquitoes to guide mosquito control strategies. So far this year, the CDC has received 28 reports of mosquitoes testing positive. Those mosquito testing reports came from Arizona, California, Florida, Indiana, Louisiana, and Texas.
West Nile virus is transmitted to people by the bite of an infected mosquito, but it can also be spread to humans if they handle a dead bird that is infected. The CDC says there are no medications to treat the virus in people. Most people who are infected do not feel sick, and 1 in 5 people infected develop a fever and other symptoms like headache, body ache, or a rash.
Prevention strategies are to wear insect repellent and to wear long-sleeved shirts and long pants to avoid mosquito bites.
A version of this article originally appeared on WebMD.com.
In the past 2 weeks, new cases have been reported in Iowa and Nebraska, adding to previous 2023 reports from Arizona, Georgia, Illinois, Louisiana, Oregon, Pennsylvania, and Wyoming. A mosquito at a monitoring site near Houston tested positive last week for the potentially fatal virus, prompting local health officials to begin evening spray operations in the area where the mosquito was found, according to an announcement from Harris County Public Health.
According to the CDC, which compiles local reports, there have been 13 human cases of West Nile virus in 2023. In 2022, there were 1,126 cases, including 90 deaths.
Among this year’s 13 cases reported to the CDC so far, eight people add severe neuroinvasive disease, which means the disease spread to the nervous system. Such severe symptoms typically occur in 1 in every 150 cases of West Nile virus and can include encephalitis, which is inflammation of the brain, or meningitis, which is inflammation of the membranes that surround the brain and spinal cord. Three of the neuroinvasive cases occurred earlier this year amid an outbreak in Maricopa County, Arizona, where the disease is considered endemic, according to an April 28 report from the CDC.
The CDC says West Nile virus is the most common disease spread by mosquitoes in the continental United States. Local health officials sample mosquitoes to guide mosquito control strategies. So far this year, the CDC has received 28 reports of mosquitoes testing positive. Those mosquito testing reports came from Arizona, California, Florida, Indiana, Louisiana, and Texas.
West Nile virus is transmitted to people by the bite of an infected mosquito, but it can also be spread to humans if they handle a dead bird that is infected. The CDC says there are no medications to treat the virus in people. Most people who are infected do not feel sick, and 1 in 5 people infected develop a fever and other symptoms like headache, body ache, or a rash.
Prevention strategies are to wear insect repellent and to wear long-sleeved shirts and long pants to avoid mosquito bites.
A version of this article originally appeared on WebMD.com.
Reducing risk for thrombosis in patients with lung cancer
CHICAGO – Having cancer is a known risk factor for thrombosis. A patient with cancer has a fourfold risk of developing venous thromboembolism (VTE).
This risk may be increased by certain cancer drugs, which seems to be the case for the combination of innovative targeted therapies lazertinib-amivantamab, as shown in patients with advanced or metastatic non–small cell lung cancer.
A study of this increased risk of VTE was presented by Nicolas Girard, MD, a respiratory medicine specialist at Curie-Montsouris Chest Center in Paris, during the annual meeting of the American Society of Clinical Oncology.
Combination therapies
Amivantamab is an EGFR and cMET bispecific antibody, and lazertinib is a third-generation EGFR tyrosine kinase inhibitor. Prescribed after osimertinib or after osimertinib plus chemotherapy, this combination of amivantamab and lazertinib has been evaluated in several cohorts of patients with EGFR-mutated advanced non–small cell lung cancer in whom targeted therapy and chemotherapy has failed.
The antitumor activity appears to be improved when both therapies are given in combination. The side effects generally are acceptable. It is these side effects, particularly the rate of VTEs, that Dr. Girard and his colleagues are interested in.
The researchers collated the data from the ongoing CHRYSALIS, CHRYSALIS-2, and LASER201 clinical trials, which assess the efficacy of these new agents as monotherapy or in combination. They initially investigated all reported thrombotic events and ruled out those that occurred during or after the 30 days before disease progression.
Increased thrombosis risk
The analysis included 560 patients who had been given amivantamab as monotherapy, 536 patients who had received amivantamab plus lazertinib in combination, and 252 who had taken lazertinib as monotherapy. The incidence of thromboembolic events was higher among patients who received amivantamab plus lazertinib in combination (21%) than in those who were given amivantamab (11%) or lazertinib (11%) as monotherapy.
The first thromboembolic event occurred an average of 84.5 days after starting treatment with amivantamab, 79 days after starting the combination therapy, and 170 days after starting treatment with lazertinib. For the amivantamab plus lazertinib combination, most VTEs developed in the first 4 months of treatment. The most common VTEs were pulmonary embolism and deep vein thrombosis.
The incidence of severe thrombotic events (grade ≥ 3), which was relatively low (amivantamab, 5%; amivantamab plus lazertinib, 6%; lazertinib, 6%) was similar regardless of the treatment, and there were no grade 5 thrombotic events among patients treated with the combination of both targeted therapies.
The significant risk factors for VTEs identified in this study were being age 60 years or older, having a score of 1 on the ECOG Performance Status Scale, and response to treatment (P < .05).
At a press conference organized by the Institut Curie before the ASCO conference, Dr. Girard said, “There has been shown to be an increased risk of blood clots with the use of this combination of targeted therapies. Preventive measures should therefore also be put forward, such as adding anticoagulant medication. This is an important study for the further development of these therapies.”
In a press release, the respiratory medicine specialist noted, “Institut Curie is particularly alert to the issue of the risk of thrombosis arising in cancer patients.” The DASTO project, dedicated to this issue and headed by the Institut Curie, “aims to cross-reference data sourced from several French cancer centers with data from the social security system to understand the risk factors, improve patient treatment, make changes to the care pathway, and prevent this unwanted occurrence from arising.”
Dr. Girard has direct links with Amgen, AstraZeneca, AbbVie, BMS, Daiichi Sankyo, Ipsen, Janssen, Roche, Lilly, Medtronic, MSD, Novartis, OSE Pharma, Pfizer, Sanofi, and Sivan.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
CHICAGO – Having cancer is a known risk factor for thrombosis. A patient with cancer has a fourfold risk of developing venous thromboembolism (VTE).
This risk may be increased by certain cancer drugs, which seems to be the case for the combination of innovative targeted therapies lazertinib-amivantamab, as shown in patients with advanced or metastatic non–small cell lung cancer.
A study of this increased risk of VTE was presented by Nicolas Girard, MD, a respiratory medicine specialist at Curie-Montsouris Chest Center in Paris, during the annual meeting of the American Society of Clinical Oncology.
Combination therapies
Amivantamab is an EGFR and cMET bispecific antibody, and lazertinib is a third-generation EGFR tyrosine kinase inhibitor. Prescribed after osimertinib or after osimertinib plus chemotherapy, this combination of amivantamab and lazertinib has been evaluated in several cohorts of patients with EGFR-mutated advanced non–small cell lung cancer in whom targeted therapy and chemotherapy has failed.
The antitumor activity appears to be improved when both therapies are given in combination. The side effects generally are acceptable. It is these side effects, particularly the rate of VTEs, that Dr. Girard and his colleagues are interested in.
The researchers collated the data from the ongoing CHRYSALIS, CHRYSALIS-2, and LASER201 clinical trials, which assess the efficacy of these new agents as monotherapy or in combination. They initially investigated all reported thrombotic events and ruled out those that occurred during or after the 30 days before disease progression.
Increased thrombosis risk
The analysis included 560 patients who had been given amivantamab as monotherapy, 536 patients who had received amivantamab plus lazertinib in combination, and 252 who had taken lazertinib as monotherapy. The incidence of thromboembolic events was higher among patients who received amivantamab plus lazertinib in combination (21%) than in those who were given amivantamab (11%) or lazertinib (11%) as monotherapy.
The first thromboembolic event occurred an average of 84.5 days after starting treatment with amivantamab, 79 days after starting the combination therapy, and 170 days after starting treatment with lazertinib. For the amivantamab plus lazertinib combination, most VTEs developed in the first 4 months of treatment. The most common VTEs were pulmonary embolism and deep vein thrombosis.
The incidence of severe thrombotic events (grade ≥ 3), which was relatively low (amivantamab, 5%; amivantamab plus lazertinib, 6%; lazertinib, 6%) was similar regardless of the treatment, and there were no grade 5 thrombotic events among patients treated with the combination of both targeted therapies.
The significant risk factors for VTEs identified in this study were being age 60 years or older, having a score of 1 on the ECOG Performance Status Scale, and response to treatment (P < .05).
At a press conference organized by the Institut Curie before the ASCO conference, Dr. Girard said, “There has been shown to be an increased risk of blood clots with the use of this combination of targeted therapies. Preventive measures should therefore also be put forward, such as adding anticoagulant medication. This is an important study for the further development of these therapies.”
In a press release, the respiratory medicine specialist noted, “Institut Curie is particularly alert to the issue of the risk of thrombosis arising in cancer patients.” The DASTO project, dedicated to this issue and headed by the Institut Curie, “aims to cross-reference data sourced from several French cancer centers with data from the social security system to understand the risk factors, improve patient treatment, make changes to the care pathway, and prevent this unwanted occurrence from arising.”
Dr. Girard has direct links with Amgen, AstraZeneca, AbbVie, BMS, Daiichi Sankyo, Ipsen, Janssen, Roche, Lilly, Medtronic, MSD, Novartis, OSE Pharma, Pfizer, Sanofi, and Sivan.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
CHICAGO – Having cancer is a known risk factor for thrombosis. A patient with cancer has a fourfold risk of developing venous thromboembolism (VTE).
This risk may be increased by certain cancer drugs, which seems to be the case for the combination of innovative targeted therapies lazertinib-amivantamab, as shown in patients with advanced or metastatic non–small cell lung cancer.
A study of this increased risk of VTE was presented by Nicolas Girard, MD, a respiratory medicine specialist at Curie-Montsouris Chest Center in Paris, during the annual meeting of the American Society of Clinical Oncology.
Combination therapies
Amivantamab is an EGFR and cMET bispecific antibody, and lazertinib is a third-generation EGFR tyrosine kinase inhibitor. Prescribed after osimertinib or after osimertinib plus chemotherapy, this combination of amivantamab and lazertinib has been evaluated in several cohorts of patients with EGFR-mutated advanced non–small cell lung cancer in whom targeted therapy and chemotherapy has failed.
The antitumor activity appears to be improved when both therapies are given in combination. The side effects generally are acceptable. It is these side effects, particularly the rate of VTEs, that Dr. Girard and his colleagues are interested in.
The researchers collated the data from the ongoing CHRYSALIS, CHRYSALIS-2, and LASER201 clinical trials, which assess the efficacy of these new agents as monotherapy or in combination. They initially investigated all reported thrombotic events and ruled out those that occurred during or after the 30 days before disease progression.
Increased thrombosis risk
The analysis included 560 patients who had been given amivantamab as monotherapy, 536 patients who had received amivantamab plus lazertinib in combination, and 252 who had taken lazertinib as monotherapy. The incidence of thromboembolic events was higher among patients who received amivantamab plus lazertinib in combination (21%) than in those who were given amivantamab (11%) or lazertinib (11%) as monotherapy.
The first thromboembolic event occurred an average of 84.5 days after starting treatment with amivantamab, 79 days after starting the combination therapy, and 170 days after starting treatment with lazertinib. For the amivantamab plus lazertinib combination, most VTEs developed in the first 4 months of treatment. The most common VTEs were pulmonary embolism and deep vein thrombosis.
The incidence of severe thrombotic events (grade ≥ 3), which was relatively low (amivantamab, 5%; amivantamab plus lazertinib, 6%; lazertinib, 6%) was similar regardless of the treatment, and there were no grade 5 thrombotic events among patients treated with the combination of both targeted therapies.
The significant risk factors for VTEs identified in this study were being age 60 years or older, having a score of 1 on the ECOG Performance Status Scale, and response to treatment (P < .05).
At a press conference organized by the Institut Curie before the ASCO conference, Dr. Girard said, “There has been shown to be an increased risk of blood clots with the use of this combination of targeted therapies. Preventive measures should therefore also be put forward, such as adding anticoagulant medication. This is an important study for the further development of these therapies.”
In a press release, the respiratory medicine specialist noted, “Institut Curie is particularly alert to the issue of the risk of thrombosis arising in cancer patients.” The DASTO project, dedicated to this issue and headed by the Institut Curie, “aims to cross-reference data sourced from several French cancer centers with data from the social security system to understand the risk factors, improve patient treatment, make changes to the care pathway, and prevent this unwanted occurrence from arising.”
Dr. Girard has direct links with Amgen, AstraZeneca, AbbVie, BMS, Daiichi Sankyo, Ipsen, Janssen, Roche, Lilly, Medtronic, MSD, Novartis, OSE Pharma, Pfizer, Sanofi, and Sivan.
This article was translated from the Medscape French Edition. A version of this article appeared on Medscape.com.
AT ASCO 2023
FDA OKs empagliflozin for children with type 2 diabetes
aged 10 years and older.
This approval represents only the second oral treatment option for children and adolescents with type 2 diabetes after metformin; the latter appears to be less effective for pediatric patients than for adults.
Injectable glucagonlike peptide–1 (GLP-1) agonists are also available for youth with type 2 diabetes. These include daily liraglutide (Victoza) and once-weekly extended-release exenatide (Bydureon/Bydureon BCise).
Jardiance has been approved for adults with type 2 diabetes since 2014, and Synjardy has been approved since 2015.
“Compared to adults, children with type 2 diabetes have limited treatment options, even though the disease and symptom onset generally progress more rapidly in children,” said Michelle Carey, MD, MPH.
“Today’s approvals provide much-needed additional treatment options for children with type 2 diabetes,” added Dr. Carey, associate director for therapeutic review for the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research.
Type 2 diabetes rising exponentially in children, mainly non-Whites
Type 2 diabetes is rising exponentially in children and adolescents in the United States.
Data from the SEARCH for Diabetes in Youth study show that the incidence of type 2 diabetes among youth rose by about 5% per year between 2002 and 2015, and it continues to rise.
A more recent study found that a doubling of cases occurred during the pandemic, with youth often presenting with more severe disease. The majority of cases are among non-White racial groups.
Safety and efficacy data for empagliflozin for children came from the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO) trial. That trial included 157 patients aged 10-17 years with A1c of 7% or above. Patients were randomly assigned to receive empagliflozin 10 mg or 25 mg daily, linagliptin (a DPP-4 inhibitor) 5 mg, or placebo for 26 weeks. Over 90% were also taking metformin, 40% in combination with insulin. All patients were given diet and exercise advice.
At week 26, the children treated with empagliflozin showed an average 0.2 percentage point decrease in A1c, compared with a 0.7-point increase among those taking placebo. Use of empagliflozin was also associated with lower fasting plasma glucose levels compared with placebo.
Side effects were similar to those seen in adults except for a higher risk of hypoglycemia, regardless of other glucose-lowering therapies that were being taken.
Reduction in A1c for participants treated with linagliptin was not statistically significant in comparison with placebo. There was a numerical reduction of 0.34% (P = .2935).
“Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it’s important to recognize and treat diabetes early in its course,” Lori Laffel, MD, lead investigator of the DINAMO study, said in a press release from BI.
“These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin [has been] the only globally available oral treatment for youth,” added Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School, Boston.
A version of this article first appeared on Medscape.com.
aged 10 years and older.
This approval represents only the second oral treatment option for children and adolescents with type 2 diabetes after metformin; the latter appears to be less effective for pediatric patients than for adults.
Injectable glucagonlike peptide–1 (GLP-1) agonists are also available for youth with type 2 diabetes. These include daily liraglutide (Victoza) and once-weekly extended-release exenatide (Bydureon/Bydureon BCise).
Jardiance has been approved for adults with type 2 diabetes since 2014, and Synjardy has been approved since 2015.
“Compared to adults, children with type 2 diabetes have limited treatment options, even though the disease and symptom onset generally progress more rapidly in children,” said Michelle Carey, MD, MPH.
“Today’s approvals provide much-needed additional treatment options for children with type 2 diabetes,” added Dr. Carey, associate director for therapeutic review for the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research.
Type 2 diabetes rising exponentially in children, mainly non-Whites
Type 2 diabetes is rising exponentially in children and adolescents in the United States.
Data from the SEARCH for Diabetes in Youth study show that the incidence of type 2 diabetes among youth rose by about 5% per year between 2002 and 2015, and it continues to rise.
A more recent study found that a doubling of cases occurred during the pandemic, with youth often presenting with more severe disease. The majority of cases are among non-White racial groups.
Safety and efficacy data for empagliflozin for children came from the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO) trial. That trial included 157 patients aged 10-17 years with A1c of 7% or above. Patients were randomly assigned to receive empagliflozin 10 mg or 25 mg daily, linagliptin (a DPP-4 inhibitor) 5 mg, or placebo for 26 weeks. Over 90% were also taking metformin, 40% in combination with insulin. All patients were given diet and exercise advice.
At week 26, the children treated with empagliflozin showed an average 0.2 percentage point decrease in A1c, compared with a 0.7-point increase among those taking placebo. Use of empagliflozin was also associated with lower fasting plasma glucose levels compared with placebo.
Side effects were similar to those seen in adults except for a higher risk of hypoglycemia, regardless of other glucose-lowering therapies that were being taken.
Reduction in A1c for participants treated with linagliptin was not statistically significant in comparison with placebo. There was a numerical reduction of 0.34% (P = .2935).
“Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it’s important to recognize and treat diabetes early in its course,” Lori Laffel, MD, lead investigator of the DINAMO study, said in a press release from BI.
“These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin [has been] the only globally available oral treatment for youth,” added Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School, Boston.
A version of this article first appeared on Medscape.com.
aged 10 years and older.
This approval represents only the second oral treatment option for children and adolescents with type 2 diabetes after metformin; the latter appears to be less effective for pediatric patients than for adults.
Injectable glucagonlike peptide–1 (GLP-1) agonists are also available for youth with type 2 diabetes. These include daily liraglutide (Victoza) and once-weekly extended-release exenatide (Bydureon/Bydureon BCise).
Jardiance has been approved for adults with type 2 diabetes since 2014, and Synjardy has been approved since 2015.
“Compared to adults, children with type 2 diabetes have limited treatment options, even though the disease and symptom onset generally progress more rapidly in children,” said Michelle Carey, MD, MPH.
“Today’s approvals provide much-needed additional treatment options for children with type 2 diabetes,” added Dr. Carey, associate director for therapeutic review for the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research.
Type 2 diabetes rising exponentially in children, mainly non-Whites
Type 2 diabetes is rising exponentially in children and adolescents in the United States.
Data from the SEARCH for Diabetes in Youth study show that the incidence of type 2 diabetes among youth rose by about 5% per year between 2002 and 2015, and it continues to rise.
A more recent study found that a doubling of cases occurred during the pandemic, with youth often presenting with more severe disease. The majority of cases are among non-White racial groups.
Safety and efficacy data for empagliflozin for children came from the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO) trial. That trial included 157 patients aged 10-17 years with A1c of 7% or above. Patients were randomly assigned to receive empagliflozin 10 mg or 25 mg daily, linagliptin (a DPP-4 inhibitor) 5 mg, or placebo for 26 weeks. Over 90% were also taking metformin, 40% in combination with insulin. All patients were given diet and exercise advice.
At week 26, the children treated with empagliflozin showed an average 0.2 percentage point decrease in A1c, compared with a 0.7-point increase among those taking placebo. Use of empagliflozin was also associated with lower fasting plasma glucose levels compared with placebo.
Side effects were similar to those seen in adults except for a higher risk of hypoglycemia, regardless of other glucose-lowering therapies that were being taken.
Reduction in A1c for participants treated with linagliptin was not statistically significant in comparison with placebo. There was a numerical reduction of 0.34% (P = .2935).
“Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it’s important to recognize and treat diabetes early in its course,” Lori Laffel, MD, lead investigator of the DINAMO study, said in a press release from BI.
“These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin [has been] the only globally available oral treatment for youth,” added Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School, Boston.
A version of this article first appeared on Medscape.com.
Few of those eligible get lung cancer screening, despite USPSTF recommendations
Only 12.8% of eligible adults get CT screening for lung cancer, despite recommendations from the U.S. Preventive Services Task Force.
Kristin G. Maki, PhD, with Karmanos Cancer Institute, Wayne State University, Detroit, led a team that estimated lung cancer screening (LCS) from the 2021 Behavioral Risk Factor Surveillance System in four states (Maine, Michigan, New Jersey, and Rhode Island).
“Increasing LCS among eligible adults is a national priority,” the authors wrote in the study, published online in JAMA Network Open. Lung cancer remains the top cause of cancer in the United States and smoking accounts for approximately 90% of cases.
Screening much higher for other cancers
The authors pointed out that screening rates for eligible people are much higher for other cancers. Melzer and colleagues wrote in a 2021 editorial that breast and colon cancer screening rates are near 70% “despite combined annual death rates less than two-thirds that of lung cancer.”
The USPSTF updated its recommendations for lung cancer screening in March 2021.
Eligibility now includes anyone aged between 50 and 80 years who has smoked at least 20 pack-years and either still smokes or quit within the last 15 years.
The researchers found that, when comparing screening by health status, the highest odds for screening were seen in those who reported they were in poor health, which is concerning, the authors note, because those patients may not be healthy enough to benefit from treatment for their lung cancer.
The odds ratio for getting screening was 2.88 (95% confidence interval, 0.85-9.77) times higher than that of the reference group, which reported excellent health.
Rates differ by state
Consistent with previous studies, this analysis found that screening rates differed by state. Their analysis, for example, showed a higher likelihood of screening for respondents in Rhode Island, compared with Maine (OR, 1.96; 95% CI, 1.05-3.67; P = .03).
Patients who reported having a primary health professional were more than five times more likely to undergo screening, compared with those without one (OR, 5.62; 95% CI, 1.19-26.49).
The authors said their results also highlight the need for Medicare coverage for screening as those with public insurance had lower odds of screening than those with private insurance (OR, 0.81; 95% CI, 0.42-1.56).
Neelima Navuluri, MD, assistant professor in the division of pulmonary, allergy, and critical care at Duke University and the Duke Global Health Institute, both in Durham, N.C., pointed out that the study highlights age, smoking status, and health care access as key factors associated with lack of uptake.
Work needed on all levels
Dr. Navuluri said in an interview that multifaceted patient-, provider- and system-level interventions are needed to improve screening rates.
“For example, we need more community engagement to increase knowledge and awareness of eligibility for lung cancer screening,” she said.
She highlighted the need for interventions around improving and streamlining shared decision-making conversations about screening (a CMS requirement that does not exist for other cancer screening).
Emphasis is needed on younger age groups, people who currently smoke, and communities of color as well as policy to improve insurance coverage of screening, she said.
Dr. Navuluri, who also works with the Durham Veterans Affairs Medical Center, was lead author on a study published in JAMA Network Open on racial disparities in screening among veterans.
“We demonstrate similar findings related to age, smoking status, and poor health status,” she said. “We discuss the need for more qualitative studies to better understand the role of these factors as well as implementation studies to assess effectiveness of various interventions to improve disparities in lung cancer screening rates.”
“Research to identify facilitators for LCS among persons who currently smoke is needed, including a focus on the role of stigma as a barrier to screening,” they wrote.
One coauthor is supported by the cancer prevention and research training program at the University of Texas MD Anderson Cancer Center and the Cancer Prevention and Research Institute of Texas. No other disclosures were reported. Dr. Navuluri receives funding from the National Comprehensive Cancer Network for work on lung cancer screening.
Only 12.8% of eligible adults get CT screening for lung cancer, despite recommendations from the U.S. Preventive Services Task Force.
Kristin G. Maki, PhD, with Karmanos Cancer Institute, Wayne State University, Detroit, led a team that estimated lung cancer screening (LCS) from the 2021 Behavioral Risk Factor Surveillance System in four states (Maine, Michigan, New Jersey, and Rhode Island).
“Increasing LCS among eligible adults is a national priority,” the authors wrote in the study, published online in JAMA Network Open. Lung cancer remains the top cause of cancer in the United States and smoking accounts for approximately 90% of cases.
Screening much higher for other cancers
The authors pointed out that screening rates for eligible people are much higher for other cancers. Melzer and colleagues wrote in a 2021 editorial that breast and colon cancer screening rates are near 70% “despite combined annual death rates less than two-thirds that of lung cancer.”
The USPSTF updated its recommendations for lung cancer screening in March 2021.
Eligibility now includes anyone aged between 50 and 80 years who has smoked at least 20 pack-years and either still smokes or quit within the last 15 years.
The researchers found that, when comparing screening by health status, the highest odds for screening were seen in those who reported they were in poor health, which is concerning, the authors note, because those patients may not be healthy enough to benefit from treatment for their lung cancer.
The odds ratio for getting screening was 2.88 (95% confidence interval, 0.85-9.77) times higher than that of the reference group, which reported excellent health.
Rates differ by state
Consistent with previous studies, this analysis found that screening rates differed by state. Their analysis, for example, showed a higher likelihood of screening for respondents in Rhode Island, compared with Maine (OR, 1.96; 95% CI, 1.05-3.67; P = .03).
Patients who reported having a primary health professional were more than five times more likely to undergo screening, compared with those without one (OR, 5.62; 95% CI, 1.19-26.49).
The authors said their results also highlight the need for Medicare coverage for screening as those with public insurance had lower odds of screening than those with private insurance (OR, 0.81; 95% CI, 0.42-1.56).
Neelima Navuluri, MD, assistant professor in the division of pulmonary, allergy, and critical care at Duke University and the Duke Global Health Institute, both in Durham, N.C., pointed out that the study highlights age, smoking status, and health care access as key factors associated with lack of uptake.
Work needed on all levels
Dr. Navuluri said in an interview that multifaceted patient-, provider- and system-level interventions are needed to improve screening rates.
“For example, we need more community engagement to increase knowledge and awareness of eligibility for lung cancer screening,” she said.
She highlighted the need for interventions around improving and streamlining shared decision-making conversations about screening (a CMS requirement that does not exist for other cancer screening).
Emphasis is needed on younger age groups, people who currently smoke, and communities of color as well as policy to improve insurance coverage of screening, she said.
Dr. Navuluri, who also works with the Durham Veterans Affairs Medical Center, was lead author on a study published in JAMA Network Open on racial disparities in screening among veterans.
“We demonstrate similar findings related to age, smoking status, and poor health status,” she said. “We discuss the need for more qualitative studies to better understand the role of these factors as well as implementation studies to assess effectiveness of various interventions to improve disparities in lung cancer screening rates.”
“Research to identify facilitators for LCS among persons who currently smoke is needed, including a focus on the role of stigma as a barrier to screening,” they wrote.
One coauthor is supported by the cancer prevention and research training program at the University of Texas MD Anderson Cancer Center and the Cancer Prevention and Research Institute of Texas. No other disclosures were reported. Dr. Navuluri receives funding from the National Comprehensive Cancer Network for work on lung cancer screening.
Only 12.8% of eligible adults get CT screening for lung cancer, despite recommendations from the U.S. Preventive Services Task Force.
Kristin G. Maki, PhD, with Karmanos Cancer Institute, Wayne State University, Detroit, led a team that estimated lung cancer screening (LCS) from the 2021 Behavioral Risk Factor Surveillance System in four states (Maine, Michigan, New Jersey, and Rhode Island).
“Increasing LCS among eligible adults is a national priority,” the authors wrote in the study, published online in JAMA Network Open. Lung cancer remains the top cause of cancer in the United States and smoking accounts for approximately 90% of cases.
Screening much higher for other cancers
The authors pointed out that screening rates for eligible people are much higher for other cancers. Melzer and colleagues wrote in a 2021 editorial that breast and colon cancer screening rates are near 70% “despite combined annual death rates less than two-thirds that of lung cancer.”
The USPSTF updated its recommendations for lung cancer screening in March 2021.
Eligibility now includes anyone aged between 50 and 80 years who has smoked at least 20 pack-years and either still smokes or quit within the last 15 years.
The researchers found that, when comparing screening by health status, the highest odds for screening were seen in those who reported they were in poor health, which is concerning, the authors note, because those patients may not be healthy enough to benefit from treatment for their lung cancer.
The odds ratio for getting screening was 2.88 (95% confidence interval, 0.85-9.77) times higher than that of the reference group, which reported excellent health.
Rates differ by state
Consistent with previous studies, this analysis found that screening rates differed by state. Their analysis, for example, showed a higher likelihood of screening for respondents in Rhode Island, compared with Maine (OR, 1.96; 95% CI, 1.05-3.67; P = .03).
Patients who reported having a primary health professional were more than five times more likely to undergo screening, compared with those without one (OR, 5.62; 95% CI, 1.19-26.49).
The authors said their results also highlight the need for Medicare coverage for screening as those with public insurance had lower odds of screening than those with private insurance (OR, 0.81; 95% CI, 0.42-1.56).
Neelima Navuluri, MD, assistant professor in the division of pulmonary, allergy, and critical care at Duke University and the Duke Global Health Institute, both in Durham, N.C., pointed out that the study highlights age, smoking status, and health care access as key factors associated with lack of uptake.
Work needed on all levels
Dr. Navuluri said in an interview that multifaceted patient-, provider- and system-level interventions are needed to improve screening rates.
“For example, we need more community engagement to increase knowledge and awareness of eligibility for lung cancer screening,” she said.
She highlighted the need for interventions around improving and streamlining shared decision-making conversations about screening (a CMS requirement that does not exist for other cancer screening).
Emphasis is needed on younger age groups, people who currently smoke, and communities of color as well as policy to improve insurance coverage of screening, she said.
Dr. Navuluri, who also works with the Durham Veterans Affairs Medical Center, was lead author on a study published in JAMA Network Open on racial disparities in screening among veterans.
“We demonstrate similar findings related to age, smoking status, and poor health status,” she said. “We discuss the need for more qualitative studies to better understand the role of these factors as well as implementation studies to assess effectiveness of various interventions to improve disparities in lung cancer screening rates.”
“Research to identify facilitators for LCS among persons who currently smoke is needed, including a focus on the role of stigma as a barrier to screening,” they wrote.
One coauthor is supported by the cancer prevention and research training program at the University of Texas MD Anderson Cancer Center and the Cancer Prevention and Research Institute of Texas. No other disclosures were reported. Dr. Navuluri receives funding from the National Comprehensive Cancer Network for work on lung cancer screening.
FROM JAMA NETWORK OPEN
Final USPSTF recommendations on anxiety, depression, suicide risk
In line with draft recommendations, the task force for the first time has endorsed screening for anxiety disorders in all adults younger than age 65 without recognized signs or symptoms of anxiety.
This “B” recommendation reflects “moderate certainty” evidence that screening for anxiety in this population has a moderate net benefit. There currently is not enough evidence to recommend for or against screening for anxiety disorders in adults 65 and older, the task force said.
The USPSTF final recommendation statements and corresponding evidence summaries were published online in the Journal of the American Medical Association, as well as on the task force website.
Jury out on screening for suicide risk
The task force continues to recommend screening all adults for depression. This “B” recommendation reflects moderate-certainty evidence that screening for major depression in adults has a moderate net benefit.
However, there is not enough evidence to recommend for or against screening for suicide risk in all adults. Therefore, the task issued an “I” statement, indicating that the balance of benefits and harms cannot be determined at present.
“We are urgently calling for more research to determine the effectiveness of screening all adults for suicide risk and screening adults 65 and older for anxiety disorders,” task force member Gbenga Ogedegbe, MD, MPH, founding director of the Institute for Excellence in Health Equity at NYU Langone Health, New York, said in a statement.
The authors of an accompanying editorial noted that a positive screen result for anxiety “should be immediately followed with clinical evaluation for suicidality”.
Murray Stein, MD, MPH, and Linda Hill, MD, MPH, both with University of California, San Diego, also noted that a positive screen for anxiety could be indicative of posttraumatic stress disorder (PTSD) and clinicians should “be prepared to follow up with requisite questions about traumatic experiences that will be needed to home in on a diagnosis of PTSD that may require additional follow-up, referral, or both.
“Anxiety disorders can be distressing and disabling, and appropriate recognition and treatment can be life-altering and, in some cases, lifesaving, for patients,” Dr. Stein and Dr. Hill pointed out.
Effective, evidence-based psychological and pharmacologic treatments for anxiety disorders are available, they added. But the recommendation to routinely screen for anxiety disorder “must be accompanied by the recognition that there are too few mental health specialists available to manage the care of all patients with anxiety disorders, and even fewer who provide services for low-income and non-English-speaking populations,” they wrote.
This research report received no commercial funding. Disclosures for task force members and editorial writers are listed with the original articles.
A version of this article originally appeared on Medscape.com.
In line with draft recommendations, the task force for the first time has endorsed screening for anxiety disorders in all adults younger than age 65 without recognized signs or symptoms of anxiety.
This “B” recommendation reflects “moderate certainty” evidence that screening for anxiety in this population has a moderate net benefit. There currently is not enough evidence to recommend for or against screening for anxiety disorders in adults 65 and older, the task force said.
The USPSTF final recommendation statements and corresponding evidence summaries were published online in the Journal of the American Medical Association, as well as on the task force website.
Jury out on screening for suicide risk
The task force continues to recommend screening all adults for depression. This “B” recommendation reflects moderate-certainty evidence that screening for major depression in adults has a moderate net benefit.
However, there is not enough evidence to recommend for or against screening for suicide risk in all adults. Therefore, the task issued an “I” statement, indicating that the balance of benefits and harms cannot be determined at present.
“We are urgently calling for more research to determine the effectiveness of screening all adults for suicide risk and screening adults 65 and older for anxiety disorders,” task force member Gbenga Ogedegbe, MD, MPH, founding director of the Institute for Excellence in Health Equity at NYU Langone Health, New York, said in a statement.
The authors of an accompanying editorial noted that a positive screen result for anxiety “should be immediately followed with clinical evaluation for suicidality”.
Murray Stein, MD, MPH, and Linda Hill, MD, MPH, both with University of California, San Diego, also noted that a positive screen for anxiety could be indicative of posttraumatic stress disorder (PTSD) and clinicians should “be prepared to follow up with requisite questions about traumatic experiences that will be needed to home in on a diagnosis of PTSD that may require additional follow-up, referral, or both.
“Anxiety disorders can be distressing and disabling, and appropriate recognition and treatment can be life-altering and, in some cases, lifesaving, for patients,” Dr. Stein and Dr. Hill pointed out.
Effective, evidence-based psychological and pharmacologic treatments for anxiety disorders are available, they added. But the recommendation to routinely screen for anxiety disorder “must be accompanied by the recognition that there are too few mental health specialists available to manage the care of all patients with anxiety disorders, and even fewer who provide services for low-income and non-English-speaking populations,” they wrote.
This research report received no commercial funding. Disclosures for task force members and editorial writers are listed with the original articles.
A version of this article originally appeared on Medscape.com.
In line with draft recommendations, the task force for the first time has endorsed screening for anxiety disorders in all adults younger than age 65 without recognized signs or symptoms of anxiety.
This “B” recommendation reflects “moderate certainty” evidence that screening for anxiety in this population has a moderate net benefit. There currently is not enough evidence to recommend for or against screening for anxiety disorders in adults 65 and older, the task force said.
The USPSTF final recommendation statements and corresponding evidence summaries were published online in the Journal of the American Medical Association, as well as on the task force website.
Jury out on screening for suicide risk
The task force continues to recommend screening all adults for depression. This “B” recommendation reflects moderate-certainty evidence that screening for major depression in adults has a moderate net benefit.
However, there is not enough evidence to recommend for or against screening for suicide risk in all adults. Therefore, the task issued an “I” statement, indicating that the balance of benefits and harms cannot be determined at present.
“We are urgently calling for more research to determine the effectiveness of screening all adults for suicide risk and screening adults 65 and older for anxiety disorders,” task force member Gbenga Ogedegbe, MD, MPH, founding director of the Institute for Excellence in Health Equity at NYU Langone Health, New York, said in a statement.
The authors of an accompanying editorial noted that a positive screen result for anxiety “should be immediately followed with clinical evaluation for suicidality”.
Murray Stein, MD, MPH, and Linda Hill, MD, MPH, both with University of California, San Diego, also noted that a positive screen for anxiety could be indicative of posttraumatic stress disorder (PTSD) and clinicians should “be prepared to follow up with requisite questions about traumatic experiences that will be needed to home in on a diagnosis of PTSD that may require additional follow-up, referral, or both.
“Anxiety disorders can be distressing and disabling, and appropriate recognition and treatment can be life-altering and, in some cases, lifesaving, for patients,” Dr. Stein and Dr. Hill pointed out.
Effective, evidence-based psychological and pharmacologic treatments for anxiety disorders are available, they added. But the recommendation to routinely screen for anxiety disorder “must be accompanied by the recognition that there are too few mental health specialists available to manage the care of all patients with anxiety disorders, and even fewer who provide services for low-income and non-English-speaking populations,” they wrote.
This research report received no commercial funding. Disclosures for task force members and editorial writers are listed with the original articles.
A version of this article originally appeared on Medscape.com.
Gilteritinib maintenance reduces relapse in MRD+ AML
The research was presented at the European Hematology Association Hybrid Congress 2023.
For the study, AML patients with the most common form of mutation in the proto-oncogene fms-like tyrosine kinase 3 (FLT3), known as the internal tandem duplication (ITD), were randomized to 24 months of maintenance therapy with either the FLT3 inhibitor gilteritinib or placebo.
The trial did not meet its primary endpoint, as there was no significant difference in relapse-free survival (RFS) between those assigned to the active drug and those given placebo, and there was no difference in overall survival rates.
However, subgroup analysis revealed that FLT3/ITD AML patients who were MRD+ after transplant, which represented approximately half of the participants, experienced a significant 48% improvement in RFS with gilteritinib versus placebo, while no benefit was seen in MRD– patients.
While acknowledging that the trial did not meet its primary endpoint, presenter Mark J. Levis, MD, PhD, program leader, hematologic malignancies and bone marrow transplant program, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, said it was nevertheless “a successful study.”
“We learned how to use these drugs and in whom,” he continued, adding: “No, not everybody needs and should get a FLT3 inhibitor post-transplant, but we can use this [MRD] assay to identify who.”
Consequently, Dr. Levis believes that gilteritinib “should be a standard of care for those who are MRD positive,” although the decision to use it “should be balanced against the potential for toxicity,” compared with not adding an additional treatment after HCT.
He told a press conference that “we’re going to certainly make sure that patients who are MRD positive get [gilteritinib],” although the MRD negative patients “are going to be more questionable,” especially because the assay that they used in the study is not “perfect.”
Dr. Levis also suggested that the trial did not meet its endpoint because of regional differences in the clinical practice, such as in the number of treatment cycles prior to HCT, the time to transplant, and the previous use of a FLT3 inhibitor, all of which may have skewed the findings.
“Everybody in the world is convinced that they’re the best transplanter,” he said, and yet “they all do it differently, and the heterogeneity is astounding.”
He added: “If we’d restricted everybody [to a] pretransplant regimen, I suspect we would have had a different result than what we’re getting here, but this is releasing the drug into the world and saying: ‘Here, transplant however you want, however it’s practiced in the real world. Tell us how this works.’ ”
Approached for comment, Claudio Brunstein, MD, PhD, vice-chair of the department of hematology and oncology in the Cleveland Clinic Taussig Cancer Institute, said that while there was “some disappointment” with the results, he was “not surprised” that the trial did not meet its primary endpoint.
He said in an interview that the patient population was not of “high enough risk” to demonstrate an overall difference between gilteritinib and placebo, although he conceded that it is “hard to get to high-risk patients in a timely way” and so conduct a trial with them.
As to the notion that variations in clinical practice could have been responsible, Dr. Brunstein pointed out that it was a randomized trial, so the issue would have applied equally to both sides.
He nevertheless believes that it is “a very important study,” and “just the fact that it was done in the context of a number of drugs coming and being approved by the [U.S. Food and Drug Administration] in AML is quite remarkable.”
This is especially the case given that “many centers are already using [gilteritinib] as off-label maintenance therapy.”
Dr. Brunstein added that it is “good news” that the drug was effective in MRD+ patients, as it shows “you can overcome that with maintenance therapy rather than keeping giving more and more chemotherapy, especially as there are patients you’re worried about giving more intensive chemotherapy to make them MRD negative.”
He pointed out, however, that the assay used in the trial was “research grade” and very sensitive to MRD and “is not available everywhere, so there is an adjustment that the community will have to do to in order to apply this data.”
“But for those who are more obviously MRD positive with less sensitive assays, gilteritinib is already something that can be used,” Dr. Brunstein said.
Presenting the findings, Dr. Levis stated: “We all know that patients with FLT3/ITD AML have a high risk of relapse and are routinely referred for transplant. And we know that the detection of measurable residual disease pretransplant is highly predictive of outcome post-transplant.”
He continued that FLT3 inhibitors are “routinely given as post-transplant maintenance ... based on some prior trials, mostly with sorafenib.”
“But uncertainty exists as to the broad applicability of these trials,” Dr. Levis said. Moreover, the use of sorafenib in this context is “off label and can be difficult to tolerate,” and “we know that most patients are cured with allogeneic transplant alone.”
Gilteritinib is already known to be well tolerated as a monotherapy, and was approved by the FDA for the treatment of adult patients with FLT3 mutation–positive relapsed or refractory AML in 2018.
The investigators therefore examined whether it would be beneficial as a post-HCT maintenance therapy in FLT3-ITD AML. Patients were required to be in morphologic remission after one or two courses of induction therapy, with Dr. Levis underlining: “We did not allow patients who had been salvaged onto the study.”
They subsequently had a marrow aspirate sample taken for MRD analysis before undergoing allogeneic transplant, with any conditioning regimen, donor, or graft-versus-host disease (GVHD) prophylaxis allowed.
Between 30 and 90 days later, patients with successful engraftment who were able to take oral medication were then randomized to 24 months of maintenance therapy with either gilteritinib or placebo.
Dr. Levis showed that, among 620 patients screened at 110 centers in 16 countries, 356 were randomized between Aug. 15, 2017, and July 8, 2020. The median age was 53 years, and 49% of gilteritinib patients and 48% of those given placebo were female.
He noted that there was a “fairly even global distribution” of patients from North America, Europe, and the Asia/Pacific region, and that 60% of patients underwent a myeloablative conditioning regimen. Approximately the same proportion had received an FLT3 inhibitor prior to HCT.
MRD positivity, assessed at a cell count of ≥ 10-6, was observed pre-HCT in 47% of patients in both treatment groups, and in 50% of gilteritinib patients and 51% of placebo patients at both pre- and post-transplant assessments.
The treatment regimen was completed by 52.8% of patients assigned to gilteritinib and 53.9% in the placebo arm. Dr. Levis said that 18.5% and 20.3% of patients, respectively, experienced a grade 3/4 treatment emergent acute GVHD event, while 32.6% and 21.5%, respectively, had a grade ≥ 3 treatment emergent infection.
He noted that “adverse events were clearly more common in the gilteritinib arm and often led to either dose reduction or interruption, or withdrawal of treatment.”
The most common grade ≥ 3 treatment emergent adverse event was a decrease in neutrophil count, seen in 24.7% of gilteritinib patients and 7.9% of those given placebo, followed by reduced platelet count, in 15.2% and 5.6%, respectively, and anemia, in 6.2% and 1.7%, respectively.
Turning to the efficacy outcomes, Dr. Levis reported that the trial did not meet its primary endpoint, with no significant difference in RFS between the gilteritinib and placebo arms, at a hazard ratio of 0.679 (P = .0518). There was also no significant difference in the key secondary objective of overall survival, at a hazard ratio of 0.846 (P = .4394).
However, Dr. Levis noted that there was a “clear difference in the benefit of gilteritinib by region,” and, “at every level,” MRD predicted a benefit from gilteritinib, which he said was a “big surprise” and “really leapt out in the subgroup analysis.”
He explained that the researchers used a modified version of a two-step assay that has been used in previous studies, and was able to detect MRD at a sensitivity of approximately 1x10-6. “In our study, 98% of participants had samples pre- and post-[transplant].”
Regardless of treatment arm, MRD positivity measured at that sensitivity was associated with a significant reduction in overall survival, at a hazard ratio versus MRD– status of 0.514 (P = .0025).
When stratifying the patients by MRD status, the researchers found that, among MRD+ participants, gilteritinib was associated with a significant improvement in RFS, at a hazard ratio versus placebo of 0.515 (P = .0065), while there was no significant difference in MRD– patients.
Stratifying the patients by their conditioning regimen prior to HCT also revealed differences, with those undergoing myeloablative conditioning having significantly greater overall survival than those who underwent reduced-intensity conditioning, at a hazard ratio for death of 0.529 (P = .0027).
Dr. Levis said there is “no surprise there,” and the result could reflect the selection of fitter, younger patients to undergo the more intensive regimen.
He then showed that MRD+ patients who had undergone myeloablative conditioning had better overall survival with gilteritinib than placebo, at a hazard ratio for death of 0.418 (P = .0087). Again, the difference disappeared when looking at MRD– patients.
“So conditioning doesn’t help you in the setting of MRD,” Dr. Levis said.
Finally, he took a deeper dive into the regional differences in outcomes, noting that patients in the Asia/Pacific region, where gilteritinib showed no benefit over placebo, “were 10 years younger” than those in other regions, “tended to get myeloablative conditioning, and hardly ever used FLT3 inhibitors.”
In contrast, North American patients, who experienced a significant gilteritinib benefit in terms of RFS, underwent HCT an average of 26 days earlier than those elsewhere, and received fewer courses of chemotherapy pre-HCT. Moreover, 93.5% received an FLT3 inhibitor pretransplant.
The study was funded by Astellas Pharma Global Development. Dr. Levis declares relationships with Abbvie, Amgen, Astellas, Bristol-Myers-Squibb, Daiichi-Sankyo, GlaxoSmithKline, Jazz, Menarini, Pfizer, Sumitomo-Dainippon, Syndax, Takeda. Dr. Brunstein declares no relevant relationships.
The research was presented at the European Hematology Association Hybrid Congress 2023.
For the study, AML patients with the most common form of mutation in the proto-oncogene fms-like tyrosine kinase 3 (FLT3), known as the internal tandem duplication (ITD), were randomized to 24 months of maintenance therapy with either the FLT3 inhibitor gilteritinib or placebo.
The trial did not meet its primary endpoint, as there was no significant difference in relapse-free survival (RFS) between those assigned to the active drug and those given placebo, and there was no difference in overall survival rates.
However, subgroup analysis revealed that FLT3/ITD AML patients who were MRD+ after transplant, which represented approximately half of the participants, experienced a significant 48% improvement in RFS with gilteritinib versus placebo, while no benefit was seen in MRD– patients.
While acknowledging that the trial did not meet its primary endpoint, presenter Mark J. Levis, MD, PhD, program leader, hematologic malignancies and bone marrow transplant program, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, said it was nevertheless “a successful study.”
“We learned how to use these drugs and in whom,” he continued, adding: “No, not everybody needs and should get a FLT3 inhibitor post-transplant, but we can use this [MRD] assay to identify who.”
Consequently, Dr. Levis believes that gilteritinib “should be a standard of care for those who are MRD positive,” although the decision to use it “should be balanced against the potential for toxicity,” compared with not adding an additional treatment after HCT.
He told a press conference that “we’re going to certainly make sure that patients who are MRD positive get [gilteritinib],” although the MRD negative patients “are going to be more questionable,” especially because the assay that they used in the study is not “perfect.”
Dr. Levis also suggested that the trial did not meet its endpoint because of regional differences in the clinical practice, such as in the number of treatment cycles prior to HCT, the time to transplant, and the previous use of a FLT3 inhibitor, all of which may have skewed the findings.
“Everybody in the world is convinced that they’re the best transplanter,” he said, and yet “they all do it differently, and the heterogeneity is astounding.”
He added: “If we’d restricted everybody [to a] pretransplant regimen, I suspect we would have had a different result than what we’re getting here, but this is releasing the drug into the world and saying: ‘Here, transplant however you want, however it’s practiced in the real world. Tell us how this works.’ ”
Approached for comment, Claudio Brunstein, MD, PhD, vice-chair of the department of hematology and oncology in the Cleveland Clinic Taussig Cancer Institute, said that while there was “some disappointment” with the results, he was “not surprised” that the trial did not meet its primary endpoint.
He said in an interview that the patient population was not of “high enough risk” to demonstrate an overall difference between gilteritinib and placebo, although he conceded that it is “hard to get to high-risk patients in a timely way” and so conduct a trial with them.
As to the notion that variations in clinical practice could have been responsible, Dr. Brunstein pointed out that it was a randomized trial, so the issue would have applied equally to both sides.
He nevertheless believes that it is “a very important study,” and “just the fact that it was done in the context of a number of drugs coming and being approved by the [U.S. Food and Drug Administration] in AML is quite remarkable.”
This is especially the case given that “many centers are already using [gilteritinib] as off-label maintenance therapy.”
Dr. Brunstein added that it is “good news” that the drug was effective in MRD+ patients, as it shows “you can overcome that with maintenance therapy rather than keeping giving more and more chemotherapy, especially as there are patients you’re worried about giving more intensive chemotherapy to make them MRD negative.”
He pointed out, however, that the assay used in the trial was “research grade” and very sensitive to MRD and “is not available everywhere, so there is an adjustment that the community will have to do to in order to apply this data.”
“But for those who are more obviously MRD positive with less sensitive assays, gilteritinib is already something that can be used,” Dr. Brunstein said.
Presenting the findings, Dr. Levis stated: “We all know that patients with FLT3/ITD AML have a high risk of relapse and are routinely referred for transplant. And we know that the detection of measurable residual disease pretransplant is highly predictive of outcome post-transplant.”
He continued that FLT3 inhibitors are “routinely given as post-transplant maintenance ... based on some prior trials, mostly with sorafenib.”
“But uncertainty exists as to the broad applicability of these trials,” Dr. Levis said. Moreover, the use of sorafenib in this context is “off label and can be difficult to tolerate,” and “we know that most patients are cured with allogeneic transplant alone.”
Gilteritinib is already known to be well tolerated as a monotherapy, and was approved by the FDA for the treatment of adult patients with FLT3 mutation–positive relapsed or refractory AML in 2018.
The investigators therefore examined whether it would be beneficial as a post-HCT maintenance therapy in FLT3-ITD AML. Patients were required to be in morphologic remission after one or two courses of induction therapy, with Dr. Levis underlining: “We did not allow patients who had been salvaged onto the study.”
They subsequently had a marrow aspirate sample taken for MRD analysis before undergoing allogeneic transplant, with any conditioning regimen, donor, or graft-versus-host disease (GVHD) prophylaxis allowed.
Between 30 and 90 days later, patients with successful engraftment who were able to take oral medication were then randomized to 24 months of maintenance therapy with either gilteritinib or placebo.
Dr. Levis showed that, among 620 patients screened at 110 centers in 16 countries, 356 were randomized between Aug. 15, 2017, and July 8, 2020. The median age was 53 years, and 49% of gilteritinib patients and 48% of those given placebo were female.
He noted that there was a “fairly even global distribution” of patients from North America, Europe, and the Asia/Pacific region, and that 60% of patients underwent a myeloablative conditioning regimen. Approximately the same proportion had received an FLT3 inhibitor prior to HCT.
MRD positivity, assessed at a cell count of ≥ 10-6, was observed pre-HCT in 47% of patients in both treatment groups, and in 50% of gilteritinib patients and 51% of placebo patients at both pre- and post-transplant assessments.
The treatment regimen was completed by 52.8% of patients assigned to gilteritinib and 53.9% in the placebo arm. Dr. Levis said that 18.5% and 20.3% of patients, respectively, experienced a grade 3/4 treatment emergent acute GVHD event, while 32.6% and 21.5%, respectively, had a grade ≥ 3 treatment emergent infection.
He noted that “adverse events were clearly more common in the gilteritinib arm and often led to either dose reduction or interruption, or withdrawal of treatment.”
The most common grade ≥ 3 treatment emergent adverse event was a decrease in neutrophil count, seen in 24.7% of gilteritinib patients and 7.9% of those given placebo, followed by reduced platelet count, in 15.2% and 5.6%, respectively, and anemia, in 6.2% and 1.7%, respectively.
Turning to the efficacy outcomes, Dr. Levis reported that the trial did not meet its primary endpoint, with no significant difference in RFS between the gilteritinib and placebo arms, at a hazard ratio of 0.679 (P = .0518). There was also no significant difference in the key secondary objective of overall survival, at a hazard ratio of 0.846 (P = .4394).
However, Dr. Levis noted that there was a “clear difference in the benefit of gilteritinib by region,” and, “at every level,” MRD predicted a benefit from gilteritinib, which he said was a “big surprise” and “really leapt out in the subgroup analysis.”
He explained that the researchers used a modified version of a two-step assay that has been used in previous studies, and was able to detect MRD at a sensitivity of approximately 1x10-6. “In our study, 98% of participants had samples pre- and post-[transplant].”
Regardless of treatment arm, MRD positivity measured at that sensitivity was associated with a significant reduction in overall survival, at a hazard ratio versus MRD– status of 0.514 (P = .0025).
When stratifying the patients by MRD status, the researchers found that, among MRD+ participants, gilteritinib was associated with a significant improvement in RFS, at a hazard ratio versus placebo of 0.515 (P = .0065), while there was no significant difference in MRD– patients.
Stratifying the patients by their conditioning regimen prior to HCT also revealed differences, with those undergoing myeloablative conditioning having significantly greater overall survival than those who underwent reduced-intensity conditioning, at a hazard ratio for death of 0.529 (P = .0027).
Dr. Levis said there is “no surprise there,” and the result could reflect the selection of fitter, younger patients to undergo the more intensive regimen.
He then showed that MRD+ patients who had undergone myeloablative conditioning had better overall survival with gilteritinib than placebo, at a hazard ratio for death of 0.418 (P = .0087). Again, the difference disappeared when looking at MRD– patients.
“So conditioning doesn’t help you in the setting of MRD,” Dr. Levis said.
Finally, he took a deeper dive into the regional differences in outcomes, noting that patients in the Asia/Pacific region, where gilteritinib showed no benefit over placebo, “were 10 years younger” than those in other regions, “tended to get myeloablative conditioning, and hardly ever used FLT3 inhibitors.”
In contrast, North American patients, who experienced a significant gilteritinib benefit in terms of RFS, underwent HCT an average of 26 days earlier than those elsewhere, and received fewer courses of chemotherapy pre-HCT. Moreover, 93.5% received an FLT3 inhibitor pretransplant.
The study was funded by Astellas Pharma Global Development. Dr. Levis declares relationships with Abbvie, Amgen, Astellas, Bristol-Myers-Squibb, Daiichi-Sankyo, GlaxoSmithKline, Jazz, Menarini, Pfizer, Sumitomo-Dainippon, Syndax, Takeda. Dr. Brunstein declares no relevant relationships.
The research was presented at the European Hematology Association Hybrid Congress 2023.
For the study, AML patients with the most common form of mutation in the proto-oncogene fms-like tyrosine kinase 3 (FLT3), known as the internal tandem duplication (ITD), were randomized to 24 months of maintenance therapy with either the FLT3 inhibitor gilteritinib or placebo.
The trial did not meet its primary endpoint, as there was no significant difference in relapse-free survival (RFS) between those assigned to the active drug and those given placebo, and there was no difference in overall survival rates.
However, subgroup analysis revealed that FLT3/ITD AML patients who were MRD+ after transplant, which represented approximately half of the participants, experienced a significant 48% improvement in RFS with gilteritinib versus placebo, while no benefit was seen in MRD– patients.
While acknowledging that the trial did not meet its primary endpoint, presenter Mark J. Levis, MD, PhD, program leader, hematologic malignancies and bone marrow transplant program, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, said it was nevertheless “a successful study.”
“We learned how to use these drugs and in whom,” he continued, adding: “No, not everybody needs and should get a FLT3 inhibitor post-transplant, but we can use this [MRD] assay to identify who.”
Consequently, Dr. Levis believes that gilteritinib “should be a standard of care for those who are MRD positive,” although the decision to use it “should be balanced against the potential for toxicity,” compared with not adding an additional treatment after HCT.
He told a press conference that “we’re going to certainly make sure that patients who are MRD positive get [gilteritinib],” although the MRD negative patients “are going to be more questionable,” especially because the assay that they used in the study is not “perfect.”
Dr. Levis also suggested that the trial did not meet its endpoint because of regional differences in the clinical practice, such as in the number of treatment cycles prior to HCT, the time to transplant, and the previous use of a FLT3 inhibitor, all of which may have skewed the findings.
“Everybody in the world is convinced that they’re the best transplanter,” he said, and yet “they all do it differently, and the heterogeneity is astounding.”
He added: “If we’d restricted everybody [to a] pretransplant regimen, I suspect we would have had a different result than what we’re getting here, but this is releasing the drug into the world and saying: ‘Here, transplant however you want, however it’s practiced in the real world. Tell us how this works.’ ”
Approached for comment, Claudio Brunstein, MD, PhD, vice-chair of the department of hematology and oncology in the Cleveland Clinic Taussig Cancer Institute, said that while there was “some disappointment” with the results, he was “not surprised” that the trial did not meet its primary endpoint.
He said in an interview that the patient population was not of “high enough risk” to demonstrate an overall difference between gilteritinib and placebo, although he conceded that it is “hard to get to high-risk patients in a timely way” and so conduct a trial with them.
As to the notion that variations in clinical practice could have been responsible, Dr. Brunstein pointed out that it was a randomized trial, so the issue would have applied equally to both sides.
He nevertheless believes that it is “a very important study,” and “just the fact that it was done in the context of a number of drugs coming and being approved by the [U.S. Food and Drug Administration] in AML is quite remarkable.”
This is especially the case given that “many centers are already using [gilteritinib] as off-label maintenance therapy.”
Dr. Brunstein added that it is “good news” that the drug was effective in MRD+ patients, as it shows “you can overcome that with maintenance therapy rather than keeping giving more and more chemotherapy, especially as there are patients you’re worried about giving more intensive chemotherapy to make them MRD negative.”
He pointed out, however, that the assay used in the trial was “research grade” and very sensitive to MRD and “is not available everywhere, so there is an adjustment that the community will have to do to in order to apply this data.”
“But for those who are more obviously MRD positive with less sensitive assays, gilteritinib is already something that can be used,” Dr. Brunstein said.
Presenting the findings, Dr. Levis stated: “We all know that patients with FLT3/ITD AML have a high risk of relapse and are routinely referred for transplant. And we know that the detection of measurable residual disease pretransplant is highly predictive of outcome post-transplant.”
He continued that FLT3 inhibitors are “routinely given as post-transplant maintenance ... based on some prior trials, mostly with sorafenib.”
“But uncertainty exists as to the broad applicability of these trials,” Dr. Levis said. Moreover, the use of sorafenib in this context is “off label and can be difficult to tolerate,” and “we know that most patients are cured with allogeneic transplant alone.”
Gilteritinib is already known to be well tolerated as a monotherapy, and was approved by the FDA for the treatment of adult patients with FLT3 mutation–positive relapsed or refractory AML in 2018.
The investigators therefore examined whether it would be beneficial as a post-HCT maintenance therapy in FLT3-ITD AML. Patients were required to be in morphologic remission after one or two courses of induction therapy, with Dr. Levis underlining: “We did not allow patients who had been salvaged onto the study.”
They subsequently had a marrow aspirate sample taken for MRD analysis before undergoing allogeneic transplant, with any conditioning regimen, donor, or graft-versus-host disease (GVHD) prophylaxis allowed.
Between 30 and 90 days later, patients with successful engraftment who were able to take oral medication were then randomized to 24 months of maintenance therapy with either gilteritinib or placebo.
Dr. Levis showed that, among 620 patients screened at 110 centers in 16 countries, 356 were randomized between Aug. 15, 2017, and July 8, 2020. The median age was 53 years, and 49% of gilteritinib patients and 48% of those given placebo were female.
He noted that there was a “fairly even global distribution” of patients from North America, Europe, and the Asia/Pacific region, and that 60% of patients underwent a myeloablative conditioning regimen. Approximately the same proportion had received an FLT3 inhibitor prior to HCT.
MRD positivity, assessed at a cell count of ≥ 10-6, was observed pre-HCT in 47% of patients in both treatment groups, and in 50% of gilteritinib patients and 51% of placebo patients at both pre- and post-transplant assessments.
The treatment regimen was completed by 52.8% of patients assigned to gilteritinib and 53.9% in the placebo arm. Dr. Levis said that 18.5% and 20.3% of patients, respectively, experienced a grade 3/4 treatment emergent acute GVHD event, while 32.6% and 21.5%, respectively, had a grade ≥ 3 treatment emergent infection.
He noted that “adverse events were clearly more common in the gilteritinib arm and often led to either dose reduction or interruption, or withdrawal of treatment.”
The most common grade ≥ 3 treatment emergent adverse event was a decrease in neutrophil count, seen in 24.7% of gilteritinib patients and 7.9% of those given placebo, followed by reduced platelet count, in 15.2% and 5.6%, respectively, and anemia, in 6.2% and 1.7%, respectively.
Turning to the efficacy outcomes, Dr. Levis reported that the trial did not meet its primary endpoint, with no significant difference in RFS between the gilteritinib and placebo arms, at a hazard ratio of 0.679 (P = .0518). There was also no significant difference in the key secondary objective of overall survival, at a hazard ratio of 0.846 (P = .4394).
However, Dr. Levis noted that there was a “clear difference in the benefit of gilteritinib by region,” and, “at every level,” MRD predicted a benefit from gilteritinib, which he said was a “big surprise” and “really leapt out in the subgroup analysis.”
He explained that the researchers used a modified version of a two-step assay that has been used in previous studies, and was able to detect MRD at a sensitivity of approximately 1x10-6. “In our study, 98% of participants had samples pre- and post-[transplant].”
Regardless of treatment arm, MRD positivity measured at that sensitivity was associated with a significant reduction in overall survival, at a hazard ratio versus MRD– status of 0.514 (P = .0025).
When stratifying the patients by MRD status, the researchers found that, among MRD+ participants, gilteritinib was associated with a significant improvement in RFS, at a hazard ratio versus placebo of 0.515 (P = .0065), while there was no significant difference in MRD– patients.
Stratifying the patients by their conditioning regimen prior to HCT also revealed differences, with those undergoing myeloablative conditioning having significantly greater overall survival than those who underwent reduced-intensity conditioning, at a hazard ratio for death of 0.529 (P = .0027).
Dr. Levis said there is “no surprise there,” and the result could reflect the selection of fitter, younger patients to undergo the more intensive regimen.
He then showed that MRD+ patients who had undergone myeloablative conditioning had better overall survival with gilteritinib than placebo, at a hazard ratio for death of 0.418 (P = .0087). Again, the difference disappeared when looking at MRD– patients.
“So conditioning doesn’t help you in the setting of MRD,” Dr. Levis said.
Finally, he took a deeper dive into the regional differences in outcomes, noting that patients in the Asia/Pacific region, where gilteritinib showed no benefit over placebo, “were 10 years younger” than those in other regions, “tended to get myeloablative conditioning, and hardly ever used FLT3 inhibitors.”
In contrast, North American patients, who experienced a significant gilteritinib benefit in terms of RFS, underwent HCT an average of 26 days earlier than those elsewhere, and received fewer courses of chemotherapy pre-HCT. Moreover, 93.5% received an FLT3 inhibitor pretransplant.
The study was funded by Astellas Pharma Global Development. Dr. Levis declares relationships with Abbvie, Amgen, Astellas, Bristol-Myers-Squibb, Daiichi-Sankyo, GlaxoSmithKline, Jazz, Menarini, Pfizer, Sumitomo-Dainippon, Syndax, Takeda. Dr. Brunstein declares no relevant relationships.
AT EHA 2023
Warts difficult to eradicate in immunocompromised children
.
Only a quarter of patients (24%) who were undergoing active cancer treatment experienced complete resolution of their warts, compared with 63.3% of patients who were not on active treatment.
In addition, warts persisted or worsened in 56.0% of patients receiving active treatment compared with 13.4% of those who were not receiving it.
“These data enable providers treating warts in children with cancer to have an educated discussion regarding the expected clinical progression of warts and the likelihood of response to wart therapy while on and off anti-cancer treatment,” the authors wrote in the study, published in Pediatric Dermatology.
In immunocompromised children, warts are more common than in the general pediatric population, and more resistant to treatment. But as the authors noted, data on the course and prognosis of warts in pediatric patients who are actively receiving anti-cancer therapy compared with patients who have completed treatment are limited.
Tina Ho, MD, PhD, of the department of dermatology, and colleagues from Boston Children’s Hospital, sought to analyze the clinical course of warts treated in this patient population at their institution over a 10-year period. They conducted a retrospective study of 72 children who were treated for cancer between 2011 and 2021, and who had also been treated for warts.
The median age of the cohort was 12 years, and they were followed for a median of 2 years following their diagnosis of warts. Within this group, more than half (55%) had hematologic malignancies, while 27% had a history of bone marrow transplantation.
Of note, the authors pointed out, 54% of the patients had plantar warts, and 60% of patients (38 of 63) with a documented number of warts had more than five at the time of presentation.
The treatment regimens that the children had received varied, with 81% of patients receiving cytotoxic chemotherapy and 23% of patients on targeted therapies that included immunotherapy.
The warts were most commonly treated with cryotherapy and topical salicylic acid; this was the case for those actively receiving oncology treatment or those who had completed their treatment regimens.
Outcomes of wart treatments were available in 25 of the patients undergoing active cancer treatment and in 30 of those who had completed treatment. For children on active oncology treatment, 5 (20%) achieved partial resolution, 6 (24%) achieved complete resolution, and 14 (56%) experienced persistence or worsening of their warts following therapy. Those who had completed treatment had better outcomes: Seven (23.3%) had a partial response, 19 (63.3%) had complete resolution, and 4 (13.4%) had persistence or worsening of warts after treatment of warts.
The authors also pointed out the treatment of warts can be painful, expensive, and time-consuming. “It is thus imperative that the risks and benefits of these treatments are carefully considered before proceeding with treatment,” wrote Dr. Ho and colleagues. “This is especially true in medically complex children with cancer who may be fearful of procedures and spend significant portions of their young lives within the medical system.”
Limitations to the study include its retrospective design and small sample size. Clinical data were not uniformly complete, and follow-up intervals varied among the participants. Also, it was conducted at a single-institution and at a large tertiary center, so the results may not be fully generalizable.
The authors declared no conflict of interest. No outside funding source was listed.
.
Only a quarter of patients (24%) who were undergoing active cancer treatment experienced complete resolution of their warts, compared with 63.3% of patients who were not on active treatment.
In addition, warts persisted or worsened in 56.0% of patients receiving active treatment compared with 13.4% of those who were not receiving it.
“These data enable providers treating warts in children with cancer to have an educated discussion regarding the expected clinical progression of warts and the likelihood of response to wart therapy while on and off anti-cancer treatment,” the authors wrote in the study, published in Pediatric Dermatology.
In immunocompromised children, warts are more common than in the general pediatric population, and more resistant to treatment. But as the authors noted, data on the course and prognosis of warts in pediatric patients who are actively receiving anti-cancer therapy compared with patients who have completed treatment are limited.
Tina Ho, MD, PhD, of the department of dermatology, and colleagues from Boston Children’s Hospital, sought to analyze the clinical course of warts treated in this patient population at their institution over a 10-year period. They conducted a retrospective study of 72 children who were treated for cancer between 2011 and 2021, and who had also been treated for warts.
The median age of the cohort was 12 years, and they were followed for a median of 2 years following their diagnosis of warts. Within this group, more than half (55%) had hematologic malignancies, while 27% had a history of bone marrow transplantation.
Of note, the authors pointed out, 54% of the patients had plantar warts, and 60% of patients (38 of 63) with a documented number of warts had more than five at the time of presentation.
The treatment regimens that the children had received varied, with 81% of patients receiving cytotoxic chemotherapy and 23% of patients on targeted therapies that included immunotherapy.
The warts were most commonly treated with cryotherapy and topical salicylic acid; this was the case for those actively receiving oncology treatment or those who had completed their treatment regimens.
Outcomes of wart treatments were available in 25 of the patients undergoing active cancer treatment and in 30 of those who had completed treatment. For children on active oncology treatment, 5 (20%) achieved partial resolution, 6 (24%) achieved complete resolution, and 14 (56%) experienced persistence or worsening of their warts following therapy. Those who had completed treatment had better outcomes: Seven (23.3%) had a partial response, 19 (63.3%) had complete resolution, and 4 (13.4%) had persistence or worsening of warts after treatment of warts.
The authors also pointed out the treatment of warts can be painful, expensive, and time-consuming. “It is thus imperative that the risks and benefits of these treatments are carefully considered before proceeding with treatment,” wrote Dr. Ho and colleagues. “This is especially true in medically complex children with cancer who may be fearful of procedures and spend significant portions of their young lives within the medical system.”
Limitations to the study include its retrospective design and small sample size. Clinical data were not uniformly complete, and follow-up intervals varied among the participants. Also, it was conducted at a single-institution and at a large tertiary center, so the results may not be fully generalizable.
The authors declared no conflict of interest. No outside funding source was listed.
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Only a quarter of patients (24%) who were undergoing active cancer treatment experienced complete resolution of their warts, compared with 63.3% of patients who were not on active treatment.
In addition, warts persisted or worsened in 56.0% of patients receiving active treatment compared with 13.4% of those who were not receiving it.
“These data enable providers treating warts in children with cancer to have an educated discussion regarding the expected clinical progression of warts and the likelihood of response to wart therapy while on and off anti-cancer treatment,” the authors wrote in the study, published in Pediatric Dermatology.
In immunocompromised children, warts are more common than in the general pediatric population, and more resistant to treatment. But as the authors noted, data on the course and prognosis of warts in pediatric patients who are actively receiving anti-cancer therapy compared with patients who have completed treatment are limited.
Tina Ho, MD, PhD, of the department of dermatology, and colleagues from Boston Children’s Hospital, sought to analyze the clinical course of warts treated in this patient population at their institution over a 10-year period. They conducted a retrospective study of 72 children who were treated for cancer between 2011 and 2021, and who had also been treated for warts.
The median age of the cohort was 12 years, and they were followed for a median of 2 years following their diagnosis of warts. Within this group, more than half (55%) had hematologic malignancies, while 27% had a history of bone marrow transplantation.
Of note, the authors pointed out, 54% of the patients had plantar warts, and 60% of patients (38 of 63) with a documented number of warts had more than five at the time of presentation.
The treatment regimens that the children had received varied, with 81% of patients receiving cytotoxic chemotherapy and 23% of patients on targeted therapies that included immunotherapy.
The warts were most commonly treated with cryotherapy and topical salicylic acid; this was the case for those actively receiving oncology treatment or those who had completed their treatment regimens.
Outcomes of wart treatments were available in 25 of the patients undergoing active cancer treatment and in 30 of those who had completed treatment. For children on active oncology treatment, 5 (20%) achieved partial resolution, 6 (24%) achieved complete resolution, and 14 (56%) experienced persistence or worsening of their warts following therapy. Those who had completed treatment had better outcomes: Seven (23.3%) had a partial response, 19 (63.3%) had complete resolution, and 4 (13.4%) had persistence or worsening of warts after treatment of warts.
The authors also pointed out the treatment of warts can be painful, expensive, and time-consuming. “It is thus imperative that the risks and benefits of these treatments are carefully considered before proceeding with treatment,” wrote Dr. Ho and colleagues. “This is especially true in medically complex children with cancer who may be fearful of procedures and spend significant portions of their young lives within the medical system.”
Limitations to the study include its retrospective design and small sample size. Clinical data were not uniformly complete, and follow-up intervals varied among the participants. Also, it was conducted at a single-institution and at a large tertiary center, so the results may not be fully generalizable.
The authors declared no conflict of interest. No outside funding source was listed.
FROM PEDIATRIC DERMATOLOGY
Prognostic factors of SCCs in organ transplant recipients worse compared with general population
, results from a dual cohort study demonstrated.
The findings build on previous research and underscore the need for early diagnosis and aggressive surveillance in this patient population, corresponding author Adele C. Green, MBBS, PhD, professor and senior scientist at the QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia, and colleagues wrote in the study, which was published online in JAMA Dermatology. “Squamous cell carcinomas (SCCs) of the skin develop up to 77 times more frequently in immunosuppressed organ transplant recipients (OTRs) than the general population,” they wrote. “Because SCCs cause substantially more morbidity and death in the former, they are postulated to be innately more aggressive than in immunocompetent patients, but OTRs’ higher SCC mortality may simply reflect greater SCC tumor burdens per patient.”
In what is believed to be the first study of its kind, Dr. Green and colleagues drew data from two cohort studies to evaluate five key clinicopathologic indicators of poor SCC outcomes in organ transplant recipients, and in those from the general population in Queensland, Australia: cephalic location, perineural invasion, invasion to/beyond subcutaneous fat, poor differentiation, and tumor size greater than 20 mm. The study population included organ transplant recipients at high risk of skin cancer, who were enrolled in the Skin Tumours in Allograft Recipients (STAR) study, and those from a population-based cohort, the QSkin Sun and Health Study. STAR consisted of lung transplant recipients and kidney and liver transplant recipients at high risk of skin cancer who were recruited from tertiary centers and diagnosed with histopathologically confirmed SCC from 2012 to 2015. QSkin consisted of individuals from Queensland’s general adult population diagnosed with SCCs from 2012 to 2015.
SCC cases in QSkin were ascertained through Australia’s universal health insurance agency and linked with histopathology records. Next, the researchers performed data analysis from both cohort studies to determine the prevalence ratio (PR) of head/neck location, perineural invasion, tumor invasion to/beyond subcutaneous fat, poor cellular differentiation, and tumor diameter greater than 20 mm among SCCs among organ transplant recipients compared with the general population.
After combining the two studies, the researchers compared 741 SCCs excised from 191 organ transplant recipients and 2,558 SCCs excised from 1,507 individuals in the general population. Their median ages were similar (62.7 and 63.7 years, respectively) and most were male (78% and 63.4%, respectively).
As for site of involvement, SCCs developed most often on the head and neck in the transplant recipients (38.6%) and on the arms and hands in the general population (35.2%). After adjustment for age and sex, perineural invasion of SCCs was more than twice as common in transplant recipients than among cases in the general population, as was invasion to/beyond subcutaneous fat (PR of 2.37 for both associations).
In other findings, compared with SCCs in the general population, poorly vs. well-differentiated SCCs were more than threefold more common in transplant recipients (PR, 3.45), while the prevalence of tumors greater than 20 mm vs. 20 mm or smaller was moderately higher in transplant recipients (PR, 1.52).
“These findings are considered generalizable, confirming that OTRs’ poorer SCC outcomes are associated with not only their sheer numbers of SCC tumors, but also with a strong shift toward more invasive, less differentiated, and larger SCC tumors, in agreement with previous findings,” the researchers wrote. “This shift is likely associated with decreased immunosurveillance resulting from immunosuppressive therapy (since carcinogenesis decelerates with therapy cessation) interacting with effects of high UV radiation exposure.”
They acknowledged certain limitations of their analysis, chiefly the lack of central review of SCCs to ensure standard assessment of histopathologic features “including caliber of nerves with perineural invasion and cell differentiation; such a review would not have been feasible logistically.”
The study was supported by grants from the National Health and Medical Research Council of Australia. The researchers reported having no disclosures related to the submitted work.
, results from a dual cohort study demonstrated.
The findings build on previous research and underscore the need for early diagnosis and aggressive surveillance in this patient population, corresponding author Adele C. Green, MBBS, PhD, professor and senior scientist at the QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia, and colleagues wrote in the study, which was published online in JAMA Dermatology. “Squamous cell carcinomas (SCCs) of the skin develop up to 77 times more frequently in immunosuppressed organ transplant recipients (OTRs) than the general population,” they wrote. “Because SCCs cause substantially more morbidity and death in the former, they are postulated to be innately more aggressive than in immunocompetent patients, but OTRs’ higher SCC mortality may simply reflect greater SCC tumor burdens per patient.”
In what is believed to be the first study of its kind, Dr. Green and colleagues drew data from two cohort studies to evaluate five key clinicopathologic indicators of poor SCC outcomes in organ transplant recipients, and in those from the general population in Queensland, Australia: cephalic location, perineural invasion, invasion to/beyond subcutaneous fat, poor differentiation, and tumor size greater than 20 mm. The study population included organ transplant recipients at high risk of skin cancer, who were enrolled in the Skin Tumours in Allograft Recipients (STAR) study, and those from a population-based cohort, the QSkin Sun and Health Study. STAR consisted of lung transplant recipients and kidney and liver transplant recipients at high risk of skin cancer who were recruited from tertiary centers and diagnosed with histopathologically confirmed SCC from 2012 to 2015. QSkin consisted of individuals from Queensland’s general adult population diagnosed with SCCs from 2012 to 2015.
SCC cases in QSkin were ascertained through Australia’s universal health insurance agency and linked with histopathology records. Next, the researchers performed data analysis from both cohort studies to determine the prevalence ratio (PR) of head/neck location, perineural invasion, tumor invasion to/beyond subcutaneous fat, poor cellular differentiation, and tumor diameter greater than 20 mm among SCCs among organ transplant recipients compared with the general population.
After combining the two studies, the researchers compared 741 SCCs excised from 191 organ transplant recipients and 2,558 SCCs excised from 1,507 individuals in the general population. Their median ages were similar (62.7 and 63.7 years, respectively) and most were male (78% and 63.4%, respectively).
As for site of involvement, SCCs developed most often on the head and neck in the transplant recipients (38.6%) and on the arms and hands in the general population (35.2%). After adjustment for age and sex, perineural invasion of SCCs was more than twice as common in transplant recipients than among cases in the general population, as was invasion to/beyond subcutaneous fat (PR of 2.37 for both associations).
In other findings, compared with SCCs in the general population, poorly vs. well-differentiated SCCs were more than threefold more common in transplant recipients (PR, 3.45), while the prevalence of tumors greater than 20 mm vs. 20 mm or smaller was moderately higher in transplant recipients (PR, 1.52).
“These findings are considered generalizable, confirming that OTRs’ poorer SCC outcomes are associated with not only their sheer numbers of SCC tumors, but also with a strong shift toward more invasive, less differentiated, and larger SCC tumors, in agreement with previous findings,” the researchers wrote. “This shift is likely associated with decreased immunosurveillance resulting from immunosuppressive therapy (since carcinogenesis decelerates with therapy cessation) interacting with effects of high UV radiation exposure.”
They acknowledged certain limitations of their analysis, chiefly the lack of central review of SCCs to ensure standard assessment of histopathologic features “including caliber of nerves with perineural invasion and cell differentiation; such a review would not have been feasible logistically.”
The study was supported by grants from the National Health and Medical Research Council of Australia. The researchers reported having no disclosures related to the submitted work.
, results from a dual cohort study demonstrated.
The findings build on previous research and underscore the need for early diagnosis and aggressive surveillance in this patient population, corresponding author Adele C. Green, MBBS, PhD, professor and senior scientist at the QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia, and colleagues wrote in the study, which was published online in JAMA Dermatology. “Squamous cell carcinomas (SCCs) of the skin develop up to 77 times more frequently in immunosuppressed organ transplant recipients (OTRs) than the general population,” they wrote. “Because SCCs cause substantially more morbidity and death in the former, they are postulated to be innately more aggressive than in immunocompetent patients, but OTRs’ higher SCC mortality may simply reflect greater SCC tumor burdens per patient.”
In what is believed to be the first study of its kind, Dr. Green and colleagues drew data from two cohort studies to evaluate five key clinicopathologic indicators of poor SCC outcomes in organ transplant recipients, and in those from the general population in Queensland, Australia: cephalic location, perineural invasion, invasion to/beyond subcutaneous fat, poor differentiation, and tumor size greater than 20 mm. The study population included organ transplant recipients at high risk of skin cancer, who were enrolled in the Skin Tumours in Allograft Recipients (STAR) study, and those from a population-based cohort, the QSkin Sun and Health Study. STAR consisted of lung transplant recipients and kidney and liver transplant recipients at high risk of skin cancer who were recruited from tertiary centers and diagnosed with histopathologically confirmed SCC from 2012 to 2015. QSkin consisted of individuals from Queensland’s general adult population diagnosed with SCCs from 2012 to 2015.
SCC cases in QSkin were ascertained through Australia’s universal health insurance agency and linked with histopathology records. Next, the researchers performed data analysis from both cohort studies to determine the prevalence ratio (PR) of head/neck location, perineural invasion, tumor invasion to/beyond subcutaneous fat, poor cellular differentiation, and tumor diameter greater than 20 mm among SCCs among organ transplant recipients compared with the general population.
After combining the two studies, the researchers compared 741 SCCs excised from 191 organ transplant recipients and 2,558 SCCs excised from 1,507 individuals in the general population. Their median ages were similar (62.7 and 63.7 years, respectively) and most were male (78% and 63.4%, respectively).
As for site of involvement, SCCs developed most often on the head and neck in the transplant recipients (38.6%) and on the arms and hands in the general population (35.2%). After adjustment for age and sex, perineural invasion of SCCs was more than twice as common in transplant recipients than among cases in the general population, as was invasion to/beyond subcutaneous fat (PR of 2.37 for both associations).
In other findings, compared with SCCs in the general population, poorly vs. well-differentiated SCCs were more than threefold more common in transplant recipients (PR, 3.45), while the prevalence of tumors greater than 20 mm vs. 20 mm or smaller was moderately higher in transplant recipients (PR, 1.52).
“These findings are considered generalizable, confirming that OTRs’ poorer SCC outcomes are associated with not only their sheer numbers of SCC tumors, but also with a strong shift toward more invasive, less differentiated, and larger SCC tumors, in agreement with previous findings,” the researchers wrote. “This shift is likely associated with decreased immunosurveillance resulting from immunosuppressive therapy (since carcinogenesis decelerates with therapy cessation) interacting with effects of high UV radiation exposure.”
They acknowledged certain limitations of their analysis, chiefly the lack of central review of SCCs to ensure standard assessment of histopathologic features “including caliber of nerves with perineural invasion and cell differentiation; such a review would not have been feasible logistically.”
The study was supported by grants from the National Health and Medical Research Council of Australia. The researchers reported having no disclosures related to the submitted work.
FROM JAMA DERMATOLOGY