Conference Coverage

Research on pain management during placement of intrauterine devices (IUD) is lacking, but most studies so far indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are not effective, according to a poster presented at Pain Week 2024 in Las Vegas.

Roughly 79% of the 14 studies included in the systematic review found NSAIDs — one of the most common drugs clinicians advise patients to take before placement — did not diminish discomfort.

“We’re challenging the current practice of using just NSAIDs as a first-line of treatment,” said Kevin Rowland, PhD, professor and chair of biomedical sciences at Tilman J. Fertitta Family College of Medicine in Houston, who helped conduct the meta-analysis. “We need additional measures.”

Some studies found the drugs offered virtually no improvement for patients, while the biggest drop in pain shown in one study was about 40%. The range of pain levels women reported while using NSAIDs was between 1.8 and 7.3 on the visual analog scale (VAS), with an average score of 4.25.

The review included 10 types of NSAIDs and dosages administered to patients before the procedure. One intramuscular NSAID was included while the remaining were oral. All studies were peer-reviewed, used the VAS pain scale, and were not limited to any specific population.

The findings highlight a longstanding but unresolved problem in reproductive health: An overall lack of effective pain management strategies for gynecologic procedures.

“We went into this having a pretty good idea of what we were going to find because [the lack of NSAID efficacy] has been shown before, it’s been talked about before, and we’re just not listening as a medical community,” said Isabella D. Martingano, an MD candidate at Tilman J. Fertitta Family College of Medicine, who led the review.

The research also points to a lack of robust studies on pain during IUD placement, said Emma Lakey, a coauthor and medical student at Tilman J. Fertitta Family College of Medicine.

“We were only able to review 14 studies, which was enough to go off of, but considering we were looking for trials about pain control for a procedure that helps prevent pregnancy, that’s just not enough research,” Ms. Lakey said.

Discomfort associated with IUD placement ranges from mild to severe, can last for over a week, and includes cramping, bleeding, lightheadedness, nausea, and fainting. Some research suggests that providers may underestimate the level of pain the procedures cause.

“Unfortunately, the pain associated with IUD insertion and removal has been underplayed for a long time and many practitioners in the field likely haven’t counseled patients fully on what the procedure will feel like,” said Jennifer Chin, MD, an ob.gyn. and assistant professor of obstetrics and gynecology at the University of Washington in Seattle.

NSAIDs are not mentioned in the recently expanded guidelines on IUD placement from the US Centers for Disease Control and Prevention (CDC). The CDC recommends lidocaine paracervical blocks, gels, sprays, and creams, plus counseling women about pain ahead of the procedures.

IUDs are one of the most effective forms of birth control, with a failure rate below 1%.

Yet hearing about painful placement keeps many women from seeking out an IUD or replacing an existing device, Dr. Rowland said. The review adds to the body of evidence that current strategies are not working and that more research is needed, he said.

According to Dr. Chin, making IUDs more accessible means taking a more personalized approach to pain management while understanding that what may be a painless procedure for one patient may be excruciating for another.

Dr. Chin offers a range of options for her patients, including NSAIDs, lorazepam for anxiety, paracervical blocks, lidocaine jelly and spray, intravenous sedation, and general anesthesia. She also talks to her patients through the procedure and provides guided imagery and meditation.

“We should always make sure we’re prioritizing the patients and providing evidence-based, compassionate, and individualized care,” said Dr. Chin. “Each patient comes to us in a particular context and with a specific set of experiences and history that will make a difference in how we’re best able to take care of them.”

The authors reported no disclosures and no sources of funding. Dr. Chin reported no disclosures.
 

A version of this article first appeared on Medscape.com.

Research on pain management during placement of intrauterine devices (IUD) is lacking, but most studies so far indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are not effective, according to a poster presented at Pain Week 2024 in Las Vegas.

Roughly 79% of the 14 studies included in the systematic review found NSAIDs — one of the most common drugs clinicians advise patients to take before placement — did not diminish discomfort.

“We’re challenging the current practice of using just NSAIDs as a first-line of treatment,” said Kevin Rowland, PhD, professor and chair of biomedical sciences at Tilman J. Fertitta Family College of Medicine in Houston, who helped conduct the meta-analysis. “We need additional measures.”

Some studies found the drugs offered virtually no improvement for patients, while the biggest drop in pain shown in one study was about 40%. The range of pain levels women reported while using NSAIDs was between 1.8 and 7.3 on the visual analog scale (VAS), with an average score of 4.25.

The review included 10 types of NSAIDs and dosages administered to patients before the procedure. One intramuscular NSAID was included while the remaining were oral. All studies were peer-reviewed, used the VAS pain scale, and were not limited to any specific population.

The findings highlight a longstanding but unresolved problem in reproductive health: An overall lack of effective pain management strategies for gynecologic procedures.

“We went into this having a pretty good idea of what we were going to find because [the lack of NSAID efficacy] has been shown before, it’s been talked about before, and we’re just not listening as a medical community,” said Isabella D. Martingano, an MD candidate at Tilman J. Fertitta Family College of Medicine, who led the review.

The research also points to a lack of robust studies on pain during IUD placement, said Emma Lakey, a coauthor and medical student at Tilman J. Fertitta Family College of Medicine.

“We were only able to review 14 studies, which was enough to go off of, but considering we were looking for trials about pain control for a procedure that helps prevent pregnancy, that’s just not enough research,” Ms. Lakey said.

Discomfort associated with IUD placement ranges from mild to severe, can last for over a week, and includes cramping, bleeding, lightheadedness, nausea, and fainting. Some research suggests that providers may underestimate the level of pain the procedures cause.

“Unfortunately, the pain associated with IUD insertion and removal has been underplayed for a long time and many practitioners in the field likely haven’t counseled patients fully on what the procedure will feel like,” said Jennifer Chin, MD, an ob.gyn. and assistant professor of obstetrics and gynecology at the University of Washington in Seattle.

NSAIDs are not mentioned in the recently expanded guidelines on IUD placement from the US Centers for Disease Control and Prevention (CDC). The CDC recommends lidocaine paracervical blocks, gels, sprays, and creams, plus counseling women about pain ahead of the procedures.

IUDs are one of the most effective forms of birth control, with a failure rate below 1%.

Yet hearing about painful placement keeps many women from seeking out an IUD or replacing an existing device, Dr. Rowland said. The review adds to the body of evidence that current strategies are not working and that more research is needed, he said.

According to Dr. Chin, making IUDs more accessible means taking a more personalized approach to pain management while understanding that what may be a painless procedure for one patient may be excruciating for another.

Dr. Chin offers a range of options for her patients, including NSAIDs, lorazepam for anxiety, paracervical blocks, lidocaine jelly and spray, intravenous sedation, and general anesthesia. She also talks to her patients through the procedure and provides guided imagery and meditation.

“We should always make sure we’re prioritizing the patients and providing evidence-based, compassionate, and individualized care,” said Dr. Chin. “Each patient comes to us in a particular context and with a specific set of experiences and history that will make a difference in how we’re best able to take care of them.”

The authors reported no disclosures and no sources of funding. Dr. Chin reported no disclosures.
 

A version of this article first appeared on Medscape.com.

Research on pain management during placement of intrauterine devices (IUD) is lacking, but most studies so far indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) are not effective, according to a poster presented at Pain Week 2024 in Las Vegas.

Roughly 79% of the 14 studies included in the systematic review found NSAIDs — one of the most common drugs clinicians advise patients to take before placement — did not diminish discomfort.

“We’re challenging the current practice of using just NSAIDs as a first-line of treatment,” said Kevin Rowland, PhD, professor and chair of biomedical sciences at Tilman J. Fertitta Family College of Medicine in Houston, who helped conduct the meta-analysis. “We need additional measures.”

Some studies found the drugs offered virtually no improvement for patients, while the biggest drop in pain shown in one study was about 40%. The range of pain levels women reported while using NSAIDs was between 1.8 and 7.3 on the visual analog scale (VAS), with an average score of 4.25.

The review included 10 types of NSAIDs and dosages administered to patients before the procedure. One intramuscular NSAID was included while the remaining were oral. All studies were peer-reviewed, used the VAS pain scale, and were not limited to any specific population.

The findings highlight a longstanding but unresolved problem in reproductive health: An overall lack of effective pain management strategies for gynecologic procedures.

“We went into this having a pretty good idea of what we were going to find because [the lack of NSAID efficacy] has been shown before, it’s been talked about before, and we’re just not listening as a medical community,” said Isabella D. Martingano, an MD candidate at Tilman J. Fertitta Family College of Medicine, who led the review.

The research also points to a lack of robust studies on pain during IUD placement, said Emma Lakey, a coauthor and medical student at Tilman J. Fertitta Family College of Medicine.

“We were only able to review 14 studies, which was enough to go off of, but considering we were looking for trials about pain control for a procedure that helps prevent pregnancy, that’s just not enough research,” Ms. Lakey said.

Discomfort associated with IUD placement ranges from mild to severe, can last for over a week, and includes cramping, bleeding, lightheadedness, nausea, and fainting. Some research suggests that providers may underestimate the level of pain the procedures cause.

“Unfortunately, the pain associated with IUD insertion and removal has been underplayed for a long time and many practitioners in the field likely haven’t counseled patients fully on what the procedure will feel like,” said Jennifer Chin, MD, an ob.gyn. and assistant professor of obstetrics and gynecology at the University of Washington in Seattle.

NSAIDs are not mentioned in the recently expanded guidelines on IUD placement from the US Centers for Disease Control and Prevention (CDC). The CDC recommends lidocaine paracervical blocks, gels, sprays, and creams, plus counseling women about pain ahead of the procedures.

IUDs are one of the most effective forms of birth control, with a failure rate below 1%.

Yet hearing about painful placement keeps many women from seeking out an IUD or replacing an existing device, Dr. Rowland said. The review adds to the body of evidence that current strategies are not working and that more research is needed, he said.

According to Dr. Chin, making IUDs more accessible means taking a more personalized approach to pain management while understanding that what may be a painless procedure for one patient may be excruciating for another.

Dr. Chin offers a range of options for her patients, including NSAIDs, lorazepam for anxiety, paracervical blocks, lidocaine jelly and spray, intravenous sedation, and general anesthesia. She also talks to her patients through the procedure and provides guided imagery and meditation.

“We should always make sure we’re prioritizing the patients and providing evidence-based, compassionate, and individualized care,” said Dr. Chin. “Each patient comes to us in a particular context and with a specific set of experiences and history that will make a difference in how we’re best able to take care of them.”

The authors reported no disclosures and no sources of funding. Dr. Chin reported no disclosures.
 

A version of this article first appeared on Medscape.com.

MADRID — A daily 8-hour eating window controls blood glucose whether followed early or late in the day by people at risk for type 2 diabetes, showed a time-restricted eating (TRE) study presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The study, examining shifting the time of day for the 8-hour eating window along with a tightly controlled diet, found that 8 hours of TRE — whether early or late in the day — led to a significant improvement in the time spent within a normal daily blood glucose range and in glycemic variability.

“We didn’t show a benefit in terms of early versus late TRE, but we did show a benefit of time-restricted eating within a window of 8 h/d,” said study lead Kelly Bowden Davies, MSc, PhD, from Manchester Metropolitan University, Manchester, England, when presenting the work. “It doesn’t matter when you restrict eating, but if you restrict it to 8 hours then, according to our study, it benefits glycemic control in people at risk of type 2 diabetes.”

The researcher added that the effect was seen after only 3 days, and “demonstrates its therapeutic role in adults at risk of type 2 diabetes, which warrants investigation in the longer term.”

The current study examined the effect of shifting the time of day for the TRE window from early (8 AM-4 PM) to late (12 PM-8 PM) in people at risk of developing type 2 diabetes due to a lifestyle characterized as sedentary and poor diet.

Previous studies indicate that TRE, which limits when, but not what, individuals eat, can improve insulin sensitivity and A1c in people at risk for type 2 diabetes.

But Dr. Bowden Davies pointed out that the effect of TRE on glycemic variability remained unclear. While prior work had attributed the positive effects of TRE to reduced energy intake, this study provided a diet where energy consumption matched energy expenditure — taking into account sex, age, weight, height, and activity level, termed a “eucaloric” diet.

“Some research groups recognize that if we manipulate the time at which we eat, then we can better align with circadian metabolic rhythms to improve whole body insulin sensitivity and glycemic variability,” explained Dr. Bowden Davies. “It may be that eating in the morning may be better aligned [with circadian rhythms] and cause greater improvement in glucose control.”
 

Three-Day TRE Plan Led to Blood Glucose Control

In a cross-over study design, all 15 participants were randomized to follow the early and late TRE regimens with a 7-day washout period in the middle. Participants had a mean body mass index (BMI) of 27.7 kg/m², had a mean waist circumference of 73 cm, were sedentary, and followed a poor diet.

“Participants were normoglycemic so had good glucose control, but due to having overweight and obesity, they are considered as having risk factors for the development of type 2 diabetes,” noted Dr. Bowden Davies.

Before the TRE period, participants provided researchers with a dietary record. If they started on the early TRE, they crossed over to the late TRE after the washout period, and vice versa, she explained.

Continuous glucose monitoring (FreeStyle Libre 2, Abbott Laboratories) was carried out across the study to assess the daily time spent in euglycemia (3.9-7.8 mmol/L) and provide markers of glycemic variability, including mean absolute glucose, coefficient of variation, and mean amplitude of glucose excursions. Blood draws both pre- and post-TRE period provided biochemical measurements, and anthropometric readings were also taken.

There were nine female participants, with a mean age of 52 years, a BMI of 28 kg/m², and an A1c level of 37.9 mmol/mol (5.6%). They tended to snack across an eating period of 14 h/d or more (habitual eating). They were assigned to two different investigational eating patterns for 3-day durations: Early or late, and these findings were compared with those from participants who continued their habitual eating.

Participants were provided with a eucaloric, standardized diet [50% carbohydrates, 30% fat, and 20% protein] to be eaten during the TRE period, whereas they ate as usual (ie, as and what they wanted) when not on the TRE regimen.

No changes were seen in the biochemistry markers assessed. “Given they only followed the TRE for 3 days, this is unsurprising,” remarked Dr. Bowden Davies. “We did see weight loss after only 3 days of TRE of around 1.1 kg across the two interventions,” she reported.

Referring to the early vs late TRE regimen, she added that “we didn’t see a benefit [no significant differences in glycemic control] of early compared with late TRE, but we did see a benefit of restricting the eating window to 8 h/d, so both conditions [early and late TRE regimens] had a benefit on glucose control.”

Variables of blood glucose control were also reduced while on the TRE regimen compared with habitual eating (more than 14 h/d), with significantly increased time spent within the normal blood glucose range on average by 3.3%, and also reduced mean absolute glucose by 0.6 mmol/L, coefficient of variation by 2.6%, and mean amplitude of glucose excursions by 0.4 mmol/L.

“Within 3 days, this is quite striking,” Dr. Bowden Davies pointed out.

She added that these data were interim analyses, but “these are positive in terms of participants seeing a benefit in glucose control and glycemic variability, which is a risk factor for developing type 2 diabetes but also for microvascular complications. We also saw improved time in range in terms of tight glucose control.

“Even in 3 days, there were small, subtle differences which are subclinical — but this is not a clinical cohort. The results are statistically significant and a promising piece of data to suggest a feasible intervention that could be translated across different populations,” she said, adding that over a longer time period, changes between TRE timing might show changes in people at risk for type 2 diabetes who don’t have compromised circadian rhythms.

Moderating the session was Lutgarda Bozzetto, MD, from the University of Naples Federico II, Naples, Italy. She told this news organization, “It’s a hot topic right now, and the finding that there’s no difference in the time of day when the restricted eating is done suggests that in people at risk of diabetes, the hormonal flux and cycle involved in blood glucose control is not so strong or sensitive.”

Using a continuous glucose monitor, they can look at their blood glucose levels after eating, and this might “be powerful in guiding behavioral change,” said Dr. Bozzetto.

Abbott Laboratories funded the continuous glucose monitoring. Neither Dr. Bowden Davies nor Dr. Bozzetto had any other relevant financial disclosures.

A version of this article first appeared on Medscape.com.

MADRID — A daily 8-hour eating window controls blood glucose whether followed early or late in the day by people at risk for type 2 diabetes, showed a time-restricted eating (TRE) study presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The study, examining shifting the time of day for the 8-hour eating window along with a tightly controlled diet, found that 8 hours of TRE — whether early or late in the day — led to a significant improvement in the time spent within a normal daily blood glucose range and in glycemic variability.

“We didn’t show a benefit in terms of early versus late TRE, but we did show a benefit of time-restricted eating within a window of 8 h/d,” said study lead Kelly Bowden Davies, MSc, PhD, from Manchester Metropolitan University, Manchester, England, when presenting the work. “It doesn’t matter when you restrict eating, but if you restrict it to 8 hours then, according to our study, it benefits glycemic control in people at risk of type 2 diabetes.”

The researcher added that the effect was seen after only 3 days, and “demonstrates its therapeutic role in adults at risk of type 2 diabetes, which warrants investigation in the longer term.”

The current study examined the effect of shifting the time of day for the TRE window from early (8 AM-4 PM) to late (12 PM-8 PM) in people at risk of developing type 2 diabetes due to a lifestyle characterized as sedentary and poor diet.

Previous studies indicate that TRE, which limits when, but not what, individuals eat, can improve insulin sensitivity and A1c in people at risk for type 2 diabetes.

But Dr. Bowden Davies pointed out that the effect of TRE on glycemic variability remained unclear. While prior work had attributed the positive effects of TRE to reduced energy intake, this study provided a diet where energy consumption matched energy expenditure — taking into account sex, age, weight, height, and activity level, termed a “eucaloric” diet.

“Some research groups recognize that if we manipulate the time at which we eat, then we can better align with circadian metabolic rhythms to improve whole body insulin sensitivity and glycemic variability,” explained Dr. Bowden Davies. “It may be that eating in the morning may be better aligned [with circadian rhythms] and cause greater improvement in glucose control.”
 

Three-Day TRE Plan Led to Blood Glucose Control

In a cross-over study design, all 15 participants were randomized to follow the early and late TRE regimens with a 7-day washout period in the middle. Participants had a mean body mass index (BMI) of 27.7 kg/m², had a mean waist circumference of 73 cm, were sedentary, and followed a poor diet.

“Participants were normoglycemic so had good glucose control, but due to having overweight and obesity, they are considered as having risk factors for the development of type 2 diabetes,” noted Dr. Bowden Davies.

Before the TRE period, participants provided researchers with a dietary record. If they started on the early TRE, they crossed over to the late TRE after the washout period, and vice versa, she explained.

Continuous glucose monitoring (FreeStyle Libre 2, Abbott Laboratories) was carried out across the study to assess the daily time spent in euglycemia (3.9-7.8 mmol/L) and provide markers of glycemic variability, including mean absolute glucose, coefficient of variation, and mean amplitude of glucose excursions. Blood draws both pre- and post-TRE period provided biochemical measurements, and anthropometric readings were also taken.

There were nine female participants, with a mean age of 52 years, a BMI of 28 kg/m², and an A1c level of 37.9 mmol/mol (5.6%). They tended to snack across an eating period of 14 h/d or more (habitual eating). They were assigned to two different investigational eating patterns for 3-day durations: Early or late, and these findings were compared with those from participants who continued their habitual eating.

Participants were provided with a eucaloric, standardized diet [50% carbohydrates, 30% fat, and 20% protein] to be eaten during the TRE period, whereas they ate as usual (ie, as and what they wanted) when not on the TRE regimen.

No changes were seen in the biochemistry markers assessed. “Given they only followed the TRE for 3 days, this is unsurprising,” remarked Dr. Bowden Davies. “We did see weight loss after only 3 days of TRE of around 1.1 kg across the two interventions,” she reported.

Referring to the early vs late TRE regimen, she added that “we didn’t see a benefit [no significant differences in glycemic control] of early compared with late TRE, but we did see a benefit of restricting the eating window to 8 h/d, so both conditions [early and late TRE regimens] had a benefit on glucose control.”

Variables of blood glucose control were also reduced while on the TRE regimen compared with habitual eating (more than 14 h/d), with significantly increased time spent within the normal blood glucose range on average by 3.3%, and also reduced mean absolute glucose by 0.6 mmol/L, coefficient of variation by 2.6%, and mean amplitude of glucose excursions by 0.4 mmol/L.

“Within 3 days, this is quite striking,” Dr. Bowden Davies pointed out.

She added that these data were interim analyses, but “these are positive in terms of participants seeing a benefit in glucose control and glycemic variability, which is a risk factor for developing type 2 diabetes but also for microvascular complications. We also saw improved time in range in terms of tight glucose control.

“Even in 3 days, there were small, subtle differences which are subclinical — but this is not a clinical cohort. The results are statistically significant and a promising piece of data to suggest a feasible intervention that could be translated across different populations,” she said, adding that over a longer time period, changes between TRE timing might show changes in people at risk for type 2 diabetes who don’t have compromised circadian rhythms.

Moderating the session was Lutgarda Bozzetto, MD, from the University of Naples Federico II, Naples, Italy. She told this news organization, “It’s a hot topic right now, and the finding that there’s no difference in the time of day when the restricted eating is done suggests that in people at risk of diabetes, the hormonal flux and cycle involved in blood glucose control is not so strong or sensitive.”

Using a continuous glucose monitor, they can look at their blood glucose levels after eating, and this might “be powerful in guiding behavioral change,” said Dr. Bozzetto.

Abbott Laboratories funded the continuous glucose monitoring. Neither Dr. Bowden Davies nor Dr. Bozzetto had any other relevant financial disclosures.

A version of this article first appeared on Medscape.com.

MADRID — A daily 8-hour eating window controls blood glucose whether followed early or late in the day by people at risk for type 2 diabetes, showed a time-restricted eating (TRE) study presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The study, examining shifting the time of day for the 8-hour eating window along with a tightly controlled diet, found that 8 hours of TRE — whether early or late in the day — led to a significant improvement in the time spent within a normal daily blood glucose range and in glycemic variability.

“We didn’t show a benefit in terms of early versus late TRE, but we did show a benefit of time-restricted eating within a window of 8 h/d,” said study lead Kelly Bowden Davies, MSc, PhD, from Manchester Metropolitan University, Manchester, England, when presenting the work. “It doesn’t matter when you restrict eating, but if you restrict it to 8 hours then, according to our study, it benefits glycemic control in people at risk of type 2 diabetes.”

The researcher added that the effect was seen after only 3 days, and “demonstrates its therapeutic role in adults at risk of type 2 diabetes, which warrants investigation in the longer term.”

The current study examined the effect of shifting the time of day for the TRE window from early (8 AM-4 PM) to late (12 PM-8 PM) in people at risk of developing type 2 diabetes due to a lifestyle characterized as sedentary and poor diet.

Previous studies indicate that TRE, which limits when, but not what, individuals eat, can improve insulin sensitivity and A1c in people at risk for type 2 diabetes.

But Dr. Bowden Davies pointed out that the effect of TRE on glycemic variability remained unclear. While prior work had attributed the positive effects of TRE to reduced energy intake, this study provided a diet where energy consumption matched energy expenditure — taking into account sex, age, weight, height, and activity level, termed a “eucaloric” diet.

“Some research groups recognize that if we manipulate the time at which we eat, then we can better align with circadian metabolic rhythms to improve whole body insulin sensitivity and glycemic variability,” explained Dr. Bowden Davies. “It may be that eating in the morning may be better aligned [with circadian rhythms] and cause greater improvement in glucose control.”
 

Three-Day TRE Plan Led to Blood Glucose Control

In a cross-over study design, all 15 participants were randomized to follow the early and late TRE regimens with a 7-day washout period in the middle. Participants had a mean body mass index (BMI) of 27.7 kg/m², had a mean waist circumference of 73 cm, were sedentary, and followed a poor diet.

“Participants were normoglycemic so had good glucose control, but due to having overweight and obesity, they are considered as having risk factors for the development of type 2 diabetes,” noted Dr. Bowden Davies.

Before the TRE period, participants provided researchers with a dietary record. If they started on the early TRE, they crossed over to the late TRE after the washout period, and vice versa, she explained.

Continuous glucose monitoring (FreeStyle Libre 2, Abbott Laboratories) was carried out across the study to assess the daily time spent in euglycemia (3.9-7.8 mmol/L) and provide markers of glycemic variability, including mean absolute glucose, coefficient of variation, and mean amplitude of glucose excursions. Blood draws both pre- and post-TRE period provided biochemical measurements, and anthropometric readings were also taken.

There were nine female participants, with a mean age of 52 years, a BMI of 28 kg/m², and an A1c level of 37.9 mmol/mol (5.6%). They tended to snack across an eating period of 14 h/d or more (habitual eating). They were assigned to two different investigational eating patterns for 3-day durations: Early or late, and these findings were compared with those from participants who continued their habitual eating.

Participants were provided with a eucaloric, standardized diet [50% carbohydrates, 30% fat, and 20% protein] to be eaten during the TRE period, whereas they ate as usual (ie, as and what they wanted) when not on the TRE regimen.

No changes were seen in the biochemistry markers assessed. “Given they only followed the TRE for 3 days, this is unsurprising,” remarked Dr. Bowden Davies. “We did see weight loss after only 3 days of TRE of around 1.1 kg across the two interventions,” she reported.

Referring to the early vs late TRE regimen, she added that “we didn’t see a benefit [no significant differences in glycemic control] of early compared with late TRE, but we did see a benefit of restricting the eating window to 8 h/d, so both conditions [early and late TRE regimens] had a benefit on glucose control.”

Variables of blood glucose control were also reduced while on the TRE regimen compared with habitual eating (more than 14 h/d), with significantly increased time spent within the normal blood glucose range on average by 3.3%, and also reduced mean absolute glucose by 0.6 mmol/L, coefficient of variation by 2.6%, and mean amplitude of glucose excursions by 0.4 mmol/L.

“Within 3 days, this is quite striking,” Dr. Bowden Davies pointed out.

She added that these data were interim analyses, but “these are positive in terms of participants seeing a benefit in glucose control and glycemic variability, which is a risk factor for developing type 2 diabetes but also for microvascular complications. We also saw improved time in range in terms of tight glucose control.

“Even in 3 days, there were small, subtle differences which are subclinical — but this is not a clinical cohort. The results are statistically significant and a promising piece of data to suggest a feasible intervention that could be translated across different populations,” she said, adding that over a longer time period, changes between TRE timing might show changes in people at risk for type 2 diabetes who don’t have compromised circadian rhythms.

Moderating the session was Lutgarda Bozzetto, MD, from the University of Naples Federico II, Naples, Italy. She told this news organization, “It’s a hot topic right now, and the finding that there’s no difference in the time of day when the restricted eating is done suggests that in people at risk of diabetes, the hormonal flux and cycle involved in blood glucose control is not so strong or sensitive.”

Using a continuous glucose monitor, they can look at their blood glucose levels after eating, and this might “be powerful in guiding behavioral change,” said Dr. Bozzetto.

Abbott Laboratories funded the continuous glucose monitoring. Neither Dr. Bowden Davies nor Dr. Bozzetto had any other relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Research offers promising insights into the ideal frontline therapies for mantle cell lymphoma (MCL), but there are continued unmet needs in the relapsed/refractory setting, blood cancer specialists told colleagues. 

In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.

On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.

Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
 

Frontline MCL: Age Helps Determine Best Approach

“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said. 

Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”

For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.

Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.

The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said. 

“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”

What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival. 

However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option. 

Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising. 
 

Relapsed/Refractory MCL: Better Options Are Still Needed

In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”

Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”

Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”

However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.” 

Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.

“All of these tools are in clinical trials, and hopefully some of them will help,” he said.

Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
 

A version of this article first appeared on Medscape.com.

Research offers promising insights into the ideal frontline therapies for mantle cell lymphoma (MCL), but there are continued unmet needs in the relapsed/refractory setting, blood cancer specialists told colleagues. 

In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.

On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.

Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
 

Frontline MCL: Age Helps Determine Best Approach

“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said. 

Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”

For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.

Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.

The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said. 

“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”

What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival. 

However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option. 

Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising. 
 

Relapsed/Refractory MCL: Better Options Are Still Needed

In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”

Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”

Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”

However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.” 

Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.

“All of these tools are in clinical trials, and hopefully some of them will help,” he said.

Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
 

A version of this article first appeared on Medscape.com.

Research offers promising insights into the ideal frontline therapies for mantle cell lymphoma (MCL), but there are continued unmet needs in the relapsed/refractory setting, blood cancer specialists told colleagues. 

In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.

On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.

Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
 

Frontline MCL: Age Helps Determine Best Approach

“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said. 

Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”

For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.

Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.

The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said. 

“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”

What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival. 

However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option. 

Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising. 
 

Relapsed/Refractory MCL: Better Options Are Still Needed

In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”

Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”

Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”

However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.” 

Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.

“All of these tools are in clinical trials, and hopefully some of them will help,” he said.

Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
 

A version of this article first appeared on Medscape.com.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a game changer for the treatment of multiple myeloma (MM), but questions remain as to how — and when — the immunotherapy will best be used for patients who experience disease relapse.

Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.

Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
 

Dr. Patel: Yes, Earlier Is Better

A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.

“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”

Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.

CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.

When it comes to toxicity, yes, it is a concern, she said.

“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”

Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”

“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”

Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.

Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.

The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”

“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.

Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
 

Dr. Usmani: Reserve CAR T for Later Relapse

Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.

There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.

“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.

The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.

“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.

The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.

As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.

“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.

DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.

“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.

Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.

“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”

“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.

“The great thing is we have all these options for our patients,” he said.

Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.

A version of this article first appeared on Medscape.com.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a game changer for the treatment of multiple myeloma (MM), but questions remain as to how — and when — the immunotherapy will best be used for patients who experience disease relapse.

Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.

Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
 

Dr. Patel: Yes, Earlier Is Better

A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.

“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”

Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.

CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.

When it comes to toxicity, yes, it is a concern, she said.

“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”

Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”

“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”

Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.

Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.

The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”

“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.

Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
 

Dr. Usmani: Reserve CAR T for Later Relapse

Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.

There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.

“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.

The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.

“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.

The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.

As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.

“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.

DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.

“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.

Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.

“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”

“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.

“The great thing is we have all these options for our patients,” he said.

Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.

A version of this article first appeared on Medscape.com.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a game changer for the treatment of multiple myeloma (MM), but questions remain as to how — and when — the immunotherapy will best be used for patients who experience disease relapse.

Will CAR T be best used in early relapse? Experts debated this question at the annual meeting of the Society of Hematologic Oncology. Based on attendees’ votes, at least one side of the debate emerged victorious.

Krina Patel, MD, an associate professor at the University of Texas MD Anderson Cancer Center, Houston, came out swinging with earnest support for using CAR T in early relapse. Saad Z. Usmani, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York City, and Cornell University, Ithaca, New York, argued in favor of being “a little more circumspect.”
 

Dr. Patel: Yes, Earlier Is Better

A pre-debate audience poll leaned Dr. Patel’s way, with about 59% of 73 votes favoring CAR T in early relapse, 33% favoring reserving CAR T for patients who relapse after three or more lines of therapy, and 8% undecided.

“CAR T is not just a drug — it’s an actual therapy that takes a lot of logistics, as well as bridging therapy and all these other things to take into account,” said Dr. Patel. “And again, when I can go earlier, I have control over some of this.”

Furthermore, randomized phase 3 data from the KarMMA-3 study and the CARTITUDE-4 study showed that multiple standard therapies were not as good as CAR T in the early relapse setting, she said, pointing to the respective hazard ratios for disease progression or death with CAR T vs standard therapies of 0.49 and 0.26.

CARTITUDE-4 also suggested that manufacturing failures are more likely in later relapse — when time is already of greater essence, she said, noting that it can take an additional 3 months when restarting the process.

When it comes to toxicity, yes, it is a concern, she said.

“But we know how to decrease toxicity,” she stressed. “And again, with our second- and third-line approaches, we actually have better therapies to give for bridging.”

Quality of life is another important consideration, Dr. Patel said, noting only CAR T offers a “one-and-done” therapy that helps patients “truly feel better.”

“They’re not having to come into hospitals as often, and this is not just for months; it’s for years,” she said. “To be able to give that to somebody is huge, and again, we have objective data that show that compared to our standard of care therapies, patients do better in almost every realm of quality of life metrics.”

Dr. Patel also pointed to recent data from a retrospective study showing that for bridging therapy, less is more when disease is controlled, and in the early-line setting, more and safer options are available for reducing tumor burden.

Early CAR T is better for older or frail patients as well, she argued, noting that these patients don’t have time to wait, and a new study demonstrates that they tend to do well with CAR T in the early relapse setting.

The choice for early CAR T is clear in patients with high-risk disease, but Dr. Patel stressed that it shouldn’t be reserved for those patients, asking, “When has anything worked well for patients with high-risk disease and not [also] better for standard-risk patients?”

“And why give only 20%-25% of your patients [who actually reach fifth-line treatment] access to something that we know has really revolutionized myeloma therapy?” she said.

Many patients don’t have access, and that’s an issue, she acknowledged, adding: “But for those who do, we really should be giving it to them as soon as possible.”
 

Dr. Usmani: Reserve CAR T for Later Relapse

Not so fast, said Dr. Usmani. “All of these therapies are doing wonders for our patients, and we believe in them, but we have to be a little circumspect in looking at this data more closely and not just with emotions,” he added, noting that many options exist for patients in a first or second relapse, and new options are emerging.

There is also a “harsh reality” in terms of CAR T availability, he noted, explaining that, in 2021, about 180,000 people were living with MM, and about two thirds of those had relapsed disease. Meanwhile, fewer than 1000 CAR T products have been delivered each year for patients with relapsed MM since they were approved in this setting in the United States.

“So, it’s a pipe dream, seriously, that we will be able to utilize CAR T for all patients in early relapsed disease,” he said, adding that capacity will remain an issue because of limited resources.

The existing data, including from KarMMa-3 and CARTITUDE-4, show little potential for long-term benefit with early vs later CAR T.

“There is no plateau,” he said of the survival curves in KarMMa-3, underscoring the lack of a difference in overall survival benefit based on CAR T timing.

The CARTITUDE-4 curves “look great,” and it may be that a “small plateau emerges,” but they don’t demonstrate a benefit of earlier vs later CAR T, he said.

As Dr. Patel noted, there are few treatment options for patients with anti-CD38 monoclonal antibody and immunomodulatory drug resistance at first relapse. However, that situation will soon change, Dr. Usmani stated.

“Guess what? Belamaf is coming to the rescue!” he said of the off-the-shelf and more accessible B-cell maturation antigen-targeted antibody-drug conjugate belantamab mafodotin, which has recently been evaluated in the DREAMM 7 and DREAMM 8 trials.

DREAMM 7 demonstrated improved survival vs daratumumab, bortezomib, and dexamethasone in the relapsed/refractory MM setting when used in combination with bortezomib and dexamethasone. DREAMM 8 shows similar benefit with belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in lenalidomide-exposed patients with relapsed or refractory MM.

“Belamaf combinations in the one to three lines [of prior therapy] setting look really good,” he said, noting a particular benefit for progression-free survival and a trend toward improved overall survival.

Considering these factors, as well as the risk for cytopenias and the subsequent risk for infection in most patients who undergo CAR T-cell therapy and the known potential risk for secondary malignancies, Dr. Usmani said that he will remain “in the camp of being really careful in selecting CAR T patients for early relapse” until more is known about the risks.

“CAR T for all is not the answer. I think we have to be careful in picking CAR T patients; it’s not a zero-sum game here,” he said, stressing that “there are too many unknowns with the use of early CAR T therapy.”

“It makes sense in some, but not for everyone,” he said, emphasizing the importance of including patients in the discussion.

“The great thing is we have all these options for our patients,” he said.

Dr. Usmani persuaded at least a few colleagues: The final vote showed 42% of 124 voters supported early CAR T, compared with 52% who supported CAR T after three or more lines of therapy and 6% who remained undecided.

A version of this article first appeared on Medscape.com.

TOPLINE:

MADRID — Elevated interleukin (IL) 6 levels are associated with an increased risk for obesity-related cancers in patients newly diagnosed with type 2 diabetes (T2D), potentially enabling the identification of higher-risk individuals through a simple blood test.

METHODOLOGY:

• T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
• Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
• They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
• At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.

TAKEAWAY:

• Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
• Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
• The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
• The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.

IN PRACTICE:

“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.

SOURCE:

The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

LIMITATIONS:

No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.

DISCLOSURES:

The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

MADRID — Elevated interleukin (IL) 6 levels are associated with an increased risk for obesity-related cancers in patients newly diagnosed with type 2 diabetes (T2D), potentially enabling the identification of higher-risk individuals through a simple blood test.

METHODOLOGY:

• T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
• Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
• They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
• At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.

TAKEAWAY:

• Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
• Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
• The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
• The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.

IN PRACTICE:

“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.

SOURCE:

The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

LIMITATIONS:

No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.

DISCLOSURES:

The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

MADRID — Elevated interleukin (IL) 6 levels are associated with an increased risk for obesity-related cancers in patients newly diagnosed with type 2 diabetes (T2D), potentially enabling the identification of higher-risk individuals through a simple blood test.

METHODOLOGY:

• T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
• Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
• They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
• At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.

TAKEAWAY:

• Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
• Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
• The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
• The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.

IN PRACTICE:

“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.

SOURCE:

The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

LIMITATIONS:

No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.

DISCLOSURES:

The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

VIENNA — Physicians are called to record clinical details of patients with asthma undergoing biologic therapy to monitor clinical remission and keep an eye on eosinophilic granulomatosis with polyangiitis (EGPA) symptoms as patients come off the medications, according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.

Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.

Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.

In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
 

Defining Clinical Remission in Asthma

Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.

To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.

GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.

An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”

He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
 

Biologics and EGPA

In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.

The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.

The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.

The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships. 

A version of this article appeared on Medscape.com.

VIENNA — Physicians are called to record clinical details of patients with asthma undergoing biologic therapy to monitor clinical remission and keep an eye on eosinophilic granulomatosis with polyangiitis (EGPA) symptoms as patients come off the medications, according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.

Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.

Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.

In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
 

Defining Clinical Remission in Asthma

Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.

To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.

GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.

An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”

He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
 

Biologics and EGPA

In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.

The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.

The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.

The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships. 

A version of this article appeared on Medscape.com.

VIENNA — Physicians are called to record clinical details of patients with asthma undergoing biologic therapy to monitor clinical remission and keep an eye on eosinophilic granulomatosis with polyangiitis (EGPA) symptoms as patients come off the medications, according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.

Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.

Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.

In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
 

Defining Clinical Remission in Asthma

Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.

To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.

GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.

An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”

He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
 

Biologics and EGPA

In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.

The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.

The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.

The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships. 

A version of this article appeared on Medscape.com.

MADRID — Night owls — individuals with late chronotypes — may be at an increased risk for type 2 diabetes (T2D), beyond the risks conferred by an unhealthy lifestyle, research presented at the annual meeting of the European Association for the Study of Diabetes suggested.

In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.

“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.

“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”

“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”

The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.

Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.

During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.

Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm² more visceral fat, and 14% more liver fat.
 

Body Clock Out of Sync?

“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.

“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”

Might trying to adjust chronotype earlier in life have an effect on risk?

“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”

Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.

“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”

Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”

Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”

Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.

“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.

“However environmental factors and family history can play an important role too,” he added.

Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.

No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

MADRID — Night owls — individuals with late chronotypes — may be at an increased risk for type 2 diabetes (T2D), beyond the risks conferred by an unhealthy lifestyle, research presented at the annual meeting of the European Association for the Study of Diabetes suggested.

In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.

“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.

“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”

“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”

The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.

Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.

During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.

Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm² more visceral fat, and 14% more liver fat.
 

Body Clock Out of Sync?

“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.

“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”

Might trying to adjust chronotype earlier in life have an effect on risk?

“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”

Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.

“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”

Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”

Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”

Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.

“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.

“However environmental factors and family history can play an important role too,” he added.

Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.

No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

MADRID — Night owls — individuals with late chronotypes — may be at an increased risk for type 2 diabetes (T2D), beyond the risks conferred by an unhealthy lifestyle, research presented at the annual meeting of the European Association for the Study of Diabetes suggested.

In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.

“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.

“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”

“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”

The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.

Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.

During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.

Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm² more visceral fat, and 14% more liver fat.
 

Body Clock Out of Sync?

“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.

“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”

Might trying to adjust chronotype earlier in life have an effect on risk?

“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”

Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.

“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”

Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”

Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”

Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.

“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.

“However environmental factors and family history can play an important role too,” he added.

Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.

No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Bruton’s tyrosine kinase inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib have revolutionized the treatment of chronic lymphocytic leukemia (CLL). But should patients take a break from them?

At the annual meeting of the Society of Hematologic Oncology, two hematologist-oncologists — Inhye Ahn, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and Kerry A. Rogers, MD, of Ohio State University in Columbus — faced off in a debate. Ahn said the drugs can indeed be discontinued, while Rogers argued against stopping the medications.

“When I talk to my own patient about standard of care options in CLL, I use the analogy of a marathon and a sprint,” Dr. Ahn said. A marathon refers to continuous treatment with Bruton’s kinase inhibitors given daily for years, while the sprint refers to the combination of venetoclax with an anti-CD20 monoclonal antibody given over 12 cycles for the frontline regimen and 2 years for refractory CLL.

“I tell them these are both considered very efficacious regimens and well tolerated, one is by IV [the venetoclax regimen] and the other isn’t [Bruton’s kinase inhibitors], and they have different toxicity profile. I ask them what would you do? The most common question that I get from my patient is, ‘why would anyone do a marathon?’ ”

It’s not solely the length of treatment that’s important, Dr. Ahn said, as toxicities from the long-term use of Bruton’s kinase inhibitors build up over time and can lead to hypertension, arrhythmia, and sudden cardiac death.

In addition, she said, infections can occur, as well as hampered vaccine response, an important risk in the era of the COVID-19 pandemic. The cost of the drugs is high and adds up over time, and continuous use can boost resistance.

Is there a way to turn the marathon of Bruton’s kinase inhibitor use into a sprint without hurting patients? The answer is yes, through temporary discontinuation, Dr. Ahn said, although she cautioned that early cessation could lead to disease flare. “We dipped into our own database of 84 CLL patients treated with ibrutinib, and our conclusion was that temporary dose interruption or dose reduction did not impact progression-free survival”

Moving forward, she said, “more research is needed to define the optimal regimen that would lead to treatment cessation, the optimal patient population, who would benefit most from the cessation strategy, treatment duration, and how we define success.” For her part, Dr. Rogers argued that the continuous use of Bruton’s kinase inhibitors is “really the most effective treatment we have in CLL.”

It’s clear that “responses deepen with continued treatment,” Dr. Rogers said, noting that remission times grow over years of treatment. She highlighted a 2022 study of patients with CLL who took ibrutinib that found complete remission or complete remission with incomplete hematologic recovery was 7% at 12 months and 34% at 7 years. When patients quit taking the drugs, “you don’t get to maximize your patient’s response to this treatment.”

Dr. Rogers also noted that the RESONATE-2 trial found that ibrutinib is linked to the longest median progression-free survival of any CLL treatment at 8.9 years. “That really struck me a very effective initial therapy.”

Indeed, “when you’re offering someone initial therapy with a Bruton’s kinase inhibitor as a continuous treatment strategy, you can tell people that they can expect a normal lifespan with this approach. That’s extremely important when you’re talking to patients about whether they might want to alter their leukemia treatment.”

Finally, she noted that discontinuation of ibrutinib was linked to shorter survival in early research. “This was the first suggestion that discontinuation is not good.”

Dr. Rogers said that discontinuing the drugs is sometimes necessary because of adverse events, but patients can “certainly switch to a more tolerable Bruton’s kinase inhibitor. With the options available today, that should be a strategy that’s considered.”

Audience members at the debate were invited to respond to a live online survey about whether Bruton’s kinase inhibitors can be discontinued. Among 49 respondents, most (52.3%) said no, 42.8% said yes, and the rest were undecided/other.

Disclosures for the speakers were not provided. Dr. Ahn disclosed consulting for BeiGene and AstraZeneca. Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Janssen, and Novartis; consulting for AstraZeneca, BeiGene, Janssen, Pharmacyclics, AbbVie, Genentech, and LOXO@Lilly; and receiving travel funding from AstraZeneca.

A version of this article appeared on Medscape.com.

Bruton’s tyrosine kinase inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib have revolutionized the treatment of chronic lymphocytic leukemia (CLL). But should patients take a break from them?

At the annual meeting of the Society of Hematologic Oncology, two hematologist-oncologists — Inhye Ahn, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and Kerry A. Rogers, MD, of Ohio State University in Columbus — faced off in a debate. Ahn said the drugs can indeed be discontinued, while Rogers argued against stopping the medications.

“When I talk to my own patient about standard of care options in CLL, I use the analogy of a marathon and a sprint,” Dr. Ahn said. A marathon refers to continuous treatment with Bruton’s kinase inhibitors given daily for years, while the sprint refers to the combination of venetoclax with an anti-CD20 monoclonal antibody given over 12 cycles for the frontline regimen and 2 years for refractory CLL.

“I tell them these are both considered very efficacious regimens and well tolerated, one is by IV [the venetoclax regimen] and the other isn’t [Bruton’s kinase inhibitors], and they have different toxicity profile. I ask them what would you do? The most common question that I get from my patient is, ‘why would anyone do a marathon?’ ”

It’s not solely the length of treatment that’s important, Dr. Ahn said, as toxicities from the long-term use of Bruton’s kinase inhibitors build up over time and can lead to hypertension, arrhythmia, and sudden cardiac death.

In addition, she said, infections can occur, as well as hampered vaccine response, an important risk in the era of the COVID-19 pandemic. The cost of the drugs is high and adds up over time, and continuous use can boost resistance.

Is there a way to turn the marathon of Bruton’s kinase inhibitor use into a sprint without hurting patients? The answer is yes, through temporary discontinuation, Dr. Ahn said, although she cautioned that early cessation could lead to disease flare. “We dipped into our own database of 84 CLL patients treated with ibrutinib, and our conclusion was that temporary dose interruption or dose reduction did not impact progression-free survival”

Moving forward, she said, “more research is needed to define the optimal regimen that would lead to treatment cessation, the optimal patient population, who would benefit most from the cessation strategy, treatment duration, and how we define success.” For her part, Dr. Rogers argued that the continuous use of Bruton’s kinase inhibitors is “really the most effective treatment we have in CLL.”

It’s clear that “responses deepen with continued treatment,” Dr. Rogers said, noting that remission times grow over years of treatment. She highlighted a 2022 study of patients with CLL who took ibrutinib that found complete remission or complete remission with incomplete hematologic recovery was 7% at 12 months and 34% at 7 years. When patients quit taking the drugs, “you don’t get to maximize your patient’s response to this treatment.”

Dr. Rogers also noted that the RESONATE-2 trial found that ibrutinib is linked to the longest median progression-free survival of any CLL treatment at 8.9 years. “That really struck me a very effective initial therapy.”

Indeed, “when you’re offering someone initial therapy with a Bruton’s kinase inhibitor as a continuous treatment strategy, you can tell people that they can expect a normal lifespan with this approach. That’s extremely important when you’re talking to patients about whether they might want to alter their leukemia treatment.”

Finally, she noted that discontinuation of ibrutinib was linked to shorter survival in early research. “This was the first suggestion that discontinuation is not good.”

Dr. Rogers said that discontinuing the drugs is sometimes necessary because of adverse events, but patients can “certainly switch to a more tolerable Bruton’s kinase inhibitor. With the options available today, that should be a strategy that’s considered.”

Audience members at the debate were invited to respond to a live online survey about whether Bruton’s kinase inhibitors can be discontinued. Among 49 respondents, most (52.3%) said no, 42.8% said yes, and the rest were undecided/other.

Disclosures for the speakers were not provided. Dr. Ahn disclosed consulting for BeiGene and AstraZeneca. Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Janssen, and Novartis; consulting for AstraZeneca, BeiGene, Janssen, Pharmacyclics, AbbVie, Genentech, and LOXO@Lilly; and receiving travel funding from AstraZeneca.

A version of this article appeared on Medscape.com.

Bruton’s tyrosine kinase inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib have revolutionized the treatment of chronic lymphocytic leukemia (CLL). But should patients take a break from them?

At the annual meeting of the Society of Hematologic Oncology, two hematologist-oncologists — Inhye Ahn, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and Kerry A. Rogers, MD, of Ohio State University in Columbus — faced off in a debate. Ahn said the drugs can indeed be discontinued, while Rogers argued against stopping the medications.

“When I talk to my own patient about standard of care options in CLL, I use the analogy of a marathon and a sprint,” Dr. Ahn said. A marathon refers to continuous treatment with Bruton’s kinase inhibitors given daily for years, while the sprint refers to the combination of venetoclax with an anti-CD20 monoclonal antibody given over 12 cycles for the frontline regimen and 2 years for refractory CLL.

“I tell them these are both considered very efficacious regimens and well tolerated, one is by IV [the venetoclax regimen] and the other isn’t [Bruton’s kinase inhibitors], and they have different toxicity profile. I ask them what would you do? The most common question that I get from my patient is, ‘why would anyone do a marathon?’ ”

It’s not solely the length of treatment that’s important, Dr. Ahn said, as toxicities from the long-term use of Bruton’s kinase inhibitors build up over time and can lead to hypertension, arrhythmia, and sudden cardiac death.

In addition, she said, infections can occur, as well as hampered vaccine response, an important risk in the era of the COVID-19 pandemic. The cost of the drugs is high and adds up over time, and continuous use can boost resistance.

Is there a way to turn the marathon of Bruton’s kinase inhibitor use into a sprint without hurting patients? The answer is yes, through temporary discontinuation, Dr. Ahn said, although she cautioned that early cessation could lead to disease flare. “We dipped into our own database of 84 CLL patients treated with ibrutinib, and our conclusion was that temporary dose interruption or dose reduction did not impact progression-free survival”

Moving forward, she said, “more research is needed to define the optimal regimen that would lead to treatment cessation, the optimal patient population, who would benefit most from the cessation strategy, treatment duration, and how we define success.” For her part, Dr. Rogers argued that the continuous use of Bruton’s kinase inhibitors is “really the most effective treatment we have in CLL.”

It’s clear that “responses deepen with continued treatment,” Dr. Rogers said, noting that remission times grow over years of treatment. She highlighted a 2022 study of patients with CLL who took ibrutinib that found complete remission or complete remission with incomplete hematologic recovery was 7% at 12 months and 34% at 7 years. When patients quit taking the drugs, “you don’t get to maximize your patient’s response to this treatment.”

Dr. Rogers also noted that the RESONATE-2 trial found that ibrutinib is linked to the longest median progression-free survival of any CLL treatment at 8.9 years. “That really struck me a very effective initial therapy.”

Indeed, “when you’re offering someone initial therapy with a Bruton’s kinase inhibitor as a continuous treatment strategy, you can tell people that they can expect a normal lifespan with this approach. That’s extremely important when you’re talking to patients about whether they might want to alter their leukemia treatment.”

Finally, she noted that discontinuation of ibrutinib was linked to shorter survival in early research. “This was the first suggestion that discontinuation is not good.”

Dr. Rogers said that discontinuing the drugs is sometimes necessary because of adverse events, but patients can “certainly switch to a more tolerable Bruton’s kinase inhibitor. With the options available today, that should be a strategy that’s considered.”

Audience members at the debate were invited to respond to a live online survey about whether Bruton’s kinase inhibitors can be discontinued. Among 49 respondents, most (52.3%) said no, 42.8% said yes, and the rest were undecided/other.

Disclosures for the speakers were not provided. Dr. Ahn disclosed consulting for BeiGene and AstraZeneca. Dr. Rogers disclosed receiving research funding from Genentech, AbbVie, Janssen, and Novartis; consulting for AstraZeneca, BeiGene, Janssen, Pharmacyclics, AbbVie, Genentech, and LOXO@Lilly; and receiving travel funding from AstraZeneca.

A version of this article appeared on Medscape.com.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.