BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

BALTIMORE – In the absence of MRI evidence of mesial temporal sclerosis (MTS), sparing the hippocampus during anterior temporal lobectomy for refractory epilepsy reduces memory loss without affecting the procedure’s efficacy, according to a review from researchers at Thomas Jefferson University in Philadelphia.

Often, the hippocampus and other mesial structures are removed even if they appear normal. The concern is that even normal looking tissue could harbor epileptogenic elements and leaving them in tact could reduce postoperative seizure control, explained senior investigator and neurologist Michael Sperling, MD, director of the Jefferson Comprehensive Epilepsy Center.

He and his colleagues wanted to see if that was really true, so they compared outcomes in 21 patients who had mesial-sparing lobectomies with 19 patients who had the standard approach. Cases and controls were matched for age, preoperative seizure frequency, side of surgery, and other factors. None of the patients had MTS.

There was no significant difference in postoperative seizure recurrence between the two groups (P = .974). The standard procedure had a slight edge early on, but at 2.5 years, just over 60% of patients in both groups were seizure free. At 5 years, about 50% were seizure free, and almost 40% in both arms at 7.5 years.

About two-thirds of patients in each arm had pre- and postoperative verbal memory testing, with similar duration from surgery to postop evaluation. There was no change among the hippocampus-sparing patients, but a roughly one standard deviation drop in delayed recall and logical memory on the California Verbal Learning Test in the standard group.

Even so, it wasn’t enough to affect employment, which the investigators used as a surrogate for disability; postoperative employment was comparable in both groups. People mostly retained their jobs, and there was no difference in job loss. A few people in each arm actually found jobs after surgery.

The investigators concluded that “it is reasonable to recommend mesial temporal sparing procedure in patients with dominant neocortical temporal lobe epilepsy when the hippocampus appears normal in the MRI. However, as resecting the mesial temporal structures was not associated with a greater chance of becoming unemployed following the surgery, there appears to be no major contraindication to performing an [anterior temporal lobectomy] if clinically warranted.”

The results are reassuring. “My bias walking in was that” seizure recurrence would be worse after hippocampal-sparing surgery. “I was pleased to see that it was about the same. If you want to try to preserve verbal memory and the MRI is normal, you can get away with sparing the mesial temporal structures, and still get a good seizure outcome,” Dr. Sperling said at the annual meeting of the American Epilepsy Society, where the study was presented.

“But if you have to take the hippocampus for whatever reason, the functional consequence of a decline in verbal memory is not severe enough as to be disabling,” which is “one of the big concerns” with temporal lobectomy, he said.

The findings “will make us more likely to recommend mesial-sparing surgery, but at the same time” perhaps not be quite as worried about disability with the standard approach.

Temporal lobe epilepsy with normal mesial structures isn’t very common, which explains the small numbers in the series. It’s possible subtle difference in seizure control and employment outcomes would have been found with a larger series, “but obviously there were no major differences. I think the fundamental questions have been answered to my satisfaction,” Dr. Sperling said.

Overall, “it’s better to operate and try to cure people than to worry that you will make their memory worse when the consequences of having uncontrolled epilepsy is a higher death rate,” he said.

There were about equal numbers of men and women in the review; patients were in their early 30s, on average; and most had left-sided surgery. Just over half in each arm had preoperative tonic-clonic seizures. The mean duration of epilepsy was 14.9 years in the mesial-sparing group, and 8.6 years in the standard arm.

There was no funding for the review, and Dr. Sperling didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Goldstein L et al. AES 2019. Abstract 1.339.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

mschneider@mdedge.com

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

mschneider@mdedge.com

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

mschneider@mdedge.com

PHILADELPHIA – Nearly half of patients with ST-elevation MI and multivessel coronary artery disease in the landmark COMPLETE trial had an obstructive coronary lesion with vulnerable plaque morphology in a segment far from the culprit lesion, Natalia Pinilla-Echeverri, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

This novel finding from an optical coherence tomography (OCT) substudy of COMPLETE provides a likely mechanistic explanation for the major clinical benefits documented in the full COMPLETE trial, noted Dr. Pinilla-Echeverri, a cardiologist at the Population Health Research Institute at McMaster University, Hamilton, Ont.

COMPLETE was a multinational trial which randomized 4,041 ST-elevation MI (STEMI) patients with multivessel disease to culprit lesion–only percutaneous coronary intervention (PCI) or additional routine angiography–guided staged PCI of nonculprit obstructive lesions with at least 70% stenosis. As previously reported, the risk of the coprimary composite endpoint comprising cardiovascular death, new MI, or ischemia-driven revascularization was reduced by 49% over 3 years of follow-up in the group with staged PCI of nonculprit lesions, with an impressive number needed to treat of just 13 (N Engl J Med. 2019 Oct 10;381[15]:1411-21).

Dr. Pinella-Echeverri reported on the 93 patients who participated in the OCT substudy, the purpose of which was to determine the prevalence of high-risk, vulnerable plaque in obstructive and nonobstructive nonculprit lesions. For this purpose, vulnerable plaque was defined as thin-cap fibroatheroma (TCFA), a coronary lesion known to pose high risk of worsening stenosis, plaque rupture, and cardiovascular events.

Of note, these 93 patients had a total of 425 diseased segments: 150 obstructive and 275 nonobstructive.

“This is reassuring that the concept of acute coronary syndrome implies a diffuse pathophysiology of affecting not only the culprit segment but the coronary vasculature as a whole,” Dr. Pinella-Echeverri observed.

The main study finding, however, was that TCFA was significantly more prevalent in obstructive, compared with nonobstructive, nonculprit lesions by a margin of 35% to 23%. The obstructive and nonobstructive TCFA lesions had a similar lipid-rich composition; however, the obstructive ones were significantly longer and had a smaller mean lumen area.

When breaking down the prevalence of TCFA per patient, 47% of patients had a nonculprit obstructive lesion with vulnerable plaque morphology. Another 20% had nonobstructive TCFA lesions. And only 32% of the STEMI patients had no TCFA in their obstructive or nonobstructive segments.

Bruce Jancin/MDedge News

Discussant Frans Van de Werf, MD, PhD, commented: “This [OCT substudy result] immediately explains the clinical benefit observed with preventive PCI in STEMI patients with obstructive multivessel disease.”

The finding that 20% of the STEMI patients had nonobstructive lesions with vulnerable plaque morphology by OCT provides powerful support for the current guideline-recommended strategy of immediately starting STEMI patients on intensive lipid-lowering therapy, added Dr. Van de Werf, professor of medicine at the Catholic University of Leuven (Belgium).

He argued that the decision to revascularize nonculprit lesions by means of PCI versus the more complete revascularization achieved via coronary artery bypass graft surgery shouldn’t be made during the initial primary PCI, citing evidence that when the decision gets made at that time, coronary artery bypass grafting (CABG) is less likely to be chosen.

“I believe that OCT and [fractional flow reserve] should not be performed during the index primary PCI, not only for the comfort of the patient, but also for the better selection of complete revascularization. Interventional cardiologists should not forget that CABG might be a better revascularization treatment in some cases, such as left main disease and diabetes mellitus,” the cardiologist cautioned.

The COMPLETE OCT Substudy was supported by Abbott Vascular, the Population Health Research Institute, Hamilton Health Sciences, and the Canadian Institutes of Health Research.

bjancin@mdedge.com

PHILADELPHIA – Nearly half of patients with ST-elevation MI and multivessel coronary artery disease in the landmark COMPLETE trial had an obstructive coronary lesion with vulnerable plaque morphology in a segment far from the culprit lesion, Natalia Pinilla-Echeverri, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

This novel finding from an optical coherence tomography (OCT) substudy of COMPLETE provides a likely mechanistic explanation for the major clinical benefits documented in the full COMPLETE trial, noted Dr. Pinilla-Echeverri, a cardiologist at the Population Health Research Institute at McMaster University, Hamilton, Ont.

COMPLETE was a multinational trial which randomized 4,041 ST-elevation MI (STEMI) patients with multivessel disease to culprit lesion–only percutaneous coronary intervention (PCI) or additional routine angiography–guided staged PCI of nonculprit obstructive lesions with at least 70% stenosis. As previously reported, the risk of the coprimary composite endpoint comprising cardiovascular death, new MI, or ischemia-driven revascularization was reduced by 49% over 3 years of follow-up in the group with staged PCI of nonculprit lesions, with an impressive number needed to treat of just 13 (N Engl J Med. 2019 Oct 10;381[15]:1411-21).

Dr. Pinella-Echeverri reported on the 93 patients who participated in the OCT substudy, the purpose of which was to determine the prevalence of high-risk, vulnerable plaque in obstructive and nonobstructive nonculprit lesions. For this purpose, vulnerable plaque was defined as thin-cap fibroatheroma (TCFA), a coronary lesion known to pose high risk of worsening stenosis, plaque rupture, and cardiovascular events.

Of note, these 93 patients had a total of 425 diseased segments: 150 obstructive and 275 nonobstructive.

“This is reassuring that the concept of acute coronary syndrome implies a diffuse pathophysiology of affecting not only the culprit segment but the coronary vasculature as a whole,” Dr. Pinella-Echeverri observed.

The main study finding, however, was that TCFA was significantly more prevalent in obstructive, compared with nonobstructive, nonculprit lesions by a margin of 35% to 23%. The obstructive and nonobstructive TCFA lesions had a similar lipid-rich composition; however, the obstructive ones were significantly longer and had a smaller mean lumen area.

When breaking down the prevalence of TCFA per patient, 47% of patients had a nonculprit obstructive lesion with vulnerable plaque morphology. Another 20% had nonobstructive TCFA lesions. And only 32% of the STEMI patients had no TCFA in their obstructive or nonobstructive segments.

Bruce Jancin/MDedge News

Discussant Frans Van de Werf, MD, PhD, commented: “This [OCT substudy result] immediately explains the clinical benefit observed with preventive PCI in STEMI patients with obstructive multivessel disease.”

The finding that 20% of the STEMI patients had nonobstructive lesions with vulnerable plaque morphology by OCT provides powerful support for the current guideline-recommended strategy of immediately starting STEMI patients on intensive lipid-lowering therapy, added Dr. Van de Werf, professor of medicine at the Catholic University of Leuven (Belgium).

He argued that the decision to revascularize nonculprit lesions by means of PCI versus the more complete revascularization achieved via coronary artery bypass graft surgery shouldn’t be made during the initial primary PCI, citing evidence that when the decision gets made at that time, coronary artery bypass grafting (CABG) is less likely to be chosen.

“I believe that OCT and [fractional flow reserve] should not be performed during the index primary PCI, not only for the comfort of the patient, but also for the better selection of complete revascularization. Interventional cardiologists should not forget that CABG might be a better revascularization treatment in some cases, such as left main disease and diabetes mellitus,” the cardiologist cautioned.

The COMPLETE OCT Substudy was supported by Abbott Vascular, the Population Health Research Institute, Hamilton Health Sciences, and the Canadian Institutes of Health Research.

bjancin@mdedge.com

PHILADELPHIA – Nearly half of patients with ST-elevation MI and multivessel coronary artery disease in the landmark COMPLETE trial had an obstructive coronary lesion with vulnerable plaque morphology in a segment far from the culprit lesion, Natalia Pinilla-Echeverri, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

This novel finding from an optical coherence tomography (OCT) substudy of COMPLETE provides a likely mechanistic explanation for the major clinical benefits documented in the full COMPLETE trial, noted Dr. Pinilla-Echeverri, a cardiologist at the Population Health Research Institute at McMaster University, Hamilton, Ont.

COMPLETE was a multinational trial which randomized 4,041 ST-elevation MI (STEMI) patients with multivessel disease to culprit lesion–only percutaneous coronary intervention (PCI) or additional routine angiography–guided staged PCI of nonculprit obstructive lesions with at least 70% stenosis. As previously reported, the risk of the coprimary composite endpoint comprising cardiovascular death, new MI, or ischemia-driven revascularization was reduced by 49% over 3 years of follow-up in the group with staged PCI of nonculprit lesions, with an impressive number needed to treat of just 13 (N Engl J Med. 2019 Oct 10;381[15]:1411-21).

Dr. Pinella-Echeverri reported on the 93 patients who participated in the OCT substudy, the purpose of which was to determine the prevalence of high-risk, vulnerable plaque in obstructive and nonobstructive nonculprit lesions. For this purpose, vulnerable plaque was defined as thin-cap fibroatheroma (TCFA), a coronary lesion known to pose high risk of worsening stenosis, plaque rupture, and cardiovascular events.

Of note, these 93 patients had a total of 425 diseased segments: 150 obstructive and 275 nonobstructive.

“This is reassuring that the concept of acute coronary syndrome implies a diffuse pathophysiology of affecting not only the culprit segment but the coronary vasculature as a whole,” Dr. Pinella-Echeverri observed.

The main study finding, however, was that TCFA was significantly more prevalent in obstructive, compared with nonobstructive, nonculprit lesions by a margin of 35% to 23%. The obstructive and nonobstructive TCFA lesions had a similar lipid-rich composition; however, the obstructive ones were significantly longer and had a smaller mean lumen area.

When breaking down the prevalence of TCFA per patient, 47% of patients had a nonculprit obstructive lesion with vulnerable plaque morphology. Another 20% had nonobstructive TCFA lesions. And only 32% of the STEMI patients had no TCFA in their obstructive or nonobstructive segments.

Bruce Jancin/MDedge News

Discussant Frans Van de Werf, MD, PhD, commented: “This [OCT substudy result] immediately explains the clinical benefit observed with preventive PCI in STEMI patients with obstructive multivessel disease.”

The finding that 20% of the STEMI patients had nonobstructive lesions with vulnerable plaque morphology by OCT provides powerful support for the current guideline-recommended strategy of immediately starting STEMI patients on intensive lipid-lowering therapy, added Dr. Van de Werf, professor of medicine at the Catholic University of Leuven (Belgium).

He argued that the decision to revascularize nonculprit lesions by means of PCI versus the more complete revascularization achieved via coronary artery bypass graft surgery shouldn’t be made during the initial primary PCI, citing evidence that when the decision gets made at that time, coronary artery bypass grafting (CABG) is less likely to be chosen.

“I believe that OCT and [fractional flow reserve] should not be performed during the index primary PCI, not only for the comfort of the patient, but also for the better selection of complete revascularization. Interventional cardiologists should not forget that CABG might be a better revascularization treatment in some cases, such as left main disease and diabetes mellitus,” the cardiologist cautioned.

The COMPLETE OCT Substudy was supported by Abbott Vascular, the Population Health Research Institute, Hamilton Health Sciences, and the Canadian Institutes of Health Research.

bjancin@mdedge.com

PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.

Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.

Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.

“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.

He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
 

The results

Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.

Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.

Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.

The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.

Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.

In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.

“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.

One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.

“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.

Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
 

bjancin@mdedge.com

SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141

PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.

Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.

Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.

“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.

He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
 

The results

Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.

Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.

Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.

The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.

Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.

In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.

“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.

One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.

“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.

Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
 

bjancin@mdedge.com

SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141

PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.

Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.

Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.

“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.

He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
 

The results

Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.

Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.

Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.

The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.

Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.

In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.

“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.

One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.

“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.

Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
 

bjancin@mdedge.com

SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

Groceries, maybe a new shirt, and now some veterans can fit in some shopping at their next health care visit. In a pilot project, the US Department of Veterans Affairs (VA) is partnering with Walmart to offer veterans easy access to health care at 5 sites.

The VA-led ATLAS (Accessing telehealth through local area stations) program is part of the VA Anywhere to Anywhere telehealth initiative, which aims to provide care to veterans no matter where they live. Other telehealth pilot sites are in Wisconsin, Michigan, and Iowa. In addition to Walmart, ATLAS sites are located at American Legion posts and Veterans of Foreign Wars (VFW) posts.

The local VA facility associated with the ATLAS site determines which clinical services the site offers. The health care services do not require hands-on exams. Clinical services may include, for instance, primary care, mental health counseling, clinical pharmacy, nutrition services, and social work. On-site attendants provide information, help the veterans get started, troubleshoot technical issues, and clean the space between appointments. Walmart donated equipment and space, where veterans can meet with a VA provider in a private room via video technology.

Last year, nearly 500,000 veterans logged > 1.3 million VA video telehealth encounters. It is the “way of the future,” says VA Secretary Robert Wilkie. “Veterans need the expansion of choice, and this partnership is vital to affording them convenient access to VA health care services where they live.”

Daryl Risinger, Chief Growth Officer for Walmart US Health and Wellness, is a veteran of the Air Force, and has a son and son-in-law serving. He says, “I know firsthand how important support and access is for our military, especially when it comes to health care. …This is another way we are helping our communities live better.”

For a veteran to attend an appointment at an ATLAS site, the site must be associated with the VA Medical Center where the veteran is enrolled. Family members who receive care through the VA can also visit ATLAS sites for select appointments.

Groceries, maybe a new shirt, and now some veterans can fit in some shopping at their next health care visit. In a pilot project, the US Department of Veterans Affairs (VA) is partnering with Walmart to offer veterans easy access to health care at 5 sites.

The VA-led ATLAS (Accessing telehealth through local area stations) program is part of the VA Anywhere to Anywhere telehealth initiative, which aims to provide care to veterans no matter where they live. Other telehealth pilot sites are in Wisconsin, Michigan, and Iowa. In addition to Walmart, ATLAS sites are located at American Legion posts and Veterans of Foreign Wars (VFW) posts.

The local VA facility associated with the ATLAS site determines which clinical services the site offers. The health care services do not require hands-on exams. Clinical services may include, for instance, primary care, mental health counseling, clinical pharmacy, nutrition services, and social work. On-site attendants provide information, help the veterans get started, troubleshoot technical issues, and clean the space between appointments. Walmart donated equipment and space, where veterans can meet with a VA provider in a private room via video technology.

Last year, nearly 500,000 veterans logged > 1.3 million VA video telehealth encounters. It is the “way of the future,” says VA Secretary Robert Wilkie. “Veterans need the expansion of choice, and this partnership is vital to affording them convenient access to VA health care services where they live.”

Daryl Risinger, Chief Growth Officer for Walmart US Health and Wellness, is a veteran of the Air Force, and has a son and son-in-law serving. He says, “I know firsthand how important support and access is for our military, especially when it comes to health care. …This is another way we are helping our communities live better.”

For a veteran to attend an appointment at an ATLAS site, the site must be associated with the VA Medical Center where the veteran is enrolled. Family members who receive care through the VA can also visit ATLAS sites for select appointments.

Groceries, maybe a new shirt, and now some veterans can fit in some shopping at their next health care visit. In a pilot project, the US Department of Veterans Affairs (VA) is partnering with Walmart to offer veterans easy access to health care at 5 sites.

The VA-led ATLAS (Accessing telehealth through local area stations) program is part of the VA Anywhere to Anywhere telehealth initiative, which aims to provide care to veterans no matter where they live. Other telehealth pilot sites are in Wisconsin, Michigan, and Iowa. In addition to Walmart, ATLAS sites are located at American Legion posts and Veterans of Foreign Wars (VFW) posts.

The local VA facility associated with the ATLAS site determines which clinical services the site offers. The health care services do not require hands-on exams. Clinical services may include, for instance, primary care, mental health counseling, clinical pharmacy, nutrition services, and social work. On-site attendants provide information, help the veterans get started, troubleshoot technical issues, and clean the space between appointments. Walmart donated equipment and space, where veterans can meet with a VA provider in a private room via video technology.

Last year, nearly 500,000 veterans logged > 1.3 million VA video telehealth encounters. It is the “way of the future,” says VA Secretary Robert Wilkie. “Veterans need the expansion of choice, and this partnership is vital to affording them convenient access to VA health care services where they live.”

Daryl Risinger, Chief Growth Officer for Walmart US Health and Wellness, is a veteran of the Air Force, and has a son and son-in-law serving. He says, “I know firsthand how important support and access is for our military, especially when it comes to health care. …This is another way we are helping our communities live better.”

For a veteran to attend an appointment at an ATLAS site, the site must be associated with the VA Medical Center where the veteran is enrolled. Family members who receive care through the VA can also visit ATLAS sites for select appointments.

The Food and Drug Administration has approved teprotumumab-trbw (Tepezza) as the first drug for treating thyroid eye disease, according to a press release.

Olivier Le Moal/Getty Images

Thyroid eye disease is a rare, progressive, autoimmune condition that causes the eyes to bulge (proptosis) and can lead to blindness. Until now, treatment has focused on managing its symptoms – which can include eye pain, double vision, or sensitivity to light – with steroids, and in some cases, multiple invasive surgeries.

The human monoclonal antibody and a targeted inhibitor of the insulinlike growth factor-1 receptor is administered to patients once every 3 weeks, for a total of eight infusions, according to a statement from Horizon Therapeutics, which manufactures the drug.

The approval was based on the findings from two similarly designed, parallel-group studies (Studies 1 and 2) involving 170 patients with thyroid eye disease who were randomized to receive either teprotumumab or placebo. Of those receiving the study drug, 71% in Study 1 and 83% in Study 2 had a reduction of more than 2 mm in eye protrusion, compared with 20% and 10%, respectively, among the placebo participants.

The most common adverse reactions in patients receiving teprotumumab were muscle spasm, nausea, alopecia, diarrhea, fatigue, and hyperglycemia. The treatment is contraindicated for pregnancy.

The Food and Drug Administration has approved teprotumumab-trbw (Tepezza) as the first drug for treating thyroid eye disease, according to a press release.

Olivier Le Moal/Getty Images

Thyroid eye disease is a rare, progressive, autoimmune condition that causes the eyes to bulge (proptosis) and can lead to blindness. Until now, treatment has focused on managing its symptoms – which can include eye pain, double vision, or sensitivity to light – with steroids, and in some cases, multiple invasive surgeries.

The human monoclonal antibody and a targeted inhibitor of the insulinlike growth factor-1 receptor is administered to patients once every 3 weeks, for a total of eight infusions, according to a statement from Horizon Therapeutics, which manufactures the drug.

The approval was based on the findings from two similarly designed, parallel-group studies (Studies 1 and 2) involving 170 patients with thyroid eye disease who were randomized to receive either teprotumumab or placebo. Of those receiving the study drug, 71% in Study 1 and 83% in Study 2 had a reduction of more than 2 mm in eye protrusion, compared with 20% and 10%, respectively, among the placebo participants.

The most common adverse reactions in patients receiving teprotumumab were muscle spasm, nausea, alopecia, diarrhea, fatigue, and hyperglycemia. The treatment is contraindicated for pregnancy.

The Food and Drug Administration has approved teprotumumab-trbw (Tepezza) as the first drug for treating thyroid eye disease, according to a press release.

Olivier Le Moal/Getty Images

Thyroid eye disease is a rare, progressive, autoimmune condition that causes the eyes to bulge (proptosis) and can lead to blindness. Until now, treatment has focused on managing its symptoms – which can include eye pain, double vision, or sensitivity to light – with steroids, and in some cases, multiple invasive surgeries.

The human monoclonal antibody and a targeted inhibitor of the insulinlike growth factor-1 receptor is administered to patients once every 3 weeks, for a total of eight infusions, according to a statement from Horizon Therapeutics, which manufactures the drug.

The approval was based on the findings from two similarly designed, parallel-group studies (Studies 1 and 2) involving 170 patients with thyroid eye disease who were randomized to receive either teprotumumab or placebo. Of those receiving the study drug, 71% in Study 1 and 83% in Study 2 had a reduction of more than 2 mm in eye protrusion, compared with 20% and 10%, respectively, among the placebo participants.

The most common adverse reactions in patients receiving teprotumumab were muscle spasm, nausea, alopecia, diarrhea, fatigue, and hyperglycemia. The treatment is contraindicated for pregnancy.

The first case of the novel coronavirus, named 2019-nCoV, in the United States has been diagnosed in a traveler from China who came through Seattle-Tacoma International Airport on Jan 15, the Centers for Disease Control and Prevention announced today at a press briefing.

CDC/John Hierholzer, MD

The outbreak began at a animal and meat market in China and now has spread to at least three other countries, including Thailand, Japan and South Korea. While originally thought to be spreading from animal to person, it appears that limited person-to-person transmission is occurring, although it is currently unknown how easily this virus spreads between people.

More than 300 cases have been reported and six deaths have occurred. Fourteen health care workers have been infected.

Scott Lindquist, MD, MPH, Washington state epidemiologist, said at the briefing that the patient, a man who had been in Wuhan, arrived at Sea-Tac on Jan. 15, 2 days before airport screening had been initiated. He was symptom free at the time of his arrival and probably would not have been identified as infected with 2019-nCoV. The patient had been aware of the public health and news media coverage of 2019-nCoV and, after developing symptoms, contacted his health care provider on Jan. 19. The patient did not fly directly from Wuhan, but Dr. Lindquist said that he has been fully cooperative and has been helpful to authorities in tracing his route and contacts. The man is being treated at Providence Regional Medical Center, Everett, Wash.

The CDC obtained a specimen from the patient immediately and identified the 2019-nCoV within 24 hours.

Screening at airports is part of a multipart strategy to address this type of infection that includes public health information dissemination, patient education, as well as hospital preparation and training exercises. Currently, a strategy referred to as “funneling” is being implemented wherein travelers from China are rerouted and reticketed to one of the five airports conducting screening. At present, JFK in New York, San Francisco International, Los Angeles International, Hartsfield-Jackson Atlanta International Airport, and Chicago O’Hare International Airport are conducting inbound traveler screening.

The CDC is working in close cooperation with the Department of Homeland Security and the Federal Aviation Administration to coordinate travel screenings and reroutings. In addition, the CDC is working with the World Health Organization and the international global health community to share information about this outbreak. The CDC also has staff on site in Wuhan and is communicating with local health authorities. The CDC has activated its Emergency Operations Center to better provide ongoing support to the 2019-nCoV response. Currently, the focus is on tracing contacts and the means of transmission of this virus.

Updates on the outbreak will be posted on the CDC coronavirus website.
 

tborden@mdedge.com

CORRECTION: 1/21/2020: The name of the medical center where the 2019-nCoV patient is being treated was corrected.

The first case of the novel coronavirus, named 2019-nCoV, in the United States has been diagnosed in a traveler from China who came through Seattle-Tacoma International Airport on Jan 15, the Centers for Disease Control and Prevention announced today at a press briefing.

CDC/John Hierholzer, MD

The outbreak began at a animal and meat market in China and now has spread to at least three other countries, including Thailand, Japan and South Korea. While originally thought to be spreading from animal to person, it appears that limited person-to-person transmission is occurring, although it is currently unknown how easily this virus spreads between people.

More than 300 cases have been reported and six deaths have occurred. Fourteen health care workers have been infected.

Scott Lindquist, MD, MPH, Washington state epidemiologist, said at the briefing that the patient, a man who had been in Wuhan, arrived at Sea-Tac on Jan. 15, 2 days before airport screening had been initiated. He was symptom free at the time of his arrival and probably would not have been identified as infected with 2019-nCoV. The patient had been aware of the public health and news media coverage of 2019-nCoV and, after developing symptoms, contacted his health care provider on Jan. 19. The patient did not fly directly from Wuhan, but Dr. Lindquist said that he has been fully cooperative and has been helpful to authorities in tracing his route and contacts. The man is being treated at Providence Regional Medical Center, Everett, Wash.

The CDC obtained a specimen from the patient immediately and identified the 2019-nCoV within 24 hours.

Screening at airports is part of a multipart strategy to address this type of infection that includes public health information dissemination, patient education, as well as hospital preparation and training exercises. Currently, a strategy referred to as “funneling” is being implemented wherein travelers from China are rerouted and reticketed to one of the five airports conducting screening. At present, JFK in New York, San Francisco International, Los Angeles International, Hartsfield-Jackson Atlanta International Airport, and Chicago O’Hare International Airport are conducting inbound traveler screening.

The CDC is working in close cooperation with the Department of Homeland Security and the Federal Aviation Administration to coordinate travel screenings and reroutings. In addition, the CDC is working with the World Health Organization and the international global health community to share information about this outbreak. The CDC also has staff on site in Wuhan and is communicating with local health authorities. The CDC has activated its Emergency Operations Center to better provide ongoing support to the 2019-nCoV response. Currently, the focus is on tracing contacts and the means of transmission of this virus.

Updates on the outbreak will be posted on the CDC coronavirus website.
 

tborden@mdedge.com

CORRECTION: 1/21/2020: The name of the medical center where the 2019-nCoV patient is being treated was corrected.

The first case of the novel coronavirus, named 2019-nCoV, in the United States has been diagnosed in a traveler from China who came through Seattle-Tacoma International Airport on Jan 15, the Centers for Disease Control and Prevention announced today at a press briefing.

CDC/John Hierholzer, MD

The outbreak began at a animal and meat market in China and now has spread to at least three other countries, including Thailand, Japan and South Korea. While originally thought to be spreading from animal to person, it appears that limited person-to-person transmission is occurring, although it is currently unknown how easily this virus spreads between people.

More than 300 cases have been reported and six deaths have occurred. Fourteen health care workers have been infected.

Scott Lindquist, MD, MPH, Washington state epidemiologist, said at the briefing that the patient, a man who had been in Wuhan, arrived at Sea-Tac on Jan. 15, 2 days before airport screening had been initiated. He was symptom free at the time of his arrival and probably would not have been identified as infected with 2019-nCoV. The patient had been aware of the public health and news media coverage of 2019-nCoV and, after developing symptoms, contacted his health care provider on Jan. 19. The patient did not fly directly from Wuhan, but Dr. Lindquist said that he has been fully cooperative and has been helpful to authorities in tracing his route and contacts. The man is being treated at Providence Regional Medical Center, Everett, Wash.

The CDC obtained a specimen from the patient immediately and identified the 2019-nCoV within 24 hours.

Screening at airports is part of a multipart strategy to address this type of infection that includes public health information dissemination, patient education, as well as hospital preparation and training exercises. Currently, a strategy referred to as “funneling” is being implemented wherein travelers from China are rerouted and reticketed to one of the five airports conducting screening. At present, JFK in New York, San Francisco International, Los Angeles International, Hartsfield-Jackson Atlanta International Airport, and Chicago O’Hare International Airport are conducting inbound traveler screening.

The CDC is working in close cooperation with the Department of Homeland Security and the Federal Aviation Administration to coordinate travel screenings and reroutings. In addition, the CDC is working with the World Health Organization and the international global health community to share information about this outbreak. The CDC also has staff on site in Wuhan and is communicating with local health authorities. The CDC has activated its Emergency Operations Center to better provide ongoing support to the 2019-nCoV response. Currently, the focus is on tracing contacts and the means of transmission of this virus.

Updates on the outbreak will be posted on the CDC coronavirus website.
 

tborden@mdedge.com

CORRECTION: 1/21/2020: The name of the medical center where the 2019-nCoV patient is being treated was corrected.