Tobacco use is currently at an all-time low thanks to public and private efforts, but more aggressive action from federal, state, and local governments is needed to protect the public, according to a review of tobacco control trends in the United States.

The American Lung Association (ALA) released “State of Tobacco Control” 2019, its 17th annual state-by-state analysis and list of recommended policy priorities to limit tobacco use. Although the report notes some positive steps taken by the federal and state governments, shortfalls in policy and legislation also are highlighted. The report states, “We know how and are ready to save more lives, but we need our elected officials to do much more. To many, solving America’s tobacco crisis might seem like a complex puzzle with no solution. And yet we have known for years what pieces are needed to reduce the disease and death caused by tobacco use.”

In this report, the federal government and each state are graded on a scale, A through F, for policy actions and laws to limit tobacco use. The grading methodology is based on a detailed point system cataloging the implementation and strength of specific actions and policies to limit tobacco use.
 

Areas of Impact

The report focused on six areas of public policy that affect exposure to and use of tobacco:

• Smoke-free air: Protecting the public from secondhand smoke should be a priority for policymakers, according the report, but 22 states have no smoke-free workplace laws in place. Laws restricting e-cigarettes in workplaces and public buildings have lagged behind tobacco laws in many states.
• Tobacco prevention funding: Dedicated funds to prevent tobacco addiction before it starts is a key element of a public health attack on tobacco use, but no U.S. state currently spends what the Centers for Disease Control and Prevention has recommended. Twenty years ago, the Master Settlement Agreement between the tobacco industry and 46 states and the District of Columbia guaranteed ongoing payments to the states to be used for tobacco prevention and control. Although those funds have been collected in the states to the tune of $27 billion since 1998, overall only 2.4% of those funds have been spent for this purpose, and the rest has been budgeted for other purposes.
• Tobacco taxes: Sales taxes on tobacco products have been highly effective in preventing young people from taking up tobacco use, but those taxation rates have remained unchanged in 2018 in all but the District of Columbia and Oklahoma. The tobacco industry spent $22 million in a successful effort to defeat ballot measures to increase sales taxes on tobacco in Montana and South Dakota.
• Tobacco 21: “Increasing the legal age of sale for tobacco products to 21 would decrease tobacco use by 12% and could prevent 223,000 deaths among those born between 2000 and 2019,” the report noted, citing a 2015 report by the Institute of Medicine. So far, the this restriction has been legislated in six states, the District of Columbia, and numerous local governments. The ALA considers increasing the age for tobacco sales to 21 to be a public health priority.
• Helping smokers quit: The addictive qualities of tobacco mean that many smokers struggle unsuccessfully to quit, and medical intervention is needed to help them. The report notes that current law requires that Medicaid expansion health plans and private insurance plans cover comprehensive smoking cessation treatment. However, not all states have the expanded Medicaid program, and many of those with Medicaid expansion don’t offer coverage of all Food and Drug–approved cessation treatments. Despite laws requiring smoking cessation coverage, many private insurance plans still do not include this coverage. The ALA recommends enforcement of the current law with regard to tobacco cessation insurance coverage.
• FDA regulation of tobacco products: The FDA has announced plans to make a major effort to reduce tobacco use in young people, decrease nicotine in cigarettes, and to restrict flavored tobacco products. But these plans fall short of the aggressive action needed to curb the tobacco “epidemic,” according to the report. Delayed action and timid policy have “resulted in tobacco companies becoming more emboldened to devise new and egregious ways to addict youth and sustain addiction among current users.” The ALA report points to the steep rise in e-cigarette use among youth with a 20.8% rise in high school students using these products in 2018, a rise from 11.7% in 2017. This trend is not likely to be reversed by the FDA proposals to date, which rely on voluntary action by the industry to curb youth use, sales restrictions to youth, and restrictions on some flavored tobacco products.

The report card

Federal government efforts in regulation of tobacco products, taxation, and health insurance coverage of cessation all received an F in this report, while mass media campaigns were given an A.

The states didn’t fare much better. They were graded on prevention and control funding, smoke-free air, taxation, access to cessation services, and minimum age for sales. A total of 19 states received a grade of F in four or five of these areas.

Funding for prevention and control was evaluated as the percentage of the amount recommended by the CDC, adjusted for a variety of state-specific factors such as prevalence of tobacco use, cost and complexity of conducting mass media campaigns, and proportion of the audience below 200% of the federal poverty level. A limitation of this methodology of grading funding is that it doesn’t evaluate effectiveness of the spending or the level of spending in different program categories. The higher spenders on prevention and control were Alaska at 98.1% and California at 74.5% of the CDC recommended level. The lowest spenders were Georgia at 2.8% and Missouri at 3.0%.

All but eight states received an F on minimum age for tobacco sales because most have an age limit 18 instead of the ALA and CDC recommendation of age 21.

Harold Wimmer, the CEO of the American Lung Association, wrote, “Aggressive action by our country’s federal and state policymakers is urgently required. However, ‘State of Tobacco Control’ 2019 has found a disturbing failure by federal and state governments to take action to put in place meaningful and proven-effective policies that would have prevented, and reduced tobacco use during 2018. This failure to act places the lung health and lives of Americans at risk. We have also found that this lack of action has emboldened tobacco companies to be even more brazen in producing and marketing products squarely aimed at kids, such as the JUUL e-cigarettes that look like an easily concealed USB drive, which now dominate the market driven by youth use.”

The full report is available for download at the ALA website.

tborden@mdedge.com

SOURCE: American Lung Association, “State of Tobacco Control 2019”.

Tobacco use is currently at an all-time low thanks to public and private efforts, but more aggressive action from federal, state, and local governments is needed to protect the public, according to a review of tobacco control trends in the United States.

The American Lung Association (ALA) released “State of Tobacco Control” 2019, its 17th annual state-by-state analysis and list of recommended policy priorities to limit tobacco use. Although the report notes some positive steps taken by the federal and state governments, shortfalls in policy and legislation also are highlighted. The report states, “We know how and are ready to save more lives, but we need our elected officials to do much more. To many, solving America’s tobacco crisis might seem like a complex puzzle with no solution. And yet we have known for years what pieces are needed to reduce the disease and death caused by tobacco use.”

In this report, the federal government and each state are graded on a scale, A through F, for policy actions and laws to limit tobacco use. The grading methodology is based on a detailed point system cataloging the implementation and strength of specific actions and policies to limit tobacco use.
 

Areas of Impact

The report focused on six areas of public policy that affect exposure to and use of tobacco:

• Smoke-free air: Protecting the public from secondhand smoke should be a priority for policymakers, according the report, but 22 states have no smoke-free workplace laws in place. Laws restricting e-cigarettes in workplaces and public buildings have lagged behind tobacco laws in many states.
• Tobacco prevention funding: Dedicated funds to prevent tobacco addiction before it starts is a key element of a public health attack on tobacco use, but no U.S. state currently spends what the Centers for Disease Control and Prevention has recommended. Twenty years ago, the Master Settlement Agreement between the tobacco industry and 46 states and the District of Columbia guaranteed ongoing payments to the states to be used for tobacco prevention and control. Although those funds have been collected in the states to the tune of $27 billion since 1998, overall only 2.4% of those funds have been spent for this purpose, and the rest has been budgeted for other purposes.
• Tobacco taxes: Sales taxes on tobacco products have been highly effective in preventing young people from taking up tobacco use, but those taxation rates have remained unchanged in 2018 in all but the District of Columbia and Oklahoma. The tobacco industry spent $22 million in a successful effort to defeat ballot measures to increase sales taxes on tobacco in Montana and South Dakota.
• Tobacco 21: “Increasing the legal age of sale for tobacco products to 21 would decrease tobacco use by 12% and could prevent 223,000 deaths among those born between 2000 and 2019,” the report noted, citing a 2015 report by the Institute of Medicine. So far, the this restriction has been legislated in six states, the District of Columbia, and numerous local governments. The ALA considers increasing the age for tobacco sales to 21 to be a public health priority.
• Helping smokers quit: The addictive qualities of tobacco mean that many smokers struggle unsuccessfully to quit, and medical intervention is needed to help them. The report notes that current law requires that Medicaid expansion health plans and private insurance plans cover comprehensive smoking cessation treatment. However, not all states have the expanded Medicaid program, and many of those with Medicaid expansion don’t offer coverage of all Food and Drug–approved cessation treatments. Despite laws requiring smoking cessation coverage, many private insurance plans still do not include this coverage. The ALA recommends enforcement of the current law with regard to tobacco cessation insurance coverage.
• FDA regulation of tobacco products: The FDA has announced plans to make a major effort to reduce tobacco use in young people, decrease nicotine in cigarettes, and to restrict flavored tobacco products. But these plans fall short of the aggressive action needed to curb the tobacco “epidemic,” according to the report. Delayed action and timid policy have “resulted in tobacco companies becoming more emboldened to devise new and egregious ways to addict youth and sustain addiction among current users.” The ALA report points to the steep rise in e-cigarette use among youth with a 20.8% rise in high school students using these products in 2018, a rise from 11.7% in 2017. This trend is not likely to be reversed by the FDA proposals to date, which rely on voluntary action by the industry to curb youth use, sales restrictions to youth, and restrictions on some flavored tobacco products.

The report card

Federal government efforts in regulation of tobacco products, taxation, and health insurance coverage of cessation all received an F in this report, while mass media campaigns were given an A.

The states didn’t fare much better. They were graded on prevention and control funding, smoke-free air, taxation, access to cessation services, and minimum age for sales. A total of 19 states received a grade of F in four or five of these areas.

Funding for prevention and control was evaluated as the percentage of the amount recommended by the CDC, adjusted for a variety of state-specific factors such as prevalence of tobacco use, cost and complexity of conducting mass media campaigns, and proportion of the audience below 200% of the federal poverty level. A limitation of this methodology of grading funding is that it doesn’t evaluate effectiveness of the spending or the level of spending in different program categories. The higher spenders on prevention and control were Alaska at 98.1% and California at 74.5% of the CDC recommended level. The lowest spenders were Georgia at 2.8% and Missouri at 3.0%.

All but eight states received an F on minimum age for tobacco sales because most have an age limit 18 instead of the ALA and CDC recommendation of age 21.

Harold Wimmer, the CEO of the American Lung Association, wrote, “Aggressive action by our country’s federal and state policymakers is urgently required. However, ‘State of Tobacco Control’ 2019 has found a disturbing failure by federal and state governments to take action to put in place meaningful and proven-effective policies that would have prevented, and reduced tobacco use during 2018. This failure to act places the lung health and lives of Americans at risk. We have also found that this lack of action has emboldened tobacco companies to be even more brazen in producing and marketing products squarely aimed at kids, such as the JUUL e-cigarettes that look like an easily concealed USB drive, which now dominate the market driven by youth use.”

The full report is available for download at the ALA website.

tborden@mdedge.com

SOURCE: American Lung Association, “State of Tobacco Control 2019”.

Tobacco use is currently at an all-time low thanks to public and private efforts, but more aggressive action from federal, state, and local governments is needed to protect the public, according to a review of tobacco control trends in the United States.

The American Lung Association (ALA) released “State of Tobacco Control” 2019, its 17th annual state-by-state analysis and list of recommended policy priorities to limit tobacco use. Although the report notes some positive steps taken by the federal and state governments, shortfalls in policy and legislation also are highlighted. The report states, “We know how and are ready to save more lives, but we need our elected officials to do much more. To many, solving America’s tobacco crisis might seem like a complex puzzle with no solution. And yet we have known for years what pieces are needed to reduce the disease and death caused by tobacco use.”

In this report, the federal government and each state are graded on a scale, A through F, for policy actions and laws to limit tobacco use. The grading methodology is based on a detailed point system cataloging the implementation and strength of specific actions and policies to limit tobacco use.
 

Areas of Impact

The report focused on six areas of public policy that affect exposure to and use of tobacco:

• Smoke-free air: Protecting the public from secondhand smoke should be a priority for policymakers, according the report, but 22 states have no smoke-free workplace laws in place. Laws restricting e-cigarettes in workplaces and public buildings have lagged behind tobacco laws in many states.
• Tobacco prevention funding: Dedicated funds to prevent tobacco addiction before it starts is a key element of a public health attack on tobacco use, but no U.S. state currently spends what the Centers for Disease Control and Prevention has recommended. Twenty years ago, the Master Settlement Agreement between the tobacco industry and 46 states and the District of Columbia guaranteed ongoing payments to the states to be used for tobacco prevention and control. Although those funds have been collected in the states to the tune of $27 billion since 1998, overall only 2.4% of those funds have been spent for this purpose, and the rest has been budgeted for other purposes.
• Tobacco taxes: Sales taxes on tobacco products have been highly effective in preventing young people from taking up tobacco use, but those taxation rates have remained unchanged in 2018 in all but the District of Columbia and Oklahoma. The tobacco industry spent $22 million in a successful effort to defeat ballot measures to increase sales taxes on tobacco in Montana and South Dakota.
• Tobacco 21: “Increasing the legal age of sale for tobacco products to 21 would decrease tobacco use by 12% and could prevent 223,000 deaths among those born between 2000 and 2019,” the report noted, citing a 2015 report by the Institute of Medicine. So far, the this restriction has been legislated in six states, the District of Columbia, and numerous local governments. The ALA considers increasing the age for tobacco sales to 21 to be a public health priority.
• Helping smokers quit: The addictive qualities of tobacco mean that many smokers struggle unsuccessfully to quit, and medical intervention is needed to help them. The report notes that current law requires that Medicaid expansion health plans and private insurance plans cover comprehensive smoking cessation treatment. However, not all states have the expanded Medicaid program, and many of those with Medicaid expansion don’t offer coverage of all Food and Drug–approved cessation treatments. Despite laws requiring smoking cessation coverage, many private insurance plans still do not include this coverage. The ALA recommends enforcement of the current law with regard to tobacco cessation insurance coverage.
• FDA regulation of tobacco products: The FDA has announced plans to make a major effort to reduce tobacco use in young people, decrease nicotine in cigarettes, and to restrict flavored tobacco products. But these plans fall short of the aggressive action needed to curb the tobacco “epidemic,” according to the report. Delayed action and timid policy have “resulted in tobacco companies becoming more emboldened to devise new and egregious ways to addict youth and sustain addiction among current users.” The ALA report points to the steep rise in e-cigarette use among youth with a 20.8% rise in high school students using these products in 2018, a rise from 11.7% in 2017. This trend is not likely to be reversed by the FDA proposals to date, which rely on voluntary action by the industry to curb youth use, sales restrictions to youth, and restrictions on some flavored tobacco products.

The report card

Federal government efforts in regulation of tobacco products, taxation, and health insurance coverage of cessation all received an F in this report, while mass media campaigns were given an A.

The states didn’t fare much better. They were graded on prevention and control funding, smoke-free air, taxation, access to cessation services, and minimum age for sales. A total of 19 states received a grade of F in four or five of these areas.

Funding for prevention and control was evaluated as the percentage of the amount recommended by the CDC, adjusted for a variety of state-specific factors such as prevalence of tobacco use, cost and complexity of conducting mass media campaigns, and proportion of the audience below 200% of the federal poverty level. A limitation of this methodology of grading funding is that it doesn’t evaluate effectiveness of the spending or the level of spending in different program categories. The higher spenders on prevention and control were Alaska at 98.1% and California at 74.5% of the CDC recommended level. The lowest spenders were Georgia at 2.8% and Missouri at 3.0%.

All but eight states received an F on minimum age for tobacco sales because most have an age limit 18 instead of the ALA and CDC recommendation of age 21.

Harold Wimmer, the CEO of the American Lung Association, wrote, “Aggressive action by our country’s federal and state policymakers is urgently required. However, ‘State of Tobacco Control’ 2019 has found a disturbing failure by federal and state governments to take action to put in place meaningful and proven-effective policies that would have prevented, and reduced tobacco use during 2018. This failure to act places the lung health and lives of Americans at risk. We have also found that this lack of action has emboldened tobacco companies to be even more brazen in producing and marketing products squarely aimed at kids, such as the JUUL e-cigarettes that look like an easily concealed USB drive, which now dominate the market driven by youth use.”

The full report is available for download at the ALA website.

tborden@mdedge.com

SOURCE: American Lung Association, “State of Tobacco Control 2019”.

While optimal treatment for grade 3A follicular lymphoma remains in question, either anthracycline-based chemotherapy or bendamustine appear to be preferable to cyclophosphamide, vincristine, and prednisone (CVP), results of a recent analysis suggest.

Time to progression with anthracycline-based chemotherapy was superior to that of CVP in the retrospective, multicenter study.

At the same time, clinical outcomes were comparable between anthracycline-based chemotherapy and bendamustine, according to Nirav N. Shah, MD, of the Medical College of Wisconsin, Milwaukee, and his coinvestigators.

“Both remain appropriate frontline options for this patient population,” Dr. Shah and his colleagues wrote in Clinical Lymphoma, Myeloma & Leukemia.

Frontline therapy for follicular lymphoma has evolved, and recently shifted toward bendamustine-based chemotherapy regimens in light of two large randomized trials, according to the investigators. However, optimal therapy – specifically for grade 3A follicular lymphoma – has been debated for more than 20 years, they added.

“While some approach it as an aggressive malignancy, others treat it as an indolent lymphoma,” they wrote.

Accordingly, Dr. Shah and his colleagues sought to evaluate treatment outcomes with these regimens in 103 advanced stage 3/4 follicular lymphoma patients from six centers seen over a 10-year period.

Of those patients, 65 had received anthracycline-based chemotherapy, 30 received bendamustine, and 8 received CVP. All received either rituximab or ofatumumab in combination with the chemotherapy, and about one-third went on to receive maintenance treatment with one of those two anti-CD20 antibodies.

The proportion of patients not experiencing disease progression at 24 months from the initiation of treatment was significantly different between arms, at 72% for those receiving anthracyclines, 79% for bendamustine, and 50% for CVP (P = .01).

Patients who received CVP had a significantly poorer time-to-progression outcomes versus anthracycline-based chemotherapy, an adjusted analysis showed (hazard ratio, 3.22; 95% confidence interval, 1.26-8.25; P = .01), while by contrast, there was no significant difference between bendamustine and anthracyclines on this endpoint.

Progression-free survival was likewise worse for CVP compared with anthracycline-based chemotherapy, but there was no significant difference in overall survival for either CVP or bendamustine compared with anthracycline-based chemotherapy, the investigators said.

The 5-year overall survival was estimated to be 82% for anthracycline-based chemotherapy, 74% for bendamustine, and 58% for CVP (P = .23).

Optimal treatment of grade 3A follicular lymphoma remains controversial despite these findings, the investigators noted.

“Unfortunately, this specific histology was excluded from pivotal trials comparing anthracycline-based chemotherapy to bendamustine, leaving the question of optimal frontline treatment unanswered in this subset,” they wrote.

The situation could change with a subgroup analysis of GALLIUM, which might provide some prospective data for this histology. Beyond that, it would be helpful to have prospective, randomized studies specifically enrolling grade 3A disease, Dr. Shah and his coauthors wrote.

Dr. Shah reported disclosures related to Exelixis, Oncosec, Geron, Jazz, Kite, Juno, and Lentigen Technology. Coauthors provided disclosures related to Sanofi-Genzyme, Celgene, Takeda, Otsuka, Spectrum, Merck, and Astellas, among others.

SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):95-102.

While optimal treatment for grade 3A follicular lymphoma remains in question, either anthracycline-based chemotherapy or bendamustine appear to be preferable to cyclophosphamide, vincristine, and prednisone (CVP), results of a recent analysis suggest.

Time to progression with anthracycline-based chemotherapy was superior to that of CVP in the retrospective, multicenter study.

At the same time, clinical outcomes were comparable between anthracycline-based chemotherapy and bendamustine, according to Nirav N. Shah, MD, of the Medical College of Wisconsin, Milwaukee, and his coinvestigators.

“Both remain appropriate frontline options for this patient population,” Dr. Shah and his colleagues wrote in Clinical Lymphoma, Myeloma & Leukemia.

Frontline therapy for follicular lymphoma has evolved, and recently shifted toward bendamustine-based chemotherapy regimens in light of two large randomized trials, according to the investigators. However, optimal therapy – specifically for grade 3A follicular lymphoma – has been debated for more than 20 years, they added.

“While some approach it as an aggressive malignancy, others treat it as an indolent lymphoma,” they wrote.

Accordingly, Dr. Shah and his colleagues sought to evaluate treatment outcomes with these regimens in 103 advanced stage 3/4 follicular lymphoma patients from six centers seen over a 10-year period.

Of those patients, 65 had received anthracycline-based chemotherapy, 30 received bendamustine, and 8 received CVP. All received either rituximab or ofatumumab in combination with the chemotherapy, and about one-third went on to receive maintenance treatment with one of those two anti-CD20 antibodies.

The proportion of patients not experiencing disease progression at 24 months from the initiation of treatment was significantly different between arms, at 72% for those receiving anthracyclines, 79% for bendamustine, and 50% for CVP (P = .01).

Patients who received CVP had a significantly poorer time-to-progression outcomes versus anthracycline-based chemotherapy, an adjusted analysis showed (hazard ratio, 3.22; 95% confidence interval, 1.26-8.25; P = .01), while by contrast, there was no significant difference between bendamustine and anthracyclines on this endpoint.

Progression-free survival was likewise worse for CVP compared with anthracycline-based chemotherapy, but there was no significant difference in overall survival for either CVP or bendamustine compared with anthracycline-based chemotherapy, the investigators said.

The 5-year overall survival was estimated to be 82% for anthracycline-based chemotherapy, 74% for bendamustine, and 58% for CVP (P = .23).

Optimal treatment of grade 3A follicular lymphoma remains controversial despite these findings, the investigators noted.

“Unfortunately, this specific histology was excluded from pivotal trials comparing anthracycline-based chemotherapy to bendamustine, leaving the question of optimal frontline treatment unanswered in this subset,” they wrote.

The situation could change with a subgroup analysis of GALLIUM, which might provide some prospective data for this histology. Beyond that, it would be helpful to have prospective, randomized studies specifically enrolling grade 3A disease, Dr. Shah and his coauthors wrote.

Dr. Shah reported disclosures related to Exelixis, Oncosec, Geron, Jazz, Kite, Juno, and Lentigen Technology. Coauthors provided disclosures related to Sanofi-Genzyme, Celgene, Takeda, Otsuka, Spectrum, Merck, and Astellas, among others.

SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):95-102.

While optimal treatment for grade 3A follicular lymphoma remains in question, either anthracycline-based chemotherapy or bendamustine appear to be preferable to cyclophosphamide, vincristine, and prednisone (CVP), results of a recent analysis suggest.

Time to progression with anthracycline-based chemotherapy was superior to that of CVP in the retrospective, multicenter study.

At the same time, clinical outcomes were comparable between anthracycline-based chemotherapy and bendamustine, according to Nirav N. Shah, MD, of the Medical College of Wisconsin, Milwaukee, and his coinvestigators.

“Both remain appropriate frontline options for this patient population,” Dr. Shah and his colleagues wrote in Clinical Lymphoma, Myeloma & Leukemia.

Frontline therapy for follicular lymphoma has evolved, and recently shifted toward bendamustine-based chemotherapy regimens in light of two large randomized trials, according to the investigators. However, optimal therapy – specifically for grade 3A follicular lymphoma – has been debated for more than 20 years, they added.

“While some approach it as an aggressive malignancy, others treat it as an indolent lymphoma,” they wrote.

Accordingly, Dr. Shah and his colleagues sought to evaluate treatment outcomes with these regimens in 103 advanced stage 3/4 follicular lymphoma patients from six centers seen over a 10-year period.

Of those patients, 65 had received anthracycline-based chemotherapy, 30 received bendamustine, and 8 received CVP. All received either rituximab or ofatumumab in combination with the chemotherapy, and about one-third went on to receive maintenance treatment with one of those two anti-CD20 antibodies.

The proportion of patients not experiencing disease progression at 24 months from the initiation of treatment was significantly different between arms, at 72% for those receiving anthracyclines, 79% for bendamustine, and 50% for CVP (P = .01).

Patients who received CVP had a significantly poorer time-to-progression outcomes versus anthracycline-based chemotherapy, an adjusted analysis showed (hazard ratio, 3.22; 95% confidence interval, 1.26-8.25; P = .01), while by contrast, there was no significant difference between bendamustine and anthracyclines on this endpoint.

Progression-free survival was likewise worse for CVP compared with anthracycline-based chemotherapy, but there was no significant difference in overall survival for either CVP or bendamustine compared with anthracycline-based chemotherapy, the investigators said.

The 5-year overall survival was estimated to be 82% for anthracycline-based chemotherapy, 74% for bendamustine, and 58% for CVP (P = .23).

Optimal treatment of grade 3A follicular lymphoma remains controversial despite these findings, the investigators noted.

“Unfortunately, this specific histology was excluded from pivotal trials comparing anthracycline-based chemotherapy to bendamustine, leaving the question of optimal frontline treatment unanswered in this subset,” they wrote.

The situation could change with a subgroup analysis of GALLIUM, which might provide some prospective data for this histology. Beyond that, it would be helpful to have prospective, randomized studies specifically enrolling grade 3A disease, Dr. Shah and his coauthors wrote.

Dr. Shah reported disclosures related to Exelixis, Oncosec, Geron, Jazz, Kite, Juno, and Lentigen Technology. Coauthors provided disclosures related to Sanofi-Genzyme, Celgene, Takeda, Otsuka, Spectrum, Merck, and Astellas, among others.

SOURCE: Shah NN et al. Clin Lymphoma Myeloma Leuk. 2019 Feb;19(2):95-102.

The three-drug combination of ibrutinib, high-dose methotrexate (HD-MTX), and rituximab showed positive safety and clinical outcomes in patients with recurrent/refractory primary/secondary CNS lymphoma, according to results from a phase 1b trial.

Ibrutinib has already shown single-agent activity in recurrent/refractory CNS lymphoma, Christian Grommes, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, wrote in Blood. “The primary objective was to determine the maximum tolerated dose of ibrutinib in combination with HD-MTX alone and ibrutinib in combination with HD-MTX and rituximab.”

With respect to ibrutinib dosing, the initial cohort was started at 560 mg daily, which was increased to 840 mg daily in successive cohorts using a 3+3 design. HD-MTX was administered every 2 weeks at 3.5 g/m² for a total of eight infusions, or four cycles, with each cycle lasting of 28 days.

After no dose-limiting adverse effects were seen with the ibrutinib-MTX combination, the researchers added rituximab at 500 mg/m² every 2 weeks, for a total of eight infusions, which completed the induction phase. The three-agent induction therapy was followed by daily ibrutinib monotherapy, which was maintained until discontinuation caused by malignancy progression, intolerable adverse events, or death.

“To minimize the risk of adverse events, we held ibrutinib on days of HD-MTX infusion and resumed 5 days after HD-MTX infusion or after MTX clearance,” they wrote.

After analysis, Dr. Grommes and his colleagues reported that no dose-limiting or grade 5 toxicities were detected. At a median follow-up of 19.7 months, they saw an 80% overall response rate in study patients treated with combination therapy. The median progression free survival for all 15 patients was 9.2 months and the median overall survival was not reached, with 11 of 15 patients alive.

The researchers proposed an 840-mg dose of ibrutinib for future studies.

The most frequent adverse events were lymphopenia, thrombocytopenia, anemia, and transaminase elevations. No fungal infections were seen during the study.

The researchers noted that two key limitations of the study were the nonrandomized design and small sample size. As a result, they reported that the degree of ibrutinib-specific activity in the three-drug combination remains unknown.

The study was supported by grant funding from Pharmacyclics to Memorial Sloan Kettering. The authors reported financial ties to AstraZeneca, Bristol-Myers Squibb, BTH, Kite Pharma, Pfizer, and others.

SOURCE: Grommes C et al. Blood. 2019;133(5):436-45.

The three-drug combination of ibrutinib, high-dose methotrexate (HD-MTX), and rituximab showed positive safety and clinical outcomes in patients with recurrent/refractory primary/secondary CNS lymphoma, according to results from a phase 1b trial.

Ibrutinib has already shown single-agent activity in recurrent/refractory CNS lymphoma, Christian Grommes, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, wrote in Blood. “The primary objective was to determine the maximum tolerated dose of ibrutinib in combination with HD-MTX alone and ibrutinib in combination with HD-MTX and rituximab.”

With respect to ibrutinib dosing, the initial cohort was started at 560 mg daily, which was increased to 840 mg daily in successive cohorts using a 3+3 design. HD-MTX was administered every 2 weeks at 3.5 g/m² for a total of eight infusions, or four cycles, with each cycle lasting of 28 days.

After no dose-limiting adverse effects were seen with the ibrutinib-MTX combination, the researchers added rituximab at 500 mg/m² every 2 weeks, for a total of eight infusions, which completed the induction phase. The three-agent induction therapy was followed by daily ibrutinib monotherapy, which was maintained until discontinuation caused by malignancy progression, intolerable adverse events, or death.

“To minimize the risk of adverse events, we held ibrutinib on days of HD-MTX infusion and resumed 5 days after HD-MTX infusion or after MTX clearance,” they wrote.

After analysis, Dr. Grommes and his colleagues reported that no dose-limiting or grade 5 toxicities were detected. At a median follow-up of 19.7 months, they saw an 80% overall response rate in study patients treated with combination therapy. The median progression free survival for all 15 patients was 9.2 months and the median overall survival was not reached, with 11 of 15 patients alive.

The researchers proposed an 840-mg dose of ibrutinib for future studies.

The most frequent adverse events were lymphopenia, thrombocytopenia, anemia, and transaminase elevations. No fungal infections were seen during the study.

The researchers noted that two key limitations of the study were the nonrandomized design and small sample size. As a result, they reported that the degree of ibrutinib-specific activity in the three-drug combination remains unknown.

The study was supported by grant funding from Pharmacyclics to Memorial Sloan Kettering. The authors reported financial ties to AstraZeneca, Bristol-Myers Squibb, BTH, Kite Pharma, Pfizer, and others.

SOURCE: Grommes C et al. Blood. 2019;133(5):436-45.

The three-drug combination of ibrutinib, high-dose methotrexate (HD-MTX), and rituximab showed positive safety and clinical outcomes in patients with recurrent/refractory primary/secondary CNS lymphoma, according to results from a phase 1b trial.

Ibrutinib has already shown single-agent activity in recurrent/refractory CNS lymphoma, Christian Grommes, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues, wrote in Blood. “The primary objective was to determine the maximum tolerated dose of ibrutinib in combination with HD-MTX alone and ibrutinib in combination with HD-MTX and rituximab.”

With respect to ibrutinib dosing, the initial cohort was started at 560 mg daily, which was increased to 840 mg daily in successive cohorts using a 3+3 design. HD-MTX was administered every 2 weeks at 3.5 g/m² for a total of eight infusions, or four cycles, with each cycle lasting of 28 days.

After no dose-limiting adverse effects were seen with the ibrutinib-MTX combination, the researchers added rituximab at 500 mg/m² every 2 weeks, for a total of eight infusions, which completed the induction phase. The three-agent induction therapy was followed by daily ibrutinib monotherapy, which was maintained until discontinuation caused by malignancy progression, intolerable adverse events, or death.

“To minimize the risk of adverse events, we held ibrutinib on days of HD-MTX infusion and resumed 5 days after HD-MTX infusion or after MTX clearance,” they wrote.

After analysis, Dr. Grommes and his colleagues reported that no dose-limiting or grade 5 toxicities were detected. At a median follow-up of 19.7 months, they saw an 80% overall response rate in study patients treated with combination therapy. The median progression free survival for all 15 patients was 9.2 months and the median overall survival was not reached, with 11 of 15 patients alive.

The researchers proposed an 840-mg dose of ibrutinib for future studies.

The most frequent adverse events were lymphopenia, thrombocytopenia, anemia, and transaminase elevations. No fungal infections were seen during the study.

The researchers noted that two key limitations of the study were the nonrandomized design and small sample size. As a result, they reported that the degree of ibrutinib-specific activity in the three-drug combination remains unknown.

The study was supported by grant funding from Pharmacyclics to Memorial Sloan Kettering. The authors reported financial ties to AstraZeneca, Bristol-Myers Squibb, BTH, Kite Pharma, Pfizer, and others.

SOURCE: Grommes C et al. Blood. 2019;133(5):436-45.

BROOKLYN, N.Y. – Three steps in the progressive pathology of anxiety and other pediatric psychiatric disorders are important to recognize for their critical role in guiding treatment, John T. Walkup, MD, said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

After the onset of symptoms and over the course of time, those with untreated anxiety disorders are at risk for developing impairment in adaptation and coping, and also the development of maladaptive behaviors like substance abuse and suicidal behavior, said Dr. Walkup, chair of the department of psychiatry at Ann and Robert H. Lurie Children’s Hospital of Chicago.

The focus of his presentation was on the treatment of anxiety disorders in children, but Dr. Walkup said the impact of the three-tier progression is likely relevant to any psychiatric disorder that begins in childhood.

In essence, the scope of problems becomes more complicated over time, and without early treatment, children continue to be symptomatic. But they also develop a lifestyle based on avoidance coping and might engage in maladaptive behaviors, Dr. Walkup said. As a result, the complexity of treatment increases substantially beyond just symptom control.

Providing an example, Dr. Walkup described a child of 7 years of age with separation anxiety. If treated at the time symptoms begin, Dr. Walkup explained, cognitive-behavioral therapy and medication would be expected to be both straightforward and highly effective. If left untreated until age 14, the child might accumulate impairment in independent functioning (due to avoidance coping) at a particularly important time in development.

“In those kids, you can reduce their anxiety burden with acute treatments like [cognitive-behavioral therapy] or meds, but now you also have 7 or 8 years of accumulated impairment due to avoidance coping and parental accommodation,” Dr. Walkup said. “If those kids are going to catch up developmentally, they also need life skill support in addition to symptomatic treatment for their anxiety.”

In the case of any pediatric psychiatric disorder, early treatment has the potential to thwart progression to a more complex and treatment-resistant form, but anxiety is a particularly prominent example. In most children, anxiety is relatively easy to control if caught early but a greater challenge when fears are not contained and the child accumulates ongoing impairment.

The obstacle is that many children are not diagnosed at the time of onset, said Dr. Walkup. The solution, he suggested, is better training of pediatricians and other primary care physicians not only to identify those children but to initiate treatment in uncomplicated cases.

“The person who has that longitudinal relationship with the child is their primary care provider, and this is really the person who is going to do the best job in getting to these kids early and initiating treatment,” Dr. Walkup said.

“We have a program in Chicago where we have trained primary care physicians not only to treat anxiety and depression, but we have specifically focused them on the easiest cases in their caseload, the classic phenotypes,” Dr. Walkup reported. Using a collaborative care model, this approach has been effective in building the confidence of primary care clinicians and in reaching children when symptoms are easier to control.

Importantly, anti-anxiety medication delivered in primary care could be sufficient to help children to manage anxiety effectively when parents cooperate in helping their children manage their fears.

“People suggest that we always start with CBT, but there [are no data] to support that. I think it is a conclusion drawn from the fact that CBT works and medication has side effects,” Dr. Walkup said. He appreciates the evidence that CBT is effective, but he cautioned that this therapy is not available everywhere, and pharmacologic therapies may be as or potentially more effective for some anxiety symptoms like anxiety-related physical symptoms.
 

Conversely, some have expressed the opinion that drugs might be a better option in late adolescence, when the efficacy of CBT appears to diminish, but Dr. Walkup objected to that characterization as well.

“My sense is that if you treat a 7-year-old for symptoms that have lasted a year it’s very different from treating a 17-year-old who has had symptoms for a decade,” Dr. Walkup said. Referring back to the contention that psychiatric disease in children becomes more complicated with a longer duration, this might explain why “you don’t see as much immediate success” with CBT and medication in the older age groups even if this is an effective treatment tool.

Some psychiatric disorders in children, including anxiety, might resolve with age, but early recognition and treatment should be a goal because of the potential to reduce symptoms and avoidance coping, and improve long-term outcomes, Dr. Walkup reported. Ironically, it might not be just anxiety symptoms, but poor adaptation and coping that might be the most important driver of ongoing impairment.

Dr. Walkup has served as an unpaid adviser to the Anxiety Disorders of Association of America. In addition, he has received royalties from Wolters Kluwer for CME activity on childhood anxiety.

This story was updated 2/11/2019.

BROOKLYN, N.Y. – Three steps in the progressive pathology of anxiety and other pediatric psychiatric disorders are important to recognize for their critical role in guiding treatment, John T. Walkup, MD, said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

After the onset of symptoms and over the course of time, those with untreated anxiety disorders are at risk for developing impairment in adaptation and coping, and also the development of maladaptive behaviors like substance abuse and suicidal behavior, said Dr. Walkup, chair of the department of psychiatry at Ann and Robert H. Lurie Children’s Hospital of Chicago.

The focus of his presentation was on the treatment of anxiety disorders in children, but Dr. Walkup said the impact of the three-tier progression is likely relevant to any psychiatric disorder that begins in childhood.

In essence, the scope of problems becomes more complicated over time, and without early treatment, children continue to be symptomatic. But they also develop a lifestyle based on avoidance coping and might engage in maladaptive behaviors, Dr. Walkup said. As a result, the complexity of treatment increases substantially beyond just symptom control.

Providing an example, Dr. Walkup described a child of 7 years of age with separation anxiety. If treated at the time symptoms begin, Dr. Walkup explained, cognitive-behavioral therapy and medication would be expected to be both straightforward and highly effective. If left untreated until age 14, the child might accumulate impairment in independent functioning (due to avoidance coping) at a particularly important time in development.

“In those kids, you can reduce their anxiety burden with acute treatments like [cognitive-behavioral therapy] or meds, but now you also have 7 or 8 years of accumulated impairment due to avoidance coping and parental accommodation,” Dr. Walkup said. “If those kids are going to catch up developmentally, they also need life skill support in addition to symptomatic treatment for their anxiety.”

In the case of any pediatric psychiatric disorder, early treatment has the potential to thwart progression to a more complex and treatment-resistant form, but anxiety is a particularly prominent example. In most children, anxiety is relatively easy to control if caught early but a greater challenge when fears are not contained and the child accumulates ongoing impairment.

The obstacle is that many children are not diagnosed at the time of onset, said Dr. Walkup. The solution, he suggested, is better training of pediatricians and other primary care physicians not only to identify those children but to initiate treatment in uncomplicated cases.

“The person who has that longitudinal relationship with the child is their primary care provider, and this is really the person who is going to do the best job in getting to these kids early and initiating treatment,” Dr. Walkup said.

“We have a program in Chicago where we have trained primary care physicians not only to treat anxiety and depression, but we have specifically focused them on the easiest cases in their caseload, the classic phenotypes,” Dr. Walkup reported. Using a collaborative care model, this approach has been effective in building the confidence of primary care clinicians and in reaching children when symptoms are easier to control.

Importantly, anti-anxiety medication delivered in primary care could be sufficient to help children to manage anxiety effectively when parents cooperate in helping their children manage their fears.

“People suggest that we always start with CBT, but there [are no data] to support that. I think it is a conclusion drawn from the fact that CBT works and medication has side effects,” Dr. Walkup said. He appreciates the evidence that CBT is effective, but he cautioned that this therapy is not available everywhere, and pharmacologic therapies may be as or potentially more effective for some anxiety symptoms like anxiety-related physical symptoms.
 

Conversely, some have expressed the opinion that drugs might be a better option in late adolescence, when the efficacy of CBT appears to diminish, but Dr. Walkup objected to that characterization as well.

“My sense is that if you treat a 7-year-old for symptoms that have lasted a year it’s very different from treating a 17-year-old who has had symptoms for a decade,” Dr. Walkup said. Referring back to the contention that psychiatric disease in children becomes more complicated with a longer duration, this might explain why “you don’t see as much immediate success” with CBT and medication in the older age groups even if this is an effective treatment tool.

Some psychiatric disorders in children, including anxiety, might resolve with age, but early recognition and treatment should be a goal because of the potential to reduce symptoms and avoidance coping, and improve long-term outcomes, Dr. Walkup reported. Ironically, it might not be just anxiety symptoms, but poor adaptation and coping that might be the most important driver of ongoing impairment.

Dr. Walkup has served as an unpaid adviser to the Anxiety Disorders of Association of America. In addition, he has received royalties from Wolters Kluwer for CME activity on childhood anxiety.

This story was updated 2/11/2019.

BROOKLYN, N.Y. – Three steps in the progressive pathology of anxiety and other pediatric psychiatric disorders are important to recognize for their critical role in guiding treatment, John T. Walkup, MD, said at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

After the onset of symptoms and over the course of time, those with untreated anxiety disorders are at risk for developing impairment in adaptation and coping, and also the development of maladaptive behaviors like substance abuse and suicidal behavior, said Dr. Walkup, chair of the department of psychiatry at Ann and Robert H. Lurie Children’s Hospital of Chicago.

The focus of his presentation was on the treatment of anxiety disorders in children, but Dr. Walkup said the impact of the three-tier progression is likely relevant to any psychiatric disorder that begins in childhood.

In essence, the scope of problems becomes more complicated over time, and without early treatment, children continue to be symptomatic. But they also develop a lifestyle based on avoidance coping and might engage in maladaptive behaviors, Dr. Walkup said. As a result, the complexity of treatment increases substantially beyond just symptom control.

Providing an example, Dr. Walkup described a child of 7 years of age with separation anxiety. If treated at the time symptoms begin, Dr. Walkup explained, cognitive-behavioral therapy and medication would be expected to be both straightforward and highly effective. If left untreated until age 14, the child might accumulate impairment in independent functioning (due to avoidance coping) at a particularly important time in development.

“In those kids, you can reduce their anxiety burden with acute treatments like [cognitive-behavioral therapy] or meds, but now you also have 7 or 8 years of accumulated impairment due to avoidance coping and parental accommodation,” Dr. Walkup said. “If those kids are going to catch up developmentally, they also need life skill support in addition to symptomatic treatment for their anxiety.”

In the case of any pediatric psychiatric disorder, early treatment has the potential to thwart progression to a more complex and treatment-resistant form, but anxiety is a particularly prominent example. In most children, anxiety is relatively easy to control if caught early but a greater challenge when fears are not contained and the child accumulates ongoing impairment.

The obstacle is that many children are not diagnosed at the time of onset, said Dr. Walkup. The solution, he suggested, is better training of pediatricians and other primary care physicians not only to identify those children but to initiate treatment in uncomplicated cases.

“The person who has that longitudinal relationship with the child is their primary care provider, and this is really the person who is going to do the best job in getting to these kids early and initiating treatment,” Dr. Walkup said.

“We have a program in Chicago where we have trained primary care physicians not only to treat anxiety and depression, but we have specifically focused them on the easiest cases in their caseload, the classic phenotypes,” Dr. Walkup reported. Using a collaborative care model, this approach has been effective in building the confidence of primary care clinicians and in reaching children when symptoms are easier to control.

Importantly, anti-anxiety medication delivered in primary care could be sufficient to help children to manage anxiety effectively when parents cooperate in helping their children manage their fears.

“People suggest that we always start with CBT, but there [are no data] to support that. I think it is a conclusion drawn from the fact that CBT works and medication has side effects,” Dr. Walkup said. He appreciates the evidence that CBT is effective, but he cautioned that this therapy is not available everywhere, and pharmacologic therapies may be as or potentially more effective for some anxiety symptoms like anxiety-related physical symptoms.
 

Conversely, some have expressed the opinion that drugs might be a better option in late adolescence, when the efficacy of CBT appears to diminish, but Dr. Walkup objected to that characterization as well.

“My sense is that if you treat a 7-year-old for symptoms that have lasted a year it’s very different from treating a 17-year-old who has had symptoms for a decade,” Dr. Walkup said. Referring back to the contention that psychiatric disease in children becomes more complicated with a longer duration, this might explain why “you don’t see as much immediate success” with CBT and medication in the older age groups even if this is an effective treatment tool.

Some psychiatric disorders in children, including anxiety, might resolve with age, but early recognition and treatment should be a goal because of the potential to reduce symptoms and avoidance coping, and improve long-term outcomes, Dr. Walkup reported. Ironically, it might not be just anxiety symptoms, but poor adaptation and coping that might be the most important driver of ongoing impairment.

Dr. Walkup has served as an unpaid adviser to the Anxiety Disorders of Association of America. In addition, he has received royalties from Wolters Kluwer for CME activity on childhood anxiety.

This story was updated 2/11/2019.

Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.

Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.

“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.

Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.

Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.

“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.

Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.

The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.

“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”

The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.

SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.

Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.

Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.

“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.

Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.

Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.

“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.

Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.

The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.

“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”

The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.

SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.

Daratumumab is safe but ineffective for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and CD38 expression of at least 50%, according to findings from a recent phase 2 trial.

Unfortunately, the study met headwinds early on, when initial screening of 112 patients with available tumor samples showed that only about half (56%) had CD38 expression of at least 50%, reported lead author Giles Salles, MD, PhD, of Claude Bernard University in Lyon, France, and his colleagues. The cutoff was based on preclinical models, suggesting that daratumumab-induced cytotoxicity depends on a high level of CD38 expression.

“Only 36 [patients] were eligible for study enrollment, questioning the generalizability of the study population,” the investigators wrote in Clinical Lymphoma, Myeloma & Leukemia.

Of these 36 patients, 15 had diffuse large B-cell lymphoma (DLBCL), 16 had follicular lymphoma (FL), and 5 had mantle cell lymphoma (MCL). Median CD38 expression was 70%. Patients were given 16 mg/kg of IV daratumumab once a week for two cycles, then every 2 weeks for four cycles, and finally on a monthly basis. Cycles were 28 days long. The primary endpoint was overall response rate. Safety and pharmacokinetics were also evaluated.

Results were generally disappointing, with ORR occurring in two patients (12.5%) with FL and one patient (6.7%) with DLBCL. No patients with MCL responded before the study was terminated. On a more encouraging note, 10 of 16 patients with FL maintained stable disease.

“All 16 patients in the FL cohort had progressed/relapsed on their prior treatment regimen; therefore, the maintenance of stable disease in the FL cohort may suggest some clinical benefit of daratumumab in this subset of NHL,” the investigators wrote.

Pharmacokinetics and safety data were similar to those from multiple myeloma studies of daratumumab; no new safety signals or instances of immunogenicity were encountered. The most common grade 3 or higher treatment-related adverse event was thrombocytopenia, which occurred in 11.1% of patients. Infusion-related reactions occurred in 72.2% of patients, but none were grade 4 and only three reactions were grade 3.

The investigators suggested that daratumumab may still play a role in NHL treatment, but not as a single agent.

“It is possible that daratumumab-based combination therapy would have allowed for more responses to be achieved within the current study,” the investigators wrote. “NHL is an extremely heterogeneous disease and the identification of predictive biomarkers and molecular genetics may provide new personalized therapies.”

The study was funded by Janssen Research & Development; two study authors reported employment by Janssen. Others reported financial ties to Janssen, Celgene, Roche, Gilead, Novartis, Amgen, and others.

SOURCE: Salles G et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.013.

SAN FRANCISCO – Interrogation of the pancreatic cancer genome and transcriptome identifies distinct molecular subtypes that have differing prognosis and response to chemotherapy, according to new data from the COMPASS trial reported at the 2019 GI Cancers Symposium.

“We now have two standard chemotherapy regimens that we use in the first-line setting, modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine–nab-paclitaxel, but we lack any real biomarker strategies on which to choose for treatments, and many of our clinical trials in pancreas cancer have failed,” noted senior investigator Jennifer J. Knox, MD, FRCPC, codirector of the McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto.

In the past year, genomic profiling studies using different platforms have yielded similar results, suggesting that about 30% of patients with pancreatic cancer have actionable mutations that could help guide treatment choices.

The COMPASS trial prospectively recruited patients with advanced pancreatic ductal adenocarcinoma prior to first-line chemotherapy for tumor whole-genome sequencing and RNA sequencing. The trial previously established feasibility, with sequencing successfully completed in more than 90% of patients and availability of whole-genome results before the first disease assessment CT scan at 8 weeks (Clin Cancer Res. 2018;24[6]:1344-54).

New outcomes data for the 150 patients in the intention-to-treat population showed that overall survival was almost 4 months longer for those having a classic modified Moffitt RNA expression signature compared with those having a basal-like one. Similarly, it was more than 2 months longer for those having high versus low expression of the transcription factor GATA6.

In addition, among the subset of patients given mFOLFIRINOX, those having the classic signature were two-thirds less likely to die than were those having the basal-like signature.

“The RNA signature and GATA6 seem to discriminate two prognostic groups in advanced pancreas cancer. The basal-like cohort, or GATA6-low, may be particularly resistant to mFOLFIRINOX,” Dr. Knox said. “GATA6, and perhaps other markers, need to be validated as predictive biomarkers so that we can discover and use more effective therapies earlier on for our patients.

“COMPASS provides a very rich discovery set for other hypotheses and collaborators,” she said, noting that the investigators are adding trial data to the Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) project and to the Accelerate Research in Genomic Oncology (ARGO) project of the International Cancer Genome Consortium.

Rationally based treatment decisions

The COMPASS trial “will show us ... how we should move forward,” said invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the Gastrointestinal Cancers Program, USC Norris Comprehensive Cancer Center, Los Angeles. “We don’t necessarily have the answer today to what the best treatment options are, but this is the first step to understand and develop rationally based treatment decisions for these molecularly characterized groups,” he said.

Susan London/MDedge

Whole-genome sequencing has been critically important for finding mutations in single genes, the proverbial needles in the haystack, he maintained. But in the future, the emphasis will likely be on combinations of mutations and other alterations.

Study details

Most of the 150 COMPASS patients had metastatic disease (87%), and they were about evenly split between receiving mFOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy, Dr. Knox reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Genomic profiling revealed that roughly 40% overall had potentially actionable variants: alterations in the presence of KRAS wild type (8%), homologous recombination deficiency involving BRCA (6%), and others (25%) such as activating PIK3CA mutations or HER2 amplification.

In findings that Dr. Knox called “quite striking,” among patients given mFOLFIRINOX, median progression-free survival was 7.17 months for those with the RNA classic expression signature versus 2.50 months for those with the RNA basal-like signature (hazard ratio, 0.17; P less than .0001). In contrast, among patients given gemcitabine plus nab-paclitaxel, there was no significant difference by signature (5.65 vs. 4.93 months; P = .69).

GATA6 expression was strongly related to signature type, with classic tumors having high expression and basal-like tumors having low expression (P less than .0001).

Overall survival was similarly better for patients with classic versus basal-like tumors (8.8 vs. 5.2 months; HR, 0.53; P = .006) and for patients with GATA6 high- versus low-expression tumors (8.2 vs. 5.8 months; HR, 0.66; P = .08).

In the whole cohort, overall survival differed across subsets according to RNA signature and type of chemotherapy received (P = .0134). When analysis was restricted to patients given mFOLFIRINOX, median overall survival was 10.1 months with the classic signature but just 5.3 months with the basal-like signature (HR, 0.33; P = .0005).

A multivariate analysis among all chemotherapy-treated patients confirmed the survival benefit of classic signature over basal-like signature (HR, 0.55; P = .03).

Dr. Knox disclosed that she has a consulting or advisory role with Lilly, Merck, and Bristol-Myers Squibb; that she receives honoraria from Novartis; and that she receives research funding from AstraZeneca and Merck. The study is sponsored by University Health Network, Toronto.

SOURCE: O’Kane GM et al. GI Cancers Symposium, Abstract 188.

SAN FRANCISCO – Interrogation of the pancreatic cancer genome and transcriptome identifies distinct molecular subtypes that have differing prognosis and response to chemotherapy, according to new data from the COMPASS trial reported at the 2019 GI Cancers Symposium.

“We now have two standard chemotherapy regimens that we use in the first-line setting, modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine–nab-paclitaxel, but we lack any real biomarker strategies on which to choose for treatments, and many of our clinical trials in pancreas cancer have failed,” noted senior investigator Jennifer J. Knox, MD, FRCPC, codirector of the McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto.

In the past year, genomic profiling studies using different platforms have yielded similar results, suggesting that about 30% of patients with pancreatic cancer have actionable mutations that could help guide treatment choices.

The COMPASS trial prospectively recruited patients with advanced pancreatic ductal adenocarcinoma prior to first-line chemotherapy for tumor whole-genome sequencing and RNA sequencing. The trial previously established feasibility, with sequencing successfully completed in more than 90% of patients and availability of whole-genome results before the first disease assessment CT scan at 8 weeks (Clin Cancer Res. 2018;24[6]:1344-54).

New outcomes data for the 150 patients in the intention-to-treat population showed that overall survival was almost 4 months longer for those having a classic modified Moffitt RNA expression signature compared with those having a basal-like one. Similarly, it was more than 2 months longer for those having high versus low expression of the transcription factor GATA6.

In addition, among the subset of patients given mFOLFIRINOX, those having the classic signature were two-thirds less likely to die than were those having the basal-like signature.

“The RNA signature and GATA6 seem to discriminate two prognostic groups in advanced pancreas cancer. The basal-like cohort, or GATA6-low, may be particularly resistant to mFOLFIRINOX,” Dr. Knox said. “GATA6, and perhaps other markers, need to be validated as predictive biomarkers so that we can discover and use more effective therapies earlier on for our patients.

“COMPASS provides a very rich discovery set for other hypotheses and collaborators,” she said, noting that the investigators are adding trial data to the Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) project and to the Accelerate Research in Genomic Oncology (ARGO) project of the International Cancer Genome Consortium.

Rationally based treatment decisions

The COMPASS trial “will show us ... how we should move forward,” said invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the Gastrointestinal Cancers Program, USC Norris Comprehensive Cancer Center, Los Angeles. “We don’t necessarily have the answer today to what the best treatment options are, but this is the first step to understand and develop rationally based treatment decisions for these molecularly characterized groups,” he said.

Susan London/MDedge

Whole-genome sequencing has been critically important for finding mutations in single genes, the proverbial needles in the haystack, he maintained. But in the future, the emphasis will likely be on combinations of mutations and other alterations.

Study details

Most of the 150 COMPASS patients had metastatic disease (87%), and they were about evenly split between receiving mFOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy, Dr. Knox reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Genomic profiling revealed that roughly 40% overall had potentially actionable variants: alterations in the presence of KRAS wild type (8%), homologous recombination deficiency involving BRCA (6%), and others (25%) such as activating PIK3CA mutations or HER2 amplification.

In findings that Dr. Knox called “quite striking,” among patients given mFOLFIRINOX, median progression-free survival was 7.17 months for those with the RNA classic expression signature versus 2.50 months for those with the RNA basal-like signature (hazard ratio, 0.17; P less than .0001). In contrast, among patients given gemcitabine plus nab-paclitaxel, there was no significant difference by signature (5.65 vs. 4.93 months; P = .69).

GATA6 expression was strongly related to signature type, with classic tumors having high expression and basal-like tumors having low expression (P less than .0001).

Overall survival was similarly better for patients with classic versus basal-like tumors (8.8 vs. 5.2 months; HR, 0.53; P = .006) and for patients with GATA6 high- versus low-expression tumors (8.2 vs. 5.8 months; HR, 0.66; P = .08).

In the whole cohort, overall survival differed across subsets according to RNA signature and type of chemotherapy received (P = .0134). When analysis was restricted to patients given mFOLFIRINOX, median overall survival was 10.1 months with the classic signature but just 5.3 months with the basal-like signature (HR, 0.33; P = .0005).

A multivariate analysis among all chemotherapy-treated patients confirmed the survival benefit of classic signature over basal-like signature (HR, 0.55; P = .03).

Dr. Knox disclosed that she has a consulting or advisory role with Lilly, Merck, and Bristol-Myers Squibb; that she receives honoraria from Novartis; and that she receives research funding from AstraZeneca and Merck. The study is sponsored by University Health Network, Toronto.

SOURCE: O’Kane GM et al. GI Cancers Symposium, Abstract 188.

SAN FRANCISCO – Interrogation of the pancreatic cancer genome and transcriptome identifies distinct molecular subtypes that have differing prognosis and response to chemotherapy, according to new data from the COMPASS trial reported at the 2019 GI Cancers Symposium.

“We now have two standard chemotherapy regimens that we use in the first-line setting, modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine–nab-paclitaxel, but we lack any real biomarker strategies on which to choose for treatments, and many of our clinical trials in pancreas cancer have failed,” noted senior investigator Jennifer J. Knox, MD, FRCPC, codirector of the McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto.

In the past year, genomic profiling studies using different platforms have yielded similar results, suggesting that about 30% of patients with pancreatic cancer have actionable mutations that could help guide treatment choices.

The COMPASS trial prospectively recruited patients with advanced pancreatic ductal adenocarcinoma prior to first-line chemotherapy for tumor whole-genome sequencing and RNA sequencing. The trial previously established feasibility, with sequencing successfully completed in more than 90% of patients and availability of whole-genome results before the first disease assessment CT scan at 8 weeks (Clin Cancer Res. 2018;24[6]:1344-54).

New outcomes data for the 150 patients in the intention-to-treat population showed that overall survival was almost 4 months longer for those having a classic modified Moffitt RNA expression signature compared with those having a basal-like one. Similarly, it was more than 2 months longer for those having high versus low expression of the transcription factor GATA6.

In addition, among the subset of patients given mFOLFIRINOX, those having the classic signature were two-thirds less likely to die than were those having the basal-like signature.

“The RNA signature and GATA6 seem to discriminate two prognostic groups in advanced pancreas cancer. The basal-like cohort, or GATA6-low, may be particularly resistant to mFOLFIRINOX,” Dr. Knox said. “GATA6, and perhaps other markers, need to be validated as predictive biomarkers so that we can discover and use more effective therapies earlier on for our patients.

“COMPASS provides a very rich discovery set for other hypotheses and collaborators,” she said, noting that the investigators are adding trial data to the Enhanced Pancreatic Cancer Profiling for Individualized Care (EPPIC) project and to the Accelerate Research in Genomic Oncology (ARGO) project of the International Cancer Genome Consortium.

Rationally based treatment decisions

The COMPASS trial “will show us ... how we should move forward,” said invited discussant Heinz-Josef Lenz, MD, associate director for adult oncology and coleader of the Gastrointestinal Cancers Program, USC Norris Comprehensive Cancer Center, Los Angeles. “We don’t necessarily have the answer today to what the best treatment options are, but this is the first step to understand and develop rationally based treatment decisions for these molecularly characterized groups,” he said.

Susan London/MDedge

Whole-genome sequencing has been critically important for finding mutations in single genes, the proverbial needles in the haystack, he maintained. But in the future, the emphasis will likely be on combinations of mutations and other alterations.

Study details

Most of the 150 COMPASS patients had metastatic disease (87%), and they were about evenly split between receiving mFOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy, Dr. Knox reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Genomic profiling revealed that roughly 40% overall had potentially actionable variants: alterations in the presence of KRAS wild type (8%), homologous recombination deficiency involving BRCA (6%), and others (25%) such as activating PIK3CA mutations or HER2 amplification.

In findings that Dr. Knox called “quite striking,” among patients given mFOLFIRINOX, median progression-free survival was 7.17 months for those with the RNA classic expression signature versus 2.50 months for those with the RNA basal-like signature (hazard ratio, 0.17; P less than .0001). In contrast, among patients given gemcitabine plus nab-paclitaxel, there was no significant difference by signature (5.65 vs. 4.93 months; P = .69).

GATA6 expression was strongly related to signature type, with classic tumors having high expression and basal-like tumors having low expression (P less than .0001).

Overall survival was similarly better for patients with classic versus basal-like tumors (8.8 vs. 5.2 months; HR, 0.53; P = .006) and for patients with GATA6 high- versus low-expression tumors (8.2 vs. 5.8 months; HR, 0.66; P = .08).

In the whole cohort, overall survival differed across subsets according to RNA signature and type of chemotherapy received (P = .0134). When analysis was restricted to patients given mFOLFIRINOX, median overall survival was 10.1 months with the classic signature but just 5.3 months with the basal-like signature (HR, 0.33; P = .0005).

A multivariate analysis among all chemotherapy-treated patients confirmed the survival benefit of classic signature over basal-like signature (HR, 0.55; P = .03).

Dr. Knox disclosed that she has a consulting or advisory role with Lilly, Merck, and Bristol-Myers Squibb; that she receives honoraria from Novartis; and that she receives research funding from AstraZeneca and Merck. The study is sponsored by University Health Network, Toronto.

SOURCE: O’Kane GM et al. GI Cancers Symposium, Abstract 188.

By increasing urine color, 400 mg of oral riboflavin the night before gynecologic surgery makes it easier to see and confirm urine flow during intraoperative cystoscopy, according to results of a randomized, blinded, placebo-controlled trial.

The traditional go-to for that purpose, intravenous indigo carmine, has been in short supply, if possible to get at all, so surgeons have been looking for other options. Alternatives include intravenous methylene blue, intravenous fluorescein, and oral phenazopyridine, but each have their own problems, including cost, contraindications, and anaphylaxis.

So the study team turned to riboflavin – vitamin B₂ – which, in excess, turns the urine bright, sometimes almost neon yellow. It’s “safe, readily available without prescription, and inexpensive ... and should be considered for routine use,” wrote investigators led by Michael L. Stitely, MD, an ob.gyn. at the University of Otago in Dunedin, New Zealand.

The team randomized 33 women to four 100-mg capsules of riboflavin the night before surgery and 33 to four 1,000-IU capsules of vitamin D₃, which served as the placebo. Participants, clinicians, researchers, and study staff all were blinded to group allocation, the investigators noted in Obstetrics & Gynecology.

During cystoscopy, operating surgeons observed and videoed urine flow from both ureters for at least 3 minutes.

Surgeons rated urine color a median of 2 (slight yellow) in the riboflavin group, compared with 1 (clear) in the placebo arm, on a 3-point scale (P less than .001). About 13 women on riboflavin got a rating of 3 – strong yellow – versus 1 woman in the placebo arm.

The operating surgeons also said it was easier to visualize urine flow in the riboflavin group, giving a median of 5, compared with 4 in the placebo group, on a 5-point scale (P less than .013). They gave a score of 5 to 19 women in the riboflavin group but only to 8 placebo women, meaning that they “strongly agreed” that it was easy to see urine flow; a score of 4 meant that they simply agreed with the statement.

Overall, surgeons confirmed bilateral urine flow in 30 women (91%) in the riboflavin group, compared with 28 women (85%) in the placebo group (P = .71). When a blinded investigator checked the videos, their assessments of the same parameters correlated with those of the surgeons.

No significant differences were found between the groups in age, height, weight, body mass index, or ethnicity. The most common procedure was a midurethral sling (10 in the riboflavin group; 4 in the placebo arm), followed by cystoscopy with botox (4 in the riboflavin group; 7 in the placebo group). None of the women required intervention for urinary tract injury.

Among the limitations cited was the use of subjective and nonvalidated measures of urine color.

The work was funded by the Healthcare Otago Charitable Trust and the Australasian Gynaecological Endoscopy and Surgery Society. The authors reported no conflicts of interest.
 

aotto@mdedge.com

SOURCE: Stitely ML et al. Obstet Gynecol. 2019 Jan 8. doi: 10.1097/AOG.0000000000003063.

By increasing urine color, 400 mg of oral riboflavin the night before gynecologic surgery makes it easier to see and confirm urine flow during intraoperative cystoscopy, according to results of a randomized, blinded, placebo-controlled trial.

The traditional go-to for that purpose, intravenous indigo carmine, has been in short supply, if possible to get at all, so surgeons have been looking for other options. Alternatives include intravenous methylene blue, intravenous fluorescein, and oral phenazopyridine, but each have their own problems, including cost, contraindications, and anaphylaxis.

So the study team turned to riboflavin – vitamin B₂ – which, in excess, turns the urine bright, sometimes almost neon yellow. It’s “safe, readily available without prescription, and inexpensive ... and should be considered for routine use,” wrote investigators led by Michael L. Stitely, MD, an ob.gyn. at the University of Otago in Dunedin, New Zealand.

The team randomized 33 women to four 100-mg capsules of riboflavin the night before surgery and 33 to four 1,000-IU capsules of vitamin D₃, which served as the placebo. Participants, clinicians, researchers, and study staff all were blinded to group allocation, the investigators noted in Obstetrics & Gynecology.

During cystoscopy, operating surgeons observed and videoed urine flow from both ureters for at least 3 minutes.

Surgeons rated urine color a median of 2 (slight yellow) in the riboflavin group, compared with 1 (clear) in the placebo arm, on a 3-point scale (P less than .001). About 13 women on riboflavin got a rating of 3 – strong yellow – versus 1 woman in the placebo arm.

The operating surgeons also said it was easier to visualize urine flow in the riboflavin group, giving a median of 5, compared with 4 in the placebo group, on a 5-point scale (P less than .013). They gave a score of 5 to 19 women in the riboflavin group but only to 8 placebo women, meaning that they “strongly agreed” that it was easy to see urine flow; a score of 4 meant that they simply agreed with the statement.

Overall, surgeons confirmed bilateral urine flow in 30 women (91%) in the riboflavin group, compared with 28 women (85%) in the placebo group (P = .71). When a blinded investigator checked the videos, their assessments of the same parameters correlated with those of the surgeons.

No significant differences were found between the groups in age, height, weight, body mass index, or ethnicity. The most common procedure was a midurethral sling (10 in the riboflavin group; 4 in the placebo arm), followed by cystoscopy with botox (4 in the riboflavin group; 7 in the placebo group). None of the women required intervention for urinary tract injury.

Among the limitations cited was the use of subjective and nonvalidated measures of urine color.

The work was funded by the Healthcare Otago Charitable Trust and the Australasian Gynaecological Endoscopy and Surgery Society. The authors reported no conflicts of interest.
 

aotto@mdedge.com

SOURCE: Stitely ML et al. Obstet Gynecol. 2019 Jan 8. doi: 10.1097/AOG.0000000000003063.

By increasing urine color, 400 mg of oral riboflavin the night before gynecologic surgery makes it easier to see and confirm urine flow during intraoperative cystoscopy, according to results of a randomized, blinded, placebo-controlled trial.

The traditional go-to for that purpose, intravenous indigo carmine, has been in short supply, if possible to get at all, so surgeons have been looking for other options. Alternatives include intravenous methylene blue, intravenous fluorescein, and oral phenazopyridine, but each have their own problems, including cost, contraindications, and anaphylaxis.

So the study team turned to riboflavin – vitamin B₂ – which, in excess, turns the urine bright, sometimes almost neon yellow. It’s “safe, readily available without prescription, and inexpensive ... and should be considered for routine use,” wrote investigators led by Michael L. Stitely, MD, an ob.gyn. at the University of Otago in Dunedin, New Zealand.

The team randomized 33 women to four 100-mg capsules of riboflavin the night before surgery and 33 to four 1,000-IU capsules of vitamin D₃, which served as the placebo. Participants, clinicians, researchers, and study staff all were blinded to group allocation, the investigators noted in Obstetrics & Gynecology.

During cystoscopy, operating surgeons observed and videoed urine flow from both ureters for at least 3 minutes.

Surgeons rated urine color a median of 2 (slight yellow) in the riboflavin group, compared with 1 (clear) in the placebo arm, on a 3-point scale (P less than .001). About 13 women on riboflavin got a rating of 3 – strong yellow – versus 1 woman in the placebo arm.

The operating surgeons also said it was easier to visualize urine flow in the riboflavin group, giving a median of 5, compared with 4 in the placebo group, on a 5-point scale (P less than .013). They gave a score of 5 to 19 women in the riboflavin group but only to 8 placebo women, meaning that they “strongly agreed” that it was easy to see urine flow; a score of 4 meant that they simply agreed with the statement.

Overall, surgeons confirmed bilateral urine flow in 30 women (91%) in the riboflavin group, compared with 28 women (85%) in the placebo group (P = .71). When a blinded investigator checked the videos, their assessments of the same parameters correlated with those of the surgeons.

No significant differences were found between the groups in age, height, weight, body mass index, or ethnicity. The most common procedure was a midurethral sling (10 in the riboflavin group; 4 in the placebo arm), followed by cystoscopy with botox (4 in the riboflavin group; 7 in the placebo group). None of the women required intervention for urinary tract injury.

Among the limitations cited was the use of subjective and nonvalidated measures of urine color.

The work was funded by the Healthcare Otago Charitable Trust and the Australasian Gynaecological Endoscopy and Surgery Society. The authors reported no conflicts of interest.
 

aotto@mdedge.com

SOURCE: Stitely ML et al. Obstet Gynecol. 2019 Jan 8. doi: 10.1097/AOG.0000000000003063.

For patients with systemic heart failure but without diabetes, oral SGLT2s are the focus of multiple ongoing phase 3 clinical trials. Also today, influenza activity hits a seasonal high, the U.S. Supreme Court halts a Louisiana abortion law from taking effect, and cilostazol plus aspirin or clopidogrel reduces the risk of recurrent stroke.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

For patients with systemic heart failure but without diabetes, oral SGLT2s are the focus of multiple ongoing phase 3 clinical trials. Also today, influenza activity hits a seasonal high, the U.S. Supreme Court halts a Louisiana abortion law from taking effect, and cilostazol plus aspirin or clopidogrel reduces the risk of recurrent stroke.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

For patients with systemic heart failure but without diabetes, oral SGLT2s are the focus of multiple ongoing phase 3 clinical trials. Also today, influenza activity hits a seasonal high, the U.S. Supreme Court halts a Louisiana abortion law from taking effect, and cilostazol plus aspirin or clopidogrel reduces the risk of recurrent stroke.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

The numbers are stunning: 1,643% increase in rates of deaths involving synthetic opioids. A 915% increase for heroin, 830% for benzodiazepines. Even more stunning: Those are the increases only in overdose death rates for women aged 30 to 64 years.

According to CDC data, between 1999 and 2010, the largest percentage change in the rates of overall drug overdose deaths was among women aged between 45 and 64 years. But that research did not account for trends in specific drugs or consider changes in age group distributions, say researchers from the CDC’s National Center for Injury Prevention and Control.

They examined overdose death rates among women aged 30 to 64 years between 1999 and 2017. The unadjusted death rate jumped 260%, from 4,314 deaths to 18,110 deaths. Among women aged 55 to 59 years, the number of deaths involving antidepressants increased approximately 300%; among women aged 60 to 64 years, nearly 400%. The crude rate of deaths involving prescription opioids skyrocketed > 1,000%.

The drug epidemic is “evolving,” the researchers note. In 1999, overdose death rates were highest among women aged 40 to 44 years. In 2017, they were highest among women aged 50 to 54 years. And as demographics shift, prevention programs need to shift as well. As women age, the researchers say, individual experiences can change the type of substance used or misused and in the experiences of pain that might result in an opioid prescription.

The researchers note that “substantial work” has focused on informing women of childbearing age about the risks and benefits of certain drugs. The current analysis demonstrates “the remaining need” to consider middle-aged women who are at risk.

Targeted efforts are needed, and the researchers suggest interventions: Medicaid and other health insurance programs can review records of controlled substance prescribing. States and local communities can expand capacity of drug use disorder treatments and links to care, particularly adding “gender-responsive” substance use disorder treatment centers.

A “multifaceted approach involving the full spectrum of care services is likely necessary,” the researchers say. Health care practitioners who treat women for pain, depression, or anxiety can discuss treatment options that consider the unique biopsychosocial needs of women.

Health care practitioners also can consider implementing the CDC Guideline for Prescribing Opioids for Chronic Pain, which says “Opioids are not first-line or routine therapy for chronic pain.” The guideline also says before starting and periodically during opioid therapy, clinicians should discuss with patients the “known risks and realistic benefits of opioid therapy.”  In other words, listen to the women and prescribe carefully.

The numbers are stunning: 1,643% increase in rates of deaths involving synthetic opioids. A 915% increase for heroin, 830% for benzodiazepines. Even more stunning: Those are the increases only in overdose death rates for women aged 30 to 64 years.

According to CDC data, between 1999 and 2010, the largest percentage change in the rates of overall drug overdose deaths was among women aged between 45 and 64 years. But that research did not account for trends in specific drugs or consider changes in age group distributions, say researchers from the CDC’s National Center for Injury Prevention and Control.

They examined overdose death rates among women aged 30 to 64 years between 1999 and 2017. The unadjusted death rate jumped 260%, from 4,314 deaths to 18,110 deaths. Among women aged 55 to 59 years, the number of deaths involving antidepressants increased approximately 300%; among women aged 60 to 64 years, nearly 400%. The crude rate of deaths involving prescription opioids skyrocketed > 1,000%.

The drug epidemic is “evolving,” the researchers note. In 1999, overdose death rates were highest among women aged 40 to 44 years. In 2017, they were highest among women aged 50 to 54 years. And as demographics shift, prevention programs need to shift as well. As women age, the researchers say, individual experiences can change the type of substance used or misused and in the experiences of pain that might result in an opioid prescription.

The researchers note that “substantial work” has focused on informing women of childbearing age about the risks and benefits of certain drugs. The current analysis demonstrates “the remaining need” to consider middle-aged women who are at risk.

Targeted efforts are needed, and the researchers suggest interventions: Medicaid and other health insurance programs can review records of controlled substance prescribing. States and local communities can expand capacity of drug use disorder treatments and links to care, particularly adding “gender-responsive” substance use disorder treatment centers.

A “multifaceted approach involving the full spectrum of care services is likely necessary,” the researchers say. Health care practitioners who treat women for pain, depression, or anxiety can discuss treatment options that consider the unique biopsychosocial needs of women.

Health care practitioners also can consider implementing the CDC Guideline for Prescribing Opioids for Chronic Pain, which says “Opioids are not first-line or routine therapy for chronic pain.” The guideline also says before starting and periodically during opioid therapy, clinicians should discuss with patients the “known risks and realistic benefits of opioid therapy.”  In other words, listen to the women and prescribe carefully.

The numbers are stunning: 1,643% increase in rates of deaths involving synthetic opioids. A 915% increase for heroin, 830% for benzodiazepines. Even more stunning: Those are the increases only in overdose death rates for women aged 30 to 64 years.

According to CDC data, between 1999 and 2010, the largest percentage change in the rates of overall drug overdose deaths was among women aged between 45 and 64 years. But that research did not account for trends in specific drugs or consider changes in age group distributions, say researchers from the CDC’s National Center for Injury Prevention and Control.

They examined overdose death rates among women aged 30 to 64 years between 1999 and 2017. The unadjusted death rate jumped 260%, from 4,314 deaths to 18,110 deaths. Among women aged 55 to 59 years, the number of deaths involving antidepressants increased approximately 300%; among women aged 60 to 64 years, nearly 400%. The crude rate of deaths involving prescription opioids skyrocketed > 1,000%.

The drug epidemic is “evolving,” the researchers note. In 1999, overdose death rates were highest among women aged 40 to 44 years. In 2017, they were highest among women aged 50 to 54 years. And as demographics shift, prevention programs need to shift as well. As women age, the researchers say, individual experiences can change the type of substance used or misused and in the experiences of pain that might result in an opioid prescription.

The researchers note that “substantial work” has focused on informing women of childbearing age about the risks and benefits of certain drugs. The current analysis demonstrates “the remaining need” to consider middle-aged women who are at risk.

Targeted efforts are needed, and the researchers suggest interventions: Medicaid and other health insurance programs can review records of controlled substance prescribing. States and local communities can expand capacity of drug use disorder treatments and links to care, particularly adding “gender-responsive” substance use disorder treatment centers.

A “multifaceted approach involving the full spectrum of care services is likely necessary,” the researchers say. Health care practitioners who treat women for pain, depression, or anxiety can discuss treatment options that consider the unique biopsychosocial needs of women.

Health care practitioners also can consider implementing the CDC Guideline for Prescribing Opioids for Chronic Pain, which says “Opioids are not first-line or routine therapy for chronic pain.” The guideline also says before starting and periodically during opioid therapy, clinicians should discuss with patients the “known risks and realistic benefits of opioid therapy.”  In other words, listen to the women and prescribe carefully.