NEWPORT BEACH, CALIF. – Preclinical research has revealed workarounds that may make chimeric antigen receptor (CAR) T-cell therapy feasible for patients with T-cell malignancies.

Researchers have found that using allogeneic cells for CAR T-cell therapy can eliminate contamination by malignant T cells, and editing those allogeneic T cells to delete the target antigen and the T-cell receptor alpha chain (TRAC) can prevent fratricide and graft-versus-host disease (GVHD).

Additionally, an interleukin-7 molecule called NT-I7 has been shown to enhance CAR T-cell proliferation, differentiation, and tumor killing in a mouse model of a T-cell malignancy.

John F. DiPersio, MD, PhD, of Washington University in St. Louis, described this work in a presentation at the Acute Leukemia Forum of Hemedicus.
 

Obstacles to development

“The primary obstacle for targeting T-cell malignancies with a T cell is that all of the targets that are on the [malignant] T cells are also expressed on the normal T cells,” Dr. DiPersio said. “So when you put a CAR into a normal T cell, it just kills itself. It’s called fratricide.”

A second issue that has limited development is that the phenotype of the malignant T cell in the blood is similar to a normal T cell, so they can’t be separated, he explained.

“So if you were to do anything to a normal T cell, you would also be doing it, in theory, to the malignant T cell – in theory, making it resistant to therapy,” he said.

A third obstacle, which has been seen in patients with B-cell malignancies as well, is the inability to harvest enough T cells to generate effective CAR T-cell therapy.

And a fourth obstacle is that T cells from patients with malignancies may not function normally because they have been exposed to prior therapies.

Dr. DiPersio and his colleagues believe these obstacles can be overcome by creating CAR T-cell therapies using T cells derived from healthy donors or cord blood, using gene editing to remove the target antigen and TRAC, and using NT-I7 to enhance the efficacy of these universal, “off-the-shelf” CAR T cells.

The researchers have tested these theories, and achieved successes, in preclinical models. The team is now planning a clinical trial in patients at Washington University. Dr. DiPersio and his colleagues also created a company called WUGEN that will develop the universal CAR T-cell therapies if the initial proof-of-principle trial proves successful.
 

UCART7

One of the universal CAR T-cell therapies Dr. DiPersio and his colleagues have tested is UCART7, which targets CD7. Dr. DiPersio noted that CD7 is expressed on 98% of T-cell acute lymphoblastic leukemias (T-ALLs), 24% of acute myeloid leukemias, natural killer (NK) cells, and T cells.

The researchers created UCART7 by using CRISPR/Cas9 to delete CD7 and TRAC from allogeneic T cells and following this with lentiviral transduction with a third-generation CD7-CAR. The team found a way to delete both TRAC and CD7 in a single day with 95% efficiency, Dr. DiPersio noted.

“Knocking out CD7 doesn’t seem to have any impact on the expansion or trafficking of these T cells in vivo,” Dr. DiPersio said. “So we think that deleting that target in a normal T cell will not affect its overall ability to kill a target when we put a CAR into those T cells.”

In fact, the researchers’ experiments showed that UCART7 can kill T-ALL cells in vitro and target primary T-ALL in vivo without inducing GVHD (Leukemia. 2018 Sep;32[9]:1970-83.)
 

UCART2 and NT-I7

Dr. DiPersio and his colleagues have also tested UCART2, an allogeneic CAR T-cell therapy in which CD2 and TRAC are deleted. The therapy targets CD2 because this antigen is expressed on T-ALL and other T-cell and NK-cell malignancies. Experiments showed that UCART2 targets T-cell malignancies, including T-ALL and cutaneous T-cell lymphoma, in vitro.

The researchers also tested UCART2 in a mouse model of Sézary syndrome. In these experiments, UCART2 was combined with NT-I7.

NT-I7 enhanced the proliferation, persistence, and tumor killing ability of UCART2. Sézary mice that received UCART2 and NT-I7 had “virtually no tumor burden,” according to researchers, and survived longer than mice treated with UCART2 alone (Blood. 2018;132:340).

Dr. DiPersio noted that there was no cytokine release syndrome because these were immunodeficient mice. However, cytokine release syndrome may be a side effect of NT-I7 in patients as NT-I7 induces rapid expansion of CAR T cells.

Dr. DiPersio reported ownership and investment in WUGEN and Magenta Therapeutics. He also has relationships with Cellworks Group, Tioma Therapeutics, RiverVest Venture Partners, Bioline, Asterias Biotherapeutics, Amphivena Therapeutics, Bluebird Bio, Celgene, Incyte, NeoImuneTech, and MacroGenics.

The Acute Leukemia Forum is organized by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Preclinical research has revealed workarounds that may make chimeric antigen receptor (CAR) T-cell therapy feasible for patients with T-cell malignancies.

Researchers have found that using allogeneic cells for CAR T-cell therapy can eliminate contamination by malignant T cells, and editing those allogeneic T cells to delete the target antigen and the T-cell receptor alpha chain (TRAC) can prevent fratricide and graft-versus-host disease (GVHD).

Additionally, an interleukin-7 molecule called NT-I7 has been shown to enhance CAR T-cell proliferation, differentiation, and tumor killing in a mouse model of a T-cell malignancy.

John F. DiPersio, MD, PhD, of Washington University in St. Louis, described this work in a presentation at the Acute Leukemia Forum of Hemedicus.
 

Obstacles to development

“The primary obstacle for targeting T-cell malignancies with a T cell is that all of the targets that are on the [malignant] T cells are also expressed on the normal T cells,” Dr. DiPersio said. “So when you put a CAR into a normal T cell, it just kills itself. It’s called fratricide.”

A second issue that has limited development is that the phenotype of the malignant T cell in the blood is similar to a normal T cell, so they can’t be separated, he explained.

“So if you were to do anything to a normal T cell, you would also be doing it, in theory, to the malignant T cell – in theory, making it resistant to therapy,” he said.

A third obstacle, which has been seen in patients with B-cell malignancies as well, is the inability to harvest enough T cells to generate effective CAR T-cell therapy.

And a fourth obstacle is that T cells from patients with malignancies may not function normally because they have been exposed to prior therapies.

Dr. DiPersio and his colleagues believe these obstacles can be overcome by creating CAR T-cell therapies using T cells derived from healthy donors or cord blood, using gene editing to remove the target antigen and TRAC, and using NT-I7 to enhance the efficacy of these universal, “off-the-shelf” CAR T cells.

The researchers have tested these theories, and achieved successes, in preclinical models. The team is now planning a clinical trial in patients at Washington University. Dr. DiPersio and his colleagues also created a company called WUGEN that will develop the universal CAR T-cell therapies if the initial proof-of-principle trial proves successful.
 

UCART7

One of the universal CAR T-cell therapies Dr. DiPersio and his colleagues have tested is UCART7, which targets CD7. Dr. DiPersio noted that CD7 is expressed on 98% of T-cell acute lymphoblastic leukemias (T-ALLs), 24% of acute myeloid leukemias, natural killer (NK) cells, and T cells.

The researchers created UCART7 by using CRISPR/Cas9 to delete CD7 and TRAC from allogeneic T cells and following this with lentiviral transduction with a third-generation CD7-CAR. The team found a way to delete both TRAC and CD7 in a single day with 95% efficiency, Dr. DiPersio noted.

“Knocking out CD7 doesn’t seem to have any impact on the expansion or trafficking of these T cells in vivo,” Dr. DiPersio said. “So we think that deleting that target in a normal T cell will not affect its overall ability to kill a target when we put a CAR into those T cells.”

In fact, the researchers’ experiments showed that UCART7 can kill T-ALL cells in vitro and target primary T-ALL in vivo without inducing GVHD (Leukemia. 2018 Sep;32[9]:1970-83.)
 

UCART2 and NT-I7

Dr. DiPersio and his colleagues have also tested UCART2, an allogeneic CAR T-cell therapy in which CD2 and TRAC are deleted. The therapy targets CD2 because this antigen is expressed on T-ALL and other T-cell and NK-cell malignancies. Experiments showed that UCART2 targets T-cell malignancies, including T-ALL and cutaneous T-cell lymphoma, in vitro.

The researchers also tested UCART2 in a mouse model of Sézary syndrome. In these experiments, UCART2 was combined with NT-I7.

NT-I7 enhanced the proliferation, persistence, and tumor killing ability of UCART2. Sézary mice that received UCART2 and NT-I7 had “virtually no tumor burden,” according to researchers, and survived longer than mice treated with UCART2 alone (Blood. 2018;132:340).

Dr. DiPersio noted that there was no cytokine release syndrome because these were immunodeficient mice. However, cytokine release syndrome may be a side effect of NT-I7 in patients as NT-I7 induces rapid expansion of CAR T cells.

Dr. DiPersio reported ownership and investment in WUGEN and Magenta Therapeutics. He also has relationships with Cellworks Group, Tioma Therapeutics, RiverVest Venture Partners, Bioline, Asterias Biotherapeutics, Amphivena Therapeutics, Bluebird Bio, Celgene, Incyte, NeoImuneTech, and MacroGenics.

The Acute Leukemia Forum is organized by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Preclinical research has revealed workarounds that may make chimeric antigen receptor (CAR) T-cell therapy feasible for patients with T-cell malignancies.

Researchers have found that using allogeneic cells for CAR T-cell therapy can eliminate contamination by malignant T cells, and editing those allogeneic T cells to delete the target antigen and the T-cell receptor alpha chain (TRAC) can prevent fratricide and graft-versus-host disease (GVHD).

Additionally, an interleukin-7 molecule called NT-I7 has been shown to enhance CAR T-cell proliferation, differentiation, and tumor killing in a mouse model of a T-cell malignancy.

John F. DiPersio, MD, PhD, of Washington University in St. Louis, described this work in a presentation at the Acute Leukemia Forum of Hemedicus.
 

Obstacles to development

“The primary obstacle for targeting T-cell malignancies with a T cell is that all of the targets that are on the [malignant] T cells are also expressed on the normal T cells,” Dr. DiPersio said. “So when you put a CAR into a normal T cell, it just kills itself. It’s called fratricide.”

A second issue that has limited development is that the phenotype of the malignant T cell in the blood is similar to a normal T cell, so they can’t be separated, he explained.

“So if you were to do anything to a normal T cell, you would also be doing it, in theory, to the malignant T cell – in theory, making it resistant to therapy,” he said.

A third obstacle, which has been seen in patients with B-cell malignancies as well, is the inability to harvest enough T cells to generate effective CAR T-cell therapy.

And a fourth obstacle is that T cells from patients with malignancies may not function normally because they have been exposed to prior therapies.

Dr. DiPersio and his colleagues believe these obstacles can be overcome by creating CAR T-cell therapies using T cells derived from healthy donors or cord blood, using gene editing to remove the target antigen and TRAC, and using NT-I7 to enhance the efficacy of these universal, “off-the-shelf” CAR T cells.

The researchers have tested these theories, and achieved successes, in preclinical models. The team is now planning a clinical trial in patients at Washington University. Dr. DiPersio and his colleagues also created a company called WUGEN that will develop the universal CAR T-cell therapies if the initial proof-of-principle trial proves successful.
 

UCART7

One of the universal CAR T-cell therapies Dr. DiPersio and his colleagues have tested is UCART7, which targets CD7. Dr. DiPersio noted that CD7 is expressed on 98% of T-cell acute lymphoblastic leukemias (T-ALLs), 24% of acute myeloid leukemias, natural killer (NK) cells, and T cells.

The researchers created UCART7 by using CRISPR/Cas9 to delete CD7 and TRAC from allogeneic T cells and following this with lentiviral transduction with a third-generation CD7-CAR. The team found a way to delete both TRAC and CD7 in a single day with 95% efficiency, Dr. DiPersio noted.

“Knocking out CD7 doesn’t seem to have any impact on the expansion or trafficking of these T cells in vivo,” Dr. DiPersio said. “So we think that deleting that target in a normal T cell will not affect its overall ability to kill a target when we put a CAR into those T cells.”

In fact, the researchers’ experiments showed that UCART7 can kill T-ALL cells in vitro and target primary T-ALL in vivo without inducing GVHD (Leukemia. 2018 Sep;32[9]:1970-83.)
 

UCART2 and NT-I7

Dr. DiPersio and his colleagues have also tested UCART2, an allogeneic CAR T-cell therapy in which CD2 and TRAC are deleted. The therapy targets CD2 because this antigen is expressed on T-ALL and other T-cell and NK-cell malignancies. Experiments showed that UCART2 targets T-cell malignancies, including T-ALL and cutaneous T-cell lymphoma, in vitro.

The researchers also tested UCART2 in a mouse model of Sézary syndrome. In these experiments, UCART2 was combined with NT-I7.

NT-I7 enhanced the proliferation, persistence, and tumor killing ability of UCART2. Sézary mice that received UCART2 and NT-I7 had “virtually no tumor burden,” according to researchers, and survived longer than mice treated with UCART2 alone (Blood. 2018;132:340).

Dr. DiPersio noted that there was no cytokine release syndrome because these were immunodeficient mice. However, cytokine release syndrome may be a side effect of NT-I7 in patients as NT-I7 induces rapid expansion of CAR T cells.

Dr. DiPersio reported ownership and investment in WUGEN and Magenta Therapeutics. He also has relationships with Cellworks Group, Tioma Therapeutics, RiverVest Venture Partners, Bioline, Asterias Biotherapeutics, Amphivena Therapeutics, Bluebird Bio, Celgene, Incyte, NeoImuneTech, and MacroGenics.

The Acute Leukemia Forum is organized by Hemedicus, which is owned by the same company as this news organization.

[email protected]

GENEVA – Liquid biopsy appears inadequate to detect molecular aberrations in patients with non–small cell lung cancer (NSCLC) who have isolated central nervous system (CNS) progression, according to investigators.

Will Pass/MDedge News

Plasma circulating tumor DNA (ctDNA) analysis detected molecular abnormalities in almost all patients with systemic disease progression, compared with just two out of five patients with isolated brain lesions, reported lead author Mihaela Aldea, MD, who presented findings at the European Lung Cancer Conference.

Dr. Aldea, of Gustave Roussy Institute in Villejuif, France, said that “central nervous system progression is an example of hard-to-biopsy disease and is common in oncogene addicted non–small cell lung cancer, making it a potential setting to employ ctDNA analysis.” However, Dr. Aldea noted that the blood-brain barrier limits passage of molecules such as ctDNA into systemic circulation, leading to hypothetical skepticism within the medical community, despite “very limited” data.

“Currently, the actual performance of ctDNA in patients with lung cancer and isolated CNS progression remains largely unknown,” Dr. Aldea said, “so this is the question that we put in our study.”

Dr. Aldea and her colleagues screened 959 patients with NSCLC who were involved in prospective trials at Gustave Roussy between 2016 and 2018. Study inclusion required that patients have a molecular alteration detected via tissue sample and at least 1 ctDNA sample available from the time of CNS progression. Molecular alterations included ALK, EGFR, KRAS, ROS1, HER2, BRAF, TP53, and MET. Through these criteria, the study population was narrowed to 58 patients and 66 ctDNA samples, of which 21 were from patients with isolated CNS (I-CNS) progression and 45 were from patients with systemic disease progression (S-CNS). CtDNA was conducted with next generation sequencing and compared with imaging, molecular, and clinical patient data.

Most patients in the I-CNS group were female (94%), compared with about half of the S-CNS group (59%). Rates of adenocarcinoma and smoking history were relatively similar between I-CNS and S-CNS patients; in contrast, S-CNS patients had a median of two metastatic sites, compared with one in the I-CNS group. Rates of ALK, KRAS, and EGFR aberrations were slightly higher in the I-CNS group, whereas HER2, TP53, MET, and BRAF abnormalities were found only in the S-CNS group. Relating to the central hypothesis, 98% of S-CNS patients tested positive for at least one actionable driver via ctDNA analysis, compared with just 38% of I-CNS patients (P less than .0001). Resistance mutations were detected more commonly in the S-CNS group, although not significantly, which Dr. Aldea attributed to small population size.

“Plasma liquid biopsy is not a reliable marker for analyzing the molecular landscape of CNS progression,” Dr. Aldea concluded, adding that patients with isolated brain lesions may need to be treated with “more potent drugs” even when resistance mutations are not detected.

The investigators disclosed financial relationships with Celgene, Daiichi Sankyo, Eli Lilly, and others.

SOURCE: Aldea et al. ELCC 2019. Abstract 110O.

GENEVA – Liquid biopsy appears inadequate to detect molecular aberrations in patients with non–small cell lung cancer (NSCLC) who have isolated central nervous system (CNS) progression, according to investigators.

Will Pass/MDedge News

Plasma circulating tumor DNA (ctDNA) analysis detected molecular abnormalities in almost all patients with systemic disease progression, compared with just two out of five patients with isolated brain lesions, reported lead author Mihaela Aldea, MD, who presented findings at the European Lung Cancer Conference.

Dr. Aldea, of Gustave Roussy Institute in Villejuif, France, said that “central nervous system progression is an example of hard-to-biopsy disease and is common in oncogene addicted non–small cell lung cancer, making it a potential setting to employ ctDNA analysis.” However, Dr. Aldea noted that the blood-brain barrier limits passage of molecules such as ctDNA into systemic circulation, leading to hypothetical skepticism within the medical community, despite “very limited” data.

“Currently, the actual performance of ctDNA in patients with lung cancer and isolated CNS progression remains largely unknown,” Dr. Aldea said, “so this is the question that we put in our study.”

Dr. Aldea and her colleagues screened 959 patients with NSCLC who were involved in prospective trials at Gustave Roussy between 2016 and 2018. Study inclusion required that patients have a molecular alteration detected via tissue sample and at least 1 ctDNA sample available from the time of CNS progression. Molecular alterations included ALK, EGFR, KRAS, ROS1, HER2, BRAF, TP53, and MET. Through these criteria, the study population was narrowed to 58 patients and 66 ctDNA samples, of which 21 were from patients with isolated CNS (I-CNS) progression and 45 were from patients with systemic disease progression (S-CNS). CtDNA was conducted with next generation sequencing and compared with imaging, molecular, and clinical patient data.

Most patients in the I-CNS group were female (94%), compared with about half of the S-CNS group (59%). Rates of adenocarcinoma and smoking history were relatively similar between I-CNS and S-CNS patients; in contrast, S-CNS patients had a median of two metastatic sites, compared with one in the I-CNS group. Rates of ALK, KRAS, and EGFR aberrations were slightly higher in the I-CNS group, whereas HER2, TP53, MET, and BRAF abnormalities were found only in the S-CNS group. Relating to the central hypothesis, 98% of S-CNS patients tested positive for at least one actionable driver via ctDNA analysis, compared with just 38% of I-CNS patients (P less than .0001). Resistance mutations were detected more commonly in the S-CNS group, although not significantly, which Dr. Aldea attributed to small population size.

“Plasma liquid biopsy is not a reliable marker for analyzing the molecular landscape of CNS progression,” Dr. Aldea concluded, adding that patients with isolated brain lesions may need to be treated with “more potent drugs” even when resistance mutations are not detected.

The investigators disclosed financial relationships with Celgene, Daiichi Sankyo, Eli Lilly, and others.

SOURCE: Aldea et al. ELCC 2019. Abstract 110O.

GENEVA – Liquid biopsy appears inadequate to detect molecular aberrations in patients with non–small cell lung cancer (NSCLC) who have isolated central nervous system (CNS) progression, according to investigators.

Will Pass/MDedge News

Plasma circulating tumor DNA (ctDNA) analysis detected molecular abnormalities in almost all patients with systemic disease progression, compared with just two out of five patients with isolated brain lesions, reported lead author Mihaela Aldea, MD, who presented findings at the European Lung Cancer Conference.

Dr. Aldea, of Gustave Roussy Institute in Villejuif, France, said that “central nervous system progression is an example of hard-to-biopsy disease and is common in oncogene addicted non–small cell lung cancer, making it a potential setting to employ ctDNA analysis.” However, Dr. Aldea noted that the blood-brain barrier limits passage of molecules such as ctDNA into systemic circulation, leading to hypothetical skepticism within the medical community, despite “very limited” data.

“Currently, the actual performance of ctDNA in patients with lung cancer and isolated CNS progression remains largely unknown,” Dr. Aldea said, “so this is the question that we put in our study.”

Dr. Aldea and her colleagues screened 959 patients with NSCLC who were involved in prospective trials at Gustave Roussy between 2016 and 2018. Study inclusion required that patients have a molecular alteration detected via tissue sample and at least 1 ctDNA sample available from the time of CNS progression. Molecular alterations included ALK, EGFR, KRAS, ROS1, HER2, BRAF, TP53, and MET. Through these criteria, the study population was narrowed to 58 patients and 66 ctDNA samples, of which 21 were from patients with isolated CNS (I-CNS) progression and 45 were from patients with systemic disease progression (S-CNS). CtDNA was conducted with next generation sequencing and compared with imaging, molecular, and clinical patient data.

Most patients in the I-CNS group were female (94%), compared with about half of the S-CNS group (59%). Rates of adenocarcinoma and smoking history were relatively similar between I-CNS and S-CNS patients; in contrast, S-CNS patients had a median of two metastatic sites, compared with one in the I-CNS group. Rates of ALK, KRAS, and EGFR aberrations were slightly higher in the I-CNS group, whereas HER2, TP53, MET, and BRAF abnormalities were found only in the S-CNS group. Relating to the central hypothesis, 98% of S-CNS patients tested positive for at least one actionable driver via ctDNA analysis, compared with just 38% of I-CNS patients (P less than .0001). Resistance mutations were detected more commonly in the S-CNS group, although not significantly, which Dr. Aldea attributed to small population size.

“Plasma liquid biopsy is not a reliable marker for analyzing the molecular landscape of CNS progression,” Dr. Aldea concluded, adding that patients with isolated brain lesions may need to be treated with “more potent drugs” even when resistance mutations are not detected.

The investigators disclosed financial relationships with Celgene, Daiichi Sankyo, Eli Lilly, and others.

SOURCE: Aldea et al. ELCC 2019. Abstract 110O.

In anticipation of a new antiabortion tilt on the Supreme Court bench, some states are moving to further restrict the procedure during the first trimester of pregnancy or to outlaw abortion entirely if Roe v. Wade ever falls. But the rush to regulate has exposed division among groups and lawmakers who consider themselves staunch abortion opponents.

On April 11, Ohio became the latest state to ban abortions after a fetal heartbeat can be detected. For a long time, Ohio Right to Life supported a more gradual approach to restrict the procedure and deemed what’s come to be called a “heartbeat bill” too radical – until this year. Restricting abortions after a fetal heartbeat can be detected basically bans the procedure after 6 weeks’ gestation – before many women know they’re pregnant.

“We see the court as being much more favorable to prolife legislation than it has been in a generation,” spokeswoman Jamieson Gordon said. “So we figured this would be a good time to pursue the heartbeat bill as the next step in our incremental approach to end abortion on demand.”

The Ohio law contains no exception for pregnancies that are the result of rape or incest; it does have an exception for the life of the mother.

Some say the rush to pass these bills is about lawmakers competing to get their particular state’s law before the Supreme Court. The state that helps overturn Roe v. Wade would go down in history.

More than 250 bills restricting abortions have been filed in 41 states this year, according to the Guttmacher Institute, a reproductive rights research and advocacy group.

“After the appointment of Justice [Brett] Kavanaugh, there really is just an environment in state legislatures to roll back abortion rights. And so we’re seeing these bans just fly through,” said Elizabeth Nash, who monitors state laws at Guttmacher.

But the speed of passage of some of these laws masks divisions about strategy and commitment to the cause within the antiabortion movement.

Tennessee infighting over ‘heartbeat bill’

In Tennessee, for instance, there’s a philosophical split between pragmatists and idealists.

A “heartbeat bill” in the state has had high-profile support, including from Tennessee’s new governor. But the Republican attorney general warned such a law would be difficult to defend in court. And several Republicans, swayed by that logic, voted no for the legislation.

“This is an issue that is extremely important to me. It’s the reason I got into politics many years ago,” Republican state Rep. Bill Dunn said as the House approved the measure over his objection earlier this year. Dunn has said he wants to stop abortion, but that will require strategy. He pointed out that no heartbeat bill has ever been enforced. And recent laws in Iowa and Kentucky have been immediately blocked in court. The same is expected for Ohio.

“No. 1, it’ll probably never save a life if we go by what’s happened in the past,” Rep. Dunn argued on the Tennessee House floor.

But it was money that ultimately stopped the heartbeat bill this year in Tennessee. (It stalled in committee, though the state’s Senate Judiciary Committee agreed to review the bill this summer.)

Senate Speaker Randy McNally, who also opposes abortion, said he has no interest in wasting tax dollars to make a point.

Even worse, in the view of Republicans who voted against the heartbeat bill, the state could end up paying the legal fees for groups that defend abortion.

“That is a big concern,” Sen. McNally said. “We don’t want to put money in their pockets.

The last time Tennessee had a case that went to the U.S. Supreme Court, it cost roughly $1.9 million. The experience was enough to give a few antiabortion crusaders some pause. They voted last week with Democrats for a 1-year delay on a heartbeat bill, vowing to study the issue over the summer.
 

Name-calling in Oklahoma

Even if it doesn’t result in a case that upends abortion law, heavily Republican legislatures like Oklahoma’s want to be ready.

“If Roe v. Wade ever gets overturned, we won’t be prepared,” Republican Senate Pro Tempore Greg Treat said while explaining his so-called trigger bill at a committee hearing in February.

Treat’s legislation, modeled after existing laws in a handful of states, would “trigger” a state ban on abortion and make it a felony if Roe were overturned. A handful of states, including Arkansas, Kentucky, Louisiana, Mississippi, North Dakota and South Dakota, already have trigger laws on the books.

Oklahoma has some of the strictest abortion laws in the nation, such as mandatory counseling and a 72-hour waiting period. But the most conservative antiabortion activists in the state want more immediate action. So they targeted Sen. Treat and other self-described “prolife” Republicans with protests, billboards and flyers, accusing them of not being antiabortion enough.

“I’ve been called every name in the book these past few weeks,” Sen. Treat said. “I’ve had my Christianity questioned. I’ve had a member of my own caucus hold a press conference and call me a hypocrite.”

In response, Sen. Treat abandoned the trigger bill.

Now he’s trying something else – an amendment to the state constitution that would reinforce that nothing in Oklahoma law “secures or protects” the right to abortion. But that’s still not antiabortion enough for some.

“It’s going to add on to that legacy that we have of death and just status quo prolife policy that does nothing,” said Republican state Sen. Joseph Silk.

Not far enough in Georgia

In Georgia, a “heartbeat bill” passed the legislature, but has paused at Republican Gov. Brian Kemp’s desk. Supporters of abortion rights don’t want him to sign it, of course, but some antiabortion activists aren’t happy either.

“It really just does not go far enough in the protection of innocent human life,” said Georgia Right to Life executive director Zemmie Fleck, who argued that certain exceptions in his state’s bill – for abortions after rape or incest if the woman makes a police report – weaken it.

Gov. Kemp has until May 12 to sign or veto the measure.

Cost-as-no-objection Kentucky

The American Civil Liberties Union in Kentucky sued the day after a “heartbeat bill” was signed into law by Republican Gov. Matt Bevin. But even during his annual speech to the Kentucky legislature in February, Gov. Bevin acknowledged his intent to challenge Roe v. Wade.

“Some of these will go all the way to the U.S. Supreme Court. But at the end of the day, we will prevail because we stand on the side of right and we stand on the side of life,” he said.

Kentucky has become accustomed to defending abortion restrictions in court. Currently, one law that makes it a felony for a doctor to perform a common abortion in the second trimester has been suspended indefinitely.

It is unclear how much it costs Kentucky to defend abortion laws that are immediately challenged. In an emailed statement, Gov. Bevin administration spokesman Woody Maglinger wrote that the state is using in-house lawyers, and hasn’t hired outside counsel. He declined to provide a cost estimate on hours spent on these cases.

“It is impossible to place a price tag on human lives,” Mr. Maglinger wrote.

This story is part of a partnership that includes Nashville Public Radio, NPR, and Kaiser Health News. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In anticipation of a new antiabortion tilt on the Supreme Court bench, some states are moving to further restrict the procedure during the first trimester of pregnancy or to outlaw abortion entirely if Roe v. Wade ever falls. But the rush to regulate has exposed division among groups and lawmakers who consider themselves staunch abortion opponents.

On April 11, Ohio became the latest state to ban abortions after a fetal heartbeat can be detected. For a long time, Ohio Right to Life supported a more gradual approach to restrict the procedure and deemed what’s come to be called a “heartbeat bill” too radical – until this year. Restricting abortions after a fetal heartbeat can be detected basically bans the procedure after 6 weeks’ gestation – before many women know they’re pregnant.

“We see the court as being much more favorable to prolife legislation than it has been in a generation,” spokeswoman Jamieson Gordon said. “So we figured this would be a good time to pursue the heartbeat bill as the next step in our incremental approach to end abortion on demand.”

The Ohio law contains no exception for pregnancies that are the result of rape or incest; it does have an exception for the life of the mother.

Some say the rush to pass these bills is about lawmakers competing to get their particular state’s law before the Supreme Court. The state that helps overturn Roe v. Wade would go down in history.

More than 250 bills restricting abortions have been filed in 41 states this year, according to the Guttmacher Institute, a reproductive rights research and advocacy group.

“After the appointment of Justice [Brett] Kavanaugh, there really is just an environment in state legislatures to roll back abortion rights. And so we’re seeing these bans just fly through,” said Elizabeth Nash, who monitors state laws at Guttmacher.

But the speed of passage of some of these laws masks divisions about strategy and commitment to the cause within the antiabortion movement.

Tennessee infighting over ‘heartbeat bill’

In Tennessee, for instance, there’s a philosophical split between pragmatists and idealists.

A “heartbeat bill” in the state has had high-profile support, including from Tennessee’s new governor. But the Republican attorney general warned such a law would be difficult to defend in court. And several Republicans, swayed by that logic, voted no for the legislation.

“This is an issue that is extremely important to me. It’s the reason I got into politics many years ago,” Republican state Rep. Bill Dunn said as the House approved the measure over his objection earlier this year. Dunn has said he wants to stop abortion, but that will require strategy. He pointed out that no heartbeat bill has ever been enforced. And recent laws in Iowa and Kentucky have been immediately blocked in court. The same is expected for Ohio.

“No. 1, it’ll probably never save a life if we go by what’s happened in the past,” Rep. Dunn argued on the Tennessee House floor.

But it was money that ultimately stopped the heartbeat bill this year in Tennessee. (It stalled in committee, though the state’s Senate Judiciary Committee agreed to review the bill this summer.)

Senate Speaker Randy McNally, who also opposes abortion, said he has no interest in wasting tax dollars to make a point.

Even worse, in the view of Republicans who voted against the heartbeat bill, the state could end up paying the legal fees for groups that defend abortion.

“That is a big concern,” Sen. McNally said. “We don’t want to put money in their pockets.

The last time Tennessee had a case that went to the U.S. Supreme Court, it cost roughly $1.9 million. The experience was enough to give a few antiabortion crusaders some pause. They voted last week with Democrats for a 1-year delay on a heartbeat bill, vowing to study the issue over the summer.
 

Name-calling in Oklahoma

Even if it doesn’t result in a case that upends abortion law, heavily Republican legislatures like Oklahoma’s want to be ready.

“If Roe v. Wade ever gets overturned, we won’t be prepared,” Republican Senate Pro Tempore Greg Treat said while explaining his so-called trigger bill at a committee hearing in February.

Treat’s legislation, modeled after existing laws in a handful of states, would “trigger” a state ban on abortion and make it a felony if Roe were overturned. A handful of states, including Arkansas, Kentucky, Louisiana, Mississippi, North Dakota and South Dakota, already have trigger laws on the books.

Oklahoma has some of the strictest abortion laws in the nation, such as mandatory counseling and a 72-hour waiting period. But the most conservative antiabortion activists in the state want more immediate action. So they targeted Sen. Treat and other self-described “prolife” Republicans with protests, billboards and flyers, accusing them of not being antiabortion enough.

“I’ve been called every name in the book these past few weeks,” Sen. Treat said. “I’ve had my Christianity questioned. I’ve had a member of my own caucus hold a press conference and call me a hypocrite.”

In response, Sen. Treat abandoned the trigger bill.

Now he’s trying something else – an amendment to the state constitution that would reinforce that nothing in Oklahoma law “secures or protects” the right to abortion. But that’s still not antiabortion enough for some.

“It’s going to add on to that legacy that we have of death and just status quo prolife policy that does nothing,” said Republican state Sen. Joseph Silk.

Not far enough in Georgia

In Georgia, a “heartbeat bill” passed the legislature, but has paused at Republican Gov. Brian Kemp’s desk. Supporters of abortion rights don’t want him to sign it, of course, but some antiabortion activists aren’t happy either.

“It really just does not go far enough in the protection of innocent human life,” said Georgia Right to Life executive director Zemmie Fleck, who argued that certain exceptions in his state’s bill – for abortions after rape or incest if the woman makes a police report – weaken it.

Gov. Kemp has until May 12 to sign or veto the measure.

Cost-as-no-objection Kentucky

The American Civil Liberties Union in Kentucky sued the day after a “heartbeat bill” was signed into law by Republican Gov. Matt Bevin. But even during his annual speech to the Kentucky legislature in February, Gov. Bevin acknowledged his intent to challenge Roe v. Wade.

“Some of these will go all the way to the U.S. Supreme Court. But at the end of the day, we will prevail because we stand on the side of right and we stand on the side of life,” he said.

Kentucky has become accustomed to defending abortion restrictions in court. Currently, one law that makes it a felony for a doctor to perform a common abortion in the second trimester has been suspended indefinitely.

It is unclear how much it costs Kentucky to defend abortion laws that are immediately challenged. In an emailed statement, Gov. Bevin administration spokesman Woody Maglinger wrote that the state is using in-house lawyers, and hasn’t hired outside counsel. He declined to provide a cost estimate on hours spent on these cases.

“It is impossible to place a price tag on human lives,” Mr. Maglinger wrote.

This story is part of a partnership that includes Nashville Public Radio, NPR, and Kaiser Health News. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In anticipation of a new antiabortion tilt on the Supreme Court bench, some states are moving to further restrict the procedure during the first trimester of pregnancy or to outlaw abortion entirely if Roe v. Wade ever falls. But the rush to regulate has exposed division among groups and lawmakers who consider themselves staunch abortion opponents.

On April 11, Ohio became the latest state to ban abortions after a fetal heartbeat can be detected. For a long time, Ohio Right to Life supported a more gradual approach to restrict the procedure and deemed what’s come to be called a “heartbeat bill” too radical – until this year. Restricting abortions after a fetal heartbeat can be detected basically bans the procedure after 6 weeks’ gestation – before many women know they’re pregnant.

“We see the court as being much more favorable to prolife legislation than it has been in a generation,” spokeswoman Jamieson Gordon said. “So we figured this would be a good time to pursue the heartbeat bill as the next step in our incremental approach to end abortion on demand.”

The Ohio law contains no exception for pregnancies that are the result of rape or incest; it does have an exception for the life of the mother.

Some say the rush to pass these bills is about lawmakers competing to get their particular state’s law before the Supreme Court. The state that helps overturn Roe v. Wade would go down in history.

More than 250 bills restricting abortions have been filed in 41 states this year, according to the Guttmacher Institute, a reproductive rights research and advocacy group.

“After the appointment of Justice [Brett] Kavanaugh, there really is just an environment in state legislatures to roll back abortion rights. And so we’re seeing these bans just fly through,” said Elizabeth Nash, who monitors state laws at Guttmacher.

But the speed of passage of some of these laws masks divisions about strategy and commitment to the cause within the antiabortion movement.

Tennessee infighting over ‘heartbeat bill’

In Tennessee, for instance, there’s a philosophical split between pragmatists and idealists.

A “heartbeat bill” in the state has had high-profile support, including from Tennessee’s new governor. But the Republican attorney general warned such a law would be difficult to defend in court. And several Republicans, swayed by that logic, voted no for the legislation.

“This is an issue that is extremely important to me. It’s the reason I got into politics many years ago,” Republican state Rep. Bill Dunn said as the House approved the measure over his objection earlier this year. Dunn has said he wants to stop abortion, but that will require strategy. He pointed out that no heartbeat bill has ever been enforced. And recent laws in Iowa and Kentucky have been immediately blocked in court. The same is expected for Ohio.

“No. 1, it’ll probably never save a life if we go by what’s happened in the past,” Rep. Dunn argued on the Tennessee House floor.

But it was money that ultimately stopped the heartbeat bill this year in Tennessee. (It stalled in committee, though the state’s Senate Judiciary Committee agreed to review the bill this summer.)

Senate Speaker Randy McNally, who also opposes abortion, said he has no interest in wasting tax dollars to make a point.

Even worse, in the view of Republicans who voted against the heartbeat bill, the state could end up paying the legal fees for groups that defend abortion.

“That is a big concern,” Sen. McNally said. “We don’t want to put money in their pockets.

The last time Tennessee had a case that went to the U.S. Supreme Court, it cost roughly $1.9 million. The experience was enough to give a few antiabortion crusaders some pause. They voted last week with Democrats for a 1-year delay on a heartbeat bill, vowing to study the issue over the summer.
 

Name-calling in Oklahoma

Even if it doesn’t result in a case that upends abortion law, heavily Republican legislatures like Oklahoma’s want to be ready.

“If Roe v. Wade ever gets overturned, we won’t be prepared,” Republican Senate Pro Tempore Greg Treat said while explaining his so-called trigger bill at a committee hearing in February.

Treat’s legislation, modeled after existing laws in a handful of states, would “trigger” a state ban on abortion and make it a felony if Roe were overturned. A handful of states, including Arkansas, Kentucky, Louisiana, Mississippi, North Dakota and South Dakota, already have trigger laws on the books.

Oklahoma has some of the strictest abortion laws in the nation, such as mandatory counseling and a 72-hour waiting period. But the most conservative antiabortion activists in the state want more immediate action. So they targeted Sen. Treat and other self-described “prolife” Republicans with protests, billboards and flyers, accusing them of not being antiabortion enough.

“I’ve been called every name in the book these past few weeks,” Sen. Treat said. “I’ve had my Christianity questioned. I’ve had a member of my own caucus hold a press conference and call me a hypocrite.”

In response, Sen. Treat abandoned the trigger bill.

Now he’s trying something else – an amendment to the state constitution that would reinforce that nothing in Oklahoma law “secures or protects” the right to abortion. But that’s still not antiabortion enough for some.

“It’s going to add on to that legacy that we have of death and just status quo prolife policy that does nothing,” said Republican state Sen. Joseph Silk.

Not far enough in Georgia

In Georgia, a “heartbeat bill” passed the legislature, but has paused at Republican Gov. Brian Kemp’s desk. Supporters of abortion rights don’t want him to sign it, of course, but some antiabortion activists aren’t happy either.

“It really just does not go far enough in the protection of innocent human life,” said Georgia Right to Life executive director Zemmie Fleck, who argued that certain exceptions in his state’s bill – for abortions after rape or incest if the woman makes a police report – weaken it.

Gov. Kemp has until May 12 to sign or veto the measure.

Cost-as-no-objection Kentucky

The American Civil Liberties Union in Kentucky sued the day after a “heartbeat bill” was signed into law by Republican Gov. Matt Bevin. But even during his annual speech to the Kentucky legislature in February, Gov. Bevin acknowledged his intent to challenge Roe v. Wade.

“Some of these will go all the way to the U.S. Supreme Court. But at the end of the day, we will prevail because we stand on the side of right and we stand on the side of life,” he said.

Kentucky has become accustomed to defending abortion restrictions in court. Currently, one law that makes it a felony for a doctor to perform a common abortion in the second trimester has been suspended indefinitely.

It is unclear how much it costs Kentucky to defend abortion laws that are immediately challenged. In an emailed statement, Gov. Bevin administration spokesman Woody Maglinger wrote that the state is using in-house lawyers, and hasn’t hired outside counsel. He declined to provide a cost estimate on hours spent on these cases.

“It is impossible to place a price tag on human lives,” Mr. Maglinger wrote.

This story is part of a partnership that includes Nashville Public Radio, NPR, and Kaiser Health News. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

SAN FRANCISCO – Long-term maintenance therapy with hydroxychloroquine initiated after patients with systemic lupus erythematosus (SLE) have discontinued immunosuppressant medication during remission greatly reduces their likelihood of disease flare, Margherita Zen, MD, reported at an international congress on systemic lupus erythematosus.

Dr. Zen, a rheumatologist at the University of Padova in Padua, Italy, presented a retrospective study of 319 SLE patients actively followed in the Padova Lupus Cohort. All of them were treated at some point with one or more immunosuppressants, most commonly mycophenolate, azathioprine, or methotrexate. Fifty-six percent of them never discontinued immunosuppressant therapy during long-term follow-up. Of the 139 patients who did, three-quarters of them were in remission at the time of discontinuation, while the remainder discontinued immunosuppressant medication because of intolerance or poor adherence.

The research question of greatest interest to Dr. Zen and her coinvestigators was whether withdrawal of immunosuppressant medication in lupus patients who have responded well and are in remission is a sound strategy or one fraught with an unacceptably high risk of flare.

“The benefits of drug tapering and discontinuation have been proven for glucocorticoids, but there is not enough evidence available for discontinuation of immunosuppressants,” she said.

The good news: 75% of patients who discontinued immunosuppressant therapy while in remission never experienced a flare during a mean 7.6 years of follow-up after discontinuation. And the median time to flare in those who did was 4.75 years. In contrast, more than two-thirds of patients who discontinued immunosuppressants while not in remission experienced an SLE flare, and the mean time to this event was a mere 8 months. In a Cox regression analysis, patients who discontinued their immunosuppressant medication because of intolerance or poor adherence were 6.9-fold more likely to flare during follow-up than were those who quit immunosuppressants while in remission.

Patients who’d been on methotrexate were significantly more likely to flare after discontinuing the drug than were those who’d been on other immunosuppressant medications. However, flare risk post immunosuppressants was unaffected by whether the medication was given for treatment of lupus nephritis, arthritis, neuropsychiatric involvement, vasculitis, hematologic manifestations of the disease, or skin involvement.

In a multivariate logistic regression analysis, by far the strongest independent protective factor against the occurrence of flare after immunosuppressant discontinuation was maintenance therapy with hydroxychloroquine; it was associated with a 76% reduction in flare risk. Put another way, patients not on maintenance antimalarial therapy after immunosuppressant discontinuation were at an adjusted 5.3-fold increased risk of flare. Combining hydroxychloroquine with low-dose prednisone didn’t provide any added benefit beyond the antimalarial alone in terms of protection against flares.

The other protective factor was duration of remission at the time of immunosuppressant discontinuation: the longer, the better. Patients who experienced a lupus flare had been in remission for an average of 28 months when they stopped taking their immunosuppressant medication. Those who remained flare free throughout follow-up had been in remission for an average of 46 months at discontinuation.

Reassuringly, median damage accrual as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was similar in patients regardless of whether or not they discontinued immunosuppressant therapy.

Dr. Zen reported having no financial conflicts regarding this study, conducted free of commercial support.

[email protected]

SAN FRANCISCO – Long-term maintenance therapy with hydroxychloroquine initiated after patients with systemic lupus erythematosus (SLE) have discontinued immunosuppressant medication during remission greatly reduces their likelihood of disease flare, Margherita Zen, MD, reported at an international congress on systemic lupus erythematosus.

Dr. Zen, a rheumatologist at the University of Padova in Padua, Italy, presented a retrospective study of 319 SLE patients actively followed in the Padova Lupus Cohort. All of them were treated at some point with one or more immunosuppressants, most commonly mycophenolate, azathioprine, or methotrexate. Fifty-six percent of them never discontinued immunosuppressant therapy during long-term follow-up. Of the 139 patients who did, three-quarters of them were in remission at the time of discontinuation, while the remainder discontinued immunosuppressant medication because of intolerance or poor adherence.

The research question of greatest interest to Dr. Zen and her coinvestigators was whether withdrawal of immunosuppressant medication in lupus patients who have responded well and are in remission is a sound strategy or one fraught with an unacceptably high risk of flare.

“The benefits of drug tapering and discontinuation have been proven for glucocorticoids, but there is not enough evidence available for discontinuation of immunosuppressants,” she said.

The good news: 75% of patients who discontinued immunosuppressant therapy while in remission never experienced a flare during a mean 7.6 years of follow-up after discontinuation. And the median time to flare in those who did was 4.75 years. In contrast, more than two-thirds of patients who discontinued immunosuppressants while not in remission experienced an SLE flare, and the mean time to this event was a mere 8 months. In a Cox regression analysis, patients who discontinued their immunosuppressant medication because of intolerance or poor adherence were 6.9-fold more likely to flare during follow-up than were those who quit immunosuppressants while in remission.

Patients who’d been on methotrexate were significantly more likely to flare after discontinuing the drug than were those who’d been on other immunosuppressant medications. However, flare risk post immunosuppressants was unaffected by whether the medication was given for treatment of lupus nephritis, arthritis, neuropsychiatric involvement, vasculitis, hematologic manifestations of the disease, or skin involvement.

In a multivariate logistic regression analysis, by far the strongest independent protective factor against the occurrence of flare after immunosuppressant discontinuation was maintenance therapy with hydroxychloroquine; it was associated with a 76% reduction in flare risk. Put another way, patients not on maintenance antimalarial therapy after immunosuppressant discontinuation were at an adjusted 5.3-fold increased risk of flare. Combining hydroxychloroquine with low-dose prednisone didn’t provide any added benefit beyond the antimalarial alone in terms of protection against flares.

The other protective factor was duration of remission at the time of immunosuppressant discontinuation: the longer, the better. Patients who experienced a lupus flare had been in remission for an average of 28 months when they stopped taking their immunosuppressant medication. Those who remained flare free throughout follow-up had been in remission for an average of 46 months at discontinuation.

Reassuringly, median damage accrual as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was similar in patients regardless of whether or not they discontinued immunosuppressant therapy.

Dr. Zen reported having no financial conflicts regarding this study, conducted free of commercial support.

[email protected]

SAN FRANCISCO – Long-term maintenance therapy with hydroxychloroquine initiated after patients with systemic lupus erythematosus (SLE) have discontinued immunosuppressant medication during remission greatly reduces their likelihood of disease flare, Margherita Zen, MD, reported at an international congress on systemic lupus erythematosus.

Dr. Zen, a rheumatologist at the University of Padova in Padua, Italy, presented a retrospective study of 319 SLE patients actively followed in the Padova Lupus Cohort. All of them were treated at some point with one or more immunosuppressants, most commonly mycophenolate, azathioprine, or methotrexate. Fifty-six percent of them never discontinued immunosuppressant therapy during long-term follow-up. Of the 139 patients who did, three-quarters of them were in remission at the time of discontinuation, while the remainder discontinued immunosuppressant medication because of intolerance or poor adherence.

The research question of greatest interest to Dr. Zen and her coinvestigators was whether withdrawal of immunosuppressant medication in lupus patients who have responded well and are in remission is a sound strategy or one fraught with an unacceptably high risk of flare.

“The benefits of drug tapering and discontinuation have been proven for glucocorticoids, but there is not enough evidence available for discontinuation of immunosuppressants,” she said.

The good news: 75% of patients who discontinued immunosuppressant therapy while in remission never experienced a flare during a mean 7.6 years of follow-up after discontinuation. And the median time to flare in those who did was 4.75 years. In contrast, more than two-thirds of patients who discontinued immunosuppressants while not in remission experienced an SLE flare, and the mean time to this event was a mere 8 months. In a Cox regression analysis, patients who discontinued their immunosuppressant medication because of intolerance or poor adherence were 6.9-fold more likely to flare during follow-up than were those who quit immunosuppressants while in remission.

Patients who’d been on methotrexate were significantly more likely to flare after discontinuing the drug than were those who’d been on other immunosuppressant medications. However, flare risk post immunosuppressants was unaffected by whether the medication was given for treatment of lupus nephritis, arthritis, neuropsychiatric involvement, vasculitis, hematologic manifestations of the disease, or skin involvement.

In a multivariate logistic regression analysis, by far the strongest independent protective factor against the occurrence of flare after immunosuppressant discontinuation was maintenance therapy with hydroxychloroquine; it was associated with a 76% reduction in flare risk. Put another way, patients not on maintenance antimalarial therapy after immunosuppressant discontinuation were at an adjusted 5.3-fold increased risk of flare. Combining hydroxychloroquine with low-dose prednisone didn’t provide any added benefit beyond the antimalarial alone in terms of protection against flares.

The other protective factor was duration of remission at the time of immunosuppressant discontinuation: the longer, the better. Patients who experienced a lupus flare had been in remission for an average of 28 months when they stopped taking their immunosuppressant medication. Those who remained flare free throughout follow-up had been in remission for an average of 46 months at discontinuation.

Reassuringly, median damage accrual as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was similar in patients regardless of whether or not they discontinued immunosuppressant therapy.

Dr. Zen reported having no financial conflicts regarding this study, conducted free of commercial support.

[email protected]

ATLANTA – Intrapleurally administered, mesothelin-targeted chimeric antigen receptor (CAR) T cells combined with programmed death 1 (PD-1) inhibition showed CAR T-cell antitumor activity without toxicity in a phase 1 clinical trial of patients with malignant pleural disease.

The findings are encouraging, particularly given the aggressive nature of such tumors and the poor prognosis associated with mesothelin – a cell-surface antigen expressed on them, Prasad S. Adusumilli, MD, reported during a press briefing at the annual meeting of the American Association for Cancer Research.

In 21 patients, including 19 with malignant pleural mesothelioma and 1 each with metastatic lung cancer and metastatic breast cancer, a single dose of a second-generation, CD28-costimulated mesothelin CAR T-cell therapy (iCasM28z) was administered intrapleurally either with or without cyclophosphamide preconditioning.

Antitumor activity, as evidenced by the presence of CAR T cells in the blood for several months, was noted in 13 patients, and the presence of the cells was associated with a reduction in a mesothelin-related peptide in the blood, as well as with evidence of tumor regression on imaging studies, said Dr. Adusumilli, deputy chief of the thoracic service at Memorial Sloan Kettering Cancer Center, New York, and lead study author.


Intense clinical, laboratory, and radiological monitoring along with electrocardiography showed no evidence of toxicity.

“Most importantly, the neurotoxicity, serious cytokine release syndrome, and on-target off-target tumor toxicity that has been seen in other CAR T-cell trials, we did not notice in our trial,” he said.

Additionally, one patient successfully underwent curative-intent surgical resection 6 weeks after CAR T-cell infusion, followed by radiation therapy to the chest, said Dr. Adusumilli, who also is director of the mesothelioma program and head of solid tumor cell therapy at the at Memorial Sloan Kettering Cellular Therapeutic Center.

That patient is doing well at 20 months without further treatment, he noted.

Of a subset of 14 patients who received off-protocol anti-PD-1 checkpoint blockade once lack of toxicity was established for the CAR T-cell therapy, 2 achieved a complete metabolic response at 38 and 60 weeks following checkpoint blockade, 5 had a partial response, and 4 had stable disease.

The anti-PD-1 therapy was initiated in those patients based on prior preclinical data, showing that CAR T cells can become functionally exhausted in large tumors and that anti-PD-1 therapy can reactivate the exhausted cells and eradicate the tumors, he explained.

The findings are notable because malignant pleural disease from primary malignant pleural mesothelioma or secondary metastatic disease affects more than 150,000 patients a year in the United States alone, and effective therapies are lacking.

“[Our finding] strongly supports pursuing a CAR T-cell therapy combined with anti-PD-1 strategies is in solid tumors,” Dr. Adusumilli said, adding that such a trial is being planned for 2019, and another, with CAR T-cell intrinsic PD-1 dominant negative receptor (a decoy receptor) is planned for 2020.

Press briefing moderator Nilofer S. Azad, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said the findings represent “potentially the most compelling CAR T data that we’ve ever seen in solid tumors at this point,” and noted that a “vast number of patients” could potentially benefit from the approach.

Dr. Adusumilli agreed, suggesting that, with a system of regional factories and distribution centers and development of “some clever strategies,” it is possible the technology and treatment approach could be scaled up to the level necessary to help increasing numbers of patients.

Dr. Adusumilli reported receiving federal grant support from the National Cancer Institute and Department of Defense; peer-reviewed grant support from the Mesothelioma Applied Research Foundation, Experimental Therapeutics Center, Baker Street Foundation, Batishwa Fellowship, Dallepezze Foundation, Derfner Foundation, Emerson Collective Foundation, and MSK Technology Development Fund; and research grant support from OSE Immunotherapeutics, ACEA Biosciences, and Atara Biotherapeutics. He also has a licensing/royalty agreement for Mesothelin CAR and PD-1 DNR (licensed to Atara Biotherapeutics).

[email protected]

SOURCE: Adusumilli PS et al. AACR 2019, Abstract CT036.

ATLANTA – Intrapleurally administered, mesothelin-targeted chimeric antigen receptor (CAR) T cells combined with programmed death 1 (PD-1) inhibition showed CAR T-cell antitumor activity without toxicity in a phase 1 clinical trial of patients with malignant pleural disease.

The findings are encouraging, particularly given the aggressive nature of such tumors and the poor prognosis associated with mesothelin – a cell-surface antigen expressed on them, Prasad S. Adusumilli, MD, reported during a press briefing at the annual meeting of the American Association for Cancer Research.

In 21 patients, including 19 with malignant pleural mesothelioma and 1 each with metastatic lung cancer and metastatic breast cancer, a single dose of a second-generation, CD28-costimulated mesothelin CAR T-cell therapy (iCasM28z) was administered intrapleurally either with or without cyclophosphamide preconditioning.

Antitumor activity, as evidenced by the presence of CAR T cells in the blood for several months, was noted in 13 patients, and the presence of the cells was associated with a reduction in a mesothelin-related peptide in the blood, as well as with evidence of tumor regression on imaging studies, said Dr. Adusumilli, deputy chief of the thoracic service at Memorial Sloan Kettering Cancer Center, New York, and lead study author.


Intense clinical, laboratory, and radiological monitoring along with electrocardiography showed no evidence of toxicity.

“Most importantly, the neurotoxicity, serious cytokine release syndrome, and on-target off-target tumor toxicity that has been seen in other CAR T-cell trials, we did not notice in our trial,” he said.

Additionally, one patient successfully underwent curative-intent surgical resection 6 weeks after CAR T-cell infusion, followed by radiation therapy to the chest, said Dr. Adusumilli, who also is director of the mesothelioma program and head of solid tumor cell therapy at the at Memorial Sloan Kettering Cellular Therapeutic Center.

That patient is doing well at 20 months without further treatment, he noted.

Of a subset of 14 patients who received off-protocol anti-PD-1 checkpoint blockade once lack of toxicity was established for the CAR T-cell therapy, 2 achieved a complete metabolic response at 38 and 60 weeks following checkpoint blockade, 5 had a partial response, and 4 had stable disease.

The anti-PD-1 therapy was initiated in those patients based on prior preclinical data, showing that CAR T cells can become functionally exhausted in large tumors and that anti-PD-1 therapy can reactivate the exhausted cells and eradicate the tumors, he explained.

The findings are notable because malignant pleural disease from primary malignant pleural mesothelioma or secondary metastatic disease affects more than 150,000 patients a year in the United States alone, and effective therapies are lacking.

“[Our finding] strongly supports pursuing a CAR T-cell therapy combined with anti-PD-1 strategies is in solid tumors,” Dr. Adusumilli said, adding that such a trial is being planned for 2019, and another, with CAR T-cell intrinsic PD-1 dominant negative receptor (a decoy receptor) is planned for 2020.

Press briefing moderator Nilofer S. Azad, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said the findings represent “potentially the most compelling CAR T data that we’ve ever seen in solid tumors at this point,” and noted that a “vast number of patients” could potentially benefit from the approach.

Dr. Adusumilli agreed, suggesting that, with a system of regional factories and distribution centers and development of “some clever strategies,” it is possible the technology and treatment approach could be scaled up to the level necessary to help increasing numbers of patients.

Dr. Adusumilli reported receiving federal grant support from the National Cancer Institute and Department of Defense; peer-reviewed grant support from the Mesothelioma Applied Research Foundation, Experimental Therapeutics Center, Baker Street Foundation, Batishwa Fellowship, Dallepezze Foundation, Derfner Foundation, Emerson Collective Foundation, and MSK Technology Development Fund; and research grant support from OSE Immunotherapeutics, ACEA Biosciences, and Atara Biotherapeutics. He also has a licensing/royalty agreement for Mesothelin CAR and PD-1 DNR (licensed to Atara Biotherapeutics).

[email protected]

SOURCE: Adusumilli PS et al. AACR 2019, Abstract CT036.

ATLANTA – Intrapleurally administered, mesothelin-targeted chimeric antigen receptor (CAR) T cells combined with programmed death 1 (PD-1) inhibition showed CAR T-cell antitumor activity without toxicity in a phase 1 clinical trial of patients with malignant pleural disease.

The findings are encouraging, particularly given the aggressive nature of such tumors and the poor prognosis associated with mesothelin – a cell-surface antigen expressed on them, Prasad S. Adusumilli, MD, reported during a press briefing at the annual meeting of the American Association for Cancer Research.

In 21 patients, including 19 with malignant pleural mesothelioma and 1 each with metastatic lung cancer and metastatic breast cancer, a single dose of a second-generation, CD28-costimulated mesothelin CAR T-cell therapy (iCasM28z) was administered intrapleurally either with or without cyclophosphamide preconditioning.

Antitumor activity, as evidenced by the presence of CAR T cells in the blood for several months, was noted in 13 patients, and the presence of the cells was associated with a reduction in a mesothelin-related peptide in the blood, as well as with evidence of tumor regression on imaging studies, said Dr. Adusumilli, deputy chief of the thoracic service at Memorial Sloan Kettering Cancer Center, New York, and lead study author.


Intense clinical, laboratory, and radiological monitoring along with electrocardiography showed no evidence of toxicity.

“Most importantly, the neurotoxicity, serious cytokine release syndrome, and on-target off-target tumor toxicity that has been seen in other CAR T-cell trials, we did not notice in our trial,” he said.

Additionally, one patient successfully underwent curative-intent surgical resection 6 weeks after CAR T-cell infusion, followed by radiation therapy to the chest, said Dr. Adusumilli, who also is director of the mesothelioma program and head of solid tumor cell therapy at the at Memorial Sloan Kettering Cellular Therapeutic Center.

That patient is doing well at 20 months without further treatment, he noted.

Of a subset of 14 patients who received off-protocol anti-PD-1 checkpoint blockade once lack of toxicity was established for the CAR T-cell therapy, 2 achieved a complete metabolic response at 38 and 60 weeks following checkpoint blockade, 5 had a partial response, and 4 had stable disease.

The anti-PD-1 therapy was initiated in those patients based on prior preclinical data, showing that CAR T cells can become functionally exhausted in large tumors and that anti-PD-1 therapy can reactivate the exhausted cells and eradicate the tumors, he explained.

The findings are notable because malignant pleural disease from primary malignant pleural mesothelioma or secondary metastatic disease affects more than 150,000 patients a year in the United States alone, and effective therapies are lacking.

“[Our finding] strongly supports pursuing a CAR T-cell therapy combined with anti-PD-1 strategies is in solid tumors,” Dr. Adusumilli said, adding that such a trial is being planned for 2019, and another, with CAR T-cell intrinsic PD-1 dominant negative receptor (a decoy receptor) is planned for 2020.

Press briefing moderator Nilofer S. Azad, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, said the findings represent “potentially the most compelling CAR T data that we’ve ever seen in solid tumors at this point,” and noted that a “vast number of patients” could potentially benefit from the approach.

Dr. Adusumilli agreed, suggesting that, with a system of regional factories and distribution centers and development of “some clever strategies,” it is possible the technology and treatment approach could be scaled up to the level necessary to help increasing numbers of patients.

Dr. Adusumilli reported receiving federal grant support from the National Cancer Institute and Department of Defense; peer-reviewed grant support from the Mesothelioma Applied Research Foundation, Experimental Therapeutics Center, Baker Street Foundation, Batishwa Fellowship, Dallepezze Foundation, Derfner Foundation, Emerson Collective Foundation, and MSK Technology Development Fund; and research grant support from OSE Immunotherapeutics, ACEA Biosciences, and Atara Biotherapeutics. He also has a licensing/royalty agreement for Mesothelin CAR and PD-1 DNR (licensed to Atara Biotherapeutics).

[email protected]

SOURCE: Adusumilli PS et al. AACR 2019, Abstract CT036.

PHILADELPHIA – There are real concerns about whether today’s direct-to-consumer (DTC) genetic tests actually test the mutations they claim to test and of how well a tested DNA sequence tracks actual disease, Andrew D. Coyle, MD, said during a podium presentation at the annual meeting of the American College of Physicians.

Many patients don’t tell their doctors the results of DTC tests, and there’s a lot of potential for misinterpretation all around, said Dr. Coyle, assistant professor of medicine and medical education in the general internal medicine division at the Icahn School of Medicine at Mount Sinai, New York.

“I wouldn’t recommend to patients that they do [DTC testing], if they asked,” he said. “I think we probably do need to be better about asking our patients whether they’re doing this on their own, to make sure that we help them interpret it correctly, that it’s a change in risk – not a diagnosis, and not an assurance they won’t get that disease process.”

High false-positive rates have been seen in recent studies that sought to confirm genotyping data from DTC genetic test results, according to Dr. Coyle. In one 2018 study in Genetics and Medicine (2018;20:1515-21) of 49 patient samples tested for previously identified genetic variants found in raw DTC data, investigators found a 40% false positive rate, which they said underscored the importance of clinical confirmation testing to assure proper patient care, he noted.

To support his claim that many patients aren’t even telling their doctors about the DTC testing they are having done in the first place, Dr. Coyle mentioned results of a survey in Annals of Internal Medicine (2016;164[8]:513-22), which showed that only 19% of patients shared their DTC results with their primary care physicians.

He also pointed out a potential problem regarding the discussions between patients and their physicians about these test results, based on another finding reported in the paper. Of those who did tell their physicians they had DTC testing, 35% said they were “very satisfied” with how that discussion went, Dr. Coyle said.

“So they don’t tell us, and they aren’t very happy when they do tell us,” he told his audience.
 

The 23andMe test and the FDA

The 23andMe test, which was first directly marketed to consumers in 2006, was one of the DTC genetic tests discussed by Dr. Coyle. The Food and Drug Administration later halted the company’s Personal Genome Service in 2013 because of a lack of demonstrated clinical validity, Dr. Coyle noted.

Subsequently, the FDA classified carrier-screening tests as medical devices, allowing such services to come back, leading to what Dr. Coyle described as an explosion over the past few years of DTC evaluation of a variety of conditions, including celiac disease, Alzheimer’s disease, hemochromatosis, and then more recently, screening for cancer risk factors.

In 2018, 23andMe began offering DTC BRCA testing, but for 3 BRCA1/2 mutations seen in individuals of Ashkenazi Jewish descent, Dr. Coyle said.

“If someone did a BRCA test which is only testing three specific mutations seen mostly in Ashkenazi Jewish populations, they may be falsely reassured that the risk of breast cancer is low, when in fact they may have other BRCA mutations,” he said.

In real life, however, many people who order genetic tests online may not even act on the results. In a 2017 study in the Journal of Clinical Oncology, customers whose DTC genetic testing results showed elevated cancer risk were no more likely than were customers without elevated risk to change diet or exercise, engage in advanced planning behaviors, or get screened.

Dr. Coyle had no relevant disclosures to report.

PHILADELPHIA – There are real concerns about whether today’s direct-to-consumer (DTC) genetic tests actually test the mutations they claim to test and of how well a tested DNA sequence tracks actual disease, Andrew D. Coyle, MD, said during a podium presentation at the annual meeting of the American College of Physicians.

Many patients don’t tell their doctors the results of DTC tests, and there’s a lot of potential for misinterpretation all around, said Dr. Coyle, assistant professor of medicine and medical education in the general internal medicine division at the Icahn School of Medicine at Mount Sinai, New York.

“I wouldn’t recommend to patients that they do [DTC testing], if they asked,” he said. “I think we probably do need to be better about asking our patients whether they’re doing this on their own, to make sure that we help them interpret it correctly, that it’s a change in risk – not a diagnosis, and not an assurance they won’t get that disease process.”

High false-positive rates have been seen in recent studies that sought to confirm genotyping data from DTC genetic test results, according to Dr. Coyle. In one 2018 study in Genetics and Medicine (2018;20:1515-21) of 49 patient samples tested for previously identified genetic variants found in raw DTC data, investigators found a 40% false positive rate, which they said underscored the importance of clinical confirmation testing to assure proper patient care, he noted.

To support his claim that many patients aren’t even telling their doctors about the DTC testing they are having done in the first place, Dr. Coyle mentioned results of a survey in Annals of Internal Medicine (2016;164[8]:513-22), which showed that only 19% of patients shared their DTC results with their primary care physicians.

He also pointed out a potential problem regarding the discussions between patients and their physicians about these test results, based on another finding reported in the paper. Of those who did tell their physicians they had DTC testing, 35% said they were “very satisfied” with how that discussion went, Dr. Coyle said.

“So they don’t tell us, and they aren’t very happy when they do tell us,” he told his audience.
 

The 23andMe test and the FDA

The 23andMe test, which was first directly marketed to consumers in 2006, was one of the DTC genetic tests discussed by Dr. Coyle. The Food and Drug Administration later halted the company’s Personal Genome Service in 2013 because of a lack of demonstrated clinical validity, Dr. Coyle noted.

Subsequently, the FDA classified carrier-screening tests as medical devices, allowing such services to come back, leading to what Dr. Coyle described as an explosion over the past few years of DTC evaluation of a variety of conditions, including celiac disease, Alzheimer’s disease, hemochromatosis, and then more recently, screening for cancer risk factors.

In 2018, 23andMe began offering DTC BRCA testing, but for 3 BRCA1/2 mutations seen in individuals of Ashkenazi Jewish descent, Dr. Coyle said.

“If someone did a BRCA test which is only testing three specific mutations seen mostly in Ashkenazi Jewish populations, they may be falsely reassured that the risk of breast cancer is low, when in fact they may have other BRCA mutations,” he said.

In real life, however, many people who order genetic tests online may not even act on the results. In a 2017 study in the Journal of Clinical Oncology, customers whose DTC genetic testing results showed elevated cancer risk were no more likely than were customers without elevated risk to change diet or exercise, engage in advanced planning behaviors, or get screened.

Dr. Coyle had no relevant disclosures to report.

PHILADELPHIA – There are real concerns about whether today’s direct-to-consumer (DTC) genetic tests actually test the mutations they claim to test and of how well a tested DNA sequence tracks actual disease, Andrew D. Coyle, MD, said during a podium presentation at the annual meeting of the American College of Physicians.

Many patients don’t tell their doctors the results of DTC tests, and there’s a lot of potential for misinterpretation all around, said Dr. Coyle, assistant professor of medicine and medical education in the general internal medicine division at the Icahn School of Medicine at Mount Sinai, New York.

“I wouldn’t recommend to patients that they do [DTC testing], if they asked,” he said. “I think we probably do need to be better about asking our patients whether they’re doing this on their own, to make sure that we help them interpret it correctly, that it’s a change in risk – not a diagnosis, and not an assurance they won’t get that disease process.”

High false-positive rates have been seen in recent studies that sought to confirm genotyping data from DTC genetic test results, according to Dr. Coyle. In one 2018 study in Genetics and Medicine (2018;20:1515-21) of 49 patient samples tested for previously identified genetic variants found in raw DTC data, investigators found a 40% false positive rate, which they said underscored the importance of clinical confirmation testing to assure proper patient care, he noted.

To support his claim that many patients aren’t even telling their doctors about the DTC testing they are having done in the first place, Dr. Coyle mentioned results of a survey in Annals of Internal Medicine (2016;164[8]:513-22), which showed that only 19% of patients shared their DTC results with their primary care physicians.

He also pointed out a potential problem regarding the discussions between patients and their physicians about these test results, based on another finding reported in the paper. Of those who did tell their physicians they had DTC testing, 35% said they were “very satisfied” with how that discussion went, Dr. Coyle said.

“So they don’t tell us, and they aren’t very happy when they do tell us,” he told his audience.
 

The 23andMe test and the FDA

The 23andMe test, which was first directly marketed to consumers in 2006, was one of the DTC genetic tests discussed by Dr. Coyle. The Food and Drug Administration later halted the company’s Personal Genome Service in 2013 because of a lack of demonstrated clinical validity, Dr. Coyle noted.

Subsequently, the FDA classified carrier-screening tests as medical devices, allowing such services to come back, leading to what Dr. Coyle described as an explosion over the past few years of DTC evaluation of a variety of conditions, including celiac disease, Alzheimer’s disease, hemochromatosis, and then more recently, screening for cancer risk factors.

In 2018, 23andMe began offering DTC BRCA testing, but for 3 BRCA1/2 mutations seen in individuals of Ashkenazi Jewish descent, Dr. Coyle said.

“If someone did a BRCA test which is only testing three specific mutations seen mostly in Ashkenazi Jewish populations, they may be falsely reassured that the risk of breast cancer is low, when in fact they may have other BRCA mutations,” he said.

In real life, however, many people who order genetic tests online may not even act on the results. In a 2017 study in the Journal of Clinical Oncology, customers whose DTC genetic testing results showed elevated cancer risk were no more likely than were customers without elevated risk to change diet or exercise, engage in advanced planning behaviors, or get screened.

Dr. Coyle had no relevant disclosures to report.

ORLANDO – New ways of assessing and measuring the way the sense of self becomes distorted in patients with schizophrenia patients and those at risk of developing the disease are deepening understanding of the disorder, an expert said at annual congress of the Schizophrenia International Research Society.

Sohee Park, PhD, Gertrude Conaway Vanderbilt Professor of Psychology at Vanderbilt University, Nashville, Tenn., said a unified and continuous sense of self is essential to leading a functional life. But this sense of self is a complex assemblage, made up of explicit experiences and actions, a more internal awareness of our own body, as well as a “social, narrative self” involving our social identity and history. This coherent and continuous sense of self is formulated and tied together by working memory and by our ability to form expectations or predictions about what might happen next, Dr. Park said.

In schizophrenia, the sense of self becomes fragmented as these predictions – on issues such as how sensory input is perceived – break down.

Dr. Park said a more comprehensive approach is needed in understanding this breakdown if clinicians can be expected to help people with schizophrenia.

“Connection between biological disorder and personal illness experience is not really well articulated in our field,” she said. “But it’s a connection we must make if we are to understand this condition and to develop treatments and interventions that make sense and are meaningful to the person who experiences psychosis.”

With her colleagues, Dr. Park has developed a way to better measure these bodily “self-disturbances” that patients with schizophrenia experience, and how they persist over time. B-BODI – the Benson et al. Body Disturbances Inventory – is a kind of catalog of pictures representing experiences of self-disturbance, such as someone having an out-of-body experience or a person who feels her body parts changing. The pictures come with written statements, and are designed to elicit more information from the patients about their experiences, such as how vivid, disturbing, and frequent they are.

Researchers have found that these experiences of body and self-disturbances are correlated with the positive symptoms of schizophrenia – such as hallucinations and confused thoughts – as well as with loneliness. But those experiences are not correlated with negative symptoms, such as loss of ability to feel pleasure.

B-BODI scores tend to be elevated in young people who are at high risk, so the tool could be used to help with earlier identification and treatment, and the use of pictures could help patients better convey what they’re experiencing, Dr. Park said.

“Self-disturbances are difficult to verbalize,” she said. B-BODI can help verbalize these strange experiences that are hard to describe – especially in those who have difficulty communicating.

She and her colleagues have found that those at risk of schizophrenia have a more “flexible body boundary” than do those not at risk. They performed an assessment of the degree to which subjects experienced the “Pinocchio illusion,” in which subjects are blindfolded, touch their noses, and have their biceps stimulated to create the sensation that their arm is moving away from the nose – which is interpreted as the nose growing longer. They found that subjects who scored higher on the Prodromal Questionnaire Brief – an assessment of schizophrenia risk – had higher Pinocchio illusion scores.

These abnormalities in self-perception all feed into the difficulty with which people with schizophrenia have in interacting with others. To address this difficulty, her group has developed a virtual reality training program to help patients with these interactions.

In the program, the user is asked to choose an avatar to interact with by looking at the face of the avatar for a few seconds. Once chosen, the face of the avatar is fully revealed and a conversation takes place. Then the participant receives feedback. Negative symptoms of schizophrenia were significantly reduced after participation after just 10 sessions, Dr. Park said. The program has received favorable reviews from patients – one described the avatars as “very friendly” – and holds promise for helping schizophrenia patients with social situations.

“Virtual reality,” she said, “offers the ideal rehearsal space.”

This work was supported by the National Institute of Mental Health and NARSAD, formerly known as the National Alliance for Research on Schizophrenia and Depression. Dr. Park reported no financial disclosures.

ORLANDO – New ways of assessing and measuring the way the sense of self becomes distorted in patients with schizophrenia patients and those at risk of developing the disease are deepening understanding of the disorder, an expert said at annual congress of the Schizophrenia International Research Society.

Sohee Park, PhD, Gertrude Conaway Vanderbilt Professor of Psychology at Vanderbilt University, Nashville, Tenn., said a unified and continuous sense of self is essential to leading a functional life. But this sense of self is a complex assemblage, made up of explicit experiences and actions, a more internal awareness of our own body, as well as a “social, narrative self” involving our social identity and history. This coherent and continuous sense of self is formulated and tied together by working memory and by our ability to form expectations or predictions about what might happen next, Dr. Park said.

In schizophrenia, the sense of self becomes fragmented as these predictions – on issues such as how sensory input is perceived – break down.

Dr. Park said a more comprehensive approach is needed in understanding this breakdown if clinicians can be expected to help people with schizophrenia.

“Connection between biological disorder and personal illness experience is not really well articulated in our field,” she said. “But it’s a connection we must make if we are to understand this condition and to develop treatments and interventions that make sense and are meaningful to the person who experiences psychosis.”

With her colleagues, Dr. Park has developed a way to better measure these bodily “self-disturbances” that patients with schizophrenia experience, and how they persist over time. B-BODI – the Benson et al. Body Disturbances Inventory – is a kind of catalog of pictures representing experiences of self-disturbance, such as someone having an out-of-body experience or a person who feels her body parts changing. The pictures come with written statements, and are designed to elicit more information from the patients about their experiences, such as how vivid, disturbing, and frequent they are.

Researchers have found that these experiences of body and self-disturbances are correlated with the positive symptoms of schizophrenia – such as hallucinations and confused thoughts – as well as with loneliness. But those experiences are not correlated with negative symptoms, such as loss of ability to feel pleasure.

B-BODI scores tend to be elevated in young people who are at high risk, so the tool could be used to help with earlier identification and treatment, and the use of pictures could help patients better convey what they’re experiencing, Dr. Park said.

“Self-disturbances are difficult to verbalize,” she said. B-BODI can help verbalize these strange experiences that are hard to describe – especially in those who have difficulty communicating.

She and her colleagues have found that those at risk of schizophrenia have a more “flexible body boundary” than do those not at risk. They performed an assessment of the degree to which subjects experienced the “Pinocchio illusion,” in which subjects are blindfolded, touch their noses, and have their biceps stimulated to create the sensation that their arm is moving away from the nose – which is interpreted as the nose growing longer. They found that subjects who scored higher on the Prodromal Questionnaire Brief – an assessment of schizophrenia risk – had higher Pinocchio illusion scores.

These abnormalities in self-perception all feed into the difficulty with which people with schizophrenia have in interacting with others. To address this difficulty, her group has developed a virtual reality training program to help patients with these interactions.

In the program, the user is asked to choose an avatar to interact with by looking at the face of the avatar for a few seconds. Once chosen, the face of the avatar is fully revealed and a conversation takes place. Then the participant receives feedback. Negative symptoms of schizophrenia were significantly reduced after participation after just 10 sessions, Dr. Park said. The program has received favorable reviews from patients – one described the avatars as “very friendly” – and holds promise for helping schizophrenia patients with social situations.

“Virtual reality,” she said, “offers the ideal rehearsal space.”

This work was supported by the National Institute of Mental Health and NARSAD, formerly known as the National Alliance for Research on Schizophrenia and Depression. Dr. Park reported no financial disclosures.

ORLANDO – New ways of assessing and measuring the way the sense of self becomes distorted in patients with schizophrenia patients and those at risk of developing the disease are deepening understanding of the disorder, an expert said at annual congress of the Schizophrenia International Research Society.

Sohee Park, PhD, Gertrude Conaway Vanderbilt Professor of Psychology at Vanderbilt University, Nashville, Tenn., said a unified and continuous sense of self is essential to leading a functional life. But this sense of self is a complex assemblage, made up of explicit experiences and actions, a more internal awareness of our own body, as well as a “social, narrative self” involving our social identity and history. This coherent and continuous sense of self is formulated and tied together by working memory and by our ability to form expectations or predictions about what might happen next, Dr. Park said.

In schizophrenia, the sense of self becomes fragmented as these predictions – on issues such as how sensory input is perceived – break down.

Dr. Park said a more comprehensive approach is needed in understanding this breakdown if clinicians can be expected to help people with schizophrenia.

“Connection between biological disorder and personal illness experience is not really well articulated in our field,” she said. “But it’s a connection we must make if we are to understand this condition and to develop treatments and interventions that make sense and are meaningful to the person who experiences psychosis.”

With her colleagues, Dr. Park has developed a way to better measure these bodily “self-disturbances” that patients with schizophrenia experience, and how they persist over time. B-BODI – the Benson et al. Body Disturbances Inventory – is a kind of catalog of pictures representing experiences of self-disturbance, such as someone having an out-of-body experience or a person who feels her body parts changing. The pictures come with written statements, and are designed to elicit more information from the patients about their experiences, such as how vivid, disturbing, and frequent they are.

Researchers have found that these experiences of body and self-disturbances are correlated with the positive symptoms of schizophrenia – such as hallucinations and confused thoughts – as well as with loneliness. But those experiences are not correlated with negative symptoms, such as loss of ability to feel pleasure.

B-BODI scores tend to be elevated in young people who are at high risk, so the tool could be used to help with earlier identification and treatment, and the use of pictures could help patients better convey what they’re experiencing, Dr. Park said.

“Self-disturbances are difficult to verbalize,” she said. B-BODI can help verbalize these strange experiences that are hard to describe – especially in those who have difficulty communicating.

She and her colleagues have found that those at risk of schizophrenia have a more “flexible body boundary” than do those not at risk. They performed an assessment of the degree to which subjects experienced the “Pinocchio illusion,” in which subjects are blindfolded, touch their noses, and have their biceps stimulated to create the sensation that their arm is moving away from the nose – which is interpreted as the nose growing longer. They found that subjects who scored higher on the Prodromal Questionnaire Brief – an assessment of schizophrenia risk – had higher Pinocchio illusion scores.

These abnormalities in self-perception all feed into the difficulty with which people with schizophrenia have in interacting with others. To address this difficulty, her group has developed a virtual reality training program to help patients with these interactions.

In the program, the user is asked to choose an avatar to interact with by looking at the face of the avatar for a few seconds. Once chosen, the face of the avatar is fully revealed and a conversation takes place. Then the participant receives feedback. Negative symptoms of schizophrenia were significantly reduced after participation after just 10 sessions, Dr. Park said. The program has received favorable reviews from patients – one described the avatars as “very friendly” – and holds promise for helping schizophrenia patients with social situations.

“Virtual reality,” she said, “offers the ideal rehearsal space.”

This work was supported by the National Institute of Mental Health and NARSAD, formerly known as the National Alliance for Research on Schizophrenia and Depression. Dr. Park reported no financial disclosures.

ATLANTA – A combination of the epidermal growth factor receptor (EGFR)–targeted agent osimertinib (Tagrisso) with savolitinib, an investigational MET inhibitor, showed activity against MET-driven non–small cell lung cancer (NSCLC) in patients for whom prior lines of EGFR-targeted therapy had failed.

Neil Osterweil/MDedge News

Results of the phase 1b TATTON trial suggest that it may be possible to overcome MET-driven drug resistance to tyrosine kinase inhibitors (TKIs) by targeting MET amplification, said Lecia V. Sequist, MD, from the Massachusetts General Hospital Cancer Center in Boston.

“We’ve seen that up to 10% of patients at the time of acquired resistance progressing on first- or second-generation EGFR TKIs and up to 25% of patients progressing on third-generation TKIs will have resistance driven by MET amplification,” she said at a briefing at the annual meeting of the American Association for Cancer Research.

Preliminary analysis of next-generation sequencing of circulating tumor DNA showed that MET amplification was the most common resistance mechanism, occurring in 15% of patients treated for NSCLC with first-line osimertinib in the FLAURA trial. In the AURA3 trial, MET amplification was the mechanism of resistance to second-line osimertinib in 19% of patients, she said.

Savolitinib is a selective oral MET-targeted TKI that has shown preliminary antitumor activity in patients with resistance to EGFR TKIs caused by MET amplification.

Dr. Sequist presented updated interim data on two cohorts of patients enrolled in the phase 1b trial evaluating osimertinib and savolitinib in patients with advanced or metastatic NSCLC bearing EGFR mutations following failure of one or more prior EGFR-targeted TKIs. A separate cohort of patients was treated with osimertinib and selumetinib, an investigational inhibitor of MEK1/2.

In the dose-expansion phase of the trial, enrolled patients with EGFR mutation–positive and MET-positive NSCLC, and divided them into two groups: patients who received prior therapy with a first- and/or second-generation EGFR-targeted TKI who were negative for the T790M resistance mutation and patients who had received prior treatment with a third-generation EGFR TKI, regardless of mutational status.

Of 46 patients treated with first- and/or second-generation agents, 24 had partial responses for an overall response rate of 52%. Of the remaining 22 patients, 16 (35%) had stable disease for at least 6 weeks, 3 had disease progression, and 3 were not evaluable. The median time to response was 43 days.

The most common adverse events of grade 3 or greater in this cohort were nausea (4%), fatigue (7%), vomiting (4%), peripheral edema (2%), decreased white blood cell count (2%), pain (7%), AST increase (8%), rash (4%), and decreased neutrophil count (8%).

Among 48 patients treated with the combination after disease progression on a third-generation EGFR TKI, 12 had a partial response, for an overall response rate of 25%. In addition, 21 of the 36 patients without objective responses had stable disease for at least 6 weeks, 6 had disease progression, and 9 were not evaluable. The median time to response was 46 days.

In this cohort, the most common adverse events, independent of causality, included nausea (2%), vomiting (4%), diarrhea (2%), fatigue (4%), decreased appetite (6%), and myalgia (1%). “Our data suggest that the combination of osimertinib and savolitinib could overcome MET-driven resistance, but certainly further research is needed to determine the final effectiveness of these therapies,” Dr. Sequist said.

The combination is being explored in two studies: the ongoing single-arm, phase 2 SAVANNAH trial in patients with advanced EGFR-mutant, MET-positive NSCLC who had disease progression on a prior course of osimertinib; and ORCHARD, currently in the planning stages as a phase 2 trial in patients with advanced NSCLC who had disease progression on first-line osimertinib.

The ORCHARD trial will have multiple biomarker-matched and nonmatched treatment arms to examine both targeted and nontargeted combinations.

“I would say this is impressive early data,” said Roy S. Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Conn., the invited discussant in the session where Dr. Sequist presented the data.

“We need randomized trials to confirm the results, need to better define MET-selection criteria, and this could in the future be a very useful refractory EGFR therapy,” he said.

The TATTON trial is sponsored by AstraZeneca. Dr. Sequist reported serving as an advisory board member and receiving research support and honoraria from the company. Dr. Herbst reported receiving research support from AstraZeneca, Eli Lilly, and Merck, and has served as a consultant for AstraZeneca, Eli Lilly, Genentech/Roche, Merck, NextCure, and Pfizer.

SOURCES: Yu H et al. AACR 2019, Abstract CT032; Sequist LV et al. AACR 2019, Abstract CT033.

ATLANTA – A combination of the epidermal growth factor receptor (EGFR)–targeted agent osimertinib (Tagrisso) with savolitinib, an investigational MET inhibitor, showed activity against MET-driven non–small cell lung cancer (NSCLC) in patients for whom prior lines of EGFR-targeted therapy had failed.

Neil Osterweil/MDedge News

Results of the phase 1b TATTON trial suggest that it may be possible to overcome MET-driven drug resistance to tyrosine kinase inhibitors (TKIs) by targeting MET amplification, said Lecia V. Sequist, MD, from the Massachusetts General Hospital Cancer Center in Boston.

“We’ve seen that up to 10% of patients at the time of acquired resistance progressing on first- or second-generation EGFR TKIs and up to 25% of patients progressing on third-generation TKIs will have resistance driven by MET amplification,” she said at a briefing at the annual meeting of the American Association for Cancer Research.

Preliminary analysis of next-generation sequencing of circulating tumor DNA showed that MET amplification was the most common resistance mechanism, occurring in 15% of patients treated for NSCLC with first-line osimertinib in the FLAURA trial. In the AURA3 trial, MET amplification was the mechanism of resistance to second-line osimertinib in 19% of patients, she said.

Savolitinib is a selective oral MET-targeted TKI that has shown preliminary antitumor activity in patients with resistance to EGFR TKIs caused by MET amplification.

Dr. Sequist presented updated interim data on two cohorts of patients enrolled in the phase 1b trial evaluating osimertinib and savolitinib in patients with advanced or metastatic NSCLC bearing EGFR mutations following failure of one or more prior EGFR-targeted TKIs. A separate cohort of patients was treated with osimertinib and selumetinib, an investigational inhibitor of MEK1/2.

In the dose-expansion phase of the trial, enrolled patients with EGFR mutation–positive and MET-positive NSCLC, and divided them into two groups: patients who received prior therapy with a first- and/or second-generation EGFR-targeted TKI who were negative for the T790M resistance mutation and patients who had received prior treatment with a third-generation EGFR TKI, regardless of mutational status.

Of 46 patients treated with first- and/or second-generation agents, 24 had partial responses for an overall response rate of 52%. Of the remaining 22 patients, 16 (35%) had stable disease for at least 6 weeks, 3 had disease progression, and 3 were not evaluable. The median time to response was 43 days.

The most common adverse events of grade 3 or greater in this cohort were nausea (4%), fatigue (7%), vomiting (4%), peripheral edema (2%), decreased white blood cell count (2%), pain (7%), AST increase (8%), rash (4%), and decreased neutrophil count (8%).

Among 48 patients treated with the combination after disease progression on a third-generation EGFR TKI, 12 had a partial response, for an overall response rate of 25%. In addition, 21 of the 36 patients without objective responses had stable disease for at least 6 weeks, 6 had disease progression, and 9 were not evaluable. The median time to response was 46 days.

In this cohort, the most common adverse events, independent of causality, included nausea (2%), vomiting (4%), diarrhea (2%), fatigue (4%), decreased appetite (6%), and myalgia (1%). “Our data suggest that the combination of osimertinib and savolitinib could overcome MET-driven resistance, but certainly further research is needed to determine the final effectiveness of these therapies,” Dr. Sequist said.

The combination is being explored in two studies: the ongoing single-arm, phase 2 SAVANNAH trial in patients with advanced EGFR-mutant, MET-positive NSCLC who had disease progression on a prior course of osimertinib; and ORCHARD, currently in the planning stages as a phase 2 trial in patients with advanced NSCLC who had disease progression on first-line osimertinib.

The ORCHARD trial will have multiple biomarker-matched and nonmatched treatment arms to examine both targeted and nontargeted combinations.

“I would say this is impressive early data,” said Roy S. Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Conn., the invited discussant in the session where Dr. Sequist presented the data.

“We need randomized trials to confirm the results, need to better define MET-selection criteria, and this could in the future be a very useful refractory EGFR therapy,” he said.

The TATTON trial is sponsored by AstraZeneca. Dr. Sequist reported serving as an advisory board member and receiving research support and honoraria from the company. Dr. Herbst reported receiving research support from AstraZeneca, Eli Lilly, and Merck, and has served as a consultant for AstraZeneca, Eli Lilly, Genentech/Roche, Merck, NextCure, and Pfizer.

SOURCES: Yu H et al. AACR 2019, Abstract CT032; Sequist LV et al. AACR 2019, Abstract CT033.

ATLANTA – A combination of the epidermal growth factor receptor (EGFR)–targeted agent osimertinib (Tagrisso) with savolitinib, an investigational MET inhibitor, showed activity against MET-driven non–small cell lung cancer (NSCLC) in patients for whom prior lines of EGFR-targeted therapy had failed.

Neil Osterweil/MDedge News

Results of the phase 1b TATTON trial suggest that it may be possible to overcome MET-driven drug resistance to tyrosine kinase inhibitors (TKIs) by targeting MET amplification, said Lecia V. Sequist, MD, from the Massachusetts General Hospital Cancer Center in Boston.

“We’ve seen that up to 10% of patients at the time of acquired resistance progressing on first- or second-generation EGFR TKIs and up to 25% of patients progressing on third-generation TKIs will have resistance driven by MET amplification,” she said at a briefing at the annual meeting of the American Association for Cancer Research.

Preliminary analysis of next-generation sequencing of circulating tumor DNA showed that MET amplification was the most common resistance mechanism, occurring in 15% of patients treated for NSCLC with first-line osimertinib in the FLAURA trial. In the AURA3 trial, MET amplification was the mechanism of resistance to second-line osimertinib in 19% of patients, she said.

Savolitinib is a selective oral MET-targeted TKI that has shown preliminary antitumor activity in patients with resistance to EGFR TKIs caused by MET amplification.

Dr. Sequist presented updated interim data on two cohorts of patients enrolled in the phase 1b trial evaluating osimertinib and savolitinib in patients with advanced or metastatic NSCLC bearing EGFR mutations following failure of one or more prior EGFR-targeted TKIs. A separate cohort of patients was treated with osimertinib and selumetinib, an investigational inhibitor of MEK1/2.

In the dose-expansion phase of the trial, enrolled patients with EGFR mutation–positive and MET-positive NSCLC, and divided them into two groups: patients who received prior therapy with a first- and/or second-generation EGFR-targeted TKI who were negative for the T790M resistance mutation and patients who had received prior treatment with a third-generation EGFR TKI, regardless of mutational status.

Of 46 patients treated with first- and/or second-generation agents, 24 had partial responses for an overall response rate of 52%. Of the remaining 22 patients, 16 (35%) had stable disease for at least 6 weeks, 3 had disease progression, and 3 were not evaluable. The median time to response was 43 days.

The most common adverse events of grade 3 or greater in this cohort were nausea (4%), fatigue (7%), vomiting (4%), peripheral edema (2%), decreased white blood cell count (2%), pain (7%), AST increase (8%), rash (4%), and decreased neutrophil count (8%).

Among 48 patients treated with the combination after disease progression on a third-generation EGFR TKI, 12 had a partial response, for an overall response rate of 25%. In addition, 21 of the 36 patients without objective responses had stable disease for at least 6 weeks, 6 had disease progression, and 9 were not evaluable. The median time to response was 46 days.

In this cohort, the most common adverse events, independent of causality, included nausea (2%), vomiting (4%), diarrhea (2%), fatigue (4%), decreased appetite (6%), and myalgia (1%). “Our data suggest that the combination of osimertinib and savolitinib could overcome MET-driven resistance, but certainly further research is needed to determine the final effectiveness of these therapies,” Dr. Sequist said.

The combination is being explored in two studies: the ongoing single-arm, phase 2 SAVANNAH trial in patients with advanced EGFR-mutant, MET-positive NSCLC who had disease progression on a prior course of osimertinib; and ORCHARD, currently in the planning stages as a phase 2 trial in patients with advanced NSCLC who had disease progression on first-line osimertinib.

The ORCHARD trial will have multiple biomarker-matched and nonmatched treatment arms to examine both targeted and nontargeted combinations.

“I would say this is impressive early data,” said Roy S. Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Conn., the invited discussant in the session where Dr. Sequist presented the data.

“We need randomized trials to confirm the results, need to better define MET-selection criteria, and this could in the future be a very useful refractory EGFR therapy,” he said.

The TATTON trial is sponsored by AstraZeneca. Dr. Sequist reported serving as an advisory board member and receiving research support and honoraria from the company. Dr. Herbst reported receiving research support from AstraZeneca, Eli Lilly, and Merck, and has served as a consultant for AstraZeneca, Eli Lilly, Genentech/Roche, Merck, NextCure, and Pfizer.

SOURCES: Yu H et al. AACR 2019, Abstract CT032; Sequist LV et al. AACR 2019, Abstract CT033.

The use of percutaneous coronary intervention after ST-segment elevation myocardial infarction is increasing in older adults, and is associated with significantly lower in-hospital mortality, new research has found.

“Our study shows that the rates of utilization of PCI in older patients with STEMI and cardiogenic shock is rising. This rise has been paralleled by an equivalent decline in unadjusted mortality rates,” Abdulla A. Damluji, MD, and his coinvestigators wrote in an analysis published in the Journal of the American College of Cardiology.

They looked at outcomes of 317,728 cases of STEMI with cardiogenic shock during 1999-2013, of which 35% occurred in individuals aged 75 years or above.

Over the study period, the proportion of adults aged 75 years and over who underwent percutaneous coronary intervention after STEMI increased from 27% in 1999 to 56% in 2013. At the same time, in-hospital mortality rates in those patients declined from 64% in 1999 to 46% in 2013. Both differences were significant at P less than 0.001.

PCI more than halved the mortality associated with STEMI in older adults, even after adjustment for propensity score, and this was seen across all four U.S. Census Bureau regions in the analysis.


However, mortality rates were slightly higher in patients who underwent percutaneous coronary intervention and had a bleeding event, compared with those who did not have a bleeding event.

There were some significant differences in the prevalence of cardiovascular risk factors and noncardiovascular diagnoses between those who underwent percutaneous coronary intervention and those who did not. There was around a 20% higher prevalence of obesity, but a lower prevalence of valvular heart disease and heart failure, in individuals who were treated with percutaneous coronary intervention than among those who were not.

Older adults who received percutaneous coronary intervention also had a significantly lower disease burden compared with older adults who did not, and were more likely to be younger, male, and not an underrepresented minority.

“Despite the improvement in survival associated with early revascularization as reported by these studies, many older adults with multiple chronic conditions, worse disease burden, and possibly limited life expectancy as assessed by interventional cardiologists do not receive early revascularization with PCI,” wrote Dr. Damluji of Sinai Hospital of Baltimore and Johns Hopkins University, and his coauthors.

“This study was aimed to address this important selection bias by implementing different methods of propensity matching to understand the influence of early revascularization adjusting for demographic, clinical, and hospital characteristics between older adults with early revascularization versus those without revascularization.”

The study was partly supported by the Jane and Stanley F. Rodbell family. Three authors declared support from the National Institute on Aging. Two authors declared funding from private industry and one declared pharmaceutical stocks. No other conflicts of interest were declared.

SOURCE: Damluji A et al. J Am Coll Cardiol. 2019 Apr;73(15):1890-900.

The use of percutaneous coronary intervention after ST-segment elevation myocardial infarction is increasing in older adults, and is associated with significantly lower in-hospital mortality, new research has found.

“Our study shows that the rates of utilization of PCI in older patients with STEMI and cardiogenic shock is rising. This rise has been paralleled by an equivalent decline in unadjusted mortality rates,” Abdulla A. Damluji, MD, and his coinvestigators wrote in an analysis published in the Journal of the American College of Cardiology.

They looked at outcomes of 317,728 cases of STEMI with cardiogenic shock during 1999-2013, of which 35% occurred in individuals aged 75 years or above.

Over the study period, the proportion of adults aged 75 years and over who underwent percutaneous coronary intervention after STEMI increased from 27% in 1999 to 56% in 2013. At the same time, in-hospital mortality rates in those patients declined from 64% in 1999 to 46% in 2013. Both differences were significant at P less than 0.001.

PCI more than halved the mortality associated with STEMI in older adults, even after adjustment for propensity score, and this was seen across all four U.S. Census Bureau regions in the analysis.


However, mortality rates were slightly higher in patients who underwent percutaneous coronary intervention and had a bleeding event, compared with those who did not have a bleeding event.

There were some significant differences in the prevalence of cardiovascular risk factors and noncardiovascular diagnoses between those who underwent percutaneous coronary intervention and those who did not. There was around a 20% higher prevalence of obesity, but a lower prevalence of valvular heart disease and heart failure, in individuals who were treated with percutaneous coronary intervention than among those who were not.

Older adults who received percutaneous coronary intervention also had a significantly lower disease burden compared with older adults who did not, and were more likely to be younger, male, and not an underrepresented minority.

“Despite the improvement in survival associated with early revascularization as reported by these studies, many older adults with multiple chronic conditions, worse disease burden, and possibly limited life expectancy as assessed by interventional cardiologists do not receive early revascularization with PCI,” wrote Dr. Damluji of Sinai Hospital of Baltimore and Johns Hopkins University, and his coauthors.

“This study was aimed to address this important selection bias by implementing different methods of propensity matching to understand the influence of early revascularization adjusting for demographic, clinical, and hospital characteristics between older adults with early revascularization versus those without revascularization.”

The study was partly supported by the Jane and Stanley F. Rodbell family. Three authors declared support from the National Institute on Aging. Two authors declared funding from private industry and one declared pharmaceutical stocks. No other conflicts of interest were declared.

SOURCE: Damluji A et al. J Am Coll Cardiol. 2019 Apr;73(15):1890-900.

The use of percutaneous coronary intervention after ST-segment elevation myocardial infarction is increasing in older adults, and is associated with significantly lower in-hospital mortality, new research has found.

“Our study shows that the rates of utilization of PCI in older patients with STEMI and cardiogenic shock is rising. This rise has been paralleled by an equivalent decline in unadjusted mortality rates,” Abdulla A. Damluji, MD, and his coinvestigators wrote in an analysis published in the Journal of the American College of Cardiology.

They looked at outcomes of 317,728 cases of STEMI with cardiogenic shock during 1999-2013, of which 35% occurred in individuals aged 75 years or above.

Over the study period, the proportion of adults aged 75 years and over who underwent percutaneous coronary intervention after STEMI increased from 27% in 1999 to 56% in 2013. At the same time, in-hospital mortality rates in those patients declined from 64% in 1999 to 46% in 2013. Both differences were significant at P less than 0.001.

PCI more than halved the mortality associated with STEMI in older adults, even after adjustment for propensity score, and this was seen across all four U.S. Census Bureau regions in the analysis.


However, mortality rates were slightly higher in patients who underwent percutaneous coronary intervention and had a bleeding event, compared with those who did not have a bleeding event.

There were some significant differences in the prevalence of cardiovascular risk factors and noncardiovascular diagnoses between those who underwent percutaneous coronary intervention and those who did not. There was around a 20% higher prevalence of obesity, but a lower prevalence of valvular heart disease and heart failure, in individuals who were treated with percutaneous coronary intervention than among those who were not.

Older adults who received percutaneous coronary intervention also had a significantly lower disease burden compared with older adults who did not, and were more likely to be younger, male, and not an underrepresented minority.

“Despite the improvement in survival associated with early revascularization as reported by these studies, many older adults with multiple chronic conditions, worse disease burden, and possibly limited life expectancy as assessed by interventional cardiologists do not receive early revascularization with PCI,” wrote Dr. Damluji of Sinai Hospital of Baltimore and Johns Hopkins University, and his coauthors.

“This study was aimed to address this important selection bias by implementing different methods of propensity matching to understand the influence of early revascularization adjusting for demographic, clinical, and hospital characteristics between older adults with early revascularization versus those without revascularization.”

The study was partly supported by the Jane and Stanley F. Rodbell family. Three authors declared support from the National Institute on Aging. Two authors declared funding from private industry and one declared pharmaceutical stocks. No other conflicts of interest were declared.

SOURCE: Damluji A et al. J Am Coll Cardiol. 2019 Apr;73(15):1890-900.

Background: Studies abound on the accelerated cost and health care activities of patients toward the end of life. Previous analyses of Medicare trends of medical care at the time of death have been compiled in 2000, 2005, 2009, and 2011; this study reexamines recent trends.

Study design: Retrospective cohort of a random sample of Medicare Fee-for-Service and Medicare Advantage decedents during 2000-2015.

Setting: Medicare patients in acute care hospitals, home/community, hospice inpatient care units, or nursing homes.

Synopsis: Approximately 1.4 million Medicare Fee-for-Service decedents and 870,000 Medicare Advantage decedents were studied in a random sample that included 20% of Medicare Fee-for-Service recipients in the years 2000, 2005, 2009, 2011, and 2015 and 100% of Medicare Advantage patients in the years 2011 and 2015. Deaths of Medicare Fee-for-Service recipients occurring in acute care hospitals and nursing homes decreased from 32.6% (95% confidence interval, 32.4%-32.8%) in 2000 to 19.8% (95% CI, 19.6%-20.0%) in 2015. Patients who died while receiving hospice services increased from 21.6% (95% CI, 21.5%-21.8%) in 2000 to 50.4% (95% CI, 50.2%-50.6%) in 2015. Review of Medicare Advantage data demonstrated similar shifts.

Although there are concerns about the accuracy of reported location of community deaths and these results may not be generalizable to other, non-Medicare populations, the study overall adds statistical data on death trends and suggests an improvement in the use of palliative and hospice care services.

Bottom line: Compared with previous years, fewer Medicare beneficiaries are dying in acute care settings, and more beneficiaries are receiving hospice care in other settings.

Citation: Teno J et al. Site of death, place of care, and health care transitions among U. S. Medicare beneficiaries between 2000-2015. JAMA. 2018;320(3):264-71.

Dr. Smith is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Background: Studies abound on the accelerated cost and health care activities of patients toward the end of life. Previous analyses of Medicare trends of medical care at the time of death have been compiled in 2000, 2005, 2009, and 2011; this study reexamines recent trends.

Study design: Retrospective cohort of a random sample of Medicare Fee-for-Service and Medicare Advantage decedents during 2000-2015.

Setting: Medicare patients in acute care hospitals, home/community, hospice inpatient care units, or nursing homes.

Synopsis: Approximately 1.4 million Medicare Fee-for-Service decedents and 870,000 Medicare Advantage decedents were studied in a random sample that included 20% of Medicare Fee-for-Service recipients in the years 2000, 2005, 2009, 2011, and 2015 and 100% of Medicare Advantage patients in the years 2011 and 2015. Deaths of Medicare Fee-for-Service recipients occurring in acute care hospitals and nursing homes decreased from 32.6% (95% confidence interval, 32.4%-32.8%) in 2000 to 19.8% (95% CI, 19.6%-20.0%) in 2015. Patients who died while receiving hospice services increased from 21.6% (95% CI, 21.5%-21.8%) in 2000 to 50.4% (95% CI, 50.2%-50.6%) in 2015. Review of Medicare Advantage data demonstrated similar shifts.

Although there are concerns about the accuracy of reported location of community deaths and these results may not be generalizable to other, non-Medicare populations, the study overall adds statistical data on death trends and suggests an improvement in the use of palliative and hospice care services.

Bottom line: Compared with previous years, fewer Medicare beneficiaries are dying in acute care settings, and more beneficiaries are receiving hospice care in other settings.

Citation: Teno J et al. Site of death, place of care, and health care transitions among U. S. Medicare beneficiaries between 2000-2015. JAMA. 2018;320(3):264-71.

Dr. Smith is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Background: Studies abound on the accelerated cost and health care activities of patients toward the end of life. Previous analyses of Medicare trends of medical care at the time of death have been compiled in 2000, 2005, 2009, and 2011; this study reexamines recent trends.

Study design: Retrospective cohort of a random sample of Medicare Fee-for-Service and Medicare Advantage decedents during 2000-2015.

Setting: Medicare patients in acute care hospitals, home/community, hospice inpatient care units, or nursing homes.

Synopsis: Approximately 1.4 million Medicare Fee-for-Service decedents and 870,000 Medicare Advantage decedents were studied in a random sample that included 20% of Medicare Fee-for-Service recipients in the years 2000, 2005, 2009, 2011, and 2015 and 100% of Medicare Advantage patients in the years 2011 and 2015. Deaths of Medicare Fee-for-Service recipients occurring in acute care hospitals and nursing homes decreased from 32.6% (95% confidence interval, 32.4%-32.8%) in 2000 to 19.8% (95% CI, 19.6%-20.0%) in 2015. Patients who died while receiving hospice services increased from 21.6% (95% CI, 21.5%-21.8%) in 2000 to 50.4% (95% CI, 50.2%-50.6%) in 2015. Review of Medicare Advantage data demonstrated similar shifts.

Although there are concerns about the accuracy of reported location of community deaths and these results may not be generalizable to other, non-Medicare populations, the study overall adds statistical data on death trends and suggests an improvement in the use of palliative and hospice care services.

Bottom line: Compared with previous years, fewer Medicare beneficiaries are dying in acute care settings, and more beneficiaries are receiving hospice care in other settings.

Citation: Teno J et al. Site of death, place of care, and health care transitions among U. S. Medicare beneficiaries between 2000-2015. JAMA. 2018;320(3):264-71.

Dr. Smith is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.