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Enhanced recovery also enhances unplanned patient contact
TUCSON, ARIZ. – A retrospective study at the Mayo Clinic Arizona found a near doubling in the percentage of patients who had contact with the medical system in the 2 weeks following surgery.
“That’s a big change and a burden for the clinician, so they need to anticipate that,” Rachael Haverland, MD, a fellow at Mayo Clinic Arizona, Phoenix, said in an interview at the annual scientific meeting of the Society of Gynecologic Surgeons.
“A lot of research has gone into the safety profile of ERAS, the cost-effectiveness of ERAS, and the effects on the patient, but there has not been a lot of research on how it affects the clinician’s practice. I think it’s very important for physicians to know that so that they can plan ahead, maybe add more clinical staff to help with some of these phone calls, and maybe setting aside special clinic time for unscheduled visits to address some of these patient concerns,” she added.
The most common issues revolve around pain management – how to take medications and how to manage pain in the context of few restrictions – suggesting that preoperative counseling could help. “Setting expectations for pain, going through their medication regimen after surgery so they know what medications they can take, how to control their pain, and their restrictions. We don’t have many restrictions. We want them walking even the same day, and there are no dietary restrictions. Just reiterating some of those facts, because it’s still new, especially to patients. They’re not used to having limited restrictions,” Dr. Haverland said.
Other patient concerns included dysuria and frequency of urination following surgery. The least common questions were related to activity restrictions, according to Dr. Haverland.
The researchers are developing a preoperative video for ERAS that they hope will improve matters. It aims to anticipate patient questions before and after surgery, and they plan to track its impact on clinician burden. “I’m hoping that when we do our next set of data that it cuts down on some of those unscheduled patient hours,” she said.
The researchers examined data from 200 hysterectomy patients. A total of 90 underwent surgery in 2012, before ERAS was implemented, and 110 in 2014, 1 year after ERAS was begun. They looked at patient phone calls, ED visits, and unscheduled postoperative visits.
Before ERAS, in the 2 weeks after surgery, 42.2% of patients had any medical care. That rose to 74.5% after ERAS. The difference seemed to be driven by phone calls, which rose from 38.9% before ERAS to 68.2% after (P less than .0001). There also was a trend toward more in-person visits (12.2% vs. 21.8%; odds ratio, 2.00; P = .08) and unscheduled office visits (10.0% vs. 18.2%; P = .01).
Patients undergoing a concomitant sling procedure were more likely to seek in-person medical care within 2 weeks regardless of ERAS protocol (OR, 3.16; P = .04). The researchers found no significant differences in readmission rates, operative time, blood loss, or ED visits.
The study received no funding. Dr. Haverland reported no relevant financial disclosures.
SOURCE: Haverland R et al. SGS 2019, Oral Poster 05.
TUCSON, ARIZ. – A retrospective study at the Mayo Clinic Arizona found a near doubling in the percentage of patients who had contact with the medical system in the 2 weeks following surgery.
“That’s a big change and a burden for the clinician, so they need to anticipate that,” Rachael Haverland, MD, a fellow at Mayo Clinic Arizona, Phoenix, said in an interview at the annual scientific meeting of the Society of Gynecologic Surgeons.
“A lot of research has gone into the safety profile of ERAS, the cost-effectiveness of ERAS, and the effects on the patient, but there has not been a lot of research on how it affects the clinician’s practice. I think it’s very important for physicians to know that so that they can plan ahead, maybe add more clinical staff to help with some of these phone calls, and maybe setting aside special clinic time for unscheduled visits to address some of these patient concerns,” she added.
The most common issues revolve around pain management – how to take medications and how to manage pain in the context of few restrictions – suggesting that preoperative counseling could help. “Setting expectations for pain, going through their medication regimen after surgery so they know what medications they can take, how to control their pain, and their restrictions. We don’t have many restrictions. We want them walking even the same day, and there are no dietary restrictions. Just reiterating some of those facts, because it’s still new, especially to patients. They’re not used to having limited restrictions,” Dr. Haverland said.
Other patient concerns included dysuria and frequency of urination following surgery. The least common questions were related to activity restrictions, according to Dr. Haverland.
The researchers are developing a preoperative video for ERAS that they hope will improve matters. It aims to anticipate patient questions before and after surgery, and they plan to track its impact on clinician burden. “I’m hoping that when we do our next set of data that it cuts down on some of those unscheduled patient hours,” she said.
The researchers examined data from 200 hysterectomy patients. A total of 90 underwent surgery in 2012, before ERAS was implemented, and 110 in 2014, 1 year after ERAS was begun. They looked at patient phone calls, ED visits, and unscheduled postoperative visits.
Before ERAS, in the 2 weeks after surgery, 42.2% of patients had any medical care. That rose to 74.5% after ERAS. The difference seemed to be driven by phone calls, which rose from 38.9% before ERAS to 68.2% after (P less than .0001). There also was a trend toward more in-person visits (12.2% vs. 21.8%; odds ratio, 2.00; P = .08) and unscheduled office visits (10.0% vs. 18.2%; P = .01).
Patients undergoing a concomitant sling procedure were more likely to seek in-person medical care within 2 weeks regardless of ERAS protocol (OR, 3.16; P = .04). The researchers found no significant differences in readmission rates, operative time, blood loss, or ED visits.
The study received no funding. Dr. Haverland reported no relevant financial disclosures.
SOURCE: Haverland R et al. SGS 2019, Oral Poster 05.
TUCSON, ARIZ. – A retrospective study at the Mayo Clinic Arizona found a near doubling in the percentage of patients who had contact with the medical system in the 2 weeks following surgery.
“That’s a big change and a burden for the clinician, so they need to anticipate that,” Rachael Haverland, MD, a fellow at Mayo Clinic Arizona, Phoenix, said in an interview at the annual scientific meeting of the Society of Gynecologic Surgeons.
“A lot of research has gone into the safety profile of ERAS, the cost-effectiveness of ERAS, and the effects on the patient, but there has not been a lot of research on how it affects the clinician’s practice. I think it’s very important for physicians to know that so that they can plan ahead, maybe add more clinical staff to help with some of these phone calls, and maybe setting aside special clinic time for unscheduled visits to address some of these patient concerns,” she added.
The most common issues revolve around pain management – how to take medications and how to manage pain in the context of few restrictions – suggesting that preoperative counseling could help. “Setting expectations for pain, going through their medication regimen after surgery so they know what medications they can take, how to control their pain, and their restrictions. We don’t have many restrictions. We want them walking even the same day, and there are no dietary restrictions. Just reiterating some of those facts, because it’s still new, especially to patients. They’re not used to having limited restrictions,” Dr. Haverland said.
Other patient concerns included dysuria and frequency of urination following surgery. The least common questions were related to activity restrictions, according to Dr. Haverland.
The researchers are developing a preoperative video for ERAS that they hope will improve matters. It aims to anticipate patient questions before and after surgery, and they plan to track its impact on clinician burden. “I’m hoping that when we do our next set of data that it cuts down on some of those unscheduled patient hours,” she said.
The researchers examined data from 200 hysterectomy patients. A total of 90 underwent surgery in 2012, before ERAS was implemented, and 110 in 2014, 1 year after ERAS was begun. They looked at patient phone calls, ED visits, and unscheduled postoperative visits.
Before ERAS, in the 2 weeks after surgery, 42.2% of patients had any medical care. That rose to 74.5% after ERAS. The difference seemed to be driven by phone calls, which rose from 38.9% before ERAS to 68.2% after (P less than .0001). There also was a trend toward more in-person visits (12.2% vs. 21.8%; odds ratio, 2.00; P = .08) and unscheduled office visits (10.0% vs. 18.2%; P = .01).
Patients undergoing a concomitant sling procedure were more likely to seek in-person medical care within 2 weeks regardless of ERAS protocol (OR, 3.16; P = .04). The researchers found no significant differences in readmission rates, operative time, blood loss, or ED visits.
The study received no funding. Dr. Haverland reported no relevant financial disclosures.
SOURCE: Haverland R et al. SGS 2019, Oral Poster 05.
REPORTING FROM SGS 2019
Survey: Bias against female surgeons persists
BALTIMORE – Most male surgeons welcome and support their female colleagues in the workplace, but a survey of male surgeons reports that bias against women in surgery persists, and may be even more acute among younger surgeons, according to a presentation at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.
“Is there a bias against women in surgery?” asked Michalina Jadick, who presented the results on behalf of AdventHealth Hospital Tampa. “Yes, there is, and understanding this problem is imperative when learning how to fix it.”
A freshman at Boston University who conducted the survey of male surgeons as part of a mentoring program for young women at AdventHealth, Ms. Jadick reported on results of an online survey completed by 190 male surgeons. She noted that, while women represent more than 50% of medical school students, they constitute only 19% of general surgeons in the United States. “Especially in the face of a projected shortage of practicing surgeons, it is more important now than ever to investigate, understand, and work to eliminate the barriers encountered by this large and unique talent pool,” she said.
The anonymous survey was extensive, including 70 five-point Likert-scale questions and 63 multiple choice and binary answers. Regarding the male surgeons who completed the survey, 84% were attendings with more than 5 years of experience, and 8% had less than 5 years in surgery. The remainder were residents, fellows and interns.
When asked if women are as capable as their male counterparts, 80% agreed, with the remainder split between “disagree” or “no opinion.”
“Although this is very small in comparison, that’s actually pretty significant,” Ms. Jadick said of the 10% who disagreed.
When asked if women make good surgeons, 67% agreed, 10% disagreed, and 23% selected neither. “We found that older male surgeons were more likely to believe women make successful surgeons, as opposed to younger male doctors,” Ms. Jadick said. She called this finding “surprising” because younger doctors are expected to have more progressive ideas. “However, this response seems to indicate otherwise, and that’s an important part of the conversation.”
When asked if women have the same advancement opportunities as men, 75% agreed and 9% disagreed. When the question was flipped – that is, if men have more opportunities than women – 32% agreed and 43% disagreed. Half of responders concurred that women are discouraged from entering surgery because program directors question their ability to complete surgical training, yet 95% agreed that men and women residents receive equal training. “This is especially a problem,” Ms. Jadick said of the latter finding.
The survey also found wide disparities in how male surgeons feel about family roles. A high percentage – 80% – agreed that a woman can be both a good surgeon and a good parent. But an even higher percentage – 96% – said a man could be good in both roles. “When looking at the disagreement to these statements, 13% said it is not possible for a woman to be both a good surgeon and a good parent, while not one single male respondent said the same for men,” Ms. Jadick said. Of the men surveyed, 84% agreed that female surgeons are under greater pressure than men to balance work and family life.
Exploring the family issue even deeper, 46% of the respondents said that having children adversely affects a female surgeon professionally, whereas only 9% said the same of men. Conversely, 31% said children do not affect a female surgeon’s career, but 81% said children do not affect a male surgeon’s career.
“Clearly the topic of family obligations is a huge issue in the context of gender discrimination against women in surgery, and this is the case even though many have indicated that women and men have similar commitment to families outside of work,” Ms. Jadick said. “This has proven to be a big part of the issue in the past and likely moving forward as well. That’s why it’s of paramount importance for us to take this into consideration and understand that it’s happening.”
When asked about working with women in the operating room, 20% of male respondents agreed that women surgeons are aggressive coworkers, and 19% said that it’s easier to work with male colleagues. This attitude may be a function of the stereotype of women being deferential to leadership rather than assuming it, she said.
When asked frankly if discrimination exists in surgery today, 43% answered “yes” – but 57% said “no” or “unsure.”
“This finding clearly portrays the problem does persist in surgery, and therefore, it’s very important for [male] surgeons in particular to remain aware of that problem and actively work to eliminate that disparity within that work environment,” Ms. Jadick said.
However, the 57% who said discrimination is not a problem is more unsettling, she said. “That’s incredibly significant because the first step to solving any problem is recognizing that there is one,” Ms. Jadick said. “However, then we must commit to solving it. Only by promoting an equitable and inclusive work environment that promotes the engagement of women can we improve the future of surgery for the betterment of all of its stakeholders, especially patients.”
Ms. Jadick had no financial relationships to disclose.
BALTIMORE – Most male surgeons welcome and support their female colleagues in the workplace, but a survey of male surgeons reports that bias against women in surgery persists, and may be even more acute among younger surgeons, according to a presentation at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.
“Is there a bias against women in surgery?” asked Michalina Jadick, who presented the results on behalf of AdventHealth Hospital Tampa. “Yes, there is, and understanding this problem is imperative when learning how to fix it.”
A freshman at Boston University who conducted the survey of male surgeons as part of a mentoring program for young women at AdventHealth, Ms. Jadick reported on results of an online survey completed by 190 male surgeons. She noted that, while women represent more than 50% of medical school students, they constitute only 19% of general surgeons in the United States. “Especially in the face of a projected shortage of practicing surgeons, it is more important now than ever to investigate, understand, and work to eliminate the barriers encountered by this large and unique talent pool,” she said.
The anonymous survey was extensive, including 70 five-point Likert-scale questions and 63 multiple choice and binary answers. Regarding the male surgeons who completed the survey, 84% were attendings with more than 5 years of experience, and 8% had less than 5 years in surgery. The remainder were residents, fellows and interns.
When asked if women are as capable as their male counterparts, 80% agreed, with the remainder split between “disagree” or “no opinion.”
“Although this is very small in comparison, that’s actually pretty significant,” Ms. Jadick said of the 10% who disagreed.
When asked if women make good surgeons, 67% agreed, 10% disagreed, and 23% selected neither. “We found that older male surgeons were more likely to believe women make successful surgeons, as opposed to younger male doctors,” Ms. Jadick said. She called this finding “surprising” because younger doctors are expected to have more progressive ideas. “However, this response seems to indicate otherwise, and that’s an important part of the conversation.”
When asked if women have the same advancement opportunities as men, 75% agreed and 9% disagreed. When the question was flipped – that is, if men have more opportunities than women – 32% agreed and 43% disagreed. Half of responders concurred that women are discouraged from entering surgery because program directors question their ability to complete surgical training, yet 95% agreed that men and women residents receive equal training. “This is especially a problem,” Ms. Jadick said of the latter finding.
The survey also found wide disparities in how male surgeons feel about family roles. A high percentage – 80% – agreed that a woman can be both a good surgeon and a good parent. But an even higher percentage – 96% – said a man could be good in both roles. “When looking at the disagreement to these statements, 13% said it is not possible for a woman to be both a good surgeon and a good parent, while not one single male respondent said the same for men,” Ms. Jadick said. Of the men surveyed, 84% agreed that female surgeons are under greater pressure than men to balance work and family life.
Exploring the family issue even deeper, 46% of the respondents said that having children adversely affects a female surgeon professionally, whereas only 9% said the same of men. Conversely, 31% said children do not affect a female surgeon’s career, but 81% said children do not affect a male surgeon’s career.
“Clearly the topic of family obligations is a huge issue in the context of gender discrimination against women in surgery, and this is the case even though many have indicated that women and men have similar commitment to families outside of work,” Ms. Jadick said. “This has proven to be a big part of the issue in the past and likely moving forward as well. That’s why it’s of paramount importance for us to take this into consideration and understand that it’s happening.”
When asked about working with women in the operating room, 20% of male respondents agreed that women surgeons are aggressive coworkers, and 19% said that it’s easier to work with male colleagues. This attitude may be a function of the stereotype of women being deferential to leadership rather than assuming it, she said.
When asked frankly if discrimination exists in surgery today, 43% answered “yes” – but 57% said “no” or “unsure.”
“This finding clearly portrays the problem does persist in surgery, and therefore, it’s very important for [male] surgeons in particular to remain aware of that problem and actively work to eliminate that disparity within that work environment,” Ms. Jadick said.
However, the 57% who said discrimination is not a problem is more unsettling, she said. “That’s incredibly significant because the first step to solving any problem is recognizing that there is one,” Ms. Jadick said. “However, then we must commit to solving it. Only by promoting an equitable and inclusive work environment that promotes the engagement of women can we improve the future of surgery for the betterment of all of its stakeholders, especially patients.”
Ms. Jadick had no financial relationships to disclose.
BALTIMORE – Most male surgeons welcome and support their female colleagues in the workplace, but a survey of male surgeons reports that bias against women in surgery persists, and may be even more acute among younger surgeons, according to a presentation at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.
“Is there a bias against women in surgery?” asked Michalina Jadick, who presented the results on behalf of AdventHealth Hospital Tampa. “Yes, there is, and understanding this problem is imperative when learning how to fix it.”
A freshman at Boston University who conducted the survey of male surgeons as part of a mentoring program for young women at AdventHealth, Ms. Jadick reported on results of an online survey completed by 190 male surgeons. She noted that, while women represent more than 50% of medical school students, they constitute only 19% of general surgeons in the United States. “Especially in the face of a projected shortage of practicing surgeons, it is more important now than ever to investigate, understand, and work to eliminate the barriers encountered by this large and unique talent pool,” she said.
The anonymous survey was extensive, including 70 five-point Likert-scale questions and 63 multiple choice and binary answers. Regarding the male surgeons who completed the survey, 84% were attendings with more than 5 years of experience, and 8% had less than 5 years in surgery. The remainder were residents, fellows and interns.
When asked if women are as capable as their male counterparts, 80% agreed, with the remainder split between “disagree” or “no opinion.”
“Although this is very small in comparison, that’s actually pretty significant,” Ms. Jadick said of the 10% who disagreed.
When asked if women make good surgeons, 67% agreed, 10% disagreed, and 23% selected neither. “We found that older male surgeons were more likely to believe women make successful surgeons, as opposed to younger male doctors,” Ms. Jadick said. She called this finding “surprising” because younger doctors are expected to have more progressive ideas. “However, this response seems to indicate otherwise, and that’s an important part of the conversation.”
When asked if women have the same advancement opportunities as men, 75% agreed and 9% disagreed. When the question was flipped – that is, if men have more opportunities than women – 32% agreed and 43% disagreed. Half of responders concurred that women are discouraged from entering surgery because program directors question their ability to complete surgical training, yet 95% agreed that men and women residents receive equal training. “This is especially a problem,” Ms. Jadick said of the latter finding.
The survey also found wide disparities in how male surgeons feel about family roles. A high percentage – 80% – agreed that a woman can be both a good surgeon and a good parent. But an even higher percentage – 96% – said a man could be good in both roles. “When looking at the disagreement to these statements, 13% said it is not possible for a woman to be both a good surgeon and a good parent, while not one single male respondent said the same for men,” Ms. Jadick said. Of the men surveyed, 84% agreed that female surgeons are under greater pressure than men to balance work and family life.
Exploring the family issue even deeper, 46% of the respondents said that having children adversely affects a female surgeon professionally, whereas only 9% said the same of men. Conversely, 31% said children do not affect a female surgeon’s career, but 81% said children do not affect a male surgeon’s career.
“Clearly the topic of family obligations is a huge issue in the context of gender discrimination against women in surgery, and this is the case even though many have indicated that women and men have similar commitment to families outside of work,” Ms. Jadick said. “This has proven to be a big part of the issue in the past and likely moving forward as well. That’s why it’s of paramount importance for us to take this into consideration and understand that it’s happening.”
When asked about working with women in the operating room, 20% of male respondents agreed that women surgeons are aggressive coworkers, and 19% said that it’s easier to work with male colleagues. This attitude may be a function of the stereotype of women being deferential to leadership rather than assuming it, she said.
When asked frankly if discrimination exists in surgery today, 43% answered “yes” – but 57% said “no” or “unsure.”
“This finding clearly portrays the problem does persist in surgery, and therefore, it’s very important for [male] surgeons in particular to remain aware of that problem and actively work to eliminate that disparity within that work environment,” Ms. Jadick said.
However, the 57% who said discrimination is not a problem is more unsettling, she said. “That’s incredibly significant because the first step to solving any problem is recognizing that there is one,” Ms. Jadick said. “However, then we must commit to solving it. Only by promoting an equitable and inclusive work environment that promotes the engagement of women can we improve the future of surgery for the betterment of all of its stakeholders, especially patients.”
Ms. Jadick had no financial relationships to disclose.
REPORTING FROM SAGES 2019
First-line afatinib responses encouraging across diverse population of EGFR TKI-naive patients
GENEVA – For EGFR TKI-naive patients with EGFR-positive non–small cell lung cancer (NSCLC), afatinib appears safe and effective in a “real-world” setting, based on results of a phase 3b study.
Across a diverse population of patients, including those with brain metastases, uncommon mutations, multiple lines of prior therapy, and/or an Eastern Cooperative Oncology Group (ECOG) performance status of 2, afatinib delivered “encouraging” responses, reported lead author Antonio Passaro, MD, PhD, of the European Institute of Oncology in Milan. During his presentation at the European Lung Cancer Conference, Dr. Passaro described the safety profile as “predictable and manageable.”
The findings follow on the heels of the LUX-Lung trials, which showed that afatinib could match the progression-free survival (PFS) achieved with gefitinib, at about 11 months, while beating chemotherapy, which was associated with a PFS of approximately 5-7 months.
“However,” the investigators noted in their abstract, “in real-world practice chemotherapy remains a first-line choice.”
The present study aimed to demonstrate the real-world potential of afatinib across treatment lines, Dr. Passaro said at the meeting, presented by the European Society for Medical Oncology.
The patient population was diverse, with multiple treatment lines represented. The majority of patients (78%) received afatinib as first-line treatment, while smaller groups received the treatment as second-line (17%), or third-line or greater (5%). About one-third of the patients (36%) had an ECOG score of 0, about half (57%) had a score of 1, and a small group (8%) had a score of 2. A minority of patients had brain metastases (17%) and/or uncommon mutations (13%). Patients received 40 mg of afatinib daily; dose reduction to 20 mg was allowed if necessary.
Analysis showed that patients received afatinib for a median of almost 1 year (359 days). Slightly more than half of the patients (54%) got reduced doses because of adverse events, most commonly, diarrhea (25%) and rash (11%). About one out of five patients (22%) discontinued treatment entirely.
Secondarily, the investigators analyzed efficacy, reporting that the objective response rate was 46% and the disease control rate was 86%. During his presentation, Dr. Passaro focused on median time to symptomatic progression (TTSP) and median progression-free survival (PFS), describing these outcomes in relation to patient subgroups. Across all patients, TTSP was 14.9 months and PFS was 13.4 months. Among subgroups, patients receiving afatinib as first-line therapy had the best median PFS, at 13.8 months, which was comparable with those who received the treatment second-line (13.2 months). In contrast, patients receiving afatinib as a third-line treatment or later had noticeably shorter PFS, at 6.6 months. Baseline ECOG performance status showed a similar trend; patients with scores of 0 had a median PFS of 15.4 months, compared with 12.9 months for those with a score of 1, and 6.2 months with a score of 2. Patients with brain metastases fared worse than did those without (PFS 10.1 months vs. 13.9 months), and patients with uncommon mutations had shorter PFS than that of those with common mutations (6.0 months vs. 14.1 months). TTSP durations paralleled the above PFS trends.Boehringer Ingelheim funded the study. The investigators reported financial relationships with Roche, MSD, Bristol-Myers Squibb, AstraZeneca, and others.
SOURCE: Passaro et al. ELCC 2019. Abstract 115O.
GENEVA – For EGFR TKI-naive patients with EGFR-positive non–small cell lung cancer (NSCLC), afatinib appears safe and effective in a “real-world” setting, based on results of a phase 3b study.
Across a diverse population of patients, including those with brain metastases, uncommon mutations, multiple lines of prior therapy, and/or an Eastern Cooperative Oncology Group (ECOG) performance status of 2, afatinib delivered “encouraging” responses, reported lead author Antonio Passaro, MD, PhD, of the European Institute of Oncology in Milan. During his presentation at the European Lung Cancer Conference, Dr. Passaro described the safety profile as “predictable and manageable.”
The findings follow on the heels of the LUX-Lung trials, which showed that afatinib could match the progression-free survival (PFS) achieved with gefitinib, at about 11 months, while beating chemotherapy, which was associated with a PFS of approximately 5-7 months.
“However,” the investigators noted in their abstract, “in real-world practice chemotherapy remains a first-line choice.”
The present study aimed to demonstrate the real-world potential of afatinib across treatment lines, Dr. Passaro said at the meeting, presented by the European Society for Medical Oncology.
The patient population was diverse, with multiple treatment lines represented. The majority of patients (78%) received afatinib as first-line treatment, while smaller groups received the treatment as second-line (17%), or third-line or greater (5%). About one-third of the patients (36%) had an ECOG score of 0, about half (57%) had a score of 1, and a small group (8%) had a score of 2. A minority of patients had brain metastases (17%) and/or uncommon mutations (13%). Patients received 40 mg of afatinib daily; dose reduction to 20 mg was allowed if necessary.
Analysis showed that patients received afatinib for a median of almost 1 year (359 days). Slightly more than half of the patients (54%) got reduced doses because of adverse events, most commonly, diarrhea (25%) and rash (11%). About one out of five patients (22%) discontinued treatment entirely.
Secondarily, the investigators analyzed efficacy, reporting that the objective response rate was 46% and the disease control rate was 86%. During his presentation, Dr. Passaro focused on median time to symptomatic progression (TTSP) and median progression-free survival (PFS), describing these outcomes in relation to patient subgroups. Across all patients, TTSP was 14.9 months and PFS was 13.4 months. Among subgroups, patients receiving afatinib as first-line therapy had the best median PFS, at 13.8 months, which was comparable with those who received the treatment second-line (13.2 months). In contrast, patients receiving afatinib as a third-line treatment or later had noticeably shorter PFS, at 6.6 months. Baseline ECOG performance status showed a similar trend; patients with scores of 0 had a median PFS of 15.4 months, compared with 12.9 months for those with a score of 1, and 6.2 months with a score of 2. Patients with brain metastases fared worse than did those without (PFS 10.1 months vs. 13.9 months), and patients with uncommon mutations had shorter PFS than that of those with common mutations (6.0 months vs. 14.1 months). TTSP durations paralleled the above PFS trends.Boehringer Ingelheim funded the study. The investigators reported financial relationships with Roche, MSD, Bristol-Myers Squibb, AstraZeneca, and others.
SOURCE: Passaro et al. ELCC 2019. Abstract 115O.
GENEVA – For EGFR TKI-naive patients with EGFR-positive non–small cell lung cancer (NSCLC), afatinib appears safe and effective in a “real-world” setting, based on results of a phase 3b study.
Across a diverse population of patients, including those with brain metastases, uncommon mutations, multiple lines of prior therapy, and/or an Eastern Cooperative Oncology Group (ECOG) performance status of 2, afatinib delivered “encouraging” responses, reported lead author Antonio Passaro, MD, PhD, of the European Institute of Oncology in Milan. During his presentation at the European Lung Cancer Conference, Dr. Passaro described the safety profile as “predictable and manageable.”
The findings follow on the heels of the LUX-Lung trials, which showed that afatinib could match the progression-free survival (PFS) achieved with gefitinib, at about 11 months, while beating chemotherapy, which was associated with a PFS of approximately 5-7 months.
“However,” the investigators noted in their abstract, “in real-world practice chemotherapy remains a first-line choice.”
The present study aimed to demonstrate the real-world potential of afatinib across treatment lines, Dr. Passaro said at the meeting, presented by the European Society for Medical Oncology.
The patient population was diverse, with multiple treatment lines represented. The majority of patients (78%) received afatinib as first-line treatment, while smaller groups received the treatment as second-line (17%), or third-line or greater (5%). About one-third of the patients (36%) had an ECOG score of 0, about half (57%) had a score of 1, and a small group (8%) had a score of 2. A minority of patients had brain metastases (17%) and/or uncommon mutations (13%). Patients received 40 mg of afatinib daily; dose reduction to 20 mg was allowed if necessary.
Analysis showed that patients received afatinib for a median of almost 1 year (359 days). Slightly more than half of the patients (54%) got reduced doses because of adverse events, most commonly, diarrhea (25%) and rash (11%). About one out of five patients (22%) discontinued treatment entirely.
Secondarily, the investigators analyzed efficacy, reporting that the objective response rate was 46% and the disease control rate was 86%. During his presentation, Dr. Passaro focused on median time to symptomatic progression (TTSP) and median progression-free survival (PFS), describing these outcomes in relation to patient subgroups. Across all patients, TTSP was 14.9 months and PFS was 13.4 months. Among subgroups, patients receiving afatinib as first-line therapy had the best median PFS, at 13.8 months, which was comparable with those who received the treatment second-line (13.2 months). In contrast, patients receiving afatinib as a third-line treatment or later had noticeably shorter PFS, at 6.6 months. Baseline ECOG performance status showed a similar trend; patients with scores of 0 had a median PFS of 15.4 months, compared with 12.9 months for those with a score of 1, and 6.2 months with a score of 2. Patients with brain metastases fared worse than did those without (PFS 10.1 months vs. 13.9 months), and patients with uncommon mutations had shorter PFS than that of those with common mutations (6.0 months vs. 14.1 months). TTSP durations paralleled the above PFS trends.Boehringer Ingelheim funded the study. The investigators reported financial relationships with Roche, MSD, Bristol-Myers Squibb, AstraZeneca, and others.
SOURCE: Passaro et al. ELCC 2019. Abstract 115O.
REPORTING FROM ELCC 2019
Creating CAR T-cell therapies for T-cell malignancies
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.
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.
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.
EXPERT ANALYSIS FROM ALF 2019
Liquid biopsy falls short for isolated brain lesions in lung cancer
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.
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.
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.
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.
REPORTING FROM ELCC 2019
Key clinical point: Plasma circulating tumor DNA (ctDNA) analysis appears inadequate to detect molecular aberrations in patients with non–small cell lung cancer (NSCLC) who have isolated central nervous system (CNS) progression.
Major finding: In patients with at least 1 known NSCLC molecular alteration, ctDNA analysis was positive in 38% of those with isolated CNS disease, compared with 98% of those with systemic disease progression (P less than .0001).
Study details: A retrospective analysis of 66 patients with NSCLC, drawn from a screened population of 959 patients.
Disclosures: The investigators disclosed financial relationships with Celgene, Daiichi Sankyo, Eli Lilly, and others.
Source: Aldea et al. ELCC 2019. Abstract 110O.
‘Heartbeat bills’ give state lawmakers pause on antiabortion tactics
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.
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.
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.
Here’s a top strategy for immunosuppressant discontinuation in SLE
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.
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.
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.
REPORTING FROM LUPUS 2019
Novel CAR T, anti-PD-1 combo shows promise in MPD
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).
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).
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).
SOURCE: Adusumilli PS et al. AACR 2019, Abstract CT036.
REPORTING FROM AACR 2019
Direct-to-consumer genetic testing fraught with validity concerns
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.
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.
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.
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.
EXPERT ANALYSIS FROM INTERNAL MEDICINE 2019
Sense of self targeted by schizophrenia research
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.
, 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.
, 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.
, 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.
REPORTING FROM SIRS 2019