I have been amazed at psychiatrists who could see a patient who was obviously acutely psychotic and tell whether they had schizophrenia or bipolar disorder while the patient was acutely psychotic. I am amazed because I cannot do it, although I used to think I could.

Earlier in my career, I would see patients who were floridly psychotic who would have all the symptoms of schizophrenia, and I would think “Yep, they have schizophrenia, all right.” After all, when I was starting out in psychiatry, I thought that Schneiderian first-rank symptoms were pathognomonic of schizophrenia, but research later showed that these first-rank symptoms could also be characteristic of dissociative disorder.

I quickly learned that some of the patients I thought had schizophrenia would recover and return to their premorbid level of functioning after the psychotic episode. Accordingly, by definition – for example, there was not a deterioration of psychosocial functioning after their psychotic episode – I would have to revise their diagnosis to bipolar disorder.

Finally, I got hip and realized that I could not determine patients’ diagnoses when they were acutely psychotic, and I started diagnosing patients as having a psychosis not otherwise specified (NOS).

Of course, using the NOS designation made many of my academic colleagues scoff at my diagnostic skills, but then I read the DSM-IV Guidebook by Frances, First, and Pincus (1995), and it was explained the NOS designation was wrongly maligned. Apparently, it was learned that there was extensive comorbidity between various diagnostic categories, and, it was explicated, approximately 50% of patients could not fit neatly into any specific diagnostic category. In fact, regarding psychotic and affective disorders, depending on how good a history patients and/or their family could deliver, it would sometimes take the resolution of the patients’ psychosis before it became clear that they were or were not going to return to premorbid functioning or continue to show significant psychosocial deterioration.

Since psychiatrists do not yet have objective diagnostic tests to determine whether a psychotic patient has some form of schizophrenia or bipolar disorder, it seems to me that we should be more prudent about diagnosing a patient with either two diagnoses, because I do not think we can tell the patients’ post psychotic outcomes.

I recently had one patient who had been hospitalized for 39 days, and, who was so acutely floridly psychotic, I did not think she was going to recover. She was on antipsychotic medication at bedtime and other mood stabilizers during the day, but she had to be in soft restraints for a significant period of time and was getting several antipsychotic medication injections daily because she was extremely rambunctious and dangerously disruptive on the medical-surgical/psychiatric floor. Finally, when I reluctantly added lithium to her treatment regimen (I was unenthusiastic about putting her on lithium, which had worked for her in the past, because her kidneys were not functioning well and she had arrived at the hospital with lithium toxicity), she recovered. The transformation was remarkable.

So, it seems to me that a functional outcome assessment should determine the difference between patients who have bipolar disorder and schizophrenia as, by definition, if you do not have a deterioration in your psychosocial functioning you probably have bipolar disorder, and if you do have a deterioration in your psychosocial functioning you probably have schizophrenia. From a practical standpoint, post psychotic functioning is a major distinction between these two diagnoses by definition, and, since we don’t have objective measures to delineate bipolar disorder from schizophrenia (some studies have shown there is remarkable overlap between these two disorders), it seems to me we should give more consideration to post psychotic functioning, instead of trying to nail the patients’ diagnoses when they are acutely psychotic.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s medical/surgical-psychiatry inpatient unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. Be sure to check out Dr. Bell’s new book Fetal Alcohol Exposure in the African-American Community.

I have been amazed at psychiatrists who could see a patient who was obviously acutely psychotic and tell whether they had schizophrenia or bipolar disorder while the patient was acutely psychotic. I am amazed because I cannot do it, although I used to think I could.

Earlier in my career, I would see patients who were floridly psychotic who would have all the symptoms of schizophrenia, and I would think “Yep, they have schizophrenia, all right.” After all, when I was starting out in psychiatry, I thought that Schneiderian first-rank symptoms were pathognomonic of schizophrenia, but research later showed that these first-rank symptoms could also be characteristic of dissociative disorder.

I quickly learned that some of the patients I thought had schizophrenia would recover and return to their premorbid level of functioning after the psychotic episode. Accordingly, by definition – for example, there was not a deterioration of psychosocial functioning after their psychotic episode – I would have to revise their diagnosis to bipolar disorder.

Finally, I got hip and realized that I could not determine patients’ diagnoses when they were acutely psychotic, and I started diagnosing patients as having a psychosis not otherwise specified (NOS).

Of course, using the NOS designation made many of my academic colleagues scoff at my diagnostic skills, but then I read the DSM-IV Guidebook by Frances, First, and Pincus (1995), and it was explained the NOS designation was wrongly maligned. Apparently, it was learned that there was extensive comorbidity between various diagnostic categories, and, it was explicated, approximately 50% of patients could not fit neatly into any specific diagnostic category. In fact, regarding psychotic and affective disorders, depending on how good a history patients and/or their family could deliver, it would sometimes take the resolution of the patients’ psychosis before it became clear that they were or were not going to return to premorbid functioning or continue to show significant psychosocial deterioration.

Since psychiatrists do not yet have objective diagnostic tests to determine whether a psychotic patient has some form of schizophrenia or bipolar disorder, it seems to me that we should be more prudent about diagnosing a patient with either two diagnoses, because I do not think we can tell the patients’ post psychotic outcomes.

I recently had one patient who had been hospitalized for 39 days, and, who was so acutely floridly psychotic, I did not think she was going to recover. She was on antipsychotic medication at bedtime and other mood stabilizers during the day, but she had to be in soft restraints for a significant period of time and was getting several antipsychotic medication injections daily because she was extremely rambunctious and dangerously disruptive on the medical-surgical/psychiatric floor. Finally, when I reluctantly added lithium to her treatment regimen (I was unenthusiastic about putting her on lithium, which had worked for her in the past, because her kidneys were not functioning well and she had arrived at the hospital with lithium toxicity), she recovered. The transformation was remarkable.

So, it seems to me that a functional outcome assessment should determine the difference between patients who have bipolar disorder and schizophrenia as, by definition, if you do not have a deterioration in your psychosocial functioning you probably have bipolar disorder, and if you do have a deterioration in your psychosocial functioning you probably have schizophrenia. From a practical standpoint, post psychotic functioning is a major distinction between these two diagnoses by definition, and, since we don’t have objective measures to delineate bipolar disorder from schizophrenia (some studies have shown there is remarkable overlap between these two disorders), it seems to me we should give more consideration to post psychotic functioning, instead of trying to nail the patients’ diagnoses when they are acutely psychotic.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s medical/surgical-psychiatry inpatient unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. Be sure to check out Dr. Bell’s new book Fetal Alcohol Exposure in the African-American Community.

I have been amazed at psychiatrists who could see a patient who was obviously acutely psychotic and tell whether they had schizophrenia or bipolar disorder while the patient was acutely psychotic. I am amazed because I cannot do it, although I used to think I could.

Earlier in my career, I would see patients who were floridly psychotic who would have all the symptoms of schizophrenia, and I would think “Yep, they have schizophrenia, all right.” After all, when I was starting out in psychiatry, I thought that Schneiderian first-rank symptoms were pathognomonic of schizophrenia, but research later showed that these first-rank symptoms could also be characteristic of dissociative disorder.

I quickly learned that some of the patients I thought had schizophrenia would recover and return to their premorbid level of functioning after the psychotic episode. Accordingly, by definition – for example, there was not a deterioration of psychosocial functioning after their psychotic episode – I would have to revise their diagnosis to bipolar disorder.

Finally, I got hip and realized that I could not determine patients’ diagnoses when they were acutely psychotic, and I started diagnosing patients as having a psychosis not otherwise specified (NOS).

Of course, using the NOS designation made many of my academic colleagues scoff at my diagnostic skills, but then I read the DSM-IV Guidebook by Frances, First, and Pincus (1995), and it was explained the NOS designation was wrongly maligned. Apparently, it was learned that there was extensive comorbidity between various diagnostic categories, and, it was explicated, approximately 50% of patients could not fit neatly into any specific diagnostic category. In fact, regarding psychotic and affective disorders, depending on how good a history patients and/or their family could deliver, it would sometimes take the resolution of the patients’ psychosis before it became clear that they were or were not going to return to premorbid functioning or continue to show significant psychosocial deterioration.

Since psychiatrists do not yet have objective diagnostic tests to determine whether a psychotic patient has some form of schizophrenia or bipolar disorder, it seems to me that we should be more prudent about diagnosing a patient with either two diagnoses, because I do not think we can tell the patients’ post psychotic outcomes.

I recently had one patient who had been hospitalized for 39 days, and, who was so acutely floridly psychotic, I did not think she was going to recover. She was on antipsychotic medication at bedtime and other mood stabilizers during the day, but she had to be in soft restraints for a significant period of time and was getting several antipsychotic medication injections daily because she was extremely rambunctious and dangerously disruptive on the medical-surgical/psychiatric floor. Finally, when I reluctantly added lithium to her treatment regimen (I was unenthusiastic about putting her on lithium, which had worked for her in the past, because her kidneys were not functioning well and she had arrived at the hospital with lithium toxicity), she recovered. The transformation was remarkable.

So, it seems to me that a functional outcome assessment should determine the difference between patients who have bipolar disorder and schizophrenia as, by definition, if you do not have a deterioration in your psychosocial functioning you probably have bipolar disorder, and if you do have a deterioration in your psychosocial functioning you probably have schizophrenia. From a practical standpoint, post psychotic functioning is a major distinction between these two diagnoses by definition, and, since we don’t have objective measures to delineate bipolar disorder from schizophrenia (some studies have shown there is remarkable overlap between these two disorders), it seems to me we should give more consideration to post psychotic functioning, instead of trying to nail the patients’ diagnoses when they are acutely psychotic.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s medical/surgical-psychiatry inpatient unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. Be sure to check out Dr. Bell’s new book Fetal Alcohol Exposure in the African-American Community.

The Food and Drug Administration has ordered companies to immediately cease selling transvaginal mesh intended for pelvic organ prolapse (POP) repair.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The mandate came after Boston Scientific and Coloplast failed to provide adequate safety and efficacy information to the federal regulatory body in the wake of a 2016 reclassification to Class III (high-risk) devices, according to an FDA press statement. Both companies were required to submit a premarket approval application to continue marketing the mesh in the United States. Boston Scientific did file two PMAs, one for each of its transvaginal mesh products, but the FDA said the applications did not contain the required efficacy and safety data.

Both companies will have 10 days to submit their plan to withdraw these products from the market.

“In order for these mesh devices to stay on the market, we determined that we needed evidence that they worked better than surgery without the use of mesh to repair POP. That evidence was lacking in these premarket applications, and we couldn’t assure women that these devices were safe and effective long term,” said Jeffrey Shuren, MD, director of FDA’s Center for Devices and Radiological Health. “Patient safety is our highest priority, and women must have access to safe medical devices that provide relief from symptoms and better management of their medical conditions. The FDA has committed to taking forceful new actions to enhance device safety and encourage innovations that lead to safer medical devices, so that patients have access to safe and effective medical devices and the information they need to make informed decisions about their care.”

The deadline for submitting premarket approval applications for POP repair with transvaginal mesh was July 5, 2018. Manufacturers that did not file PMAs were required to pull their devices from the market. Those that did could keep selling the mesh while FDA reviewed their PMAs.

Boston Scientific submitted PMAs for its two devices, the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair System. Coloplast filed a PMA for its device, Restorelle DirectFix Anterior. But in February, the FDA convened an advisory panel to discuss just how to evaluate the safety and efficacy of the products.

To prove efficacy, the panel concluded, transvaginal POP repair with mesh should be better than repair with native tissue at 36 months, and the safety should be superior to repair with native tissue repair. The FDA agreed. However, the submitted premarket approval application did not include these kinds of data. Therefore, the agency declined to approve the devices.

In addition to stopping U.S. sales, FDA has required Boston Scientific and Coloplast to continue safety and efficacy follow-up of all women included in their 522 studies.

Coloplast did not have a press or public statement on its website as of April 16. Boston Scientific did have one.

“Up to 50% of women in the U.S. will suffer from POP during their lives, and we believe these women should have access to safe and effective treatment options,” according to the statement. “As a global leader in the pelvic floor space, we remain steadfast in our commitment to helping women live better and healthier lives. We also remain confident in the benefits and safety of our treatments for POP, and we look forward to continuing to work with the FDA on our PMAs for the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair Matrix, which are currently under review.”

The FDA statement also included advice to women who have had the mesh procedure for POP, and for their physicians

“Women who have had transvaginal mesh placed for the surgical repair of POP should continue with their annual and other routine check-ups and follow-up care. There is no need to take additional action if they are satisfied with their surgery and are not having complications or symptoms. Patients should notify their health care professionals if they have complications or symptoms, including persistent vaginal bleeding or discharge, pelvic or groin pain, or pain with sex. They should also let their health care professional know if they have surgical mesh, especially if they plan to have another surgery or other medical procedures. Women who were planning to have mesh placed transvaginally for the repair of POP should discuss other treatment options with their doctors.”

msullivan@mdedge.com

The Food and Drug Administration has ordered companies to immediately cease selling transvaginal mesh intended for pelvic organ prolapse (POP) repair.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The mandate came after Boston Scientific and Coloplast failed to provide adequate safety and efficacy information to the federal regulatory body in the wake of a 2016 reclassification to Class III (high-risk) devices, according to an FDA press statement. Both companies were required to submit a premarket approval application to continue marketing the mesh in the United States. Boston Scientific did file two PMAs, one for each of its transvaginal mesh products, but the FDA said the applications did not contain the required efficacy and safety data.

Both companies will have 10 days to submit their plan to withdraw these products from the market.

“In order for these mesh devices to stay on the market, we determined that we needed evidence that they worked better than surgery without the use of mesh to repair POP. That evidence was lacking in these premarket applications, and we couldn’t assure women that these devices were safe and effective long term,” said Jeffrey Shuren, MD, director of FDA’s Center for Devices and Radiological Health. “Patient safety is our highest priority, and women must have access to safe medical devices that provide relief from symptoms and better management of their medical conditions. The FDA has committed to taking forceful new actions to enhance device safety and encourage innovations that lead to safer medical devices, so that patients have access to safe and effective medical devices and the information they need to make informed decisions about their care.”

The deadline for submitting premarket approval applications for POP repair with transvaginal mesh was July 5, 2018. Manufacturers that did not file PMAs were required to pull their devices from the market. Those that did could keep selling the mesh while FDA reviewed their PMAs.

Boston Scientific submitted PMAs for its two devices, the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair System. Coloplast filed a PMA for its device, Restorelle DirectFix Anterior. But in February, the FDA convened an advisory panel to discuss just how to evaluate the safety and efficacy of the products.

To prove efficacy, the panel concluded, transvaginal POP repair with mesh should be better than repair with native tissue at 36 months, and the safety should be superior to repair with native tissue repair. The FDA agreed. However, the submitted premarket approval application did not include these kinds of data. Therefore, the agency declined to approve the devices.

In addition to stopping U.S. sales, FDA has required Boston Scientific and Coloplast to continue safety and efficacy follow-up of all women included in their 522 studies.

Coloplast did not have a press or public statement on its website as of April 16. Boston Scientific did have one.

“Up to 50% of women in the U.S. will suffer from POP during their lives, and we believe these women should have access to safe and effective treatment options,” according to the statement. “As a global leader in the pelvic floor space, we remain steadfast in our commitment to helping women live better and healthier lives. We also remain confident in the benefits and safety of our treatments for POP, and we look forward to continuing to work with the FDA on our PMAs for the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair Matrix, which are currently under review.”

The FDA statement also included advice to women who have had the mesh procedure for POP, and for their physicians

“Women who have had transvaginal mesh placed for the surgical repair of POP should continue with their annual and other routine check-ups and follow-up care. There is no need to take additional action if they are satisfied with their surgery and are not having complications or symptoms. Patients should notify their health care professionals if they have complications or symptoms, including persistent vaginal bleeding or discharge, pelvic or groin pain, or pain with sex. They should also let their health care professional know if they have surgical mesh, especially if they plan to have another surgery or other medical procedures. Women who were planning to have mesh placed transvaginally for the repair of POP should discuss other treatment options with their doctors.”

msullivan@mdedge.com

The Food and Drug Administration has ordered companies to immediately cease selling transvaginal mesh intended for pelvic organ prolapse (POP) repair.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The mandate came after Boston Scientific and Coloplast failed to provide adequate safety and efficacy information to the federal regulatory body in the wake of a 2016 reclassification to Class III (high-risk) devices, according to an FDA press statement. Both companies were required to submit a premarket approval application to continue marketing the mesh in the United States. Boston Scientific did file two PMAs, one for each of its transvaginal mesh products, but the FDA said the applications did not contain the required efficacy and safety data.

Both companies will have 10 days to submit their plan to withdraw these products from the market.

“In order for these mesh devices to stay on the market, we determined that we needed evidence that they worked better than surgery without the use of mesh to repair POP. That evidence was lacking in these premarket applications, and we couldn’t assure women that these devices were safe and effective long term,” said Jeffrey Shuren, MD, director of FDA’s Center for Devices and Radiological Health. “Patient safety is our highest priority, and women must have access to safe medical devices that provide relief from symptoms and better management of their medical conditions. The FDA has committed to taking forceful new actions to enhance device safety and encourage innovations that lead to safer medical devices, so that patients have access to safe and effective medical devices and the information they need to make informed decisions about their care.”

The deadline for submitting premarket approval applications for POP repair with transvaginal mesh was July 5, 2018. Manufacturers that did not file PMAs were required to pull their devices from the market. Those that did could keep selling the mesh while FDA reviewed their PMAs.

Boston Scientific submitted PMAs for its two devices, the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair System. Coloplast filed a PMA for its device, Restorelle DirectFix Anterior. But in February, the FDA convened an advisory panel to discuss just how to evaluate the safety and efficacy of the products.

To prove efficacy, the panel concluded, transvaginal POP repair with mesh should be better than repair with native tissue at 36 months, and the safety should be superior to repair with native tissue repair. The FDA agreed. However, the submitted premarket approval application did not include these kinds of data. Therefore, the agency declined to approve the devices.

In addition to stopping U.S. sales, FDA has required Boston Scientific and Coloplast to continue safety and efficacy follow-up of all women included in their 522 studies.

Coloplast did not have a press or public statement on its website as of April 16. Boston Scientific did have one.

“Up to 50% of women in the U.S. will suffer from POP during their lives, and we believe these women should have access to safe and effective treatment options,” according to the statement. “As a global leader in the pelvic floor space, we remain steadfast in our commitment to helping women live better and healthier lives. We also remain confident in the benefits and safety of our treatments for POP, and we look forward to continuing to work with the FDA on our PMAs for the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair Matrix, which are currently under review.”

The FDA statement also included advice to women who have had the mesh procedure for POP, and for their physicians

“Women who have had transvaginal mesh placed for the surgical repair of POP should continue with their annual and other routine check-ups and follow-up care. There is no need to take additional action if they are satisfied with their surgery and are not having complications or symptoms. Patients should notify their health care professionals if they have complications or symptoms, including persistent vaginal bleeding or discharge, pelvic or groin pain, or pain with sex. They should also let their health care professional know if they have surgical mesh, especially if they plan to have another surgery or other medical procedures. Women who were planning to have mesh placed transvaginally for the repair of POP should discuss other treatment options with their doctors.”

msullivan@mdedge.com

TUCSON, ARIZ. – Enhanced recovery after surgery (ERAS) has been demonstrated to improve patient outcomes after hysterectomy, but physicians should be prepared for a significant uptick in unscheduled patient encounters. 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. – Enhanced recovery after surgery (ERAS) has been demonstrated to improve patient outcomes after hysterectomy, but physicians should be prepared for a significant uptick in unscheduled patient encounters. 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. – Enhanced recovery after surgery (ERAS) has been demonstrated to improve patient outcomes after hysterectomy, but physicians should be prepared for a significant uptick in unscheduled patient encounters. 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.

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.

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.

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.

jensmith@mdedge.com

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.

jensmith@mdedge.com

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.

jensmith@mdedge.com

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

Will Pass/MDedge News

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

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

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

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

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

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

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

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

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

Will Pass/MDedge News

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

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

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

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

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

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

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

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

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

Will Pass/MDedge News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tennessee infighting over ‘heartbeat bill’

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

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

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

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

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

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

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

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

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

Name-calling in Oklahoma

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

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

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

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

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

In response, Sen. Treat abandoned the trigger bill.

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

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

Not far enough in Georgia

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

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

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

Cost-as-no-objection Kentucky

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tennessee infighting over ‘heartbeat bill’

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

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

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

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

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

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

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

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

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

Name-calling in Oklahoma

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

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

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

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

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

In response, Sen. Treat abandoned the trigger bill.

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

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

Not far enough in Georgia

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

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

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

Cost-as-no-objection Kentucky

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tennessee infighting over ‘heartbeat bill’

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

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

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

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

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

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

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

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

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

Name-calling in Oklahoma

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

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

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

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

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

In response, Sen. Treat abandoned the trigger bill.

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

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

Not far enough in Georgia

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

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

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

Cost-as-no-objection Kentucky

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

bjancin@mdedge.com

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.

bjancin@mdedge.com

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.

bjancin@mdedge.com

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).

sworcester@mdedge.com

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).

sworcester@mdedge.com

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).

sworcester@mdedge.com

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