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Case shows clinical assessment supersedes psychological screening tools
AUSTIN, TEX. – Using psychological screenings for law enforcement employment decisions can be a worthwhile supplement to more traditional hiring procedures, but such tools should be used with caution, a recent case study suggests.
“Pre-employment psychological evaluations for police officers are increasingly utilizing self-reported personality assessments to identify attributes in candidates that have shown to correlate with job performance outcomes,” Ann Marie Mckenzie Cassidy, DO, of Icahn School of Medicine at Mount Sinai, New York, and her colleagues wrote in an abstract presented at the annual meeting of the American Academy of Psychiatry and the Law.
“As research supporting the predictive power of written self-reported measurements expands, the call for this empirically validated data to be weighted over clinician judgment is becoming more substantive,” the researchers wrote. “The following case exemplifies a psychological evaluation where test results were either inconclusive or strongly conflicted with the clinical picture of the candidate.”
The applicant was a 34-year-old male Army veteran who received an honorable discharge after three deployments. Though he had no relevant medical or formal psychiatric history or drug use, he said he did drink alcohol heavily for a short time after joining the Army. He also had four speeding citations and one drag racing citation.
His personal history revealed several problems, including a military write-up for yelling at a subordinate and a history of difficulties working with his supervisor.
“While working as a car mechanic, he was unable to resolve a conflict with a difficult customer” and quit his job without notice, leading his employer to say he would not hire the applicant again. Yet, the applicant “denied interpersonal issues at work” and said he did not recall the yelling incident. He also said the situation where he quit with only 2 hours’ notice was unfair.
The applicant reported stress, “feeling down and having a diminished interest in activities” following his deployment in Iraq, but he turned down treatment for his stress. He also “used unprofessional language during the examination, and, when asked to refrain from cursing, he did not express concern about this conduct.”
His psychological test results on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), however, suggested “a pattern of positive impression management and defensiveness that is not likely to accurately represent existing psychopathology,” the researchers reported. “Closer review suggests the applicant is apt to see himself as having high moral standards and not having aggressive impulses,” they wrote. Similarly, the applicant’s Sixteen Personality Factor Questionnaire results “reflected an individual who is tough-minded, with low anxiety, who is emotionally stable, deferential, and relaxed.”
These two tools’ findings conflicted with the applicant’s history and presentation, and the examiner deemed him “psychologically unsuitable for hire.”
The researchers said this case reinforces the importance of investigating how empirical data – even with tools such as the MMPI-2, whose predictive power has been validated in several studies – are weighted and used with clinical psychological assessments.
the researchers concluded. “Until there is greater exploration of divergent or complementary testing findings and clinical judgment, test data should not be weighted over clinical judgment in psychological evaluations.”
AUSTIN, TEX. – Using psychological screenings for law enforcement employment decisions can be a worthwhile supplement to more traditional hiring procedures, but such tools should be used with caution, a recent case study suggests.
“Pre-employment psychological evaluations for police officers are increasingly utilizing self-reported personality assessments to identify attributes in candidates that have shown to correlate with job performance outcomes,” Ann Marie Mckenzie Cassidy, DO, of Icahn School of Medicine at Mount Sinai, New York, and her colleagues wrote in an abstract presented at the annual meeting of the American Academy of Psychiatry and the Law.
“As research supporting the predictive power of written self-reported measurements expands, the call for this empirically validated data to be weighted over clinician judgment is becoming more substantive,” the researchers wrote. “The following case exemplifies a psychological evaluation where test results were either inconclusive or strongly conflicted with the clinical picture of the candidate.”
The applicant was a 34-year-old male Army veteran who received an honorable discharge after three deployments. Though he had no relevant medical or formal psychiatric history or drug use, he said he did drink alcohol heavily for a short time after joining the Army. He also had four speeding citations and one drag racing citation.
His personal history revealed several problems, including a military write-up for yelling at a subordinate and a history of difficulties working with his supervisor.
“While working as a car mechanic, he was unable to resolve a conflict with a difficult customer” and quit his job without notice, leading his employer to say he would not hire the applicant again. Yet, the applicant “denied interpersonal issues at work” and said he did not recall the yelling incident. He also said the situation where he quit with only 2 hours’ notice was unfair.
The applicant reported stress, “feeling down and having a diminished interest in activities” following his deployment in Iraq, but he turned down treatment for his stress. He also “used unprofessional language during the examination, and, when asked to refrain from cursing, he did not express concern about this conduct.”
His psychological test results on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), however, suggested “a pattern of positive impression management and defensiveness that is not likely to accurately represent existing psychopathology,” the researchers reported. “Closer review suggests the applicant is apt to see himself as having high moral standards and not having aggressive impulses,” they wrote. Similarly, the applicant’s Sixteen Personality Factor Questionnaire results “reflected an individual who is tough-minded, with low anxiety, who is emotionally stable, deferential, and relaxed.”
These two tools’ findings conflicted with the applicant’s history and presentation, and the examiner deemed him “psychologically unsuitable for hire.”
The researchers said this case reinforces the importance of investigating how empirical data – even with tools such as the MMPI-2, whose predictive power has been validated in several studies – are weighted and used with clinical psychological assessments.
the researchers concluded. “Until there is greater exploration of divergent or complementary testing findings and clinical judgment, test data should not be weighted over clinical judgment in psychological evaluations.”
AUSTIN, TEX. – Using psychological screenings for law enforcement employment decisions can be a worthwhile supplement to more traditional hiring procedures, but such tools should be used with caution, a recent case study suggests.
“Pre-employment psychological evaluations for police officers are increasingly utilizing self-reported personality assessments to identify attributes in candidates that have shown to correlate with job performance outcomes,” Ann Marie Mckenzie Cassidy, DO, of Icahn School of Medicine at Mount Sinai, New York, and her colleagues wrote in an abstract presented at the annual meeting of the American Academy of Psychiatry and the Law.
“As research supporting the predictive power of written self-reported measurements expands, the call for this empirically validated data to be weighted over clinician judgment is becoming more substantive,” the researchers wrote. “The following case exemplifies a psychological evaluation where test results were either inconclusive or strongly conflicted with the clinical picture of the candidate.”
The applicant was a 34-year-old male Army veteran who received an honorable discharge after three deployments. Though he had no relevant medical or formal psychiatric history or drug use, he said he did drink alcohol heavily for a short time after joining the Army. He also had four speeding citations and one drag racing citation.
His personal history revealed several problems, including a military write-up for yelling at a subordinate and a history of difficulties working with his supervisor.
“While working as a car mechanic, he was unable to resolve a conflict with a difficult customer” and quit his job without notice, leading his employer to say he would not hire the applicant again. Yet, the applicant “denied interpersonal issues at work” and said he did not recall the yelling incident. He also said the situation where he quit with only 2 hours’ notice was unfair.
The applicant reported stress, “feeling down and having a diminished interest in activities” following his deployment in Iraq, but he turned down treatment for his stress. He also “used unprofessional language during the examination, and, when asked to refrain from cursing, he did not express concern about this conduct.”
His psychological test results on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), however, suggested “a pattern of positive impression management and defensiveness that is not likely to accurately represent existing psychopathology,” the researchers reported. “Closer review suggests the applicant is apt to see himself as having high moral standards and not having aggressive impulses,” they wrote. Similarly, the applicant’s Sixteen Personality Factor Questionnaire results “reflected an individual who is tough-minded, with low anxiety, who is emotionally stable, deferential, and relaxed.”
These two tools’ findings conflicted with the applicant’s history and presentation, and the examiner deemed him “psychologically unsuitable for hire.”
The researchers said this case reinforces the importance of investigating how empirical data – even with tools such as the MMPI-2, whose predictive power has been validated in several studies – are weighted and used with clinical psychological assessments.
the researchers concluded. “Until there is greater exploration of divergent or complementary testing findings and clinical judgment, test data should not be weighted over clinical judgment in psychological evaluations.”
REPORTING FROM THE AAPL ANNUAL MEETING
Cervical bupivacaine blocks pain after laparoscopic hysterectomy
LAS VEGAS – according to a small trial at the University of Tennessee, Chattanooga.
Twenty-one women were randomized to 0.5% bupivacaine, 5 mL injected into the cervix at the 3 o’clock position, and 5 mL injected into at the 9 o’clock position to a depth of 3 cm, after anesthesia induction but before insertion of the uterine manipulator. A control group of 20 women received 5 mL of 0.9% saline injected into the same positions. Surgeons were blinded to the randomization.
A stopwatch was started at extubation, and the women were asked to rate their pain on a 10-point visual analogue scale exactly at 30 and 60 minutes.
The bupivacaine group had less pain at both 30 minutes (3.2 versus 5.7 points, P = .01) and 60 minutes (2.3 versus 5.9 points, P less than .001); 71% of women in the bupivacaine group had an average score of 4 or less, indicating adequate pain control, versus just 25% in the control arm (P = .003)
“This is something we should be considering” routinely for laparoscopic hysterectomy, an audience member said after hearing the presentation at a meeting sponsored by AAGL.
Another audience member was concerned about urinary retention, but there was no increase in the treatment arm, said lead investigator Steven Radtke, MD, a former ob.gyn. surgery fellow at the university, but now at Texas Tech University, El Paso.
There have been many prior attempts to reduce pain after laparoscopic hysterectomy, such as infiltrating port sites with local anesthetic, but the results have been marginal at best, and almost all of them have focused on the abdominal wall as the source of pain.
The investigators thought that pain was more related to perimetrium dissection, colpotomy, and other parts of the operation. There also have been good studies showing that agents injected into the cervix infuse throughout the area. The team decided to try bupivacaine because it’s inexpensive and has a good duration of action, about 8 hours.
There were no significant demographic or intraoperative differences between the groups. On average, women were in their mid-40s, with a body mass index of about 31 kg/m2. The operations took about 2 hours, and were for benign indications, such as fibroids. Oophorectomy was the only concomitant procedure allowed.
The investigators are interested in repeating their investigation with liposomal bupivacaine (Exparel), which has a duration of action past 24 hours. It’s much more expensive, but the strong trial results justify the cost, Dr. Radtke said.
There was no external funding, and Dr. Radtke didn’t have any disclosures.
SOURCE: Radtke S et al. 2018 AAGL Global Congress, Abstract 130.
LAS VEGAS – according to a small trial at the University of Tennessee, Chattanooga.
Twenty-one women were randomized to 0.5% bupivacaine, 5 mL injected into the cervix at the 3 o’clock position, and 5 mL injected into at the 9 o’clock position to a depth of 3 cm, after anesthesia induction but before insertion of the uterine manipulator. A control group of 20 women received 5 mL of 0.9% saline injected into the same positions. Surgeons were blinded to the randomization.
A stopwatch was started at extubation, and the women were asked to rate their pain on a 10-point visual analogue scale exactly at 30 and 60 minutes.
The bupivacaine group had less pain at both 30 minutes (3.2 versus 5.7 points, P = .01) and 60 minutes (2.3 versus 5.9 points, P less than .001); 71% of women in the bupivacaine group had an average score of 4 or less, indicating adequate pain control, versus just 25% in the control arm (P = .003)
“This is something we should be considering” routinely for laparoscopic hysterectomy, an audience member said after hearing the presentation at a meeting sponsored by AAGL.
Another audience member was concerned about urinary retention, but there was no increase in the treatment arm, said lead investigator Steven Radtke, MD, a former ob.gyn. surgery fellow at the university, but now at Texas Tech University, El Paso.
There have been many prior attempts to reduce pain after laparoscopic hysterectomy, such as infiltrating port sites with local anesthetic, but the results have been marginal at best, and almost all of them have focused on the abdominal wall as the source of pain.
The investigators thought that pain was more related to perimetrium dissection, colpotomy, and other parts of the operation. There also have been good studies showing that agents injected into the cervix infuse throughout the area. The team decided to try bupivacaine because it’s inexpensive and has a good duration of action, about 8 hours.
There were no significant demographic or intraoperative differences between the groups. On average, women were in their mid-40s, with a body mass index of about 31 kg/m2. The operations took about 2 hours, and were for benign indications, such as fibroids. Oophorectomy was the only concomitant procedure allowed.
The investigators are interested in repeating their investigation with liposomal bupivacaine (Exparel), which has a duration of action past 24 hours. It’s much more expensive, but the strong trial results justify the cost, Dr. Radtke said.
There was no external funding, and Dr. Radtke didn’t have any disclosures.
SOURCE: Radtke S et al. 2018 AAGL Global Congress, Abstract 130.
LAS VEGAS – according to a small trial at the University of Tennessee, Chattanooga.
Twenty-one women were randomized to 0.5% bupivacaine, 5 mL injected into the cervix at the 3 o’clock position, and 5 mL injected into at the 9 o’clock position to a depth of 3 cm, after anesthesia induction but before insertion of the uterine manipulator. A control group of 20 women received 5 mL of 0.9% saline injected into the same positions. Surgeons were blinded to the randomization.
A stopwatch was started at extubation, and the women were asked to rate their pain on a 10-point visual analogue scale exactly at 30 and 60 minutes.
The bupivacaine group had less pain at both 30 minutes (3.2 versus 5.7 points, P = .01) and 60 minutes (2.3 versus 5.9 points, P less than .001); 71% of women in the bupivacaine group had an average score of 4 or less, indicating adequate pain control, versus just 25% in the control arm (P = .003)
“This is something we should be considering” routinely for laparoscopic hysterectomy, an audience member said after hearing the presentation at a meeting sponsored by AAGL.
Another audience member was concerned about urinary retention, but there was no increase in the treatment arm, said lead investigator Steven Radtke, MD, a former ob.gyn. surgery fellow at the university, but now at Texas Tech University, El Paso.
There have been many prior attempts to reduce pain after laparoscopic hysterectomy, such as infiltrating port sites with local anesthetic, but the results have been marginal at best, and almost all of them have focused on the abdominal wall as the source of pain.
The investigators thought that pain was more related to perimetrium dissection, colpotomy, and other parts of the operation. There also have been good studies showing that agents injected into the cervix infuse throughout the area. The team decided to try bupivacaine because it’s inexpensive and has a good duration of action, about 8 hours.
There were no significant demographic or intraoperative differences between the groups. On average, women were in their mid-40s, with a body mass index of about 31 kg/m2. The operations took about 2 hours, and were for benign indications, such as fibroids. Oophorectomy was the only concomitant procedure allowed.
The investigators are interested in repeating their investigation with liposomal bupivacaine (Exparel), which has a duration of action past 24 hours. It’s much more expensive, but the strong trial results justify the cost, Dr. Radtke said.
There was no external funding, and Dr. Radtke didn’t have any disclosures.
SOURCE: Radtke S et al. 2018 AAGL Global Congress, Abstract 130.
REPORTING FROM AAGL GLOBAL CONGRESS
Key clinical point: Postoperative pain can be significantly reduced by injecting the cervix with bupivacaine prior to laparoscopic hysterectomy.
Major finding: The bupivacaine group had less pain at both 30 minutes (3.2 versus 5.7 points, P = .01) and 60 minutes (2.3 versus 5.9 points, P less than .001).
Study details: In a randomized study, 21 women received bupivacaine anesthesia and 20 control women were injected with saline.
Disclosures: There was no external funding, and Dr. Radtke didn’t have any disclosures.
Source: Radtke S et al. 2018 AAGL Global Congress, Abstract 130.
Sickle cell disease guidelines release set for early 2019
, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.
The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.
Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.
Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.
The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.
Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.
Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
, according to Robert Liem, MD, chair of the American Society of Hematology coordination panel for the initiative.
The new clinical practice recommendations will expand on 2014 guidelines published by the National Heart, Lung, and Blood Institute in a way that will help both hematologists and nonhematologists who take care of patients with sickle cell disease, Dr. Liem said in a video interview at the annual meeting of the American Society of Hematology.
Five different guidelines are under development to cover different aspects of acute and chronic complications of sickle cell disease, including pain, cardiopulmonary and kidney disease, cerebrovascular disease, transfusion support, and stem cell transplantation.
Watch the video to learn more about the guideline effort from the perspective of Dr. Liem, who is also the director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
FROM ASH 2018
Nocturnal hypoxemia predicts incident atrial fibrillation in sleep apnea patients
Researchers have found a significant independent association between nocturnal hypoxemia and risk of incident atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA), which they believe may help prevent the development of AF in this population, according to recent research published in the journal CHEST®.
“These findings are consistent with those of previous studies suggesting that these groups, who are typically at somewhat lower risk of [atrial fibrillation], might be especially vulnerable to the effects of [obstructive sleep apnea] and hypoxemia,” Tetyana Kendzerska, MD, PhD, of the University of Ottawa in Ottawa, and her colleagues wrote in their study.
They performed an analysis of 8,256 patients with data linked to a provincial health administrative database who had suspected OSA who underwent a sleep study at a large academic hospital between 1994 and 2010. The patients were median 47 years old; 62% of the cohort were men, 28% had an apnea-hypopnea index (AHI) of greater than 30 events per hour, and 6% spent more than 30% of the time during sleep with less than 90% oxygen saturation.
Overall, 173 of 8,256 patients (2.1%) developed AF during the study period. In patients with suspected OSA and who were arrhythmia free, nocturnal hypoxemia significantly increased the risk of incident hospitalized AF (hazard ratio, 2.47; 95% confidence interval, 1.64-3.71) over median 10 years of follow-up (interquartile range, 7-13 years) after the researchers controlled for age, sex, chronic obstructive pulmonary disease, history of heart failure, smoking status, nocturnal hypoxemia, and pulmonary embolism, and this association remained significant after adjustment for body mass index and hypertension (HR, 1.77; 95% CI, 1.15-2.74).
“These findings support a relationship between OSA, chronic nocturnal hypoxemia, and the development of [atrial fibrillation], and may be used to identify those patients with OSA who are at greatest risk of developing AF.”
Researchers cited the observational design, retrospective data collection, and examining hospitalized AF only as limitations in the study. However, they noted that clinical data was collected prospectively and the inability to adjust to positive airway pressure would push results to the null with regard to unstudied confounders.
The authors reported no relevant conflicts of interest.
SOURCE: Kendzerska T et al. CHEST. 2018;doi:10.1016/j.chest.2018.08.1075.
Researchers have found a significant independent association between nocturnal hypoxemia and risk of incident atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA), which they believe may help prevent the development of AF in this population, according to recent research published in the journal CHEST®.
“These findings are consistent with those of previous studies suggesting that these groups, who are typically at somewhat lower risk of [atrial fibrillation], might be especially vulnerable to the effects of [obstructive sleep apnea] and hypoxemia,” Tetyana Kendzerska, MD, PhD, of the University of Ottawa in Ottawa, and her colleagues wrote in their study.
They performed an analysis of 8,256 patients with data linked to a provincial health administrative database who had suspected OSA who underwent a sleep study at a large academic hospital between 1994 and 2010. The patients were median 47 years old; 62% of the cohort were men, 28% had an apnea-hypopnea index (AHI) of greater than 30 events per hour, and 6% spent more than 30% of the time during sleep with less than 90% oxygen saturation.
Overall, 173 of 8,256 patients (2.1%) developed AF during the study period. In patients with suspected OSA and who were arrhythmia free, nocturnal hypoxemia significantly increased the risk of incident hospitalized AF (hazard ratio, 2.47; 95% confidence interval, 1.64-3.71) over median 10 years of follow-up (interquartile range, 7-13 years) after the researchers controlled for age, sex, chronic obstructive pulmonary disease, history of heart failure, smoking status, nocturnal hypoxemia, and pulmonary embolism, and this association remained significant after adjustment for body mass index and hypertension (HR, 1.77; 95% CI, 1.15-2.74).
“These findings support a relationship between OSA, chronic nocturnal hypoxemia, and the development of [atrial fibrillation], and may be used to identify those patients with OSA who are at greatest risk of developing AF.”
Researchers cited the observational design, retrospective data collection, and examining hospitalized AF only as limitations in the study. However, they noted that clinical data was collected prospectively and the inability to adjust to positive airway pressure would push results to the null with regard to unstudied confounders.
The authors reported no relevant conflicts of interest.
SOURCE: Kendzerska T et al. CHEST. 2018;doi:10.1016/j.chest.2018.08.1075.
Researchers have found a significant independent association between nocturnal hypoxemia and risk of incident atrial fibrillation (AF) in patients with obstructive sleep apnea (OSA), which they believe may help prevent the development of AF in this population, according to recent research published in the journal CHEST®.
“These findings are consistent with those of previous studies suggesting that these groups, who are typically at somewhat lower risk of [atrial fibrillation], might be especially vulnerable to the effects of [obstructive sleep apnea] and hypoxemia,” Tetyana Kendzerska, MD, PhD, of the University of Ottawa in Ottawa, and her colleagues wrote in their study.
They performed an analysis of 8,256 patients with data linked to a provincial health administrative database who had suspected OSA who underwent a sleep study at a large academic hospital between 1994 and 2010. The patients were median 47 years old; 62% of the cohort were men, 28% had an apnea-hypopnea index (AHI) of greater than 30 events per hour, and 6% spent more than 30% of the time during sleep with less than 90% oxygen saturation.
Overall, 173 of 8,256 patients (2.1%) developed AF during the study period. In patients with suspected OSA and who were arrhythmia free, nocturnal hypoxemia significantly increased the risk of incident hospitalized AF (hazard ratio, 2.47; 95% confidence interval, 1.64-3.71) over median 10 years of follow-up (interquartile range, 7-13 years) after the researchers controlled for age, sex, chronic obstructive pulmonary disease, history of heart failure, smoking status, nocturnal hypoxemia, and pulmonary embolism, and this association remained significant after adjustment for body mass index and hypertension (HR, 1.77; 95% CI, 1.15-2.74).
“These findings support a relationship between OSA, chronic nocturnal hypoxemia, and the development of [atrial fibrillation], and may be used to identify those patients with OSA who are at greatest risk of developing AF.”
Researchers cited the observational design, retrospective data collection, and examining hospitalized AF only as limitations in the study. However, they noted that clinical data was collected prospectively and the inability to adjust to positive airway pressure would push results to the null with regard to unstudied confounders.
The authors reported no relevant conflicts of interest.
SOURCE: Kendzerska T et al. CHEST. 2018;doi:10.1016/j.chest.2018.08.1075.
FROM CHEST
Key clinical point: In patients with suspected obstructive sleep apnea and who were arrhythmia free, nocturnal hypoxemia increased the risk of incident hospitalized atrial fibrillation by 77%.
Major finding: Nocturnal hypoxemia significantly predicted atrial fibrillation (hazard ratio, 2.47; 95% confidence interval, 1.64-3.71) and remained significant after adjustment for body mass index and hypertension (HR, 1.77; 95% CI, 1.15-2.74).
Study details: An observational study of 8,256 arrhythmia-free patients with suspected obstructive sleep apnea who underwent a sleep study at a large academic hospital between 1994 and 2010.
Disclosures: The authors report no relevant conflicts of interest.
Source: Kendzerska T et al. CHEST. 2018;doi:10.1016/j.chest.2018.08.1075.
Emapalumab safe, effective in pediatric primary hemophagocytic lymphohistiocytosis
, according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.
The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.
Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.
Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.
Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.
In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.
The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.
The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.
Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.
Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.
In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.
There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.
However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”
The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.
SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.
, according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.
The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.
Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.
Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.
Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.
In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.
The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.
The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.
Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.
Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.
In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.
There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.
However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”
The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.
SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.
, according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.
The recently approved agent should be considered a new therapeutic option for this rare and life-threatening syndrome because of its targeted mode of action, Dr. Locatelli and his coinvestigators reported at the annual meeting of the American Society of Hematology.
Multiple lines of evidence have pointed to interferon gamma as a “rational target” in this disease, and elevated levels of interferon gamma are consistently observed in patients with HLH, Dr. Locatelli said in a press conference at the meeting.
Emapalumab binds to its target with high affinity, recognizing both free and receptor-bound interferon gamma, he added.
Primary HLH is a rare, life-threatening syndrome of hyperinflammation, characterized by prolonged fever, cytopenias, and splenomegaly and hepatomegaly, among other clinical manifestations, Dr. Locatelli said.
In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.
The patients received emapalumab intravenously with concomitant dexamethasone for up to 8 weeks, or extended to the point of allogeneic hematopoietic stem cell transplantation (HSCT), if needed.
The study met its primary endpoint of overall response rate higher than 40%, Dr. Locatelli reported. The overall response rate was 64.7% for all 34 treated patients (95% confidence interval, 46% to 80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42% to 81%; P = .0134), reported data show.
Response was rapid, occurring at a median of 8 days after starting emapalumab, and patients were in response for a median of 75% of days during treatment, Dr. Locatelli said.
Common adverse events in the study included infections, infusion-related reactions, pyrexia, and hypertension, while one patient had disseminated histoplasmosis that resolved with appropriate treatment, according to investigators.
In light of these results, the Food and Drug Administration approved emapalumab on Nov. 20, 2018, for the treatment of pediatric and adult patients with primary HLH with refractory, recurrent or progressive disease, or intolerance to conventional HLH treatments.
There is “certainly room for enlarging the indication” to first-line treatment of HLH once a sufficient number of previously untreated patients have been treated with the monoclonal antibody, Dr. Locatelli said.
However, a randomized trial would not be feasible, he said. “It’s a very rare disease, and it would be almost impossible to run a prospective, randomized trial in a reasonable period of time.”
The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, Inc., AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.
SOURCE: Locatelli F et al. ASH 2018; Abstract LBA-6.
FROM ASH 2018
Key clinical point: Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis.
Major finding: The overall response rate was 64.7% for all 34 treated patients (95% CI, 46%-80%; P = .0031), and 63% for the 27 patients who had failed prior therapy (95% CI, 42%-81%; P = .0134).
Study details: In the open-label, single-arm, pivotal study, 34 children with primary HLH were treated: 7 who were treatment naive and 27 who had failed conventional HLH therapy.
Disclosures: The study described by Dr. Locatelli was sponsored by Novimmune. Study authors provided disclosures related to Sobi, Novimmune, Rocket Pharmaceuticals, AB2Bio, Novartis, Eli Lilly, Sanofi, UCB, Pfizer, and Abbvie. Two authors reported employment with Novimmune.
Source: Locatelli F et al. ASH 2018; Abstract LBA-6.
Prenatal, postnatal neuroimaging IDs most Zika-related brain injuries
Prenatal ultrasound can identify most abnormalities in fetuses exposed to Zika virus during pregnancy, and neuroimaging after birth can detect infant exposure in cases that appeared normal on prenatal ultrasound, according to research published in JAMA Pediatrics.
“Absence of prolonged maternal viremia did not have predictive associations with normal fetal or neonatal brain imaging,” Sarah B. Mulkey, MD, PhD, from the division of fetal and transitional medicine at Children’s National Health System, in Washington, and her colleagues wrote. “Postnatal imaging can detect changes not seen on fetal imaging, supporting the current CDC [Centers for Disease Control and Prevention] recommendation for postnatal cranial [ultrasound].”
Dr. Mulkey and her colleagues performed a prospective cohort analysis of 82 pregnant women from Colombia and the United States who had clinical evidence of probable exposure to the Zika virus through travel (U.S. cases, 2 patients), physician referral, or community cases during June 2016-June 2017. Pregnant women underwent fetal MRI or ultrasound during the second or third trimesters between 4 weeks and 10 weeks after symptom onset, with infants undergoing brain MRI and cranial ultrasound after birth.
Of those 82 pregnancies, there were 80 live births, 1 case of termination because of severe fetal brain abnormalities, and 1 near-term fetal death of unknown cause. There was one death 3 days after birth and one instance of neurosurgical intervention from encephalocele. The researchers found 3 of 82 cases (4%) displayed fetal abnormalities from MRI, which consisted of 2 cases of heterotopias and malformations in cortical development and 1 case with parietal encephalocele, Chiari II malformation, and microcephaly. One infant had a normal ultrasound despite abnormalities displayed on fetal MRI.
After birth, of the 79 infants with normal ultrasound results, 53 infants underwent a postnatal brain MRI and Dr. Mulkey and her associates found 7 cases with mild abnormalities (13%). There were 57 infants who underwent cranial ultrasound, which yielded 21 cases of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification; these were poorly characterized by MRI.
“Normal fetal imaging had predictive associations with normal postnatal imaging or mild postnatal imaging findings unlikely to be of significant clinical consequence,” they said.
Nonetheless, “there is a need for long-term follow-up to assess the neurodevelopmental significance of these early neuroimaging findings, both normal and abnormal; such studies are in progress,” Dr. Mulkey and her colleagues said.
The researchers noted the timing of maternal infections and symptoms as well as the Zika testing, ultrasound, and MRI performance, technique during fetal MRI, and incomplete prenatal testing in the cohort as limitations in the study.
This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr. Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
SOURCE: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4138.
While the study by Mulkey et al. adds to the body of evidence of prenatal and postnatal brain abnormalities, there are still many unanswered questions about the Zika virus and how to handle its unique diagnostic and clinical challenges, Margaret A. Honein, PhD, MPH, and Denise J. Jamieson, MD, MPH, wrote in a related editorial.
For example, Centers for Disease Control and Prevention recommendations state that infants with possible Zika exposure should receive an ophthalmologic and ultrasonographic examination at 1 month, and if the hearing test used otoacoustic emissions methods only, an automated auditory brainstem response test should be administered. While Mulkey et al. examined brain abnormalities in utero and in infants, it is not clear whether all CDC guidelines were followed in these cases.
In addition, because there is no reliable way to determine whether infants acquired Zika virus through the mother or through vertical transmission, assessing the proportion of congenitally infected infants or vertical-transmission infected infants who have neurodevelopmental disabilities and defects is not possible, they said. More longitudinal studies are needed to study the effects of the Zika virus and to prepare for the next outbreak.
“Zika was affecting pregnant women and their infants years before its teratogenic effect was recognized, and Zika will remain a serious risk to pregnant women and their infants until we have a safe vaccine that can fully prevent Zika virus infection during pregnancy,” they said. “Until then, ongoing public health efforts are essential to protect mothers and babies from this threat and ensure all disabilities associated with Zika virus infection are promptly identified, so that timely interventions can be provided.”
Dr. Honein is from the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, and Dr. Jamieson is from the department of gynecology & obstetrics at Emory University School of Medicine, Atlanta. These comments summarize their editorial in response to Mulkey et al. (JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4164). They reported no relevant conflicts of interest.
While the study by Mulkey et al. adds to the body of evidence of prenatal and postnatal brain abnormalities, there are still many unanswered questions about the Zika virus and how to handle its unique diagnostic and clinical challenges, Margaret A. Honein, PhD, MPH, and Denise J. Jamieson, MD, MPH, wrote in a related editorial.
For example, Centers for Disease Control and Prevention recommendations state that infants with possible Zika exposure should receive an ophthalmologic and ultrasonographic examination at 1 month, and if the hearing test used otoacoustic emissions methods only, an automated auditory brainstem response test should be administered. While Mulkey et al. examined brain abnormalities in utero and in infants, it is not clear whether all CDC guidelines were followed in these cases.
In addition, because there is no reliable way to determine whether infants acquired Zika virus through the mother or through vertical transmission, assessing the proportion of congenitally infected infants or vertical-transmission infected infants who have neurodevelopmental disabilities and defects is not possible, they said. More longitudinal studies are needed to study the effects of the Zika virus and to prepare for the next outbreak.
“Zika was affecting pregnant women and their infants years before its teratogenic effect was recognized, and Zika will remain a serious risk to pregnant women and their infants until we have a safe vaccine that can fully prevent Zika virus infection during pregnancy,” they said. “Until then, ongoing public health efforts are essential to protect mothers and babies from this threat and ensure all disabilities associated with Zika virus infection are promptly identified, so that timely interventions can be provided.”
Dr. Honein is from the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, and Dr. Jamieson is from the department of gynecology & obstetrics at Emory University School of Medicine, Atlanta. These comments summarize their editorial in response to Mulkey et al. (JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4164). They reported no relevant conflicts of interest.
While the study by Mulkey et al. adds to the body of evidence of prenatal and postnatal brain abnormalities, there are still many unanswered questions about the Zika virus and how to handle its unique diagnostic and clinical challenges, Margaret A. Honein, PhD, MPH, and Denise J. Jamieson, MD, MPH, wrote in a related editorial.
For example, Centers for Disease Control and Prevention recommendations state that infants with possible Zika exposure should receive an ophthalmologic and ultrasonographic examination at 1 month, and if the hearing test used otoacoustic emissions methods only, an automated auditory brainstem response test should be administered. While Mulkey et al. examined brain abnormalities in utero and in infants, it is not clear whether all CDC guidelines were followed in these cases.
In addition, because there is no reliable way to determine whether infants acquired Zika virus through the mother or through vertical transmission, assessing the proportion of congenitally infected infants or vertical-transmission infected infants who have neurodevelopmental disabilities and defects is not possible, they said. More longitudinal studies are needed to study the effects of the Zika virus and to prepare for the next outbreak.
“Zika was affecting pregnant women and their infants years before its teratogenic effect was recognized, and Zika will remain a serious risk to pregnant women and their infants until we have a safe vaccine that can fully prevent Zika virus infection during pregnancy,” they said. “Until then, ongoing public health efforts are essential to protect mothers and babies from this threat and ensure all disabilities associated with Zika virus infection are promptly identified, so that timely interventions can be provided.”
Dr. Honein is from the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention, and Dr. Jamieson is from the department of gynecology & obstetrics at Emory University School of Medicine, Atlanta. These comments summarize their editorial in response to Mulkey et al. (JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4164). They reported no relevant conflicts of interest.
Prenatal ultrasound can identify most abnormalities in fetuses exposed to Zika virus during pregnancy, and neuroimaging after birth can detect infant exposure in cases that appeared normal on prenatal ultrasound, according to research published in JAMA Pediatrics.
“Absence of prolonged maternal viremia did not have predictive associations with normal fetal or neonatal brain imaging,” Sarah B. Mulkey, MD, PhD, from the division of fetal and transitional medicine at Children’s National Health System, in Washington, and her colleagues wrote. “Postnatal imaging can detect changes not seen on fetal imaging, supporting the current CDC [Centers for Disease Control and Prevention] recommendation for postnatal cranial [ultrasound].”
Dr. Mulkey and her colleagues performed a prospective cohort analysis of 82 pregnant women from Colombia and the United States who had clinical evidence of probable exposure to the Zika virus through travel (U.S. cases, 2 patients), physician referral, or community cases during June 2016-June 2017. Pregnant women underwent fetal MRI or ultrasound during the second or third trimesters between 4 weeks and 10 weeks after symptom onset, with infants undergoing brain MRI and cranial ultrasound after birth.
Of those 82 pregnancies, there were 80 live births, 1 case of termination because of severe fetal brain abnormalities, and 1 near-term fetal death of unknown cause. There was one death 3 days after birth and one instance of neurosurgical intervention from encephalocele. The researchers found 3 of 82 cases (4%) displayed fetal abnormalities from MRI, which consisted of 2 cases of heterotopias and malformations in cortical development and 1 case with parietal encephalocele, Chiari II malformation, and microcephaly. One infant had a normal ultrasound despite abnormalities displayed on fetal MRI.
After birth, of the 79 infants with normal ultrasound results, 53 infants underwent a postnatal brain MRI and Dr. Mulkey and her associates found 7 cases with mild abnormalities (13%). There were 57 infants who underwent cranial ultrasound, which yielded 21 cases of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification; these were poorly characterized by MRI.
“Normal fetal imaging had predictive associations with normal postnatal imaging or mild postnatal imaging findings unlikely to be of significant clinical consequence,” they said.
Nonetheless, “there is a need for long-term follow-up to assess the neurodevelopmental significance of these early neuroimaging findings, both normal and abnormal; such studies are in progress,” Dr. Mulkey and her colleagues said.
The researchers noted the timing of maternal infections and symptoms as well as the Zika testing, ultrasound, and MRI performance, technique during fetal MRI, and incomplete prenatal testing in the cohort as limitations in the study.
This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr. Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
SOURCE: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4138.
Prenatal ultrasound can identify most abnormalities in fetuses exposed to Zika virus during pregnancy, and neuroimaging after birth can detect infant exposure in cases that appeared normal on prenatal ultrasound, according to research published in JAMA Pediatrics.
“Absence of prolonged maternal viremia did not have predictive associations with normal fetal or neonatal brain imaging,” Sarah B. Mulkey, MD, PhD, from the division of fetal and transitional medicine at Children’s National Health System, in Washington, and her colleagues wrote. “Postnatal imaging can detect changes not seen on fetal imaging, supporting the current CDC [Centers for Disease Control and Prevention] recommendation for postnatal cranial [ultrasound].”
Dr. Mulkey and her colleagues performed a prospective cohort analysis of 82 pregnant women from Colombia and the United States who had clinical evidence of probable exposure to the Zika virus through travel (U.S. cases, 2 patients), physician referral, or community cases during June 2016-June 2017. Pregnant women underwent fetal MRI or ultrasound during the second or third trimesters between 4 weeks and 10 weeks after symptom onset, with infants undergoing brain MRI and cranial ultrasound after birth.
Of those 82 pregnancies, there were 80 live births, 1 case of termination because of severe fetal brain abnormalities, and 1 near-term fetal death of unknown cause. There was one death 3 days after birth and one instance of neurosurgical intervention from encephalocele. The researchers found 3 of 82 cases (4%) displayed fetal abnormalities from MRI, which consisted of 2 cases of heterotopias and malformations in cortical development and 1 case with parietal encephalocele, Chiari II malformation, and microcephaly. One infant had a normal ultrasound despite abnormalities displayed on fetal MRI.
After birth, of the 79 infants with normal ultrasound results, 53 infants underwent a postnatal brain MRI and Dr. Mulkey and her associates found 7 cases with mild abnormalities (13%). There were 57 infants who underwent cranial ultrasound, which yielded 21 cases of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification; these were poorly characterized by MRI.
“Normal fetal imaging had predictive associations with normal postnatal imaging or mild postnatal imaging findings unlikely to be of significant clinical consequence,” they said.
Nonetheless, “there is a need for long-term follow-up to assess the neurodevelopmental significance of these early neuroimaging findings, both normal and abnormal; such studies are in progress,” Dr. Mulkey and her colleagues said.
The researchers noted the timing of maternal infections and symptoms as well as the Zika testing, ultrasound, and MRI performance, technique during fetal MRI, and incomplete prenatal testing in the cohort as limitations in the study.
This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr. Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
SOURCE: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26. doi: 10.1001/jamapediatrics.2018.4138.
FROM JAMA PEDIATRICS
Key clinical point:
Major finding: In 82 pregnant women, prenatal neuroimaging identified fetal abnormalities in 3 cases, while postnatal neuroimaging in 53 of the remaining 79 cases yielded an additional 7 cases with mild abnormalities.
Study details: A prospective longitudinal cohort study of 82 pregnant women with clinical evidence of probable Zika infection in Colombia and the United States.
Disclosures: This study was funded in part by Children’s National Health System and by a philanthropic gift from the Ikaria Healthcare Fund. Dr Mulkey received research support from the Thrasher Research Fund and is supported by awards from the National Institutes of Health National Center for Advancing Translational Sciences. The other authors reported no relevant conflicts of interest.
Source: Mulkey SB et al. JAMA Pediatr. 2018 Nov. 26; doi: 10.1001/jamapediatrics.2018.4138.
EARLY: Angiography within 2 hours of acute non-ST event cut recurrent ischemic events
CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.
EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.
“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.
The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.
The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.
On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.
Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.
Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).
Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.
Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.
The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.
In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.
Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.
“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.
Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.
Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.
SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.
CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.
EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.
“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.
The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.
The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.
On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.
Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.
Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).
Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.
Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.
The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.
In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.
Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.
“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.
Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.
Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.
SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.
CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.
EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.
“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.
The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.
The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.
On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.
Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.
Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).
Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.
Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.
The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.
In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.
Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.
“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.
Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.
Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.
SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: Coronary angiography within 2 hours of non–ST-segment elevation acute coronary syndrome yielded improved outcomes.
Major finding: Rates of major cardiovascular events were 4.4% with early intervention and 21.3% with delayed intervention.
Study details: Prospective, multicenter, randomized clinical trial of 709 patients.
Disclosures: Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The trial received funding from the French Ministry of Health.
Source: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.
People with HIV still at increased cardiovascular risk
CHICAGO – HIV infection remained linked with an increased risk for developing a cardiovascular disease event among U.S. patients, even in a recent era of antiretroviral therapy.
U.S. health insurance beneficiaries diagnosed with an HIV infection and likely put on antiretroviral therapy sometime during 2011-2015 had a statistically significant, 21% increased risk for the combination of MIs, coronary revascularizations, stroke, and lower-extremity peripheral artery disease (PAD) in a case-control, retrospective analysis, Robert S. Rosenson, MD, said in a poster he presented at the American Heart Association scientific sessions.
“We looked at a contemporary population of people with HIV treated with antiretroviral therapy, and we looked at stroke and lower-extremity PAD [peripheral artery disease] as well as MI, while most prior studies only looked at MIs,” noted Dr. Rosenson, a professor of medicine and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai Medical Center in New York.
The analysis found no significant differences in outcomes that linked with the specific type of antiretroviral therapy patients received. The most commonly used antiretroviral drug was a non–nucleoside reverse transcriptase inhibitor, taken by about 80% of the HIV-infected patients, Dr. Rosenson said. The 2011-2015 period examined in the study largely predated the more recent era, when integrase strand transfer inhibitor drugs have increasingly become the core agent for treating HIV infection.
Another key finding in the study was that a scant 19% of the people infected with HIV received statin treatment, and only 4% were on a high-intensity dosage. The 2018 guideline on cholesterol management identifies HIV infection as one of several “risk enhancers” that boost a person’s cardiovascular disease (CVD) risk and intensify their need for statin treatment (Circulation. 2018 Nov 10. doi: 10.1161/CIR.0000000000000625).
“Hopefully use of statins will increase in people with HIV, but of course we need evidence because so far the evidence does not show benefit,” he noted. In the data Dr. Rosenson reported, the HIV-infected patients who received a statin had roughly the same elevated risk for a CVD event as did HIV-infected patients who did not get a statin.
His study used data from a U.S. commercial database that combined Medicare patients with patients covered by commercial insurers. The analysis identified 82,426 people presumed recently infected by HIV based on either a hospitalization discharge with a diagnostic code for HIV or after filling at least two prescriptions for an antiretroviral drug during January 2011–June 2015. The researchers matched these cases on a 4:1 basis with 329,704 controls from the database matched by age, sex, and year for their index date. The total study cohort averaged about 45 years old, but the people infected by HIV averaged a couple of years older and also had at baseline an increased prevalence of several CVD risk factors and comorbidities. The people with HIV had a more than threefold higher rate of tobacco use, chronic kidney disease, and liver disease, and double the rate of diagnosed depression.
In a multivariate analysis that controlled for many demographic, social, and clinical variables, the results showed that the HIV-infected people had statistically significant higher rates of every individual element in the CVD composite. They had a 26% higher rate of MIs, a 17% higher rate of MIs plus coronary revascularization, a 30% higher rate of stroke, and a doubled rate of lower-extremity PAD.
SOURCE: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.
CHICAGO – HIV infection remained linked with an increased risk for developing a cardiovascular disease event among U.S. patients, even in a recent era of antiretroviral therapy.
U.S. health insurance beneficiaries diagnosed with an HIV infection and likely put on antiretroviral therapy sometime during 2011-2015 had a statistically significant, 21% increased risk for the combination of MIs, coronary revascularizations, stroke, and lower-extremity peripheral artery disease (PAD) in a case-control, retrospective analysis, Robert S. Rosenson, MD, said in a poster he presented at the American Heart Association scientific sessions.
“We looked at a contemporary population of people with HIV treated with antiretroviral therapy, and we looked at stroke and lower-extremity PAD [peripheral artery disease] as well as MI, while most prior studies only looked at MIs,” noted Dr. Rosenson, a professor of medicine and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai Medical Center in New York.
The analysis found no significant differences in outcomes that linked with the specific type of antiretroviral therapy patients received. The most commonly used antiretroviral drug was a non–nucleoside reverse transcriptase inhibitor, taken by about 80% of the HIV-infected patients, Dr. Rosenson said. The 2011-2015 period examined in the study largely predated the more recent era, when integrase strand transfer inhibitor drugs have increasingly become the core agent for treating HIV infection.
Another key finding in the study was that a scant 19% of the people infected with HIV received statin treatment, and only 4% were on a high-intensity dosage. The 2018 guideline on cholesterol management identifies HIV infection as one of several “risk enhancers” that boost a person’s cardiovascular disease (CVD) risk and intensify their need for statin treatment (Circulation. 2018 Nov 10. doi: 10.1161/CIR.0000000000000625).
“Hopefully use of statins will increase in people with HIV, but of course we need evidence because so far the evidence does not show benefit,” he noted. In the data Dr. Rosenson reported, the HIV-infected patients who received a statin had roughly the same elevated risk for a CVD event as did HIV-infected patients who did not get a statin.
His study used data from a U.S. commercial database that combined Medicare patients with patients covered by commercial insurers. The analysis identified 82,426 people presumed recently infected by HIV based on either a hospitalization discharge with a diagnostic code for HIV or after filling at least two prescriptions for an antiretroviral drug during January 2011–June 2015. The researchers matched these cases on a 4:1 basis with 329,704 controls from the database matched by age, sex, and year for their index date. The total study cohort averaged about 45 years old, but the people infected by HIV averaged a couple of years older and also had at baseline an increased prevalence of several CVD risk factors and comorbidities. The people with HIV had a more than threefold higher rate of tobacco use, chronic kidney disease, and liver disease, and double the rate of diagnosed depression.
In a multivariate analysis that controlled for many demographic, social, and clinical variables, the results showed that the HIV-infected people had statistically significant higher rates of every individual element in the CVD composite. They had a 26% higher rate of MIs, a 17% higher rate of MIs plus coronary revascularization, a 30% higher rate of stroke, and a doubled rate of lower-extremity PAD.
SOURCE: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.
CHICAGO – HIV infection remained linked with an increased risk for developing a cardiovascular disease event among U.S. patients, even in a recent era of antiretroviral therapy.
U.S. health insurance beneficiaries diagnosed with an HIV infection and likely put on antiretroviral therapy sometime during 2011-2015 had a statistically significant, 21% increased risk for the combination of MIs, coronary revascularizations, stroke, and lower-extremity peripheral artery disease (PAD) in a case-control, retrospective analysis, Robert S. Rosenson, MD, said in a poster he presented at the American Heart Association scientific sessions.
“We looked at a contemporary population of people with HIV treated with antiretroviral therapy, and we looked at stroke and lower-extremity PAD [peripheral artery disease] as well as MI, while most prior studies only looked at MIs,” noted Dr. Rosenson, a professor of medicine and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai Medical Center in New York.
The analysis found no significant differences in outcomes that linked with the specific type of antiretroviral therapy patients received. The most commonly used antiretroviral drug was a non–nucleoside reverse transcriptase inhibitor, taken by about 80% of the HIV-infected patients, Dr. Rosenson said. The 2011-2015 period examined in the study largely predated the more recent era, when integrase strand transfer inhibitor drugs have increasingly become the core agent for treating HIV infection.
Another key finding in the study was that a scant 19% of the people infected with HIV received statin treatment, and only 4% were on a high-intensity dosage. The 2018 guideline on cholesterol management identifies HIV infection as one of several “risk enhancers” that boost a person’s cardiovascular disease (CVD) risk and intensify their need for statin treatment (Circulation. 2018 Nov 10. doi: 10.1161/CIR.0000000000000625).
“Hopefully use of statins will increase in people with HIV, but of course we need evidence because so far the evidence does not show benefit,” he noted. In the data Dr. Rosenson reported, the HIV-infected patients who received a statin had roughly the same elevated risk for a CVD event as did HIV-infected patients who did not get a statin.
His study used data from a U.S. commercial database that combined Medicare patients with patients covered by commercial insurers. The analysis identified 82,426 people presumed recently infected by HIV based on either a hospitalization discharge with a diagnostic code for HIV or after filling at least two prescriptions for an antiretroviral drug during January 2011–June 2015. The researchers matched these cases on a 4:1 basis with 329,704 controls from the database matched by age, sex, and year for their index date. The total study cohort averaged about 45 years old, but the people infected by HIV averaged a couple of years older and also had at baseline an increased prevalence of several CVD risk factors and comorbidities. The people with HIV had a more than threefold higher rate of tobacco use, chronic kidney disease, and liver disease, and double the rate of diagnosed depression.
In a multivariate analysis that controlled for many demographic, social, and clinical variables, the results showed that the HIV-infected people had statistically significant higher rates of every individual element in the CVD composite. They had a 26% higher rate of MIs, a 17% higher rate of MIs plus coronary revascularization, a 30% higher rate of stroke, and a doubled rate of lower-extremity PAD.
SOURCE: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: U.S. insurance beneficiaries newly diagnosed with HIV had a significantly higher rate of CVD events than people without HIV.
Major finding: The adjusted rate of cardiovascular disease events was 21% higher in people infected with HIV, compared with matched, uninfected people.
Study details: A retrospective, case control study of 412,130 U.S. health insurance beneficiaries.
Disclosures: The study received partial funding from Amgen. Dr. Rosenson has received honoraria from Amgen, Akcaa, and Kowa; he has been an advisor to Amgen, Regeneron, and Sanofi; and he has received research funding from Amgen, Akcaa, AstraZeneca, and The Medicines Company.
Source: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.
Cure for Sickle Cell?
Apixaban edges other direct acting anticoagulants for octogenarians, heavy menstrual bleeding in teens is often linked to bleeding disorders, and tanning use disorder should be added to the diagnostic and statistical manual of mental disorders.
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Apixaban edges other direct acting anticoagulants for octogenarians, heavy menstrual bleeding in teens is often linked to bleeding disorders, and tanning use disorder should be added to the diagnostic and statistical manual of mental disorders.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Apixaban edges other direct acting anticoagulants for octogenarians, heavy menstrual bleeding in teens is often linked to bleeding disorders, and tanning use disorder should be added to the diagnostic and statistical manual of mental disorders.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Regimen provides survival benefit in PTCL
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.