San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 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.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 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.

San Diego – State-of-the-art guidelines for treating sickle cell disease are actively being developed and could be released as early as the spring of 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.

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.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

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.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

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.

SAN DIEGO – Emapalumab, an interferon gamma-blocking antibody, controls disease activity and has a favorable safety profile in patients with primary hemophagocytic lymphohistiocytosis (HLH), according to Franco Locatelli, MD, of the department of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù, Rome.

Andrew D. Bowser/MDedge News

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.

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.

copyright Aunt_Spray/Thinkstock

“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.

copyright Aunt_Spray/Thinkstock

“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.

copyright Aunt_Spray/Thinkstock

“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.

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.

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.

mzoler@mdedge.com

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.

mzoler@mdedge.com

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.

mzoler@mdedge.com

SOURCE: Rosenson RS et al. Circulation. 2018 Nov 6;138[suppl 1]:A14410.

Sickle cell research is booming after decades of stagnation -- there is real talk for a cure. 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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Sickle cell research is booming after decades of stagnation -- there is real talk for a cure. 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
 

Sickle cell research is booming after decades of stagnation -- there is real talk for a cure. 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

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Spotify
 

Photo courtesy of ASH

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.

Photo courtesy of ASH

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.

Photo courtesy of ASH

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.

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

©ASH/Rodney White 2018

SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.

The oral proteasome inhibitor improved PFS by 39% compared to placebo.

In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.

TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.

Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).

He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.

“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.

He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.

The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.

The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).

At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.

The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.

Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.

When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”

However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.

“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.

A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.

TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.

Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc. 

© ASH/Luke Franke 2018

SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.

“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.

Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.

JULIET then

In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.

Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.

At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.

In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).

Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.

JULIET now

The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.

As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.

Fifty-four percent of patients who had achieved PR converted to CR.

The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.

Estimated relapse-free survival 12 months after documentation of an initial response was 64%.

The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.

Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.

Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.

There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.

The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc.