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Antitumor treatment may increase risk of severe events in COVID-19 patients
Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.
Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.
However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.
Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.
The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.
The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
COVID-19 treatment
Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.
For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).
Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).
“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
Outcomes
In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).
A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.
Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).
By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.
Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
Factors associated with severe events
In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).
However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.
Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
Immune checkpoint inhibitors
Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.
This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).
In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.
Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”
Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.
SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.
Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.
Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.
However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.
Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.
The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.
The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
COVID-19 treatment
Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.
For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).
Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).
“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
Outcomes
In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).
A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.
Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).
By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.
Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
Factors associated with severe events
In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).
However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.
Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
Immune checkpoint inhibitors
Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.
This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).
In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.
Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”
Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.
SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.
Cancer patients who received antitumor treatment within 14 days of COVID-19 diagnosis had an increased risk of severe events, according to data from three hospitals in Wuhan.
Patients with patchy consolidation at hospital admission also had an increased risk of severe events, defined as ICU admission, mechanical ventilation, or death.
However, these findings are limited by the small number of patients studied and the retrospective nature of the analysis, according to researchers.
Li Zhang, MD, PhD, of Tongji Hospital in Wuhan, China, presented this research at the AACR virtual meeting I. Some of the data were previously published in Annals of Oncology.
The researchers studied 28 patients with cancer among 1,276 patients with COVID-19 treated at three hospitals in Wuhan. The most common cancer types were lung (n = 7), esophageal (n = 4), and breast (n = 3). Patients had other gastrointestinal, gynecologic, genitourinary, and head and neck cancers as well.
The patients’ median age was 65 years (range, 56-70 years), 60.9% were men, 35.7% had stage IV cancer, and 28.6% had hospital-acquired COVID-19. Antitumor treatments included chemotherapy (n = 22), surgery (n = 21), radiotherapy (n = 21), targeted therapy (n = 5), and immune checkpoint inhibitors (n = 2).
COVID-19 treatment
Most patients (n = 22) received oxygen as their only respiratory intervention, although 10 received mechanical ventilation.
For systemic therapy, patients received antibiotic treatment (n = 23), corticosteroids (n = 15), intravenous immunoglobulin (n = 10), and tocilizumab (n = 1).
Antiviral treatments included umifenovir (n = 14), lopinavir/ritonavir (n = 10), ganciclovir (n = 9), ribavirin (n = 1), or a combination of antiviral drugs (n = 9).
“No cancer patients were enrolled in clinical trials, so no one received hydroxychloroquine or remdesivir,” Dr. Zhang noted.
Outcomes
In all, 15 patients (53.6%) had severe events. The median time from COVID-19 diagnosis to severe events was 7 days (range, 5-15 days).
A total of eight patients (28.6%) died – three with lung cancer, two with prostate cancer, one with liver cancer, one with rectal cancer, and one with testicular cancer.
Causes of death were acute respiratory distress syndrome (n = 5), septic shock (n = 1), suspected pulmonary embolism (n = 1), and acute myocardial infarction (n = 1).
By April 4, 14 patients had been discharged from the hospital, and 6 were still hospitalized. The median duration of hospitalization was 18.4 days for discharged patients and 29.4 days for patients still in hospital.
Follow-up CT scans showed improvement in 13 patients, no changes in 5 patients, and deterioration in 6 patients.
Factors associated with severe events
In a multivariable analysis, receiving antitumor treatment within 14 days of COVID-19 diagnosis was associated with severe events (hazard ratio, 4.079; P = .037).
However, only seven patients received antitumor treatments within 14 days of COVID-19 diagnosis – three chemotherapy, two targeted therapy, one radiotherapy, and one immune checkpoint inhibitor. Five of these seven patients had severe events.
Another factor associated with severe events in multivariable analysis was patchy consolidation on CT scan at admission (HR, 5.438; P = .01). Age and gender were not significantly associated with severe events.
Immune checkpoint inhibitors
Dr. Zhang and colleagues also analyzed a second group of cancer patients and their family members to determine if patients on immune checkpoint inhibitors have an increased risk of COVID-19.
This group included 124 cancer patients treated with immune checkpoint inhibitors for at least 2 months. The patients had a median age of 59 years (range, 54-65 years), and 61.8% were men. Most patients (95.2%) had stage IV cancer, and the most common cancers were lung (54.0%), esophageal (18.6%), and head and neck (10.7%).
In this group, only one cancer patient developed COVID-19 (via nosocomial infection). In another case, a patient’s spouse developed COVID-19, but the patient did not.
Dr. Zhang said this “limited information did not suggest cancer patients treated with immune checkpoint inhibitors were more vulnerable to COVID infection.”
Dr. Zhang and colleagues reported no conflicts of interest. This research was funded by the National Natural Science Foundation of China and Huazhong University of Science and Technology COVID-19 Rapid Response Call China.
SOURCE: Zhang L et al. Ann Oncol. 2020 Mar 26. doi: 10.1016/j.annonc.2020.03.296.
FROM AACR 2020
Prior head injury is associated with severe Parkinson’s disease phenotype
according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.
Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.
“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
An analysis of data from two cohorts
The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.
In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.
“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”
In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).
“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
The search for the underlying mechanism
Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”
The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.
SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.
according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.
Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.
“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
An analysis of data from two cohorts
The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.
In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.
“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”
In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).
“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
The search for the underlying mechanism
Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”
The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.
SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.
according to research presented online as part of the 2020 American Academy of Neurology Science Highlights.
Neurologists have identified various phenotypes among patients with Parkinson’s disease; however, the factors that determine these phenotypes, which may include genetic and environmental variables, are poorly understood. Ethan G. Brown, MD, assistant professor of neurology at the University of California, San Francisco, and colleagues hypothesized that head injury, which is a risk factor for Parkinson’s disease, would be associated with a more severe phenotype.
“Head injury is a risk factor for other conditions that involve cognitive impairment,” said Dr. Brown. “The mechanisms of how head injury contributes to neurodegenerative disease are not clear, but may be related to the initiation of an inflammatory cascade that can have a long-term, chronic effect. We hypothesized that these long-term sequelae may contribute to symptoms in Parkinson’s disease.”
An analysis of data from two cohorts
The researchers examined the relationship between head injury and clinical features by analyzing data for two cohorts of patients with Parkinson’s disease. Through an online survey, the investigators elicited information about head injury and other exposures from participants in the Parkinson’s Progression Markers Initiative (PPMI) and the Fox Insight (FI) study. Dr. Brown and colleagues determined disease phenotypes for participants in PPMI using baseline Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and 5-year change in Montreal Cognitive Assessment score. For participants in FI, the researchers determined phenotypes using baseline self-reported MDS-UPDRS-II score and self-reported cognitive impairment. They used parametric and nonparametric tests as appropriate and adjusted the results for age, sex, and smoking history.
In all, 267 participants with Parkinson’s disease in PPMI and 25,308 in FI submitted information about head injury. In the PPMI cohort, head injury before Parkinson’s disease diagnosis was associated with greater nonmotor symptom burden at enrollment. The mean MDS-UPDRS-I score was 7.73 among participants with any injury, compared with 6.19 among participants with no injury. Similarly, the mean MDS-UPDRS-I score was 8.29 among participants with severe head injury, compared with 6.19 among participants with no injury. Motor symptoms were worse among participants with severe injury (MDS-UPDRS-II score, 8.35). Among 110 participants who were followed for 5 years, patients who reported severe head injury before diagnosis had a decline in cognitive function. The mean change in Montreal Cognitive Assessment score was –0.60 for patients with severe head injury and 0.76 in those with no head injury.
“The improvement from baseline in the participants with Parkinson’s disease but without head injury was small and not statistically significant,” said Dr. Brown. The increase could have resulted from practice effect, although it is not certain, he added. “We are continuing to evaluate other, more sensitive tests of cognitive impairment to try to understand these results more completely in this population.”
In the FI cohort, participants who reported a prior head injury had more motor symptoms (MDS-UPDRS-II, 14.4), compared with those without head injury (MDS-UPDRS-II, 12.1). Also, the risk of self-reported cognitive impairment was elevated in participants who reported head injury (odds ratio, 1.58).
“The results most affected by the self-reported nature of [the] FI [data] are the cognitive impairment results,” said Dr. Brown. “Subjective cognitive impairment ... is very different from objective cognitive impairment, which could be measured through in-person testing in the PPMI cohort. Many factors may contribute to noticing cognitive decline, some of which can be measured and controlled for, but some cannot. There may be a correlation between subjective cognitive decline and true cognitive impairment, but this has not been fully studied in Parkinson’s disease.”
The search for the underlying mechanism
Clarifying whether the relationship between head injury and Parkinson’s disease phenotype is causal or whether falling is an early indication of worse symptoms will require more longitudinal data. “We would like to further characterize the differences between people with Parkinson’s disease with and without a history of head injury,” said Dr. Brown. “More detailed understanding of these phenotypic differences could point to an underlying mechanism, or whether or not other comorbid conditions are involved. We would also like to understand whether genetics plays a role.”
The PPMI and FI studies are funded by the Michael J. Fox Foundation. Dr. Brown has received compensation from HiOscar, NEJM Knowledge Plus, and Rune Labs and has received research support from Gateway Institute for Brain Research.
SOURCE: Brown EG et al. AAN 2020, Abstract S17.002.
FROM AAN 2020
Predictors of ICH after thrombectomy identified
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
(ICH), new research suggests. In a study of nearly 600 patients undergoing thrombectomy, investigators combined a modified Thrombolysis in Cerebral Ischemia (TICI) score, an Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and glucose levels (the “TAG score”) to predict risk. Results showed that each unit increase in the combination score was associated with a significant, nearly twofold greater likelihood of symptomatic ICH.
“It is very easy” to calculate the new score in a clinical setting, lead author Mayra Johana Montalvo Perero, MD, Department of Neurology, Brown University and Rhode Island Hospital, Providence, said. “You just need three variables.”
The findings were presented online as part of the 2020 American Academy of Neurology Science Highlights.
Limited data
High TAG scores are associated with symptomatic ICH in patients receiving mechanical thrombectomy, Dr. Montalvo Perero and colleagues said.
Although clinical predictors of symptomatic ICH are well established, “there is limited data in patients who underwent mechanical thrombectomy,” the researchers noted.
To learn more, they assessed 578 patients (52% women; mean age, 73 years) who had mechanical thrombectomy for acute ischemic stroke at a comprehensive stroke center. Within this cohort, 19 patients (3.3%) developed symptomatic ICH.
The investigators compared clinical and radiographic findings between patients who experienced symptomatic ICH and those who did not.
The TICI score emerged as a predictor when each unit decrease in this score was associated with greater risk for symptomatic ICH (odds ratio, 5.13; 95% confidence interval, 1.84-14.29; P = .002).
Each one-point decrease in the ASPECTS score also predicted increased risk (OR, 1.52; 95% CI, 1.1-2.0; P = .003).
“The main driver is the size of the stroke core, which is correlated with the ASPECTS score,” Dr. Montalvo Perero said.
Each 10 mg/dL increase in glucose level also correlated with increased risk (OR, 1.07; 95% CI, 1.01-1.13; P = .018).
Twice the risk
The investigators then combined these three independent variables into a weighted TAG score based on a multivariate analysis. Each unit increase in this composite score was associated with increased risk of symptomatic ICH (OR, 1.98; 95% CI, 1.48-2.66; P < .001).
There was no association between patients who received tissue plasminogen activator (tPA) and risk of symptomatic ICH, which Dr. Montalvo Perero said was surprising.
However, “that may be due to a small number” of patients with symptomatic ICH included in the study, she said. “Therefore, that would be an interesting question to ask in future studies with bigger cohorts.”
Larger studies are also needed to validate this scoring system and to test strategies to reduce risk of symptomatic ICH and make thrombectomy safer in patients with elevated TAG scores, Dr. Montalvo Perero said.
A step in the right direction?
Commenting on the study, Jeremy Payne, MD, PhD, director of the Stroke Center at Banner Health’s University Medicine Neuroscience Institute in Phoenix, Arizona, noted the importance of predicting which patients might have secondary bleeding after interventional treatment of a large vessel occlusion stroke
“In aggregate, the role of endovascular thrombectomy is quite clear, but we still struggle to predict at the individual patient level who will benefit,” said Dr. Payne, who was not involved with the research.
Transfer and treatment of these patients also carries an economic cost. “Just getting patients to our center, where about 80% of the complex stroke patients come by helicopter, costs upwards of $30,000,” Dr. Payne said. “The financial argument isn’t one we like to talk much about, but we’re committing to spending probably $100,000-$200,000 on each person’s care.”
This study “attempts to address an important issue,” he said.
Predicting who is more likely to benefit leads to the assumption that if that were to happen, “we could skip all the rigamarole of helicopters and procedures, avoid the extra expense and particularly not make things worse than they already are,” explained Dr. Payne.
Potential limitations include that this is a single-center study and is based on an analysis of 19 patients out of 578. As a result, it is not clear that these findings will necessarily be generalizable to other centers, said Dr. Payne.
The TICI and ASPECTS “are pretty obvious markers of risk,” he noted. “The glucose levels, however, are more subtly interesting.”
He also pointed out that an association between diabetes and worse stroke outcomes is well established.
“The mechanisms are poorly understood, but the role of glucose keeps popping up as a potential marker of risk, and so it’s interesting that it bubbles up in their work too,” Dr. Payne said.
Furthermore, unlike TICI and ASPECTS, glucose levels are modifiable.
“Overall, then, we will continue to study this,” Dr. Payne said. “It’s very important to refine our ability to predict which patients may receive benefit versus harm from such procedures, and this is a step in the right direction.”
Some findings were also published December 2019 in the Journal of Neurology, Neurosurgery & Psychiatry.
Montalvo Perero and Payne have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SOURCE: Motalvo Perero MJ et al. AAN 2020, Abstract S20.001.
AAN 2020
CGRP inhibitors receive reassuring real-world safety report
Stephen D. Silberstein, MD, reported online as part of the 2020 American Academy of Neurology Science Highlights.
He presented a retrospective analysis of spontaneous postmarketing reports to the Food and Drug Administration Adverse Events Reporting System (FAERS) for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).
The top-10 lists of adverse events for all three monoclonal antibodies targeting CGRP were skewed heavily towards injection-site reactions, such as injection-site pain, itching, swelling, and erythema. The rates were relatively low. For example, injection-site pain was reported at a rate of 2.94 cases per 1,000 patients exposed to erenumab, 0.8/1,000 for fremanezumab, and 4.9/1,000 for galcanezumab, according to Dr. Silberstein, professor of neurology and director of the headache center at Sidney Kimmel Medical College, Philadelphia.
Migraine, headache, and drug ineffectiveness were in the top 10 for all three medications, as is typical in FAERS reports, since no drug is effective in everyone. These events were reported at rates of 1-5/1,000 exposed patients. Constipation was reported in association with the use of erenumab at a rate of 4.9 cases/1,000 patients, but did not reach the top-10 lists for the other two CGRP antagonists.
Notably, cardiovascular events were not among the top-10 adverse events reported for any of the novel preventive agents.
“These results will be practice changing, since some physicians have been holding back from prescribing these drugs pending the results of this sort of longer-term safety data,” Dr. Silberstein predicted in an interview.
Asked to comment on the FAERS study, neurologist Holly Yancy, DO, said that she found the findings unsurprising because the adverse effects were essentially as expected based upon the earlier favorable clinical trials experience.
“These medications are living up to the expectations for good tolerability that were in place when they were initially approved by the FDA just under 2 years ago,” said Dr. Yancy, a headache specialist at the Banner–University Medicine Neuroscience Institute in Phoenix.
“Injection-site reactions were anticipated. Clinically, I’ve found that if the medications reduce migraine days and severity, patients find the risk of temporary pain, redness, or itching at the injection site is an easy trade off,” she added.
CGRP is a vasoactive peptide. There has been a theoretic concern that its pharmacologic inhibition for prevention of migraine could lead to an increased risk of adverse cardiovascular events, especially in individuals with coronary disease or a history of stroke. The absence of any such signal during the first 6 months of widespread clinical use of the CGRP inhibitors is highly encouraging, although this is an issue that warrants longer-term study, Dr. Yancy continued.
These drugs, which were expressly designed for migraine prevention, are a considerable advance over what was previously available in her view. They’re equally or more effective and considerably better tolerated than the preventive medications physicians had long been using off label, including antidepressants, antiepileptics, and cardiac drugs.
Dr. Silberstein reported financial relationships with close to two dozen pharmaceutical companies. Dr. Yancy reported serving on speakers’ bureaus for Amgen and Novartis.
SOURCE: Silverstein SD et al. AAN 2020, Abstract S58.008.
Stephen D. Silberstein, MD, reported online as part of the 2020 American Academy of Neurology Science Highlights.
He presented a retrospective analysis of spontaneous postmarketing reports to the Food and Drug Administration Adverse Events Reporting System (FAERS) for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).
The top-10 lists of adverse events for all three monoclonal antibodies targeting CGRP were skewed heavily towards injection-site reactions, such as injection-site pain, itching, swelling, and erythema. The rates were relatively low. For example, injection-site pain was reported at a rate of 2.94 cases per 1,000 patients exposed to erenumab, 0.8/1,000 for fremanezumab, and 4.9/1,000 for galcanezumab, according to Dr. Silberstein, professor of neurology and director of the headache center at Sidney Kimmel Medical College, Philadelphia.
Migraine, headache, and drug ineffectiveness were in the top 10 for all three medications, as is typical in FAERS reports, since no drug is effective in everyone. These events were reported at rates of 1-5/1,000 exposed patients. Constipation was reported in association with the use of erenumab at a rate of 4.9 cases/1,000 patients, but did not reach the top-10 lists for the other two CGRP antagonists.
Notably, cardiovascular events were not among the top-10 adverse events reported for any of the novel preventive agents.
“These results will be practice changing, since some physicians have been holding back from prescribing these drugs pending the results of this sort of longer-term safety data,” Dr. Silberstein predicted in an interview.
Asked to comment on the FAERS study, neurologist Holly Yancy, DO, said that she found the findings unsurprising because the adverse effects were essentially as expected based upon the earlier favorable clinical trials experience.
“These medications are living up to the expectations for good tolerability that were in place when they were initially approved by the FDA just under 2 years ago,” said Dr. Yancy, a headache specialist at the Banner–University Medicine Neuroscience Institute in Phoenix.
“Injection-site reactions were anticipated. Clinically, I’ve found that if the medications reduce migraine days and severity, patients find the risk of temporary pain, redness, or itching at the injection site is an easy trade off,” she added.
CGRP is a vasoactive peptide. There has been a theoretic concern that its pharmacologic inhibition for prevention of migraine could lead to an increased risk of adverse cardiovascular events, especially in individuals with coronary disease or a history of stroke. The absence of any such signal during the first 6 months of widespread clinical use of the CGRP inhibitors is highly encouraging, although this is an issue that warrants longer-term study, Dr. Yancy continued.
These drugs, which were expressly designed for migraine prevention, are a considerable advance over what was previously available in her view. They’re equally or more effective and considerably better tolerated than the preventive medications physicians had long been using off label, including antidepressants, antiepileptics, and cardiac drugs.
Dr. Silberstein reported financial relationships with close to two dozen pharmaceutical companies. Dr. Yancy reported serving on speakers’ bureaus for Amgen and Novartis.
SOURCE: Silverstein SD et al. AAN 2020, Abstract S58.008.
Stephen D. Silberstein, MD, reported online as part of the 2020 American Academy of Neurology Science Highlights.
He presented a retrospective analysis of spontaneous postmarketing reports to the Food and Drug Administration Adverse Events Reporting System (FAERS) for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).
The top-10 lists of adverse events for all three monoclonal antibodies targeting CGRP were skewed heavily towards injection-site reactions, such as injection-site pain, itching, swelling, and erythema. The rates were relatively low. For example, injection-site pain was reported at a rate of 2.94 cases per 1,000 patients exposed to erenumab, 0.8/1,000 for fremanezumab, and 4.9/1,000 for galcanezumab, according to Dr. Silberstein, professor of neurology and director of the headache center at Sidney Kimmel Medical College, Philadelphia.
Migraine, headache, and drug ineffectiveness were in the top 10 for all three medications, as is typical in FAERS reports, since no drug is effective in everyone. These events were reported at rates of 1-5/1,000 exposed patients. Constipation was reported in association with the use of erenumab at a rate of 4.9 cases/1,000 patients, but did not reach the top-10 lists for the other two CGRP antagonists.
Notably, cardiovascular events were not among the top-10 adverse events reported for any of the novel preventive agents.
“These results will be practice changing, since some physicians have been holding back from prescribing these drugs pending the results of this sort of longer-term safety data,” Dr. Silberstein predicted in an interview.
Asked to comment on the FAERS study, neurologist Holly Yancy, DO, said that she found the findings unsurprising because the adverse effects were essentially as expected based upon the earlier favorable clinical trials experience.
“These medications are living up to the expectations for good tolerability that were in place when they were initially approved by the FDA just under 2 years ago,” said Dr. Yancy, a headache specialist at the Banner–University Medicine Neuroscience Institute in Phoenix.
“Injection-site reactions were anticipated. Clinically, I’ve found that if the medications reduce migraine days and severity, patients find the risk of temporary pain, redness, or itching at the injection site is an easy trade off,” she added.
CGRP is a vasoactive peptide. There has been a theoretic concern that its pharmacologic inhibition for prevention of migraine could lead to an increased risk of adverse cardiovascular events, especially in individuals with coronary disease or a history of stroke. The absence of any such signal during the first 6 months of widespread clinical use of the CGRP inhibitors is highly encouraging, although this is an issue that warrants longer-term study, Dr. Yancy continued.
These drugs, which were expressly designed for migraine prevention, are a considerable advance over what was previously available in her view. They’re equally or more effective and considerably better tolerated than the preventive medications physicians had long been using off label, including antidepressants, antiepileptics, and cardiac drugs.
Dr. Silberstein reported financial relationships with close to two dozen pharmaceutical companies. Dr. Yancy reported serving on speakers’ bureaus for Amgen and Novartis.
SOURCE: Silverstein SD et al. AAN 2020, Abstract S58.008.
FROM AAN 2020
Anti-NMDAR encephalitis or primary psychiatric disorder?
New insights and ‘red flags’ provide clues to diagnosis
It remains difficult to distinguish anti-NMDA receptor encephalitis from a primary psychiatric disorder, but recent studies have identified clinical features and proposed screening criteria that could make it easier to identify these patients who would benefit from immunotherapy, according to an expert in the neurologic disease.
Most patients with confirmed anti-NMDA receptor encephalitis will experience substantial improvement after treatment with immunotherapy and other modalities, said Josep Dalmau, MD, PhD, professor at the Catalan Institute for Research and Advanced Studies at the University of Barcelona and adjunct professor of neurology at the University of Pennsylvania, Philadelphia.
“In our experience, being aggressive with immune therapy ... the patients do quite well, which means that basically 85%-90% of the patients substantially improved over the next few months,” Dr. Dalmau said at the annual meeting of the American Psychiatric Association, which was held as a virtual live event.
Identified for the first time a little more than a decade ago, anti-NMDA receptor encephalitis is a rare, immune-mediated disease that is usually found in children and young adults and is more common among women. It is frequently associated with ovarian tumors and teratomas, said Dr. Dalmau, and in about 90% of cases, patients will have prominent psychiatric and behavioral symptoms.
Patients develop IgG antibodies against the GluN1 subunit of the NMDA receptor. These autoantibodies represent not only a diagnostic marker of the disease, but are also pathogenic, altering NMDA receptor–related synaptic transmission, Dr. Dalmau said.
In several recent studies, investigators have attempted to cobble together a distinct phenotype on anti-NMDA receptor encephalitis to aid psychiatrists who might encounter patients with the disease, he said.
In one of the most recent studies, researchers combed the medical literature and found that, among 544 individuals with the disease, the most common psychiatric symptoms were agitation, seen in 59%, and psychotic symptoms (particularly visual-auditory hallucinations and disorganized behavior) in 54%; catatonia was seen in 42% of adults and 35% of children.
according to a report from researchers in Berlin, Dr. Dalmau added. By picking up on those clinical signs, which included seizures, catatonia, autonomic instability, or hyperkinesia, the time from symptom onset to diagnosis could be cut in half, the researchers found.
There’s also a handy acronym that could serve as a mnemonic to pick up on “diagnostic clues” of anti-NMDA receptor encephalitis among patients with new-onset psychiatric symptoms, Dr. Dalmau said.
That acronym, published in a review article by Dr. Dalmau and colleagues, is SEARCH For NMDAR-A, covering, in order: sleep dysfunction, excitement, agitation, rapid onset, child and young adult predominance, history of psychiatric disease (absent), fluctuating catatonia, negative and positive symptoms, memory deficit, decreased verbal output, antipsychotic intolerance, rule out neuroleptic malignant syndrome, and of course, antibodies (though the final “A” also stands for additional testing, including magnetic resonance imaging, cerebrospinal fluid studies, and electroencephalogram).
While the disease can be lethal, Dr. Dalmau said most patients respond to immunotherapy, and if applicable, treatment of the underlying tumor can help. The most common first-line treatments include steroids, intravenous immunoglobulin, and plasma exchange, he said, while second-line treatments include the monoclonal anti-CD20 antibody rituximab and cyclophosphamide.
Beyond immunotherapy, patients may benefit from supportive care and psychiatric treatment. Benzodiazepines are well tolerated, but Dr. Dalmau said antipsychotic intolerance is frequent, and electroconvulsive therapy has “mixed results” in these patients.
The recovery process can take months and may be complicated by hypersomnia, hyperphagia, and hypersexuality, he added.
“Some patients improve dramatically in 1 month, but this is uncommon, really,” he said, adding that an early recovery may be a “red flag” that the underlying condition is something other than anti-NMDA receptor encephalitis.
Dr. Dalmau provided disclosures related to Cellex Foundation, Safra Foundation, Caixa Health Project Foundation, and Sage Therapeutics.
SOURCE: Dalmau J. APA 2020, Abstract.
New insights and ‘red flags’ provide clues to diagnosis
New insights and ‘red flags’ provide clues to diagnosis
It remains difficult to distinguish anti-NMDA receptor encephalitis from a primary psychiatric disorder, but recent studies have identified clinical features and proposed screening criteria that could make it easier to identify these patients who would benefit from immunotherapy, according to an expert in the neurologic disease.
Most patients with confirmed anti-NMDA receptor encephalitis will experience substantial improvement after treatment with immunotherapy and other modalities, said Josep Dalmau, MD, PhD, professor at the Catalan Institute for Research and Advanced Studies at the University of Barcelona and adjunct professor of neurology at the University of Pennsylvania, Philadelphia.
“In our experience, being aggressive with immune therapy ... the patients do quite well, which means that basically 85%-90% of the patients substantially improved over the next few months,” Dr. Dalmau said at the annual meeting of the American Psychiatric Association, which was held as a virtual live event.
Identified for the first time a little more than a decade ago, anti-NMDA receptor encephalitis is a rare, immune-mediated disease that is usually found in children and young adults and is more common among women. It is frequently associated with ovarian tumors and teratomas, said Dr. Dalmau, and in about 90% of cases, patients will have prominent psychiatric and behavioral symptoms.
Patients develop IgG antibodies against the GluN1 subunit of the NMDA receptor. These autoantibodies represent not only a diagnostic marker of the disease, but are also pathogenic, altering NMDA receptor–related synaptic transmission, Dr. Dalmau said.
In several recent studies, investigators have attempted to cobble together a distinct phenotype on anti-NMDA receptor encephalitis to aid psychiatrists who might encounter patients with the disease, he said.
In one of the most recent studies, researchers combed the medical literature and found that, among 544 individuals with the disease, the most common psychiatric symptoms were agitation, seen in 59%, and psychotic symptoms (particularly visual-auditory hallucinations and disorganized behavior) in 54%; catatonia was seen in 42% of adults and 35% of children.
according to a report from researchers in Berlin, Dr. Dalmau added. By picking up on those clinical signs, which included seizures, catatonia, autonomic instability, or hyperkinesia, the time from symptom onset to diagnosis could be cut in half, the researchers found.
There’s also a handy acronym that could serve as a mnemonic to pick up on “diagnostic clues” of anti-NMDA receptor encephalitis among patients with new-onset psychiatric symptoms, Dr. Dalmau said.
That acronym, published in a review article by Dr. Dalmau and colleagues, is SEARCH For NMDAR-A, covering, in order: sleep dysfunction, excitement, agitation, rapid onset, child and young adult predominance, history of psychiatric disease (absent), fluctuating catatonia, negative and positive symptoms, memory deficit, decreased verbal output, antipsychotic intolerance, rule out neuroleptic malignant syndrome, and of course, antibodies (though the final “A” also stands for additional testing, including magnetic resonance imaging, cerebrospinal fluid studies, and electroencephalogram).
While the disease can be lethal, Dr. Dalmau said most patients respond to immunotherapy, and if applicable, treatment of the underlying tumor can help. The most common first-line treatments include steroids, intravenous immunoglobulin, and plasma exchange, he said, while second-line treatments include the monoclonal anti-CD20 antibody rituximab and cyclophosphamide.
Beyond immunotherapy, patients may benefit from supportive care and psychiatric treatment. Benzodiazepines are well tolerated, but Dr. Dalmau said antipsychotic intolerance is frequent, and electroconvulsive therapy has “mixed results” in these patients.
The recovery process can take months and may be complicated by hypersomnia, hyperphagia, and hypersexuality, he added.
“Some patients improve dramatically in 1 month, but this is uncommon, really,” he said, adding that an early recovery may be a “red flag” that the underlying condition is something other than anti-NMDA receptor encephalitis.
Dr. Dalmau provided disclosures related to Cellex Foundation, Safra Foundation, Caixa Health Project Foundation, and Sage Therapeutics.
SOURCE: Dalmau J. APA 2020, Abstract.
It remains difficult to distinguish anti-NMDA receptor encephalitis from a primary psychiatric disorder, but recent studies have identified clinical features and proposed screening criteria that could make it easier to identify these patients who would benefit from immunotherapy, according to an expert in the neurologic disease.
Most patients with confirmed anti-NMDA receptor encephalitis will experience substantial improvement after treatment with immunotherapy and other modalities, said Josep Dalmau, MD, PhD, professor at the Catalan Institute for Research and Advanced Studies at the University of Barcelona and adjunct professor of neurology at the University of Pennsylvania, Philadelphia.
“In our experience, being aggressive with immune therapy ... the patients do quite well, which means that basically 85%-90% of the patients substantially improved over the next few months,” Dr. Dalmau said at the annual meeting of the American Psychiatric Association, which was held as a virtual live event.
Identified for the first time a little more than a decade ago, anti-NMDA receptor encephalitis is a rare, immune-mediated disease that is usually found in children and young adults and is more common among women. It is frequently associated with ovarian tumors and teratomas, said Dr. Dalmau, and in about 90% of cases, patients will have prominent psychiatric and behavioral symptoms.
Patients develop IgG antibodies against the GluN1 subunit of the NMDA receptor. These autoantibodies represent not only a diagnostic marker of the disease, but are also pathogenic, altering NMDA receptor–related synaptic transmission, Dr. Dalmau said.
In several recent studies, investigators have attempted to cobble together a distinct phenotype on anti-NMDA receptor encephalitis to aid psychiatrists who might encounter patients with the disease, he said.
In one of the most recent studies, researchers combed the medical literature and found that, among 544 individuals with the disease, the most common psychiatric symptoms were agitation, seen in 59%, and psychotic symptoms (particularly visual-auditory hallucinations and disorganized behavior) in 54%; catatonia was seen in 42% of adults and 35% of children.
according to a report from researchers in Berlin, Dr. Dalmau added. By picking up on those clinical signs, which included seizures, catatonia, autonomic instability, or hyperkinesia, the time from symptom onset to diagnosis could be cut in half, the researchers found.
There’s also a handy acronym that could serve as a mnemonic to pick up on “diagnostic clues” of anti-NMDA receptor encephalitis among patients with new-onset psychiatric symptoms, Dr. Dalmau said.
That acronym, published in a review article by Dr. Dalmau and colleagues, is SEARCH For NMDAR-A, covering, in order: sleep dysfunction, excitement, agitation, rapid onset, child and young adult predominance, history of psychiatric disease (absent), fluctuating catatonia, negative and positive symptoms, memory deficit, decreased verbal output, antipsychotic intolerance, rule out neuroleptic malignant syndrome, and of course, antibodies (though the final “A” also stands for additional testing, including magnetic resonance imaging, cerebrospinal fluid studies, and electroencephalogram).
While the disease can be lethal, Dr. Dalmau said most patients respond to immunotherapy, and if applicable, treatment of the underlying tumor can help. The most common first-line treatments include steroids, intravenous immunoglobulin, and plasma exchange, he said, while second-line treatments include the monoclonal anti-CD20 antibody rituximab and cyclophosphamide.
Beyond immunotherapy, patients may benefit from supportive care and psychiatric treatment. Benzodiazepines are well tolerated, but Dr. Dalmau said antipsychotic intolerance is frequent, and electroconvulsive therapy has “mixed results” in these patients.
The recovery process can take months and may be complicated by hypersomnia, hyperphagia, and hypersexuality, he added.
“Some patients improve dramatically in 1 month, but this is uncommon, really,” he said, adding that an early recovery may be a “red flag” that the underlying condition is something other than anti-NMDA receptor encephalitis.
Dr. Dalmau provided disclosures related to Cellex Foundation, Safra Foundation, Caixa Health Project Foundation, and Sage Therapeutics.
SOURCE: Dalmau J. APA 2020, Abstract.
FROM APA 2020
Report details first case of PML with ocrelizumab alone
The case report was presented online as part of the 2020 American Academy of Neurology Science Highlights.
PML, an opportunistic infection of the brain caused by reactivation of the John Cunningham (JC) virus, has occurred with rituximab, another anti-CD20 therapy, in rare cases. Eight other cases of PML diagnosed after ocrelizumab initiation are considered carry-over cases related to prior treatment with natalizumab or fingolimod, according to Genentech, the manufacturer of ocrelizumab. No other PML cases have been associated with ocrelizumab alone.
The case without prior MS treatment was in a 78-year-old man. He presented with 2 weeks of progressive visual disturbance and confusion, said Marc L. Gordon, MD, chief of neurology at the Zucker Hillside Hospital in Glen Oaks, N.Y., and professor of neurology and psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y.
The patient had a right homonymous hemianopia. “MRI revealed an enlarging non-enhancing left parietal lesion without mass effect,” reported Dr. Gordon and colleagues. “CSF PCR revealed 1,000 copies/mL of JCV, confirming the diagnosis of PML. Blood work upon diagnosis revealed grade-2 lymphopenia ... and negative HIV serology.”
“The patient’s symptoms progressed over weeks to involve bilateral visual loss, right facial droop, and dysphasia,” they said. “Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated.” The patient did not respond to therapy and became bedbound, Dr. Gordon said in an interview. The patient received palliative care and died. An autopsy is pending.
“PML occurrence may have been multifactorial, due to a combination of the immunomodulatory function of ocrelizumab, possible immune senescence, and preceding mild lymphopenia,” Dr. Gordon and coauthors said. “This case emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections, such as the elderly.”
The patient, who was Dr. Gordon’s patient for 20 years, had monitored updates in drug development and had looked forward to starting ocrelizumab, the first therapy approved for primary progressive MS, when it became available after its approval in 2017. The patient was concerned about progressively worsening gait impairment and related falls caused by MS.
Antibodies indicated that the patient had prior exposure to JCV, but Dr. Gordon considered the risk of PML to be relatively small. Prior to treatment, the patient’s absolute lymphocyte count was normal or indicated mild lymphocytopenia, which Dr. Gordon did not consider clinically significant. The patient received ocrelizumab for 2 years without incident.
In an information sheet for health care professionals about ocrelizumab and PML prepared in February 2020, Genentech says the patient’s age and low absolute lymphocyte count are confounding factors, which distort “the assessment of association between exposure to a drug and an adverse event.
“As of January 31, 2020, no unconfounded PML cases associated with ocrelizumab therapy have been reported,” according to the document. “Out of more than 150,000 patients treated globally (clinical trials and post-marketing experience), there have been nine confirmed, confounded cases of PML in patients treated with ocrelizumab, of which eight were carry-over cases from a prior DMT.”
The prescribing information for the drug notes that no cases of PML were identified in ocrelizumab clinical trials, but that PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies. In addition, PML “has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants).
“At the first sign or symptom suggestive of PML, withhold ocrelizumab and perform an appropriate diagnostic evaluation,” the prescribing information says. “MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.”
“It is important for people to recognize that this is at least a possibility,” Dr. Gordon said. Any change in clinical symptomatology may warrant imaging, and CSF testing may be warranted if an MRI raises concerns about PML, he said.
Dr. Gordon has received research support from MSD (Merck), Eisai, AbbVie, and Janssen.
SOURCE: Sul J et al. AAN 2020. Abstract S29.001.
The case report was presented online as part of the 2020 American Academy of Neurology Science Highlights.
PML, an opportunistic infection of the brain caused by reactivation of the John Cunningham (JC) virus, has occurred with rituximab, another anti-CD20 therapy, in rare cases. Eight other cases of PML diagnosed after ocrelizumab initiation are considered carry-over cases related to prior treatment with natalizumab or fingolimod, according to Genentech, the manufacturer of ocrelizumab. No other PML cases have been associated with ocrelizumab alone.
The case without prior MS treatment was in a 78-year-old man. He presented with 2 weeks of progressive visual disturbance and confusion, said Marc L. Gordon, MD, chief of neurology at the Zucker Hillside Hospital in Glen Oaks, N.Y., and professor of neurology and psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y.
The patient had a right homonymous hemianopia. “MRI revealed an enlarging non-enhancing left parietal lesion without mass effect,” reported Dr. Gordon and colleagues. “CSF PCR revealed 1,000 copies/mL of JCV, confirming the diagnosis of PML. Blood work upon diagnosis revealed grade-2 lymphopenia ... and negative HIV serology.”
“The patient’s symptoms progressed over weeks to involve bilateral visual loss, right facial droop, and dysphasia,” they said. “Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated.” The patient did not respond to therapy and became bedbound, Dr. Gordon said in an interview. The patient received palliative care and died. An autopsy is pending.
“PML occurrence may have been multifactorial, due to a combination of the immunomodulatory function of ocrelizumab, possible immune senescence, and preceding mild lymphopenia,” Dr. Gordon and coauthors said. “This case emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections, such as the elderly.”
The patient, who was Dr. Gordon’s patient for 20 years, had monitored updates in drug development and had looked forward to starting ocrelizumab, the first therapy approved for primary progressive MS, when it became available after its approval in 2017. The patient was concerned about progressively worsening gait impairment and related falls caused by MS.
Antibodies indicated that the patient had prior exposure to JCV, but Dr. Gordon considered the risk of PML to be relatively small. Prior to treatment, the patient’s absolute lymphocyte count was normal or indicated mild lymphocytopenia, which Dr. Gordon did not consider clinically significant. The patient received ocrelizumab for 2 years without incident.
In an information sheet for health care professionals about ocrelizumab and PML prepared in February 2020, Genentech says the patient’s age and low absolute lymphocyte count are confounding factors, which distort “the assessment of association between exposure to a drug and an adverse event.
“As of January 31, 2020, no unconfounded PML cases associated with ocrelizumab therapy have been reported,” according to the document. “Out of more than 150,000 patients treated globally (clinical trials and post-marketing experience), there have been nine confirmed, confounded cases of PML in patients treated with ocrelizumab, of which eight were carry-over cases from a prior DMT.”
The prescribing information for the drug notes that no cases of PML were identified in ocrelizumab clinical trials, but that PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies. In addition, PML “has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants).
“At the first sign or symptom suggestive of PML, withhold ocrelizumab and perform an appropriate diagnostic evaluation,” the prescribing information says. “MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.”
“It is important for people to recognize that this is at least a possibility,” Dr. Gordon said. Any change in clinical symptomatology may warrant imaging, and CSF testing may be warranted if an MRI raises concerns about PML, he said.
Dr. Gordon has received research support from MSD (Merck), Eisai, AbbVie, and Janssen.
SOURCE: Sul J et al. AAN 2020. Abstract S29.001.
The case report was presented online as part of the 2020 American Academy of Neurology Science Highlights.
PML, an opportunistic infection of the brain caused by reactivation of the John Cunningham (JC) virus, has occurred with rituximab, another anti-CD20 therapy, in rare cases. Eight other cases of PML diagnosed after ocrelizumab initiation are considered carry-over cases related to prior treatment with natalizumab or fingolimod, according to Genentech, the manufacturer of ocrelizumab. No other PML cases have been associated with ocrelizumab alone.
The case without prior MS treatment was in a 78-year-old man. He presented with 2 weeks of progressive visual disturbance and confusion, said Marc L. Gordon, MD, chief of neurology at the Zucker Hillside Hospital in Glen Oaks, N.Y., and professor of neurology and psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, N.Y.
The patient had a right homonymous hemianopia. “MRI revealed an enlarging non-enhancing left parietal lesion without mass effect,” reported Dr. Gordon and colleagues. “CSF PCR revealed 1,000 copies/mL of JCV, confirming the diagnosis of PML. Blood work upon diagnosis revealed grade-2 lymphopenia ... and negative HIV serology.”
“The patient’s symptoms progressed over weeks to involve bilateral visual loss, right facial droop, and dysphasia,” they said. “Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated.” The patient did not respond to therapy and became bedbound, Dr. Gordon said in an interview. The patient received palliative care and died. An autopsy is pending.
“PML occurrence may have been multifactorial, due to a combination of the immunomodulatory function of ocrelizumab, possible immune senescence, and preceding mild lymphopenia,” Dr. Gordon and coauthors said. “This case emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections, such as the elderly.”
The patient, who was Dr. Gordon’s patient for 20 years, had monitored updates in drug development and had looked forward to starting ocrelizumab, the first therapy approved for primary progressive MS, when it became available after its approval in 2017. The patient was concerned about progressively worsening gait impairment and related falls caused by MS.
Antibodies indicated that the patient had prior exposure to JCV, but Dr. Gordon considered the risk of PML to be relatively small. Prior to treatment, the patient’s absolute lymphocyte count was normal or indicated mild lymphocytopenia, which Dr. Gordon did not consider clinically significant. The patient received ocrelizumab for 2 years without incident.
In an information sheet for health care professionals about ocrelizumab and PML prepared in February 2020, Genentech says the patient’s age and low absolute lymphocyte count are confounding factors, which distort “the assessment of association between exposure to a drug and an adverse event.
“As of January 31, 2020, no unconfounded PML cases associated with ocrelizumab therapy have been reported,” according to the document. “Out of more than 150,000 patients treated globally (clinical trials and post-marketing experience), there have been nine confirmed, confounded cases of PML in patients treated with ocrelizumab, of which eight were carry-over cases from a prior DMT.”
The prescribing information for the drug notes that no cases of PML were identified in ocrelizumab clinical trials, but that PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies. In addition, PML “has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants).
“At the first sign or symptom suggestive of PML, withhold ocrelizumab and perform an appropriate diagnostic evaluation,” the prescribing information says. “MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.”
“It is important for people to recognize that this is at least a possibility,” Dr. Gordon said. Any change in clinical symptomatology may warrant imaging, and CSF testing may be warranted if an MRI raises concerns about PML, he said.
Dr. Gordon has received research support from MSD (Merck), Eisai, AbbVie, and Janssen.
SOURCE: Sul J et al. AAN 2020. Abstract S29.001.
FROM AAN 2020
TERAVOLT data suggest high death rate in lung cancer patients with COVID-19
Registry data suggest an “unexpectedly high” mortality rate among patients with thoracic cancers who develop COVID-19, according to a presenter at the AACR virtual meeting I.
Data from the TERAVOLT registry showed a 34.6% mortality rate among 200 patients with COVID-19 and thoracic cancer, according to Marina Chiara Garassino, MD, of Fondazione IRCCS Instituto Nazionale dei Tumor in Milan, Italy, who presented the data at the meeting in a session on cancer and COVID-19.
Cancer patients infected with COVID-19 have been reported to be at increased risk of death, but the magnitude of increase is uncertain (Lancet Oncol. 2020 Mar;21[3]:335-7; JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4683).
Patients with thoracic cancer may be particularly vulnerable because of older age, tobacco use, preexisting cardiopulmonary comorbidities, and the immunosuppressive effects of treatment.
The global TERAVOLT registry was begun in late March 2020 to provide outcome data for coronavirus infections in thoracic cancer patients specifically. It is hoped that the data collected will guide patient management and define factors influencing morbidity and mortality.
Dr. Garassino said institutions from 21 countries have joined the TERAVOLT registry thus far. Currently, about 17 new patients with thoracic cancer and laboratory confirmed or clinically suspected COVID-19 are added to the registry each week.
As of April 12, 2020, there were 200 patients included in the registry. Their median age was 68 years, and 70.5% were men. Non–small cell lung cancer was the histology in 75.5% and small-cell lung cancer in 14.5% of patients. Most patients (73.5%) had stage IV disease. Approximately 27% of patients had at least three comorbid conditions.
About 74% of patients were on current cancer treatment, with 19% on tyrosine kinase inhibitors alone, 32.7% on chemotherapy alone, 23.1% on immunotherapy alone, and 13.6% on chemotherapy plus immunotherapy.
In all, 152 patients (76.0%) were hospitalized. However, 91.2% of patients were not admitted to the ICU, either because of a shortage of equipment or institutional policy.
The most common complications were pneumonia/pneumonitis (79.6%), acute respiratory distress syndrome (26.8%), multiorgan failure (7.6%), and sepsis (5.1%).
A total of 66 patients (34.6%) died. Most deaths were attributed to COVID-19 and not the underlying cancer, Dr. Garassino said.
A univariate analysis showed no association between cancer treatment and an increased risk of hospitalization or death. However, Dr. Garassino and colleagues are collecting more data to confirm these results.
In a multivariate analysis, no factors were associated with the risk of death, although data from a larger number of patients may shed more light on that issue.
TERAVOLT will continue to collect and provide data to identify characteristics associated with severe COVID-19–related illness, to guide physicians with information applicable to patients with thoracic malignancies, tailored to individual risk.
Like the COVID-19 and Cancer Consortium and the ESMO CoCare registry, TERAVOLT represents a way for the patient care and translational science communities to share lessons from the COVID-19 pandemic.
AACR plans to help share those lessons as well, in another session on COVID-19 and cancer at the AACR virtual meeting II in June and at a conference on COVID-19 and cancer in July, according to session moderator Antoni Ribas, MD, PhD, of the University of California, Los Angeles.
Dr. Garassino disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Registry data suggest an “unexpectedly high” mortality rate among patients with thoracic cancers who develop COVID-19, according to a presenter at the AACR virtual meeting I.
Data from the TERAVOLT registry showed a 34.6% mortality rate among 200 patients with COVID-19 and thoracic cancer, according to Marina Chiara Garassino, MD, of Fondazione IRCCS Instituto Nazionale dei Tumor in Milan, Italy, who presented the data at the meeting in a session on cancer and COVID-19.
Cancer patients infected with COVID-19 have been reported to be at increased risk of death, but the magnitude of increase is uncertain (Lancet Oncol. 2020 Mar;21[3]:335-7; JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4683).
Patients with thoracic cancer may be particularly vulnerable because of older age, tobacco use, preexisting cardiopulmonary comorbidities, and the immunosuppressive effects of treatment.
The global TERAVOLT registry was begun in late March 2020 to provide outcome data for coronavirus infections in thoracic cancer patients specifically. It is hoped that the data collected will guide patient management and define factors influencing morbidity and mortality.
Dr. Garassino said institutions from 21 countries have joined the TERAVOLT registry thus far. Currently, about 17 new patients with thoracic cancer and laboratory confirmed or clinically suspected COVID-19 are added to the registry each week.
As of April 12, 2020, there were 200 patients included in the registry. Their median age was 68 years, and 70.5% were men. Non–small cell lung cancer was the histology in 75.5% and small-cell lung cancer in 14.5% of patients. Most patients (73.5%) had stage IV disease. Approximately 27% of patients had at least three comorbid conditions.
About 74% of patients were on current cancer treatment, with 19% on tyrosine kinase inhibitors alone, 32.7% on chemotherapy alone, 23.1% on immunotherapy alone, and 13.6% on chemotherapy plus immunotherapy.
In all, 152 patients (76.0%) were hospitalized. However, 91.2% of patients were not admitted to the ICU, either because of a shortage of equipment or institutional policy.
The most common complications were pneumonia/pneumonitis (79.6%), acute respiratory distress syndrome (26.8%), multiorgan failure (7.6%), and sepsis (5.1%).
A total of 66 patients (34.6%) died. Most deaths were attributed to COVID-19 and not the underlying cancer, Dr. Garassino said.
A univariate analysis showed no association between cancer treatment and an increased risk of hospitalization or death. However, Dr. Garassino and colleagues are collecting more data to confirm these results.
In a multivariate analysis, no factors were associated with the risk of death, although data from a larger number of patients may shed more light on that issue.
TERAVOLT will continue to collect and provide data to identify characteristics associated with severe COVID-19–related illness, to guide physicians with information applicable to patients with thoracic malignancies, tailored to individual risk.
Like the COVID-19 and Cancer Consortium and the ESMO CoCare registry, TERAVOLT represents a way for the patient care and translational science communities to share lessons from the COVID-19 pandemic.
AACR plans to help share those lessons as well, in another session on COVID-19 and cancer at the AACR virtual meeting II in June and at a conference on COVID-19 and cancer in July, according to session moderator Antoni Ribas, MD, PhD, of the University of California, Los Angeles.
Dr. Garassino disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Registry data suggest an “unexpectedly high” mortality rate among patients with thoracic cancers who develop COVID-19, according to a presenter at the AACR virtual meeting I.
Data from the TERAVOLT registry showed a 34.6% mortality rate among 200 patients with COVID-19 and thoracic cancer, according to Marina Chiara Garassino, MD, of Fondazione IRCCS Instituto Nazionale dei Tumor in Milan, Italy, who presented the data at the meeting in a session on cancer and COVID-19.
Cancer patients infected with COVID-19 have been reported to be at increased risk of death, but the magnitude of increase is uncertain (Lancet Oncol. 2020 Mar;21[3]:335-7; JAMA. 2020 Mar 23. doi: 10.1001/jama.2020.4683).
Patients with thoracic cancer may be particularly vulnerable because of older age, tobacco use, preexisting cardiopulmonary comorbidities, and the immunosuppressive effects of treatment.
The global TERAVOLT registry was begun in late March 2020 to provide outcome data for coronavirus infections in thoracic cancer patients specifically. It is hoped that the data collected will guide patient management and define factors influencing morbidity and mortality.
Dr. Garassino said institutions from 21 countries have joined the TERAVOLT registry thus far. Currently, about 17 new patients with thoracic cancer and laboratory confirmed or clinically suspected COVID-19 are added to the registry each week.
As of April 12, 2020, there were 200 patients included in the registry. Their median age was 68 years, and 70.5% were men. Non–small cell lung cancer was the histology in 75.5% and small-cell lung cancer in 14.5% of patients. Most patients (73.5%) had stage IV disease. Approximately 27% of patients had at least three comorbid conditions.
About 74% of patients were on current cancer treatment, with 19% on tyrosine kinase inhibitors alone, 32.7% on chemotherapy alone, 23.1% on immunotherapy alone, and 13.6% on chemotherapy plus immunotherapy.
In all, 152 patients (76.0%) were hospitalized. However, 91.2% of patients were not admitted to the ICU, either because of a shortage of equipment or institutional policy.
The most common complications were pneumonia/pneumonitis (79.6%), acute respiratory distress syndrome (26.8%), multiorgan failure (7.6%), and sepsis (5.1%).
A total of 66 patients (34.6%) died. Most deaths were attributed to COVID-19 and not the underlying cancer, Dr. Garassino said.
A univariate analysis showed no association between cancer treatment and an increased risk of hospitalization or death. However, Dr. Garassino and colleagues are collecting more data to confirm these results.
In a multivariate analysis, no factors were associated with the risk of death, although data from a larger number of patients may shed more light on that issue.
TERAVOLT will continue to collect and provide data to identify characteristics associated with severe COVID-19–related illness, to guide physicians with information applicable to patients with thoracic malignancies, tailored to individual risk.
Like the COVID-19 and Cancer Consortium and the ESMO CoCare registry, TERAVOLT represents a way for the patient care and translational science communities to share lessons from the COVID-19 pandemic.
AACR plans to help share those lessons as well, in another session on COVID-19 and cancer at the AACR virtual meeting II in June and at a conference on COVID-19 and cancer in July, according to session moderator Antoni Ribas, MD, PhD, of the University of California, Los Angeles.
Dr. Garassino disclosed relationships with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM AACR 2020
Substantial very late MACE risk after PCI for SIHD
Patients with stable ischemic heart disease remain at substantial risk for major adverse cardiovascular events 1-5 years after percutaneous coronary intervention, even with contemporary second-generation drug-eluting stents, according to a pooled analysis of long-term follow-up data on 10,987 patients in 19 prospective, randomized, head-to-head metallic stent trials.
The analysis showed that, although most major adverse cardiovascular events (MACE) occurred during the first year after stenting, no plateau in MACE was reached between years 1 and 5, Mahesh V. Madhavan, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
“Further studies are required to understand the mechanisms of late events and whether improvements in stent technology, revascularization technique, and adjunctive therapies may improve outcomes in patients with SIHD [stable ischemic heart disease],” said Dr. Madhavan, a cardiology fellow at Columbia University Irving Medical Center and New York–Presbyterian Hospital.
This post hoc analysis of pooled individual patient-level data from 19 randomized trials included 10,987 metallic stent recipients with SIHD. Sixty-one percent got second-generation drug-eluting stents (DES), 25% received first-generation DES, and 15% got bare metal stents (BMS). The largest prospective head-to-head RCT was SPIRIT IV, with 2,130 patients. All five TAXUS trials were also included.
The 5-year rate of the primary composite MACE endpoint composed of cardiac death, MI, or ischemia-driven target lesion revascularization was 24.1% in patients with BMS stents, 17.9% with first-gen DES, and 13.4% with second-gen DES, reflecting the advances in stent technology over time. Most of these MACE events occurred during the first year after PCI, with rates of 18%, 8.6%, and 5.3%, respectively, in the three groups. However, the MACE rate beyond the first year out through year 5 remained substantial: 10.2% with first-gen DES, 8.5% with second-gen DES, and 7.4% in the BMS group.
The cardiac death rate from PCI through year 5 was 3.8% with second-gen DES, 3.6% with first-gen DES, and 3.3% with BMS. The MI rate was 7.7% with first-gen DES, 6.1% with BMS, and 5% with second-gen DES.
Stent thrombosis occurred during the first year in 0.9% of first-gen DES and BMS recipients and in 0.7% of patients with second-gen DES. During years 1-5, the rates were 1.6% with first-gen DES, 0.9% with second-gen devices, and 0.2% with BMS.
Second-gen DES provided a big advantage in terms of lessened need for ischemia-driven target lesion revascularization through the first 5 years, with a rate of 7.3%, compared to 18.7% in patients with first-gen DES and 10.5% with BMS.
In a multivariate regression analysis, independent predictors of MACE in the first 5 years post PCI included indicators of greater lesion and/or procedural complexity, such as left main or left anterior descending disease, greater lesion length, and more than one treated lesion, as well as standard cardiovascular risk factors, including recent smoking, hypertension, and diabetes.
In contrast, hyperlipidemia was associated with a significant 15% reduction in MACE risk, which in an interview Dr. Madhavan said may have been due to aggressive lipid-lowering therapy, although he added that this is conjecture because he and his coinvestigators didn’t have access to data on the use of guideline-directed medical therapy or antiplatelet regimens.
Asked about future prospects for reducing the substantial very late risk of MACE highlighted in his study, Dr. Madhavan cited the use of adjunctive imaging during PCI as promising.
“The currently enrolling ILUMEN IV trial, among other studies, will help determine whether imaging-guided intervention can help improve intermediate and long-term rates of MACE,” he observed.
Promising medical therapies that could potentially confer benefit in terms of reducing long-term MACE in patients who’ve undergone PCI for SIHD include novel lipid-lowering drugs, tailored antithrombotic strategies, new anti-inflammatory agents, and the SGLT2 inhibitors, Dr. Madhavan continued.
In terms of advances in stent design, he cited recent evidence that ultrathin-strut stents featuring bioresorbable polymer, such as the Orsiro stent, may reduce late stent-related MACE through 3 years.
“We’ll have to see if these benefits extend to longer-term follow-up up to 5 years,” he said.
He deemed his study results “fairly consistent” with those of the ISCHEMIA trial, where ischemic events in the patients with SIHD assigned to an initial invasive strategy continued to occur in the latter years of follow-up without any clear plateau effect (N Engl J Med. 2020 Apr 9;382[15]:1395-407).
Dr. Madhavan reported no financial conflicts regarding his study, funded by an institutional research grant from the National Heart, Lung, and Blood Institute.
Shortly following Dr. Madhavan’s presentation at ACC 2020, the study results were published online (Circ Cardiovasc Interv. 2020 Apr;13[4[:e008565. doi: 10.1161/CIRCINTERVENTIONS.119.008565).
SOURCE: Madhavan MV. ACC 2020, Abstract 909-10.
Patients with stable ischemic heart disease remain at substantial risk for major adverse cardiovascular events 1-5 years after percutaneous coronary intervention, even with contemporary second-generation drug-eluting stents, according to a pooled analysis of long-term follow-up data on 10,987 patients in 19 prospective, randomized, head-to-head metallic stent trials.
The analysis showed that, although most major adverse cardiovascular events (MACE) occurred during the first year after stenting, no plateau in MACE was reached between years 1 and 5, Mahesh V. Madhavan, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
“Further studies are required to understand the mechanisms of late events and whether improvements in stent technology, revascularization technique, and adjunctive therapies may improve outcomes in patients with SIHD [stable ischemic heart disease],” said Dr. Madhavan, a cardiology fellow at Columbia University Irving Medical Center and New York–Presbyterian Hospital.
This post hoc analysis of pooled individual patient-level data from 19 randomized trials included 10,987 metallic stent recipients with SIHD. Sixty-one percent got second-generation drug-eluting stents (DES), 25% received first-generation DES, and 15% got bare metal stents (BMS). The largest prospective head-to-head RCT was SPIRIT IV, with 2,130 patients. All five TAXUS trials were also included.
The 5-year rate of the primary composite MACE endpoint composed of cardiac death, MI, or ischemia-driven target lesion revascularization was 24.1% in patients with BMS stents, 17.9% with first-gen DES, and 13.4% with second-gen DES, reflecting the advances in stent technology over time. Most of these MACE events occurred during the first year after PCI, with rates of 18%, 8.6%, and 5.3%, respectively, in the three groups. However, the MACE rate beyond the first year out through year 5 remained substantial: 10.2% with first-gen DES, 8.5% with second-gen DES, and 7.4% in the BMS group.
The cardiac death rate from PCI through year 5 was 3.8% with second-gen DES, 3.6% with first-gen DES, and 3.3% with BMS. The MI rate was 7.7% with first-gen DES, 6.1% with BMS, and 5% with second-gen DES.
Stent thrombosis occurred during the first year in 0.9% of first-gen DES and BMS recipients and in 0.7% of patients with second-gen DES. During years 1-5, the rates were 1.6% with first-gen DES, 0.9% with second-gen devices, and 0.2% with BMS.
Second-gen DES provided a big advantage in terms of lessened need for ischemia-driven target lesion revascularization through the first 5 years, with a rate of 7.3%, compared to 18.7% in patients with first-gen DES and 10.5% with BMS.
In a multivariate regression analysis, independent predictors of MACE in the first 5 years post PCI included indicators of greater lesion and/or procedural complexity, such as left main or left anterior descending disease, greater lesion length, and more than one treated lesion, as well as standard cardiovascular risk factors, including recent smoking, hypertension, and diabetes.
In contrast, hyperlipidemia was associated with a significant 15% reduction in MACE risk, which in an interview Dr. Madhavan said may have been due to aggressive lipid-lowering therapy, although he added that this is conjecture because he and his coinvestigators didn’t have access to data on the use of guideline-directed medical therapy or antiplatelet regimens.
Asked about future prospects for reducing the substantial very late risk of MACE highlighted in his study, Dr. Madhavan cited the use of adjunctive imaging during PCI as promising.
“The currently enrolling ILUMEN IV trial, among other studies, will help determine whether imaging-guided intervention can help improve intermediate and long-term rates of MACE,” he observed.
Promising medical therapies that could potentially confer benefit in terms of reducing long-term MACE in patients who’ve undergone PCI for SIHD include novel lipid-lowering drugs, tailored antithrombotic strategies, new anti-inflammatory agents, and the SGLT2 inhibitors, Dr. Madhavan continued.
In terms of advances in stent design, he cited recent evidence that ultrathin-strut stents featuring bioresorbable polymer, such as the Orsiro stent, may reduce late stent-related MACE through 3 years.
“We’ll have to see if these benefits extend to longer-term follow-up up to 5 years,” he said.
He deemed his study results “fairly consistent” with those of the ISCHEMIA trial, where ischemic events in the patients with SIHD assigned to an initial invasive strategy continued to occur in the latter years of follow-up without any clear plateau effect (N Engl J Med. 2020 Apr 9;382[15]:1395-407).
Dr. Madhavan reported no financial conflicts regarding his study, funded by an institutional research grant from the National Heart, Lung, and Blood Institute.
Shortly following Dr. Madhavan’s presentation at ACC 2020, the study results were published online (Circ Cardiovasc Interv. 2020 Apr;13[4[:e008565. doi: 10.1161/CIRCINTERVENTIONS.119.008565).
SOURCE: Madhavan MV. ACC 2020, Abstract 909-10.
Patients with stable ischemic heart disease remain at substantial risk for major adverse cardiovascular events 1-5 years after percutaneous coronary intervention, even with contemporary second-generation drug-eluting stents, according to a pooled analysis of long-term follow-up data on 10,987 patients in 19 prospective, randomized, head-to-head metallic stent trials.
The analysis showed that, although most major adverse cardiovascular events (MACE) occurred during the first year after stenting, no plateau in MACE was reached between years 1 and 5, Mahesh V. Madhavan, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.
“Further studies are required to understand the mechanisms of late events and whether improvements in stent technology, revascularization technique, and adjunctive therapies may improve outcomes in patients with SIHD [stable ischemic heart disease],” said Dr. Madhavan, a cardiology fellow at Columbia University Irving Medical Center and New York–Presbyterian Hospital.
This post hoc analysis of pooled individual patient-level data from 19 randomized trials included 10,987 metallic stent recipients with SIHD. Sixty-one percent got second-generation drug-eluting stents (DES), 25% received first-generation DES, and 15% got bare metal stents (BMS). The largest prospective head-to-head RCT was SPIRIT IV, with 2,130 patients. All five TAXUS trials were also included.
The 5-year rate of the primary composite MACE endpoint composed of cardiac death, MI, or ischemia-driven target lesion revascularization was 24.1% in patients with BMS stents, 17.9% with first-gen DES, and 13.4% with second-gen DES, reflecting the advances in stent technology over time. Most of these MACE events occurred during the first year after PCI, with rates of 18%, 8.6%, and 5.3%, respectively, in the three groups. However, the MACE rate beyond the first year out through year 5 remained substantial: 10.2% with first-gen DES, 8.5% with second-gen DES, and 7.4% in the BMS group.
The cardiac death rate from PCI through year 5 was 3.8% with second-gen DES, 3.6% with first-gen DES, and 3.3% with BMS. The MI rate was 7.7% with first-gen DES, 6.1% with BMS, and 5% with second-gen DES.
Stent thrombosis occurred during the first year in 0.9% of first-gen DES and BMS recipients and in 0.7% of patients with second-gen DES. During years 1-5, the rates were 1.6% with first-gen DES, 0.9% with second-gen devices, and 0.2% with BMS.
Second-gen DES provided a big advantage in terms of lessened need for ischemia-driven target lesion revascularization through the first 5 years, with a rate of 7.3%, compared to 18.7% in patients with first-gen DES and 10.5% with BMS.
In a multivariate regression analysis, independent predictors of MACE in the first 5 years post PCI included indicators of greater lesion and/or procedural complexity, such as left main or left anterior descending disease, greater lesion length, and more than one treated lesion, as well as standard cardiovascular risk factors, including recent smoking, hypertension, and diabetes.
In contrast, hyperlipidemia was associated with a significant 15% reduction in MACE risk, which in an interview Dr. Madhavan said may have been due to aggressive lipid-lowering therapy, although he added that this is conjecture because he and his coinvestigators didn’t have access to data on the use of guideline-directed medical therapy or antiplatelet regimens.
Asked about future prospects for reducing the substantial very late risk of MACE highlighted in his study, Dr. Madhavan cited the use of adjunctive imaging during PCI as promising.
“The currently enrolling ILUMEN IV trial, among other studies, will help determine whether imaging-guided intervention can help improve intermediate and long-term rates of MACE,” he observed.
Promising medical therapies that could potentially confer benefit in terms of reducing long-term MACE in patients who’ve undergone PCI for SIHD include novel lipid-lowering drugs, tailored antithrombotic strategies, new anti-inflammatory agents, and the SGLT2 inhibitors, Dr. Madhavan continued.
In terms of advances in stent design, he cited recent evidence that ultrathin-strut stents featuring bioresorbable polymer, such as the Orsiro stent, may reduce late stent-related MACE through 3 years.
“We’ll have to see if these benefits extend to longer-term follow-up up to 5 years,” he said.
He deemed his study results “fairly consistent” with those of the ISCHEMIA trial, where ischemic events in the patients with SIHD assigned to an initial invasive strategy continued to occur in the latter years of follow-up without any clear plateau effect (N Engl J Med. 2020 Apr 9;382[15]:1395-407).
Dr. Madhavan reported no financial conflicts regarding his study, funded by an institutional research grant from the National Heart, Lung, and Blood Institute.
Shortly following Dr. Madhavan’s presentation at ACC 2020, the study results were published online (Circ Cardiovasc Interv. 2020 Apr;13[4[:e008565. doi: 10.1161/CIRCINTERVENTIONS.119.008565).
SOURCE: Madhavan MV. ACC 2020, Abstract 909-10.
FROM ACC 20
COVID-19: An opportunity, challenge for addiction treatment, NIDA boss says
The COVID-19 pandemic is posing significant challenges while also providing unique opportunities for patients with substance use disorders (SUD), a leading expert says.
Nora Volkow, MD, director of the National Institute on Drug Abuse, said that the pandemic has accelerated the use of telemedicine, making it easier for patients with SUD to access treatment. It has also led to the proliferation of more mental health hotlines, which is critical since the vast majority of these patients have comorbid mental illness.
In addition, COVID-19 has resulted in increased availability of “alternative” peer support mechanisms via cellphones or computers to aid individuals’ sobriety.
Dr. Volkow spoke at the virtual American Psychiatric Association Spring Highlights Meeting 2020, which is replacing the organization’s canceled annual meeting.
While methadone clinics have had to close during the pandemic, making it challenging for those on medically assisted treatment to receive methadone or buprenorphine, some of the rules and regulations have been relaxed in order to make these medications accessible without the need for in-person attendance at a clinic. In addition, the Substance Abuse and Mental Health Services Administration has relaxed some of its own regulations regarding telehealth and opioid treatment programs.
Social isolation, stigma intensified
A pandemic increases anxiety in the general population, but for patients with SUD who may be also be struggling with homelessness and comorbid mental illness, the situation can further exacerbate social stigma and isolation – leading to relapse, more overdoses, and overdose deaths, Dr. Volkow said. Social interaction is “extraordinarily important” for patients and “one of the most powerful tools we have” to build resilience.
Right now, said Dr. Volkow, “we are in the dark as to how COVID infections have affected the number of overdose deaths.”
However, she noted that
“So even through this devastation, we can actually extract something that may help others in future,” she said.
Dr. Volkow noted that during the pandemic it is critical to reinforce the importance of engaging in – and remaining in – treatment to SUD patients. It’s also crucial to make patients aware of social support systems and behavioral interventions to help them cope with stress and to mitigate relapse risk.
COVID-19 and relapse
Elie G. Aoun, MD, assistant professor of psychiatry at New York University and vice chair of the APA’s Council on Addiction Psychiatry, said in an interview that Dr. Volkow’s presentation provided “exactly the kind of accessible information” clinicians need.
Dr. Aoun said he sees the impact of the COVID-19 crisis in his practice every day. Patients with SUD “are getting the short end of the stick.”
Social distancing measures prompted by the pandemic can be “very triggering” for SUD patients, he said. One of his patients told him the current isolation, loneliness, movement restrictions, and boredom remind her of the way she felt when she used drugs.
Dr. Aoun said four of his patients have relapsed since the pandemic began. Two of them had just started treatment after years of using drugs, so this was a “major setback” for them.
He and his colleagues were “not really prepared” to provide care via video link, which he believes is not as effective as in-person sessions.
In addition to disrupting patient care, said Dr. Aoun, the pandemic is forcing the medical community to face social determinants of health, such as poverty and homelessness, as they relate to addiction disorders and whether or not someone receives care.
This article originally appeared on Medscape.com.
The COVID-19 pandemic is posing significant challenges while also providing unique opportunities for patients with substance use disorders (SUD), a leading expert says.
Nora Volkow, MD, director of the National Institute on Drug Abuse, said that the pandemic has accelerated the use of telemedicine, making it easier for patients with SUD to access treatment. It has also led to the proliferation of more mental health hotlines, which is critical since the vast majority of these patients have comorbid mental illness.
In addition, COVID-19 has resulted in increased availability of “alternative” peer support mechanisms via cellphones or computers to aid individuals’ sobriety.
Dr. Volkow spoke at the virtual American Psychiatric Association Spring Highlights Meeting 2020, which is replacing the organization’s canceled annual meeting.
While methadone clinics have had to close during the pandemic, making it challenging for those on medically assisted treatment to receive methadone or buprenorphine, some of the rules and regulations have been relaxed in order to make these medications accessible without the need for in-person attendance at a clinic. In addition, the Substance Abuse and Mental Health Services Administration has relaxed some of its own regulations regarding telehealth and opioid treatment programs.
Social isolation, stigma intensified
A pandemic increases anxiety in the general population, but for patients with SUD who may be also be struggling with homelessness and comorbid mental illness, the situation can further exacerbate social stigma and isolation – leading to relapse, more overdoses, and overdose deaths, Dr. Volkow said. Social interaction is “extraordinarily important” for patients and “one of the most powerful tools we have” to build resilience.
Right now, said Dr. Volkow, “we are in the dark as to how COVID infections have affected the number of overdose deaths.”
However, she noted that
“So even through this devastation, we can actually extract something that may help others in future,” she said.
Dr. Volkow noted that during the pandemic it is critical to reinforce the importance of engaging in – and remaining in – treatment to SUD patients. It’s also crucial to make patients aware of social support systems and behavioral interventions to help them cope with stress and to mitigate relapse risk.
COVID-19 and relapse
Elie G. Aoun, MD, assistant professor of psychiatry at New York University and vice chair of the APA’s Council on Addiction Psychiatry, said in an interview that Dr. Volkow’s presentation provided “exactly the kind of accessible information” clinicians need.
Dr. Aoun said he sees the impact of the COVID-19 crisis in his practice every day. Patients with SUD “are getting the short end of the stick.”
Social distancing measures prompted by the pandemic can be “very triggering” for SUD patients, he said. One of his patients told him the current isolation, loneliness, movement restrictions, and boredom remind her of the way she felt when she used drugs.
Dr. Aoun said four of his patients have relapsed since the pandemic began. Two of them had just started treatment after years of using drugs, so this was a “major setback” for them.
He and his colleagues were “not really prepared” to provide care via video link, which he believes is not as effective as in-person sessions.
In addition to disrupting patient care, said Dr. Aoun, the pandemic is forcing the medical community to face social determinants of health, such as poverty and homelessness, as they relate to addiction disorders and whether or not someone receives care.
This article originally appeared on Medscape.com.
The COVID-19 pandemic is posing significant challenges while also providing unique opportunities for patients with substance use disorders (SUD), a leading expert says.
Nora Volkow, MD, director of the National Institute on Drug Abuse, said that the pandemic has accelerated the use of telemedicine, making it easier for patients with SUD to access treatment. It has also led to the proliferation of more mental health hotlines, which is critical since the vast majority of these patients have comorbid mental illness.
In addition, COVID-19 has resulted in increased availability of “alternative” peer support mechanisms via cellphones or computers to aid individuals’ sobriety.
Dr. Volkow spoke at the virtual American Psychiatric Association Spring Highlights Meeting 2020, which is replacing the organization’s canceled annual meeting.
While methadone clinics have had to close during the pandemic, making it challenging for those on medically assisted treatment to receive methadone or buprenorphine, some of the rules and regulations have been relaxed in order to make these medications accessible without the need for in-person attendance at a clinic. In addition, the Substance Abuse and Mental Health Services Administration has relaxed some of its own regulations regarding telehealth and opioid treatment programs.
Social isolation, stigma intensified
A pandemic increases anxiety in the general population, but for patients with SUD who may be also be struggling with homelessness and comorbid mental illness, the situation can further exacerbate social stigma and isolation – leading to relapse, more overdoses, and overdose deaths, Dr. Volkow said. Social interaction is “extraordinarily important” for patients and “one of the most powerful tools we have” to build resilience.
Right now, said Dr. Volkow, “we are in the dark as to how COVID infections have affected the number of overdose deaths.”
However, she noted that
“So even through this devastation, we can actually extract something that may help others in future,” she said.
Dr. Volkow noted that during the pandemic it is critical to reinforce the importance of engaging in – and remaining in – treatment to SUD patients. It’s also crucial to make patients aware of social support systems and behavioral interventions to help them cope with stress and to mitigate relapse risk.
COVID-19 and relapse
Elie G. Aoun, MD, assistant professor of psychiatry at New York University and vice chair of the APA’s Council on Addiction Psychiatry, said in an interview that Dr. Volkow’s presentation provided “exactly the kind of accessible information” clinicians need.
Dr. Aoun said he sees the impact of the COVID-19 crisis in his practice every day. Patients with SUD “are getting the short end of the stick.”
Social distancing measures prompted by the pandemic can be “very triggering” for SUD patients, he said. One of his patients told him the current isolation, loneliness, movement restrictions, and boredom remind her of the way she felt when she used drugs.
Dr. Aoun said four of his patients have relapsed since the pandemic began. Two of them had just started treatment after years of using drugs, so this was a “major setback” for them.
He and his colleagues were “not really prepared” to provide care via video link, which he believes is not as effective as in-person sessions.
In addition to disrupting patient care, said Dr. Aoun, the pandemic is forcing the medical community to face social determinants of health, such as poverty and homelessness, as they relate to addiction disorders and whether or not someone receives care.
This article originally appeared on Medscape.com.
EMBRACA shows no overall survival benefit with talazoparib
Talazoparib did not confer an overall survival benefit over chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer, according to a final analysis of the phase 3 EMBRACA trial.
The progression-free survival benefit previously seen with talazoparib did not translate to an overall survival benefit. However, patient-reported quality of life continued to favor talazoparib in the final analysis, Jennifer K. Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston, reported at the AACR virtual meeting I.
The EMBRACA trial enrolled adults with HER2-negative locally advanced or metastatic breast cancer and a deleterious or suspected deleterious germline BRCA mutation. They were randomized to talazoparib at 1 mg daily (n = 287) or to physician’s choice of single-agent chemotherapy (n = 144).
In the primary analysis, talazoparib was associated with significantly improved progression-free survival. The median progression-free survival was 8.6 months in the talazoparib arm and 5.6 months in the chemotherapy arm (hazard ratio, 0.54).
“At the time of the primary analysis, the overall survival data were immature, and the hazard ratio for the interim overall survival was 0.761, which was not statistically significant,” Dr. Litton said.
However, patient-reported outcomes favored talazoparib in the primary analysis, with patients in that arm showing “significant overall improvements with a significant delay in time to clinically meaningful deterioration in multiple cancer-related and breast cancer–specific symptoms, functions, quality of life, and global health,” Dr. Litton said.
Final overall survival
At the final analysis, the median follow-up was 44.9 months for the talazoparib arm and 36.8 months for the chemotherapy arm.
The median overall survival was 19.3 months in the talazoparib arm and 19.5 months in the chemotherapy arm (HR, 0.848; P = .17)
The results were “generally consistent” across patient subgroups,” Dr. Litton said, adding that “the effect of treatment with talazoparib was also similar irrespective of BRCA status, as well as triple-negative or hormone-receptor-positive subtypes.”
Of note, most patients received poststudy therapies. These included PARP inhibitors in 4.5% of patients in the talazoparib arm and 32.6% of patients in the chemotherapy arm, and platinum drugs in 46.3% and 41.7%, respectively.
Patients who received chemotherapy on study but did not receive a subsequent PARP inhibitor or platinum therapy had both shorter total treatment duration and shorter overall survival, compared with patients who did receive subsequent treatment.
In the talazoparib arm, outcomes were similar whether or not patients received a subsequent PARP inhibitor or platinum therapy.
“Interpretation of the overall survival results may have been confounded by subsequent treatment, so two sensitivity analyses accounting for subsequent PARP inhibition or platinum therapy were carried out,” Dr. Litton said.
She noted that adjustment for poststudy treatment lowered the hazard ratio, but there was still no significant difference between the talazoparib and chemotherapy arms. These results suggest “the primary overall survival analysis underestimated the treatment benefit of talazoparib,” Dr. Litton said. She also noted that a longer platinum-free interval prior to study entry was generally associated with a longer duration of survival, particularly in the talazoparib arm.
Quality of life and safety
Patient-reported outcomes continued to favor talazoparib with extended follow-up and were consistent with the initial analysis, Dr. Litton noted.
The updated analysis revealed “a significant improvement in estimated overall change from baseline in the global health quality of life scores for those patients receiving talazoparib, while a significant deterioration was observed in patients receiving chemotherapy,” she said.
The estimated overall change in score was a 2.1-point increase in the talazoparib arm and a 5.7-point decrease in the chemotherapy arm (P = .001). The median time to clinically meaningful deterioration in global health quality of life scores was 26.3 months in the talazoparib arm and 6.7 months in the chemotherapy arm (HR, 0.385).
At the final analysis, the overall safety profile was consistent with that reported previously. Talazoparib was generally well tolerated, and no new safety signals were identified.
Grade 3/4 serious adverse events occurred in 28.3% of patients in the talazoparib arm and 27% of those in the chemotherapy arm. Adverse events led to treatment discontinuation in 7.7% and 9.5% of patients, respectively.
Most grade 3/4 adverse events were hematologic, and most were successfully managed by supportive care, including transfusions and dose modifications, Dr. Litton said.
She noted that one patient in the chemotherapy arm assigned to receive capecitabine had been diagnosed with acute myeloid leukemia at the time of the first analysis. “And now we report an additional case of [acute myeloid leukemia] in a patient who was randomized to the talazoparib arm,” Dr. Litton said.
Jury’s still out
Based on existing data, including from EMBRACA, the jury is still out on whether PARP inhibition is associated with an overall survival benefit in this setting, said invited discussant Susan Domcheck, MD, of the University of Pennsylvania in Philadelphia.
She suggested that could change with ongoing efforts to identify biomarkers for treatment response and new approaches to treatment, such as earlier lines of therapy and combinations.
“At this time, germline BRCA 1 and 2 pathogenic variants are the best predictor of PARP inhibitor sensitivity in breast cancer,” Dr. Domcheck said. “Not all the tumors are sensitive, but this is true of [estrogen receptor–positive] breast cancer and hormonal therapy, and HER2-positive breast cancer as well.”
Studies investigating approaches to improve survival are “incredibly important, because the progression-free survival is not as long as we would like it to be and there’s not an overwhelming overall survival benefit, for sure,” she said.
The EMBRACA trial was funded by Medivation (Pfizer). Dr. Litton and colleagues disclosed numerous relationships with pharmaceutical companies and other organizations. Dr. Domcheck disclosed relationships with AstraZeneca, Clovis, and Bristol Myers Squibb.
SOURCE: Litton J et al., AACR 20, Abstract CT071.
Talazoparib did not confer an overall survival benefit over chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer, according to a final analysis of the phase 3 EMBRACA trial.
The progression-free survival benefit previously seen with talazoparib did not translate to an overall survival benefit. However, patient-reported quality of life continued to favor talazoparib in the final analysis, Jennifer K. Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston, reported at the AACR virtual meeting I.
The EMBRACA trial enrolled adults with HER2-negative locally advanced or metastatic breast cancer and a deleterious or suspected deleterious germline BRCA mutation. They were randomized to talazoparib at 1 mg daily (n = 287) or to physician’s choice of single-agent chemotherapy (n = 144).
In the primary analysis, talazoparib was associated with significantly improved progression-free survival. The median progression-free survival was 8.6 months in the talazoparib arm and 5.6 months in the chemotherapy arm (hazard ratio, 0.54).
“At the time of the primary analysis, the overall survival data were immature, and the hazard ratio for the interim overall survival was 0.761, which was not statistically significant,” Dr. Litton said.
However, patient-reported outcomes favored talazoparib in the primary analysis, with patients in that arm showing “significant overall improvements with a significant delay in time to clinically meaningful deterioration in multiple cancer-related and breast cancer–specific symptoms, functions, quality of life, and global health,” Dr. Litton said.
Final overall survival
At the final analysis, the median follow-up was 44.9 months for the talazoparib arm and 36.8 months for the chemotherapy arm.
The median overall survival was 19.3 months in the talazoparib arm and 19.5 months in the chemotherapy arm (HR, 0.848; P = .17)
The results were “generally consistent” across patient subgroups,” Dr. Litton said, adding that “the effect of treatment with talazoparib was also similar irrespective of BRCA status, as well as triple-negative or hormone-receptor-positive subtypes.”
Of note, most patients received poststudy therapies. These included PARP inhibitors in 4.5% of patients in the talazoparib arm and 32.6% of patients in the chemotherapy arm, and platinum drugs in 46.3% and 41.7%, respectively.
Patients who received chemotherapy on study but did not receive a subsequent PARP inhibitor or platinum therapy had both shorter total treatment duration and shorter overall survival, compared with patients who did receive subsequent treatment.
In the talazoparib arm, outcomes were similar whether or not patients received a subsequent PARP inhibitor or platinum therapy.
“Interpretation of the overall survival results may have been confounded by subsequent treatment, so two sensitivity analyses accounting for subsequent PARP inhibition or platinum therapy were carried out,” Dr. Litton said.
She noted that adjustment for poststudy treatment lowered the hazard ratio, but there was still no significant difference between the talazoparib and chemotherapy arms. These results suggest “the primary overall survival analysis underestimated the treatment benefit of talazoparib,” Dr. Litton said. She also noted that a longer platinum-free interval prior to study entry was generally associated with a longer duration of survival, particularly in the talazoparib arm.
Quality of life and safety
Patient-reported outcomes continued to favor talazoparib with extended follow-up and were consistent with the initial analysis, Dr. Litton noted.
The updated analysis revealed “a significant improvement in estimated overall change from baseline in the global health quality of life scores for those patients receiving talazoparib, while a significant deterioration was observed in patients receiving chemotherapy,” she said.
The estimated overall change in score was a 2.1-point increase in the talazoparib arm and a 5.7-point decrease in the chemotherapy arm (P = .001). The median time to clinically meaningful deterioration in global health quality of life scores was 26.3 months in the talazoparib arm and 6.7 months in the chemotherapy arm (HR, 0.385).
At the final analysis, the overall safety profile was consistent with that reported previously. Talazoparib was generally well tolerated, and no new safety signals were identified.
Grade 3/4 serious adverse events occurred in 28.3% of patients in the talazoparib arm and 27% of those in the chemotherapy arm. Adverse events led to treatment discontinuation in 7.7% and 9.5% of patients, respectively.
Most grade 3/4 adverse events were hematologic, and most were successfully managed by supportive care, including transfusions and dose modifications, Dr. Litton said.
She noted that one patient in the chemotherapy arm assigned to receive capecitabine had been diagnosed with acute myeloid leukemia at the time of the first analysis. “And now we report an additional case of [acute myeloid leukemia] in a patient who was randomized to the talazoparib arm,” Dr. Litton said.
Jury’s still out
Based on existing data, including from EMBRACA, the jury is still out on whether PARP inhibition is associated with an overall survival benefit in this setting, said invited discussant Susan Domcheck, MD, of the University of Pennsylvania in Philadelphia.
She suggested that could change with ongoing efforts to identify biomarkers for treatment response and new approaches to treatment, such as earlier lines of therapy and combinations.
“At this time, germline BRCA 1 and 2 pathogenic variants are the best predictor of PARP inhibitor sensitivity in breast cancer,” Dr. Domcheck said. “Not all the tumors are sensitive, but this is true of [estrogen receptor–positive] breast cancer and hormonal therapy, and HER2-positive breast cancer as well.”
Studies investigating approaches to improve survival are “incredibly important, because the progression-free survival is not as long as we would like it to be and there’s not an overwhelming overall survival benefit, for sure,” she said.
The EMBRACA trial was funded by Medivation (Pfizer). Dr. Litton and colleagues disclosed numerous relationships with pharmaceutical companies and other organizations. Dr. Domcheck disclosed relationships with AstraZeneca, Clovis, and Bristol Myers Squibb.
SOURCE: Litton J et al., AACR 20, Abstract CT071.
Talazoparib did not confer an overall survival benefit over chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer, according to a final analysis of the phase 3 EMBRACA trial.
The progression-free survival benefit previously seen with talazoparib did not translate to an overall survival benefit. However, patient-reported quality of life continued to favor talazoparib in the final analysis, Jennifer K. Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston, reported at the AACR virtual meeting I.
The EMBRACA trial enrolled adults with HER2-negative locally advanced or metastatic breast cancer and a deleterious or suspected deleterious germline BRCA mutation. They were randomized to talazoparib at 1 mg daily (n = 287) or to physician’s choice of single-agent chemotherapy (n = 144).
In the primary analysis, talazoparib was associated with significantly improved progression-free survival. The median progression-free survival was 8.6 months in the talazoparib arm and 5.6 months in the chemotherapy arm (hazard ratio, 0.54).
“At the time of the primary analysis, the overall survival data were immature, and the hazard ratio for the interim overall survival was 0.761, which was not statistically significant,” Dr. Litton said.
However, patient-reported outcomes favored talazoparib in the primary analysis, with patients in that arm showing “significant overall improvements with a significant delay in time to clinically meaningful deterioration in multiple cancer-related and breast cancer–specific symptoms, functions, quality of life, and global health,” Dr. Litton said.
Final overall survival
At the final analysis, the median follow-up was 44.9 months for the talazoparib arm and 36.8 months for the chemotherapy arm.
The median overall survival was 19.3 months in the talazoparib arm and 19.5 months in the chemotherapy arm (HR, 0.848; P = .17)
The results were “generally consistent” across patient subgroups,” Dr. Litton said, adding that “the effect of treatment with talazoparib was also similar irrespective of BRCA status, as well as triple-negative or hormone-receptor-positive subtypes.”
Of note, most patients received poststudy therapies. These included PARP inhibitors in 4.5% of patients in the talazoparib arm and 32.6% of patients in the chemotherapy arm, and platinum drugs in 46.3% and 41.7%, respectively.
Patients who received chemotherapy on study but did not receive a subsequent PARP inhibitor or platinum therapy had both shorter total treatment duration and shorter overall survival, compared with patients who did receive subsequent treatment.
In the talazoparib arm, outcomes were similar whether or not patients received a subsequent PARP inhibitor or platinum therapy.
“Interpretation of the overall survival results may have been confounded by subsequent treatment, so two sensitivity analyses accounting for subsequent PARP inhibition or platinum therapy were carried out,” Dr. Litton said.
She noted that adjustment for poststudy treatment lowered the hazard ratio, but there was still no significant difference between the talazoparib and chemotherapy arms. These results suggest “the primary overall survival analysis underestimated the treatment benefit of talazoparib,” Dr. Litton said. She also noted that a longer platinum-free interval prior to study entry was generally associated with a longer duration of survival, particularly in the talazoparib arm.
Quality of life and safety
Patient-reported outcomes continued to favor talazoparib with extended follow-up and were consistent with the initial analysis, Dr. Litton noted.
The updated analysis revealed “a significant improvement in estimated overall change from baseline in the global health quality of life scores for those patients receiving talazoparib, while a significant deterioration was observed in patients receiving chemotherapy,” she said.
The estimated overall change in score was a 2.1-point increase in the talazoparib arm and a 5.7-point decrease in the chemotherapy arm (P = .001). The median time to clinically meaningful deterioration in global health quality of life scores was 26.3 months in the talazoparib arm and 6.7 months in the chemotherapy arm (HR, 0.385).
At the final analysis, the overall safety profile was consistent with that reported previously. Talazoparib was generally well tolerated, and no new safety signals were identified.
Grade 3/4 serious adverse events occurred in 28.3% of patients in the talazoparib arm and 27% of those in the chemotherapy arm. Adverse events led to treatment discontinuation in 7.7% and 9.5% of patients, respectively.
Most grade 3/4 adverse events were hematologic, and most were successfully managed by supportive care, including transfusions and dose modifications, Dr. Litton said.
She noted that one patient in the chemotherapy arm assigned to receive capecitabine had been diagnosed with acute myeloid leukemia at the time of the first analysis. “And now we report an additional case of [acute myeloid leukemia] in a patient who was randomized to the talazoparib arm,” Dr. Litton said.
Jury’s still out
Based on existing data, including from EMBRACA, the jury is still out on whether PARP inhibition is associated with an overall survival benefit in this setting, said invited discussant Susan Domcheck, MD, of the University of Pennsylvania in Philadelphia.
She suggested that could change with ongoing efforts to identify biomarkers for treatment response and new approaches to treatment, such as earlier lines of therapy and combinations.
“At this time, germline BRCA 1 and 2 pathogenic variants are the best predictor of PARP inhibitor sensitivity in breast cancer,” Dr. Domcheck said. “Not all the tumors are sensitive, but this is true of [estrogen receptor–positive] breast cancer and hormonal therapy, and HER2-positive breast cancer as well.”
Studies investigating approaches to improve survival are “incredibly important, because the progression-free survival is not as long as we would like it to be and there’s not an overwhelming overall survival benefit, for sure,” she said.
The EMBRACA trial was funded by Medivation (Pfizer). Dr. Litton and colleagues disclosed numerous relationships with pharmaceutical companies and other organizations. Dr. Domcheck disclosed relationships with AstraZeneca, Clovis, and Bristol Myers Squibb.
SOURCE: Litton J et al., AACR 20, Abstract CT071.
FROM AACR 2020