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New Data on DOAC Initiation After Stroke in AF: Final Word?
ABU DHABI, UAE — The long-standing debate as to when to start anticoagulation in patients with an acute ischemic stroke and atrial fibrillation (AF) looks as though it’s settled.
Results of the OPTIMAS trial, the largest trial to address this question, showed that Importantly, early DOAC initiation was safe with a low rate of symptomatic hemorrhage, regardless of stroke severity.
In addition, a new meta-analysis, known as CATALYST, which included all four randomized trials now available on this issue, showed a clear benefit of earlier initiation (within 4 days) versus later (5 days and up) on its primary endpoint of new ischemic stroke, symptomatic intracerebral hemorrhage, and unclassified stroke at 30 days.
The results of the OPTIMAS trial and the meta-analysis were both presented at the 16th World Stroke Congress (WSC) 2024. The OPTIMAS trial was also simultaneously published online in The Lancet.
“Our findings do not support the guideline recommended practice of delaying DOAC initiation after ischemic stroke with AF regardless of clinical stroke severity, reperfusion or prior anticoagulation,” said OPTIMAS investigator David Werring, PhD, University College London in England.
Presenting the meta-analysis, Signild Åsberg, MD, Uppsala University, Uppsala, Sweden, said his group’s findings “support the early start of DOACs (within 4 days) in clinical practice.”
Werring pointed out that starting anticoagulation early also had important logistical advantages.
“This means we can start anticoagulation before patients are discharged from hospital, thus ensuring that this important secondary prevention medication is always prescribed, when appropriate. That’s going to be a key benefit in the real world.”
Clinical Dilemma
Werring noted that AF accounts for 20%-30% of ischemic strokes, which tend to be more severe than other stroke types. The pivotal trials of DOACs did not include patients within 30 days of an acute ischemic stroke, creating a clinical dilemma on when to start this treatment.
“On the one hand, we wish to start anticoagulation early to reduce early recurrence of ischemic stroke. But on the other hand, there are concerns that if we start anticoagulation early, it could cause intracranial bleeding, including hemorrhagic transformation of the acute infarct. Guidelines on this issue are inconsistent and have called for randomized control trials in this area,” he noted.
So far, three randomized trials on DOAC timing have been conducted, which Werring said suggested early DOAC treatment is safe. However, these trials have provided limited data on moderate to severe stroke, patients with hemorrhagic transformation, or those already taking oral anticoagulants — subgroups in which there are particular concerns about early oral anticoagulation.
The OPTIMAS trial included a broad population of patients with acute ischemic stroke associated with AF including these critical subgroups.
The trial, conducted at 100 hospitals in the United Kingdom, included 3648 patients with AF and acute ischemic stroke who were randomly assigned to early (≤ 4 days from stroke symptom onset) or delayed (7-14 days) anticoagulation initiation with any DOAC.
There was no restriction on stroke severity, and patients with hemorrhagic transformation were allowed, with the exception of parenchymal hematoma type 2, a rare and severe type of hemorrhagic transformation.
Approximately 35% of patients had been taking an oral anticoagulant, mainly DOACs, prior to their stroke, and about 30% had revascularization with thrombolysis, thrombectomy, or both. Nearly 900 participants (25%) had moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥ 11).
The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days. The initial analysis aimed to show noninferiority of early DOAC initiation, with a noninferiority margin of 2 percentage points, followed by testing for superiority.
Results showed that the primary outcome occurred in 3.3% of both groups (adjusted risk difference, 0.000; 95% CI, −0.011 to 0.012), with noninferiority criteria fulfilled. Superiority was not achieved.
Symptomatic intracranial hemorrhage occurred in 0.6% of patients in the early DOAC initiation group vs 0.7% of those in the delayed group — a nonsignificant difference.
Applicable to Real-World Practice
A time-to-event analysis of the primary outcome showed that there were fewer outcomes in the first 30 days in the early DOAC initiation group, but the curves subsequently came together.
Subgroup analysis showed consistent results across all whole trial population, with no modification of the effect of early DOAC initiation according to stroke severity, reperfusion treatment, or previous anticoagulation.
Werring said that strengths of the OPTIMAS trial included a large sample size, a broad population with generalizability to real-world practice, and the inclusion of patients at higher bleeding risk than included in previous studies.
During the discussion, it was noted that the trial included few (about 3%) patients — about 3% — with very severe stroke (NIHSS score > 21), with the question of whether the findings could be applied to this group.
Werring noted that there was no evidence of heterogeneity, and if anything, patients with more severe strokes may have had a slightly greater benefit with early DOAC initiation. “So my feeling is probably these results do generalize to the more severe patients,” he said.
In a commentary accompanying The Lancet publication of the OPTIMAS trial, Else Charlotte Sandset, MD, University of Oslo, in Norway, and Diana Aguiar de Sousa, MD, Central Lisbon University Hospital Centre, Lisbon, Portugal, noted that the “increasing body of evidence strongly supports the message that initiating anticoagulation early for patients with ischaemic stroke is safe. The consistent absence of heterogeneity in safety outcomes suggests that the risk of symptomatic intracranial haemorrhage is not a major concern, even in patients with large infarcts.”
Regardless of the size of the treatment effect, initiating early anticoagulation makes sense when it can be done safely, as it helps prevent recurrent ischemic strokes and other embolic events. Early intervention reduces embolization risk, particularly in high-risk patients, and allows secondary prevention measures to begin while patients are still hospitalized, they added.
CATALYST Findings
The CATALYST meta-analysis included four trials, namely, TIMING, ELAN, OPTIMAS, and START, of early versus later DOAC administration in a total of 5411 patients with acute ischemic stroke and AF. In this meta-analysis, early was defined as within 4 days of stroke and later as 5 days or more.
The primary outcome was a composite of ischemic stroke, symptomatic, intracerebral hemorrhage, or unclassified stroke at 30 days. This was significantly reduced in the early group (2.12%) versus 3.02% in the later group, giving an odds ratio of 0.70 (95% CI, 0.50-0.98; P =.04).
The results were consistent across all subgroups, all suggesting an advantage for early DOAC.
Further analysis showed a clear benefit of early DOAC initiation in ischemic stroke with the curves separating early.
The rate of symptomatic intracerebral hemorrhage was low in both groups (0.45% in the early group and 0.40% in the later group) as was extracranial hemorrhage (0.45% vs 0.55%).
At 90 days, there were still lower event rates in the early group than the later one, but the difference was no longer statistically significant.
‘Practice Changing’ Results
Commenting on both studies, chair of the WSC session where the results of both OPTIMAS trial and the meta-analysis were presented, Craig Anderson, MD, The George Institute for Global Health, Sydney, Australia, described these latest results as “practice changing.”
“When to start anticoagulation in acute ischemic stroke patients with AF has been uncertain for a long time. The dogma has always been that we should wait. Over the years, we’ve become a little bit more confident, but now we’ve got good data from randomized trials showing that early initiation is safe, with the meta-analysis showing benefit,” he said.
“These new data from OPTIMAS will reassure clinicians that there’s no excessive harm and, more importantly, no excessive harm across all patient groups. And the meta-analysis clearly showed an upfront benefit of starting anticoagulation early. That’s a very convincing result,” he added.
Anderson cautioned that there still may be concerns about starting DOACs early in some groups, including Asian populations that have a higher bleeding risk (these trials included predominantly White patients) and people who are older or frail, who may have extensive small vessel disease.
During the discussion, several questions centered on the lack of imaging data available on the patients in the studies. Anderson said imaging data would help reassure clinicians on the safety of early anticoagulation in patients with large infarcts.
“Stroke clinicians make decisions on the basis of the patient and on the basis of the brain, and we only have the patient information at the moment. We don’t have information on the brain — that comes from imaging.”
Regardless, he believes these new data will lead to a shift in practice. “But maybe, it won’t be as dramatic as we would hope because I think some clinicians may still hesitate to apply these results to patients at high risk of bleeding. With imaging data from the studies that might change.”
The OPTIMAS trial was funded by University College London and the British Heart Foundation. Werring reported consulting fees from Novo Nordisk, National Institute for Health and Care Excellence, and Alnylam; payments or speaker honoraria from Novo Nordisk, Bayer, and AstraZeneca/Alexion; participation on a data safety monitoring board for the OXHARP trial; and participation as steering committee chair for the MACE-ICH and PLINTH trials. Åsberg received institutional research grants and lecture fees to her institution from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Institut Produits Synthése. Sandset and de Sousa were both steering committee members of the ELAN trial. Anderson reported grant funding from Penumbra and Takeda China.
A version of this article appeared on Medscape.com.
ABU DHABI, UAE — The long-standing debate as to when to start anticoagulation in patients with an acute ischemic stroke and atrial fibrillation (AF) looks as though it’s settled.
Results of the OPTIMAS trial, the largest trial to address this question, showed that Importantly, early DOAC initiation was safe with a low rate of symptomatic hemorrhage, regardless of stroke severity.
In addition, a new meta-analysis, known as CATALYST, which included all four randomized trials now available on this issue, showed a clear benefit of earlier initiation (within 4 days) versus later (5 days and up) on its primary endpoint of new ischemic stroke, symptomatic intracerebral hemorrhage, and unclassified stroke at 30 days.
The results of the OPTIMAS trial and the meta-analysis were both presented at the 16th World Stroke Congress (WSC) 2024. The OPTIMAS trial was also simultaneously published online in The Lancet.
“Our findings do not support the guideline recommended practice of delaying DOAC initiation after ischemic stroke with AF regardless of clinical stroke severity, reperfusion or prior anticoagulation,” said OPTIMAS investigator David Werring, PhD, University College London in England.
Presenting the meta-analysis, Signild Åsberg, MD, Uppsala University, Uppsala, Sweden, said his group’s findings “support the early start of DOACs (within 4 days) in clinical practice.”
Werring pointed out that starting anticoagulation early also had important logistical advantages.
“This means we can start anticoagulation before patients are discharged from hospital, thus ensuring that this important secondary prevention medication is always prescribed, when appropriate. That’s going to be a key benefit in the real world.”
Clinical Dilemma
Werring noted that AF accounts for 20%-30% of ischemic strokes, which tend to be more severe than other stroke types. The pivotal trials of DOACs did not include patients within 30 days of an acute ischemic stroke, creating a clinical dilemma on when to start this treatment.
“On the one hand, we wish to start anticoagulation early to reduce early recurrence of ischemic stroke. But on the other hand, there are concerns that if we start anticoagulation early, it could cause intracranial bleeding, including hemorrhagic transformation of the acute infarct. Guidelines on this issue are inconsistent and have called for randomized control trials in this area,” he noted.
So far, three randomized trials on DOAC timing have been conducted, which Werring said suggested early DOAC treatment is safe. However, these trials have provided limited data on moderate to severe stroke, patients with hemorrhagic transformation, or those already taking oral anticoagulants — subgroups in which there are particular concerns about early oral anticoagulation.
The OPTIMAS trial included a broad population of patients with acute ischemic stroke associated with AF including these critical subgroups.
The trial, conducted at 100 hospitals in the United Kingdom, included 3648 patients with AF and acute ischemic stroke who were randomly assigned to early (≤ 4 days from stroke symptom onset) or delayed (7-14 days) anticoagulation initiation with any DOAC.
There was no restriction on stroke severity, and patients with hemorrhagic transformation were allowed, with the exception of parenchymal hematoma type 2, a rare and severe type of hemorrhagic transformation.
Approximately 35% of patients had been taking an oral anticoagulant, mainly DOACs, prior to their stroke, and about 30% had revascularization with thrombolysis, thrombectomy, or both. Nearly 900 participants (25%) had moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥ 11).
The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days. The initial analysis aimed to show noninferiority of early DOAC initiation, with a noninferiority margin of 2 percentage points, followed by testing for superiority.
Results showed that the primary outcome occurred in 3.3% of both groups (adjusted risk difference, 0.000; 95% CI, −0.011 to 0.012), with noninferiority criteria fulfilled. Superiority was not achieved.
Symptomatic intracranial hemorrhage occurred in 0.6% of patients in the early DOAC initiation group vs 0.7% of those in the delayed group — a nonsignificant difference.
Applicable to Real-World Practice
A time-to-event analysis of the primary outcome showed that there were fewer outcomes in the first 30 days in the early DOAC initiation group, but the curves subsequently came together.
Subgroup analysis showed consistent results across all whole trial population, with no modification of the effect of early DOAC initiation according to stroke severity, reperfusion treatment, or previous anticoagulation.
Werring said that strengths of the OPTIMAS trial included a large sample size, a broad population with generalizability to real-world practice, and the inclusion of patients at higher bleeding risk than included in previous studies.
During the discussion, it was noted that the trial included few (about 3%) patients — about 3% — with very severe stroke (NIHSS score > 21), with the question of whether the findings could be applied to this group.
Werring noted that there was no evidence of heterogeneity, and if anything, patients with more severe strokes may have had a slightly greater benefit with early DOAC initiation. “So my feeling is probably these results do generalize to the more severe patients,” he said.
In a commentary accompanying The Lancet publication of the OPTIMAS trial, Else Charlotte Sandset, MD, University of Oslo, in Norway, and Diana Aguiar de Sousa, MD, Central Lisbon University Hospital Centre, Lisbon, Portugal, noted that the “increasing body of evidence strongly supports the message that initiating anticoagulation early for patients with ischaemic stroke is safe. The consistent absence of heterogeneity in safety outcomes suggests that the risk of symptomatic intracranial haemorrhage is not a major concern, even in patients with large infarcts.”
Regardless of the size of the treatment effect, initiating early anticoagulation makes sense when it can be done safely, as it helps prevent recurrent ischemic strokes and other embolic events. Early intervention reduces embolization risk, particularly in high-risk patients, and allows secondary prevention measures to begin while patients are still hospitalized, they added.
CATALYST Findings
The CATALYST meta-analysis included four trials, namely, TIMING, ELAN, OPTIMAS, and START, of early versus later DOAC administration in a total of 5411 patients with acute ischemic stroke and AF. In this meta-analysis, early was defined as within 4 days of stroke and later as 5 days or more.
The primary outcome was a composite of ischemic stroke, symptomatic, intracerebral hemorrhage, or unclassified stroke at 30 days. This was significantly reduced in the early group (2.12%) versus 3.02% in the later group, giving an odds ratio of 0.70 (95% CI, 0.50-0.98; P =.04).
The results were consistent across all subgroups, all suggesting an advantage for early DOAC.
Further analysis showed a clear benefit of early DOAC initiation in ischemic stroke with the curves separating early.
The rate of symptomatic intracerebral hemorrhage was low in both groups (0.45% in the early group and 0.40% in the later group) as was extracranial hemorrhage (0.45% vs 0.55%).
At 90 days, there were still lower event rates in the early group than the later one, but the difference was no longer statistically significant.
‘Practice Changing’ Results
Commenting on both studies, chair of the WSC session where the results of both OPTIMAS trial and the meta-analysis were presented, Craig Anderson, MD, The George Institute for Global Health, Sydney, Australia, described these latest results as “practice changing.”
“When to start anticoagulation in acute ischemic stroke patients with AF has been uncertain for a long time. The dogma has always been that we should wait. Over the years, we’ve become a little bit more confident, but now we’ve got good data from randomized trials showing that early initiation is safe, with the meta-analysis showing benefit,” he said.
“These new data from OPTIMAS will reassure clinicians that there’s no excessive harm and, more importantly, no excessive harm across all patient groups. And the meta-analysis clearly showed an upfront benefit of starting anticoagulation early. That’s a very convincing result,” he added.
Anderson cautioned that there still may be concerns about starting DOACs early in some groups, including Asian populations that have a higher bleeding risk (these trials included predominantly White patients) and people who are older or frail, who may have extensive small vessel disease.
During the discussion, several questions centered on the lack of imaging data available on the patients in the studies. Anderson said imaging data would help reassure clinicians on the safety of early anticoagulation in patients with large infarcts.
“Stroke clinicians make decisions on the basis of the patient and on the basis of the brain, and we only have the patient information at the moment. We don’t have information on the brain — that comes from imaging.”
Regardless, he believes these new data will lead to a shift in practice. “But maybe, it won’t be as dramatic as we would hope because I think some clinicians may still hesitate to apply these results to patients at high risk of bleeding. With imaging data from the studies that might change.”
The OPTIMAS trial was funded by University College London and the British Heart Foundation. Werring reported consulting fees from Novo Nordisk, National Institute for Health and Care Excellence, and Alnylam; payments or speaker honoraria from Novo Nordisk, Bayer, and AstraZeneca/Alexion; participation on a data safety monitoring board for the OXHARP trial; and participation as steering committee chair for the MACE-ICH and PLINTH trials. Åsberg received institutional research grants and lecture fees to her institution from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Institut Produits Synthése. Sandset and de Sousa were both steering committee members of the ELAN trial. Anderson reported grant funding from Penumbra and Takeda China.
A version of this article appeared on Medscape.com.
ABU DHABI, UAE — The long-standing debate as to when to start anticoagulation in patients with an acute ischemic stroke and atrial fibrillation (AF) looks as though it’s settled.
Results of the OPTIMAS trial, the largest trial to address this question, showed that Importantly, early DOAC initiation was safe with a low rate of symptomatic hemorrhage, regardless of stroke severity.
In addition, a new meta-analysis, known as CATALYST, which included all four randomized trials now available on this issue, showed a clear benefit of earlier initiation (within 4 days) versus later (5 days and up) on its primary endpoint of new ischemic stroke, symptomatic intracerebral hemorrhage, and unclassified stroke at 30 days.
The results of the OPTIMAS trial and the meta-analysis were both presented at the 16th World Stroke Congress (WSC) 2024. The OPTIMAS trial was also simultaneously published online in The Lancet.
“Our findings do not support the guideline recommended practice of delaying DOAC initiation after ischemic stroke with AF regardless of clinical stroke severity, reperfusion or prior anticoagulation,” said OPTIMAS investigator David Werring, PhD, University College London in England.
Presenting the meta-analysis, Signild Åsberg, MD, Uppsala University, Uppsala, Sweden, said his group’s findings “support the early start of DOACs (within 4 days) in clinical practice.”
Werring pointed out that starting anticoagulation early also had important logistical advantages.
“This means we can start anticoagulation before patients are discharged from hospital, thus ensuring that this important secondary prevention medication is always prescribed, when appropriate. That’s going to be a key benefit in the real world.”
Clinical Dilemma
Werring noted that AF accounts for 20%-30% of ischemic strokes, which tend to be more severe than other stroke types. The pivotal trials of DOACs did not include patients within 30 days of an acute ischemic stroke, creating a clinical dilemma on when to start this treatment.
“On the one hand, we wish to start anticoagulation early to reduce early recurrence of ischemic stroke. But on the other hand, there are concerns that if we start anticoagulation early, it could cause intracranial bleeding, including hemorrhagic transformation of the acute infarct. Guidelines on this issue are inconsistent and have called for randomized control trials in this area,” he noted.
So far, three randomized trials on DOAC timing have been conducted, which Werring said suggested early DOAC treatment is safe. However, these trials have provided limited data on moderate to severe stroke, patients with hemorrhagic transformation, or those already taking oral anticoagulants — subgroups in which there are particular concerns about early oral anticoagulation.
The OPTIMAS trial included a broad population of patients with acute ischemic stroke associated with AF including these critical subgroups.
The trial, conducted at 100 hospitals in the United Kingdom, included 3648 patients with AF and acute ischemic stroke who were randomly assigned to early (≤ 4 days from stroke symptom onset) or delayed (7-14 days) anticoagulation initiation with any DOAC.
There was no restriction on stroke severity, and patients with hemorrhagic transformation were allowed, with the exception of parenchymal hematoma type 2, a rare and severe type of hemorrhagic transformation.
Approximately 35% of patients had been taking an oral anticoagulant, mainly DOACs, prior to their stroke, and about 30% had revascularization with thrombolysis, thrombectomy, or both. Nearly 900 participants (25%) had moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥ 11).
The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days. The initial analysis aimed to show noninferiority of early DOAC initiation, with a noninferiority margin of 2 percentage points, followed by testing for superiority.
Results showed that the primary outcome occurred in 3.3% of both groups (adjusted risk difference, 0.000; 95% CI, −0.011 to 0.012), with noninferiority criteria fulfilled. Superiority was not achieved.
Symptomatic intracranial hemorrhage occurred in 0.6% of patients in the early DOAC initiation group vs 0.7% of those in the delayed group — a nonsignificant difference.
Applicable to Real-World Practice
A time-to-event analysis of the primary outcome showed that there were fewer outcomes in the first 30 days in the early DOAC initiation group, but the curves subsequently came together.
Subgroup analysis showed consistent results across all whole trial population, with no modification of the effect of early DOAC initiation according to stroke severity, reperfusion treatment, or previous anticoagulation.
Werring said that strengths of the OPTIMAS trial included a large sample size, a broad population with generalizability to real-world practice, and the inclusion of patients at higher bleeding risk than included in previous studies.
During the discussion, it was noted that the trial included few (about 3%) patients — about 3% — with very severe stroke (NIHSS score > 21), with the question of whether the findings could be applied to this group.
Werring noted that there was no evidence of heterogeneity, and if anything, patients with more severe strokes may have had a slightly greater benefit with early DOAC initiation. “So my feeling is probably these results do generalize to the more severe patients,” he said.
In a commentary accompanying The Lancet publication of the OPTIMAS trial, Else Charlotte Sandset, MD, University of Oslo, in Norway, and Diana Aguiar de Sousa, MD, Central Lisbon University Hospital Centre, Lisbon, Portugal, noted that the “increasing body of evidence strongly supports the message that initiating anticoagulation early for patients with ischaemic stroke is safe. The consistent absence of heterogeneity in safety outcomes suggests that the risk of symptomatic intracranial haemorrhage is not a major concern, even in patients with large infarcts.”
Regardless of the size of the treatment effect, initiating early anticoagulation makes sense when it can be done safely, as it helps prevent recurrent ischemic strokes and other embolic events. Early intervention reduces embolization risk, particularly in high-risk patients, and allows secondary prevention measures to begin while patients are still hospitalized, they added.
CATALYST Findings
The CATALYST meta-analysis included four trials, namely, TIMING, ELAN, OPTIMAS, and START, of early versus later DOAC administration in a total of 5411 patients with acute ischemic stroke and AF. In this meta-analysis, early was defined as within 4 days of stroke and later as 5 days or more.
The primary outcome was a composite of ischemic stroke, symptomatic, intracerebral hemorrhage, or unclassified stroke at 30 days. This was significantly reduced in the early group (2.12%) versus 3.02% in the later group, giving an odds ratio of 0.70 (95% CI, 0.50-0.98; P =.04).
The results were consistent across all subgroups, all suggesting an advantage for early DOAC.
Further analysis showed a clear benefit of early DOAC initiation in ischemic stroke with the curves separating early.
The rate of symptomatic intracerebral hemorrhage was low in both groups (0.45% in the early group and 0.40% in the later group) as was extracranial hemorrhage (0.45% vs 0.55%).
At 90 days, there were still lower event rates in the early group than the later one, but the difference was no longer statistically significant.
‘Practice Changing’ Results
Commenting on both studies, chair of the WSC session where the results of both OPTIMAS trial and the meta-analysis were presented, Craig Anderson, MD, The George Institute for Global Health, Sydney, Australia, described these latest results as “practice changing.”
“When to start anticoagulation in acute ischemic stroke patients with AF has been uncertain for a long time. The dogma has always been that we should wait. Over the years, we’ve become a little bit more confident, but now we’ve got good data from randomized trials showing that early initiation is safe, with the meta-analysis showing benefit,” he said.
“These new data from OPTIMAS will reassure clinicians that there’s no excessive harm and, more importantly, no excessive harm across all patient groups. And the meta-analysis clearly showed an upfront benefit of starting anticoagulation early. That’s a very convincing result,” he added.
Anderson cautioned that there still may be concerns about starting DOACs early in some groups, including Asian populations that have a higher bleeding risk (these trials included predominantly White patients) and people who are older or frail, who may have extensive small vessel disease.
During the discussion, several questions centered on the lack of imaging data available on the patients in the studies. Anderson said imaging data would help reassure clinicians on the safety of early anticoagulation in patients with large infarcts.
“Stroke clinicians make decisions on the basis of the patient and on the basis of the brain, and we only have the patient information at the moment. We don’t have information on the brain — that comes from imaging.”
Regardless, he believes these new data will lead to a shift in practice. “But maybe, it won’t be as dramatic as we would hope because I think some clinicians may still hesitate to apply these results to patients at high risk of bleeding. With imaging data from the studies that might change.”
The OPTIMAS trial was funded by University College London and the British Heart Foundation. Werring reported consulting fees from Novo Nordisk, National Institute for Health and Care Excellence, and Alnylam; payments or speaker honoraria from Novo Nordisk, Bayer, and AstraZeneca/Alexion; participation on a data safety monitoring board for the OXHARP trial; and participation as steering committee chair for the MACE-ICH and PLINTH trials. Åsberg received institutional research grants and lecture fees to her institution from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Institut Produits Synthése. Sandset and de Sousa were both steering committee members of the ELAN trial. Anderson reported grant funding from Penumbra and Takeda China.
A version of this article appeared on Medscape.com.
FROM WSC 2024
Study Finds Elevated Skin Cancer Risk Among US Veterans
of recent national data.
“US veterans are known to have increased risk of cancers and cancer morbidity compared to the general US population,” one of the study authors, Sepideh Ashrafzadeh, MD, a third-year dermatology resident at Massachusetts General Hospital, Boston, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the results were presented. “There have been several studies that have shown that US veterans have an increased prevalence of melanoma compared to nonveterans,” she said, noting, however, that no study has investigated the prevalence of nonmelanoma skin cancers (NMSCs), which include basal cell carcinomas and squamous cell carcinomas, compared with the general population.
To address this knowledge gap, the researchers performed a national cross-sectional study of adults aged 18 years or older from the 2019-2023 National Health Interview Surveys to examine the prevalence of melanoma and NMSCs among veterans compared with the general US population. They aggregated and tabulated the data by veteran status, defined as having served at any point in the US armed forces, reserves, or national guard, and by demographic and socioeconomic status variables. Next, they performed multivariate logistic regression for skin cancer risk adjusted for age, sex, race, ethnicity, urbanicity, and disability status.
The study population consisted of 14,301 veterans and 209,936 nonveterans. Compared with nonveterans, veterans were more likely to have been diagnosed with skin cancer at some point in their lives (7% vs 2.4%; P < .001); had a higher mean age of skin cancer diagnosis (61.1 vs 55.8 years; P < .001); were more likely to have been diagnosed with melanoma (2.8% vs 0.9%; P < .001), and were more likely to have been diagnosed with NMSC (4.4% vs 1.6%; P < .001).
The researchers found that older age, White race, non-Hispanic ethnicity, and veteran status were all associated with higher odds of developing NMSCs, even after adjusting for relevant covariates. Specifically, veterans had 1.23 higher odds of developing NMSC than the general population, while two factors were protective for developing NMSCs: Living in a rural setting (adjusted odds ratio [aOR], 0.78) and receiving supplemental security income or disability income (aOR, 0.69).
In another part of the study, the researchers evaluated demographic and socioeconomic variables associated with developing melanoma among veterans. These included the following: Male (aOR, 1.16), older age (50-64 years: aOR, 6.82; 65-74 years: aOR, 12.55; and 75 years or older: aOR, 16.16), White race (aOR, 9.24), and non-Hispanic ethnicity (aOR, 7.15).
“Veterans may have occupational risks such as sun and chemical exposure, as well as behavioral habits for sun protection, that may contribute to their elevated risk of melanoma and NMSCs,” Ashrafzadeh said. “Therefore, US veterans would benefit from targeted and regular skin cancer screenings, sun protective preventative resources such as hats and sunscreen, and access to medical and surgical care for diagnosis and treatment of skin cancers.”
Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the findings, said that a key strength of the study is that it drew from a nationally representative sample. “A limitation is that skin cancer was self-reported rather than based on documented medical histories,” Ko said. “The study confirms that skin cancer risk is higher in older individuals (> 75 as compared to < 50) and in individuals of self-reported white race and non-Hispanic ethnicity,” she added.
Neither the researchers nor Ko reported having relevant disclosures.
A version of this article first appeared on Medscape.com.
of recent national data.
“US veterans are known to have increased risk of cancers and cancer morbidity compared to the general US population,” one of the study authors, Sepideh Ashrafzadeh, MD, a third-year dermatology resident at Massachusetts General Hospital, Boston, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the results were presented. “There have been several studies that have shown that US veterans have an increased prevalence of melanoma compared to nonveterans,” she said, noting, however, that no study has investigated the prevalence of nonmelanoma skin cancers (NMSCs), which include basal cell carcinomas and squamous cell carcinomas, compared with the general population.
To address this knowledge gap, the researchers performed a national cross-sectional study of adults aged 18 years or older from the 2019-2023 National Health Interview Surveys to examine the prevalence of melanoma and NMSCs among veterans compared with the general US population. They aggregated and tabulated the data by veteran status, defined as having served at any point in the US armed forces, reserves, or national guard, and by demographic and socioeconomic status variables. Next, they performed multivariate logistic regression for skin cancer risk adjusted for age, sex, race, ethnicity, urbanicity, and disability status.
The study population consisted of 14,301 veterans and 209,936 nonveterans. Compared with nonveterans, veterans were more likely to have been diagnosed with skin cancer at some point in their lives (7% vs 2.4%; P < .001); had a higher mean age of skin cancer diagnosis (61.1 vs 55.8 years; P < .001); were more likely to have been diagnosed with melanoma (2.8% vs 0.9%; P < .001), and were more likely to have been diagnosed with NMSC (4.4% vs 1.6%; P < .001).
The researchers found that older age, White race, non-Hispanic ethnicity, and veteran status were all associated with higher odds of developing NMSCs, even after adjusting for relevant covariates. Specifically, veterans had 1.23 higher odds of developing NMSC than the general population, while two factors were protective for developing NMSCs: Living in a rural setting (adjusted odds ratio [aOR], 0.78) and receiving supplemental security income or disability income (aOR, 0.69).
In another part of the study, the researchers evaluated demographic and socioeconomic variables associated with developing melanoma among veterans. These included the following: Male (aOR, 1.16), older age (50-64 years: aOR, 6.82; 65-74 years: aOR, 12.55; and 75 years or older: aOR, 16.16), White race (aOR, 9.24), and non-Hispanic ethnicity (aOR, 7.15).
“Veterans may have occupational risks such as sun and chemical exposure, as well as behavioral habits for sun protection, that may contribute to their elevated risk of melanoma and NMSCs,” Ashrafzadeh said. “Therefore, US veterans would benefit from targeted and regular skin cancer screenings, sun protective preventative resources such as hats and sunscreen, and access to medical and surgical care for diagnosis and treatment of skin cancers.”
Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the findings, said that a key strength of the study is that it drew from a nationally representative sample. “A limitation is that skin cancer was self-reported rather than based on documented medical histories,” Ko said. “The study confirms that skin cancer risk is higher in older individuals (> 75 as compared to < 50) and in individuals of self-reported white race and non-Hispanic ethnicity,” she added.
Neither the researchers nor Ko reported having relevant disclosures.
A version of this article first appeared on Medscape.com.
of recent national data.
“US veterans are known to have increased risk of cancers and cancer morbidity compared to the general US population,” one of the study authors, Sepideh Ashrafzadeh, MD, a third-year dermatology resident at Massachusetts General Hospital, Boston, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the results were presented. “There have been several studies that have shown that US veterans have an increased prevalence of melanoma compared to nonveterans,” she said, noting, however, that no study has investigated the prevalence of nonmelanoma skin cancers (NMSCs), which include basal cell carcinomas and squamous cell carcinomas, compared with the general population.
To address this knowledge gap, the researchers performed a national cross-sectional study of adults aged 18 years or older from the 2019-2023 National Health Interview Surveys to examine the prevalence of melanoma and NMSCs among veterans compared with the general US population. They aggregated and tabulated the data by veteran status, defined as having served at any point in the US armed forces, reserves, or national guard, and by demographic and socioeconomic status variables. Next, they performed multivariate logistic regression for skin cancer risk adjusted for age, sex, race, ethnicity, urbanicity, and disability status.
The study population consisted of 14,301 veterans and 209,936 nonveterans. Compared with nonveterans, veterans were more likely to have been diagnosed with skin cancer at some point in their lives (7% vs 2.4%; P < .001); had a higher mean age of skin cancer diagnosis (61.1 vs 55.8 years; P < .001); were more likely to have been diagnosed with melanoma (2.8% vs 0.9%; P < .001), and were more likely to have been diagnosed with NMSC (4.4% vs 1.6%; P < .001).
The researchers found that older age, White race, non-Hispanic ethnicity, and veteran status were all associated with higher odds of developing NMSCs, even after adjusting for relevant covariates. Specifically, veterans had 1.23 higher odds of developing NMSC than the general population, while two factors were protective for developing NMSCs: Living in a rural setting (adjusted odds ratio [aOR], 0.78) and receiving supplemental security income or disability income (aOR, 0.69).
In another part of the study, the researchers evaluated demographic and socioeconomic variables associated with developing melanoma among veterans. These included the following: Male (aOR, 1.16), older age (50-64 years: aOR, 6.82; 65-74 years: aOR, 12.55; and 75 years or older: aOR, 16.16), White race (aOR, 9.24), and non-Hispanic ethnicity (aOR, 7.15).
“Veterans may have occupational risks such as sun and chemical exposure, as well as behavioral habits for sun protection, that may contribute to their elevated risk of melanoma and NMSCs,” Ashrafzadeh said. “Therefore, US veterans would benefit from targeted and regular skin cancer screenings, sun protective preventative resources such as hats and sunscreen, and access to medical and surgical care for diagnosis and treatment of skin cancers.”
Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Connecticut, who was asked to comment on the findings, said that a key strength of the study is that it drew from a nationally representative sample. “A limitation is that skin cancer was self-reported rather than based on documented medical histories,” Ko said. “The study confirms that skin cancer risk is higher in older individuals (> 75 as compared to < 50) and in individuals of self-reported white race and non-Hispanic ethnicity,” she added.
Neither the researchers nor Ko reported having relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ASDS 2024
Cancer’s Other Toll: Long-Term Financial Fallout for Survivors
Overall, patients with cancer tend to face higher rates of debt collection, medical collections, and bankruptcies, as well as lower credit scores, according to two new studies presented at the American College of Surgeons Clinical Congress 2024.
“These are the first studies to provide numerical evidence of financial toxicity among cancer survivors,” Benjamin C. James, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts, who worked on both studies, said in a statement. “Previous data on this topic largely relies on subjective survey reviews.”
In one study, researchers used the Massachusetts Cancer Registry to identify 99,175 patients diagnosed with cancer between 2010 and 2019 and matched them with 188,875 control individuals without cancer. Researchers then assessed financial toxicity using Experian credit bureau data for participants.
Overall, patients with cancer faced a range of financial challenges that often lasted years following their diagnosis.
Patients were nearly five times more likely to experience bankruptcy and had average credit scores nearly 80 points lower than control individuals without cancer. The drop in credit scores was more pronounced for survivors of bladder, liver, lung, and colorectal cancer (CRC) and persisted for up to 9.5 years.
For certain cancer types, in particular, “we are looking years after a diagnosis, and we see that the credit score goes down and it never comes back up,” James said.
The other study, which used a sample of 7227 patients with CRC from Massachusetts, identified several factors that correlated with lower credit scores.
Compared with patients who only had surgery, peers who underwent radiation only experienced a 62-point drop in their credit score after their diagnosis, while those who had chemotherapy alone had just over a 14-point drop in their credit score. Among patients who had combination treatments, those who underwent both surgery and radiation experienced a nearly 16-point drop in their credit score and those who had surgery and chemoradiation actually experienced a 2.59 bump, compared with those who had surgery alone.
Financial toxicity was worse for patients younger than 62 years, those identifying as Black or Hispanic individuals, unmarried individuals, those with an annual income below $52,000, and those living in deprived areas.
The studies add to findings from the 2015 North American Thyroid Cancer Survivorship Study, which reported that 50% of thyroid cancer survivors encountered financial toxicity because of their diagnosis.
James said the persistent financial strain of cancer care, even in a state like Massachusetts, which mandates universal healthcare, underscores the need for “broader policy changes and reforms, including reconsidering debt collection practices.”
“Financial security should be a priority in cancer care,” he added.
The studies had no specific funding. The authors have disclosed no relevant conflict of interest.
A version of this article first appeared on Medscape.com.
Overall, patients with cancer tend to face higher rates of debt collection, medical collections, and bankruptcies, as well as lower credit scores, according to two new studies presented at the American College of Surgeons Clinical Congress 2024.
“These are the first studies to provide numerical evidence of financial toxicity among cancer survivors,” Benjamin C. James, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts, who worked on both studies, said in a statement. “Previous data on this topic largely relies on subjective survey reviews.”
In one study, researchers used the Massachusetts Cancer Registry to identify 99,175 patients diagnosed with cancer between 2010 and 2019 and matched them with 188,875 control individuals without cancer. Researchers then assessed financial toxicity using Experian credit bureau data for participants.
Overall, patients with cancer faced a range of financial challenges that often lasted years following their diagnosis.
Patients were nearly five times more likely to experience bankruptcy and had average credit scores nearly 80 points lower than control individuals without cancer. The drop in credit scores was more pronounced for survivors of bladder, liver, lung, and colorectal cancer (CRC) and persisted for up to 9.5 years.
For certain cancer types, in particular, “we are looking years after a diagnosis, and we see that the credit score goes down and it never comes back up,” James said.
The other study, which used a sample of 7227 patients with CRC from Massachusetts, identified several factors that correlated with lower credit scores.
Compared with patients who only had surgery, peers who underwent radiation only experienced a 62-point drop in their credit score after their diagnosis, while those who had chemotherapy alone had just over a 14-point drop in their credit score. Among patients who had combination treatments, those who underwent both surgery and radiation experienced a nearly 16-point drop in their credit score and those who had surgery and chemoradiation actually experienced a 2.59 bump, compared with those who had surgery alone.
Financial toxicity was worse for patients younger than 62 years, those identifying as Black or Hispanic individuals, unmarried individuals, those with an annual income below $52,000, and those living in deprived areas.
The studies add to findings from the 2015 North American Thyroid Cancer Survivorship Study, which reported that 50% of thyroid cancer survivors encountered financial toxicity because of their diagnosis.
James said the persistent financial strain of cancer care, even in a state like Massachusetts, which mandates universal healthcare, underscores the need for “broader policy changes and reforms, including reconsidering debt collection practices.”
“Financial security should be a priority in cancer care,” he added.
The studies had no specific funding. The authors have disclosed no relevant conflict of interest.
A version of this article first appeared on Medscape.com.
Overall, patients with cancer tend to face higher rates of debt collection, medical collections, and bankruptcies, as well as lower credit scores, according to two new studies presented at the American College of Surgeons Clinical Congress 2024.
“These are the first studies to provide numerical evidence of financial toxicity among cancer survivors,” Benjamin C. James, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts, who worked on both studies, said in a statement. “Previous data on this topic largely relies on subjective survey reviews.”
In one study, researchers used the Massachusetts Cancer Registry to identify 99,175 patients diagnosed with cancer between 2010 and 2019 and matched them with 188,875 control individuals without cancer. Researchers then assessed financial toxicity using Experian credit bureau data for participants.
Overall, patients with cancer faced a range of financial challenges that often lasted years following their diagnosis.
Patients were nearly five times more likely to experience bankruptcy and had average credit scores nearly 80 points lower than control individuals without cancer. The drop in credit scores was more pronounced for survivors of bladder, liver, lung, and colorectal cancer (CRC) and persisted for up to 9.5 years.
For certain cancer types, in particular, “we are looking years after a diagnosis, and we see that the credit score goes down and it never comes back up,” James said.
The other study, which used a sample of 7227 patients with CRC from Massachusetts, identified several factors that correlated with lower credit scores.
Compared with patients who only had surgery, peers who underwent radiation only experienced a 62-point drop in their credit score after their diagnosis, while those who had chemotherapy alone had just over a 14-point drop in their credit score. Among patients who had combination treatments, those who underwent both surgery and radiation experienced a nearly 16-point drop in their credit score and those who had surgery and chemoradiation actually experienced a 2.59 bump, compared with those who had surgery alone.
Financial toxicity was worse for patients younger than 62 years, those identifying as Black or Hispanic individuals, unmarried individuals, those with an annual income below $52,000, and those living in deprived areas.
The studies add to findings from the 2015 North American Thyroid Cancer Survivorship Study, which reported that 50% of thyroid cancer survivors encountered financial toxicity because of their diagnosis.
James said the persistent financial strain of cancer care, even in a state like Massachusetts, which mandates universal healthcare, underscores the need for “broader policy changes and reforms, including reconsidering debt collection practices.”
“Financial security should be a priority in cancer care,” he added.
The studies had no specific funding. The authors have disclosed no relevant conflict of interest.
A version of this article first appeared on Medscape.com.
FROM ACSCS 2024
Mortality Rates From Early-Onset CRC Have Risen Considerably Over Last 2 Decades
PHILADELPHIA — according to a new analysis of the two largest US mortality databases.
Data from the Centers for Disease Control and Prevention’s National Center of Health Statistics (NCHS) and the Surveillance, Epidemiology, and End Results (SEER) databases provide yet more evidence of the increasing prevalence of EO-CRC, which is defined as a diagnosis of CRC in patients younger than age 50 years.
Furthermore, the researchers reported that increased mortality occurred across all patients included in the study (aged 20-54) regardless of tumor stage at diagnosis.
These findings “prompt tailoring further efforts toward raising awareness of colorectal cancer symptoms and keeping a low clinical suspicion in younger patients presenting with anemia, gastrointestinal bleeding, or change in bowel habits,” Yazan Abboud, MD, internal medicine PGY-3, assistant chief resident, and chair of resident research at Rutgers New Jersey Medical School, Newark, said in an interview.
Abboud presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Analyzing NCHS and SEER
Rising rates of EO-CRC had prompted US medical societies to recommend reducing the screening age to 45 years. The US Preventive Services Task Force officially lowered it to this age in 2021. This shift is supported by real-world evidence, which shows that earlier screening leads to a significantly reduced risk for colorectal cancer. However, because colorectal cancer cases are decreasing overall in older adults, there is considerable interest in discovering why young adults are experiencing a paradoxical uptick in EO-CRC, and what impact this is having on associated mortality.
Abboud and colleagues collected age-adjusted mortality rates for EO-CRC between 2000 and 2022 from the NCHS database. In addition, stage-specific incidence-based mortality rates between 2004-2020 were obtained from the SEER 22 database. The NCHS database covers approximately 100% of the US population, whereas the SEER 22 database, which is included within the NCHS, covers 42%.
The researchers divided patients into two cohorts based on age (20-44 years and 45-54 years) and tumor stage at diagnosis (early stage and late stage), and compared the annual percentage change (APC) and the average APC between the two groups. They also assessed trends for the entire cohort of patients aged 20-54 years.
In the NCHS database, there were 147,026 deaths in total across all ages studied resulting from EO-CRC, of which 27% (39,746) occurred in those 20-44 years of age. Although associated mortality rates decreased between 2000-2005 in all ages studied (APC, –1.56), they increased from 2005-2022 (APC, 0.87).
In the cohort aged 45-54 years, mortality decreased between 2000-2005 and increased thereafter, whereas in the cohort aged 20-44 years mortality increased steadily for the entire follow-up duration of 2000 to 2022 (APC, 0.93). A comparison of the age cohorts confirmed that those aged 20-44 years had a greater increase in mortality (average APC, 0.85; P < .001).
In the SEER 22 database, there were 4652 deaths in those with early-stage tumors across all age groups studied (average APC, 12.17). Mortality increased in patients aged 45-54 years (average APC, 11.52) with early-stage tumors, but there were insufficient numbers in those aged 20-44 years to determine this outcome.
There were 42,120 deaths in those with late-stage tumors across all age groups (average APC, 10.05) in the SEER 22 database. And increased mortality was observed in those with late-stage tumors in both age cohorts: 45-54 years (average APC, 9.58) and 20-44 years (average APC, 11.06).
“When evaluating the SEER database and stratifying the tumors by stage at diagnosis, we demonstrated increasing mortality of early-onset colorectal cancer in both early- and late-stage tumors on average over the study period,” Abboud said.
Identifying At-Risk Patients
In a comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia School of Medicine in Norfolk, said the findings speak to the need for evidence-based means of identifying younger individuals at a higher risk of EO-CRC.
“I suspect many of younger patients with CRC had their cancer detected when it was more advanced due to delayed presentation and diagnostic testing,” said Johnson, who was not involved in the study.
But it would be interesting to evaluate if the cancers in the cohort aged 20-44 years were more aggressive biologically or if these patients were dismissive of early signs or symptoms, he said.
Younger patients may dismiss “alarm” features that indicate CRC testing, said Johnson. “In particular, overt bleeding and iron deficiency need a focused evaluation in these younger cohorts.”
“Future research is needed to investigate the role of neoadjuvant chemotherapy in younger patients with early-stage colorectal cancer and evaluate patients’ outcomes,” Abboud added.
The study had no specific funding. Abboud reported no relevant financial relationships. Johnson reported serving as an adviser to ISOTHRIVE. He is also on the Medscape Gastroenterology editorial board.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a new analysis of the two largest US mortality databases.
Data from the Centers for Disease Control and Prevention’s National Center of Health Statistics (NCHS) and the Surveillance, Epidemiology, and End Results (SEER) databases provide yet more evidence of the increasing prevalence of EO-CRC, which is defined as a diagnosis of CRC in patients younger than age 50 years.
Furthermore, the researchers reported that increased mortality occurred across all patients included in the study (aged 20-54) regardless of tumor stage at diagnosis.
These findings “prompt tailoring further efforts toward raising awareness of colorectal cancer symptoms and keeping a low clinical suspicion in younger patients presenting with anemia, gastrointestinal bleeding, or change in bowel habits,” Yazan Abboud, MD, internal medicine PGY-3, assistant chief resident, and chair of resident research at Rutgers New Jersey Medical School, Newark, said in an interview.
Abboud presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Analyzing NCHS and SEER
Rising rates of EO-CRC had prompted US medical societies to recommend reducing the screening age to 45 years. The US Preventive Services Task Force officially lowered it to this age in 2021. This shift is supported by real-world evidence, which shows that earlier screening leads to a significantly reduced risk for colorectal cancer. However, because colorectal cancer cases are decreasing overall in older adults, there is considerable interest in discovering why young adults are experiencing a paradoxical uptick in EO-CRC, and what impact this is having on associated mortality.
Abboud and colleagues collected age-adjusted mortality rates for EO-CRC between 2000 and 2022 from the NCHS database. In addition, stage-specific incidence-based mortality rates between 2004-2020 were obtained from the SEER 22 database. The NCHS database covers approximately 100% of the US population, whereas the SEER 22 database, which is included within the NCHS, covers 42%.
The researchers divided patients into two cohorts based on age (20-44 years and 45-54 years) and tumor stage at diagnosis (early stage and late stage), and compared the annual percentage change (APC) and the average APC between the two groups. They also assessed trends for the entire cohort of patients aged 20-54 years.
In the NCHS database, there were 147,026 deaths in total across all ages studied resulting from EO-CRC, of which 27% (39,746) occurred in those 20-44 years of age. Although associated mortality rates decreased between 2000-2005 in all ages studied (APC, –1.56), they increased from 2005-2022 (APC, 0.87).
In the cohort aged 45-54 years, mortality decreased between 2000-2005 and increased thereafter, whereas in the cohort aged 20-44 years mortality increased steadily for the entire follow-up duration of 2000 to 2022 (APC, 0.93). A comparison of the age cohorts confirmed that those aged 20-44 years had a greater increase in mortality (average APC, 0.85; P < .001).
In the SEER 22 database, there were 4652 deaths in those with early-stage tumors across all age groups studied (average APC, 12.17). Mortality increased in patients aged 45-54 years (average APC, 11.52) with early-stage tumors, but there were insufficient numbers in those aged 20-44 years to determine this outcome.
There were 42,120 deaths in those with late-stage tumors across all age groups (average APC, 10.05) in the SEER 22 database. And increased mortality was observed in those with late-stage tumors in both age cohorts: 45-54 years (average APC, 9.58) and 20-44 years (average APC, 11.06).
“When evaluating the SEER database and stratifying the tumors by stage at diagnosis, we demonstrated increasing mortality of early-onset colorectal cancer in both early- and late-stage tumors on average over the study period,” Abboud said.
Identifying At-Risk Patients
In a comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia School of Medicine in Norfolk, said the findings speak to the need for evidence-based means of identifying younger individuals at a higher risk of EO-CRC.
“I suspect many of younger patients with CRC had their cancer detected when it was more advanced due to delayed presentation and diagnostic testing,” said Johnson, who was not involved in the study.
But it would be interesting to evaluate if the cancers in the cohort aged 20-44 years were more aggressive biologically or if these patients were dismissive of early signs or symptoms, he said.
Younger patients may dismiss “alarm” features that indicate CRC testing, said Johnson. “In particular, overt bleeding and iron deficiency need a focused evaluation in these younger cohorts.”
“Future research is needed to investigate the role of neoadjuvant chemotherapy in younger patients with early-stage colorectal cancer and evaluate patients’ outcomes,” Abboud added.
The study had no specific funding. Abboud reported no relevant financial relationships. Johnson reported serving as an adviser to ISOTHRIVE. He is also on the Medscape Gastroenterology editorial board.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a new analysis of the two largest US mortality databases.
Data from the Centers for Disease Control and Prevention’s National Center of Health Statistics (NCHS) and the Surveillance, Epidemiology, and End Results (SEER) databases provide yet more evidence of the increasing prevalence of EO-CRC, which is defined as a diagnosis of CRC in patients younger than age 50 years.
Furthermore, the researchers reported that increased mortality occurred across all patients included in the study (aged 20-54) regardless of tumor stage at diagnosis.
These findings “prompt tailoring further efforts toward raising awareness of colorectal cancer symptoms and keeping a low clinical suspicion in younger patients presenting with anemia, gastrointestinal bleeding, or change in bowel habits,” Yazan Abboud, MD, internal medicine PGY-3, assistant chief resident, and chair of resident research at Rutgers New Jersey Medical School, Newark, said in an interview.
Abboud presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Analyzing NCHS and SEER
Rising rates of EO-CRC had prompted US medical societies to recommend reducing the screening age to 45 years. The US Preventive Services Task Force officially lowered it to this age in 2021. This shift is supported by real-world evidence, which shows that earlier screening leads to a significantly reduced risk for colorectal cancer. However, because colorectal cancer cases are decreasing overall in older adults, there is considerable interest in discovering why young adults are experiencing a paradoxical uptick in EO-CRC, and what impact this is having on associated mortality.
Abboud and colleagues collected age-adjusted mortality rates for EO-CRC between 2000 and 2022 from the NCHS database. In addition, stage-specific incidence-based mortality rates between 2004-2020 were obtained from the SEER 22 database. The NCHS database covers approximately 100% of the US population, whereas the SEER 22 database, which is included within the NCHS, covers 42%.
The researchers divided patients into two cohorts based on age (20-44 years and 45-54 years) and tumor stage at diagnosis (early stage and late stage), and compared the annual percentage change (APC) and the average APC between the two groups. They also assessed trends for the entire cohort of patients aged 20-54 years.
In the NCHS database, there were 147,026 deaths in total across all ages studied resulting from EO-CRC, of which 27% (39,746) occurred in those 20-44 years of age. Although associated mortality rates decreased between 2000-2005 in all ages studied (APC, –1.56), they increased from 2005-2022 (APC, 0.87).
In the cohort aged 45-54 years, mortality decreased between 2000-2005 and increased thereafter, whereas in the cohort aged 20-44 years mortality increased steadily for the entire follow-up duration of 2000 to 2022 (APC, 0.93). A comparison of the age cohorts confirmed that those aged 20-44 years had a greater increase in mortality (average APC, 0.85; P < .001).
In the SEER 22 database, there were 4652 deaths in those with early-stage tumors across all age groups studied (average APC, 12.17). Mortality increased in patients aged 45-54 years (average APC, 11.52) with early-stage tumors, but there were insufficient numbers in those aged 20-44 years to determine this outcome.
There were 42,120 deaths in those with late-stage tumors across all age groups (average APC, 10.05) in the SEER 22 database. And increased mortality was observed in those with late-stage tumors in both age cohorts: 45-54 years (average APC, 9.58) and 20-44 years (average APC, 11.06).
“When evaluating the SEER database and stratifying the tumors by stage at diagnosis, we demonstrated increasing mortality of early-onset colorectal cancer in both early- and late-stage tumors on average over the study period,” Abboud said.
Identifying At-Risk Patients
In a comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia School of Medicine in Norfolk, said the findings speak to the need for evidence-based means of identifying younger individuals at a higher risk of EO-CRC.
“I suspect many of younger patients with CRC had their cancer detected when it was more advanced due to delayed presentation and diagnostic testing,” said Johnson, who was not involved in the study.
But it would be interesting to evaluate if the cancers in the cohort aged 20-44 years were more aggressive biologically or if these patients were dismissive of early signs or symptoms, he said.
Younger patients may dismiss “alarm” features that indicate CRC testing, said Johnson. “In particular, overt bleeding and iron deficiency need a focused evaluation in these younger cohorts.”
“Future research is needed to investigate the role of neoadjuvant chemotherapy in younger patients with early-stage colorectal cancer and evaluate patients’ outcomes,” Abboud added.
The study had no specific funding. Abboud reported no relevant financial relationships. Johnson reported serving as an adviser to ISOTHRIVE. He is also on the Medscape Gastroenterology editorial board.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Study Compares Punch Excision vs. Core Excision for Recalcitrant Keloids
according to the results of a small retrospective study.
The method “offers similar efficacy, faster healing, and fewer complications,” one of the study authors, Jinwoong Jung, MD, said in an interview following the annual meeting of the American Society for Dermatologic Surgery, where he presented the study results during an oral abstract session.
For the study, Jung, a dermatologist at Yonsei University College of Medicine, Seoul, South Korea, and colleagues retrospectively analyzed 22 patients with recalcitrant keloids treated with cryotherapy immediately following either PE or CE between May 2019 and March 2024. They used the Vancouver Scar Scale (VSS) to assess treatment efficacy.
Of the 22 patients, 16 underwent treatment with CE and 6 underwent treatment with PE. Pretreatment VSS scores showed no significant differences between the groups (P = .535). The CE group had a reduction in the VSS score from 8.13 to 4.00, while the PE group had a reduction from 7.83 to 3.67, but these declines did not differ significantly (P = .737). The PE group exhibited a shorter healing time than the CE group (a mean of 43.5 vs 63.87 days, respectively), though this difference was not statistically significant (P = .129).
“The uniqueness of this work lies in its simplified use of PE for recalcitrant keloids, which demonstrated efficacy comparable to CE, with the potential advantage of faster healing times,” Jung said. “Future studies with larger sample sizes and extended follow-up periods could help establish this approach as a standard treatment method.”
He acknowledged certain limitations of the study, including its small sample size and the lack of long-term follow-up data. The researchers reported having no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to the results of a small retrospective study.
The method “offers similar efficacy, faster healing, and fewer complications,” one of the study authors, Jinwoong Jung, MD, said in an interview following the annual meeting of the American Society for Dermatologic Surgery, where he presented the study results during an oral abstract session.
For the study, Jung, a dermatologist at Yonsei University College of Medicine, Seoul, South Korea, and colleagues retrospectively analyzed 22 patients with recalcitrant keloids treated with cryotherapy immediately following either PE or CE between May 2019 and March 2024. They used the Vancouver Scar Scale (VSS) to assess treatment efficacy.
Of the 22 patients, 16 underwent treatment with CE and 6 underwent treatment with PE. Pretreatment VSS scores showed no significant differences between the groups (P = .535). The CE group had a reduction in the VSS score from 8.13 to 4.00, while the PE group had a reduction from 7.83 to 3.67, but these declines did not differ significantly (P = .737). The PE group exhibited a shorter healing time than the CE group (a mean of 43.5 vs 63.87 days, respectively), though this difference was not statistically significant (P = .129).
“The uniqueness of this work lies in its simplified use of PE for recalcitrant keloids, which demonstrated efficacy comparable to CE, with the potential advantage of faster healing times,” Jung said. “Future studies with larger sample sizes and extended follow-up periods could help establish this approach as a standard treatment method.”
He acknowledged certain limitations of the study, including its small sample size and the lack of long-term follow-up data. The researchers reported having no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to the results of a small retrospective study.
The method “offers similar efficacy, faster healing, and fewer complications,” one of the study authors, Jinwoong Jung, MD, said in an interview following the annual meeting of the American Society for Dermatologic Surgery, where he presented the study results during an oral abstract session.
For the study, Jung, a dermatologist at Yonsei University College of Medicine, Seoul, South Korea, and colleagues retrospectively analyzed 22 patients with recalcitrant keloids treated with cryotherapy immediately following either PE or CE between May 2019 and March 2024. They used the Vancouver Scar Scale (VSS) to assess treatment efficacy.
Of the 22 patients, 16 underwent treatment with CE and 6 underwent treatment with PE. Pretreatment VSS scores showed no significant differences between the groups (P = .535). The CE group had a reduction in the VSS score from 8.13 to 4.00, while the PE group had a reduction from 7.83 to 3.67, but these declines did not differ significantly (P = .737). The PE group exhibited a shorter healing time than the CE group (a mean of 43.5 vs 63.87 days, respectively), though this difference was not statistically significant (P = .129).
“The uniqueness of this work lies in its simplified use of PE for recalcitrant keloids, which demonstrated efficacy comparable to CE, with the potential advantage of faster healing times,” Jung said. “Future studies with larger sample sizes and extended follow-up periods could help establish this approach as a standard treatment method.”
He acknowledged certain limitations of the study, including its small sample size and the lack of long-term follow-up data. The researchers reported having no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ASDS 2024
Neurologists Lack Awareness of Steroid Toxicity
SAVANNAH, GEORGIA — , results of a US survey showed.
For both MG and CIDP specialists, uncertainty around corticosteroid dosing, duration, and toxicity underscores the need for more guidance, the investigators noted. Over 85% of respondents indicated that a tool for systematically monitoring corticosteroid toxicity would be valuable.
The results indicate “a lack of knowledge by this pool of neurologists about the guidelines and what they contain,” said study investigator Gil Wolfe, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York.
Clearer guidance on how to administer corticosteroids and manage toxicities in patients with gMG and CIDP “would be welcomed by neurologists and have potential for benefit to patient care,” the team noted.
The findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Lack of Knowledge
Although guidelines for both CIDP and gMG recommend corticosteroids as first-line treatment and emphasize using the lowest effective dose to control symptoms, they do not include specific recommendations on dosing, duration, or toxicity monitoring, the researchers noted.
Despite this, a large proportion of survey respondents reported using guidelines to make clinical decisions on monitoring toxicity, with up to a third actually endorsing a guideline that doesn’t exist.
The cross-sectional, online survey was deployed in November and December 2023 and included 200 US neurologists. Of these, 99 answered questions on CIDP, and 101 answered similar questions on gMG.
To participate in the survey, respondents had to be board-certified neurologists, practicing for at least 2 years post-residency, and have treated or consulted on at least three patients with CIDP or 10 patients with gMG in the past year who were on a corticosteroid dose of at least 10 mg daily for 1 month or more.
CIDP respondents had been practicing a mean of 18.1 years since residency and were board certified in neuromuscular (20%), electrodiagnostic medicine/clinical neurophysiology (21%), and pediatric neurology (8%). Two thirds of them accepted referrals from other neurologists.
The gMG respondents had been practicing a mean of 20.5 years since residency and were board certified in neuromuscular (45%), electrodiagnostic medicine/clinical neurophysiology (35%), and pediatric neurology (17%). A total of 72% accepted referrals from other neurologists.
Respondents estimated that about 60% of their patients with gMG and 58% of patients with CIDP were being treated with corticosteroids, with gMG and CIDP respondents reporting a mean of 26.4 and 15.6 patients, respectively, meeting the study’s dosing criteria.
Appropriate Dosing
When asked what chronic, long-term (≥ 6 months) corticosteroid dose they considered safe in terms of minimizing adverse events, 43% of CIDP respondents and 51% of gMG respondents considered corticosteroid doses of 10 mg/d or less (prednisone equivalent) well tolerated; additionally, 32% and 31%, respectively, considered 20-40 mg/d well tolerated. Moreover, they said only about half of their patients would be able to taper to less than 10 mg/d in less than 6 months.
“Studies suggest safety is not seen until patients are on doses at 5 mg/d or less,” Wolfe said. “There is not enough appreciation that doses at levels we once considered safe really do pose significant risk,” he added.
“With the increasing number of treatment options in MG and to a lesser extent in CIDP, we need to do all we can to use corticosteroids as judiciously as possible and be aware of side effects our patients may not even report unless we make a pointed effort to ask about them.”
Familiarity with corticosteroid toxicities was more common among gMG respondents, of whom 77% reported being very/extremely familiar, than among 55% of CIDP respondents. Appetite/weight gain was reported among the most common adverse effects (AEs) associated with long-term CS use (reported by 68% of CIDP and 58% of gMG respondents). Other common AEs reported were insulin resistance (53% of CIDP and 50% of gMG respondents), decreased bone density (47% and 48%, respectively), immunosuppression (37% and 45%, respectively). Mood and behavioral change were noted by 56% of CIDP and 37% of gMG respondents, particularly mood swings, irritability, mania, and sleep disorders.
When asked how they balanced the risk for and benefit of corticosteroids, more than 80% of CIDP specialists reported personally monitoring for corticosteroid-related toxicity, and 42% reported they collaborated with the patient’s primary care provider. However, fewer than 10% reported ordering lab tests. Among neurologists treating gMG, 84% said they typically monitor corticosteroid toxicity independently, while 41% reported doing so in collaboration with primary care providers.
Two thirds of CIDP respondents and 53% of gMG respondents reported using guidelines to make clinical decisions on monitoring toxicity, and 34% of gMG respondents actually endorsed using the Guideline for Systematic Surveillance of Steroid Safety, which does not exist.
‘A Big Issue’ in Neurology
Commenting on the results, Said R. Beydoun, MD, professor and division chief, Neuromuscular Medicine, Department of Neurology at Keck Medicine of University of Southern California, Los Angeles, said steroid toxicity is “a big issue” in neurology.
These patients can be on chronic therapy, and they aren’t really monitored for osteoporosis or other complications, he said, adding that neurologists aren’t always taking the necessary precautions to prevent steroid toxicity.
Beydoun estimated that about half of neurologists are not adequately familiar with balancing the efficacy of corticosteroids versus in toxicity.
“Objective improvement, either on the functional scale or the muscle impairment scale — that’s really response treatment. Whereas adverse effects of a treatment are something separate. The patient may be improving but also maybe developing other complications from the treatment,” he said.
Also commenting, Ghazala Hayat, MD, professor of neurology and director of neuromuscular and clinical neurophysiology services at Saint Louis University in St. Louis, said there is a clear need for more education.
“I always say prednisone is our best friend initially, and then it becomes the worst enemy. If you don’t see lots of neuromuscular patients, you might not know even how to recognize toxicity or how to taper. Or the opposite to that, if you taper too quickly, patients relapse.”
The study was funded by argenx. Wolfe reported serving on advisory boards for Alexion, argenx, UCB, and Johnson & Johnson. Neelam Goyal, MD, is a consultant/advisor for Alexion, argenx, Amgen, Janssen, Lycia Therapeutics, and UCB and has received grant support from argenx. Beydoun reported receiving research support and consulting and speaking fees from Healey Center, Amylyx, AB Science, Sanofi, Janssen, Genentech, Regeneron, UCB, Abcuro argenx, Alnylam, AstraZeneca, Amylyx, CSL Behring, Grifols, Takeda, Octapharma, UCB, and Janssen. Hayat reported speaker and advisory roles with argenx, Alexion, and MTPA.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — , results of a US survey showed.
For both MG and CIDP specialists, uncertainty around corticosteroid dosing, duration, and toxicity underscores the need for more guidance, the investigators noted. Over 85% of respondents indicated that a tool for systematically monitoring corticosteroid toxicity would be valuable.
The results indicate “a lack of knowledge by this pool of neurologists about the guidelines and what they contain,” said study investigator Gil Wolfe, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York.
Clearer guidance on how to administer corticosteroids and manage toxicities in patients with gMG and CIDP “would be welcomed by neurologists and have potential for benefit to patient care,” the team noted.
The findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Lack of Knowledge
Although guidelines for both CIDP and gMG recommend corticosteroids as first-line treatment and emphasize using the lowest effective dose to control symptoms, they do not include specific recommendations on dosing, duration, or toxicity monitoring, the researchers noted.
Despite this, a large proportion of survey respondents reported using guidelines to make clinical decisions on monitoring toxicity, with up to a third actually endorsing a guideline that doesn’t exist.
The cross-sectional, online survey was deployed in November and December 2023 and included 200 US neurologists. Of these, 99 answered questions on CIDP, and 101 answered similar questions on gMG.
To participate in the survey, respondents had to be board-certified neurologists, practicing for at least 2 years post-residency, and have treated or consulted on at least three patients with CIDP or 10 patients with gMG in the past year who were on a corticosteroid dose of at least 10 mg daily for 1 month or more.
CIDP respondents had been practicing a mean of 18.1 years since residency and were board certified in neuromuscular (20%), electrodiagnostic medicine/clinical neurophysiology (21%), and pediatric neurology (8%). Two thirds of them accepted referrals from other neurologists.
The gMG respondents had been practicing a mean of 20.5 years since residency and were board certified in neuromuscular (45%), electrodiagnostic medicine/clinical neurophysiology (35%), and pediatric neurology (17%). A total of 72% accepted referrals from other neurologists.
Respondents estimated that about 60% of their patients with gMG and 58% of patients with CIDP were being treated with corticosteroids, with gMG and CIDP respondents reporting a mean of 26.4 and 15.6 patients, respectively, meeting the study’s dosing criteria.
Appropriate Dosing
When asked what chronic, long-term (≥ 6 months) corticosteroid dose they considered safe in terms of minimizing adverse events, 43% of CIDP respondents and 51% of gMG respondents considered corticosteroid doses of 10 mg/d or less (prednisone equivalent) well tolerated; additionally, 32% and 31%, respectively, considered 20-40 mg/d well tolerated. Moreover, they said only about half of their patients would be able to taper to less than 10 mg/d in less than 6 months.
“Studies suggest safety is not seen until patients are on doses at 5 mg/d or less,” Wolfe said. “There is not enough appreciation that doses at levels we once considered safe really do pose significant risk,” he added.
“With the increasing number of treatment options in MG and to a lesser extent in CIDP, we need to do all we can to use corticosteroids as judiciously as possible and be aware of side effects our patients may not even report unless we make a pointed effort to ask about them.”
Familiarity with corticosteroid toxicities was more common among gMG respondents, of whom 77% reported being very/extremely familiar, than among 55% of CIDP respondents. Appetite/weight gain was reported among the most common adverse effects (AEs) associated with long-term CS use (reported by 68% of CIDP and 58% of gMG respondents). Other common AEs reported were insulin resistance (53% of CIDP and 50% of gMG respondents), decreased bone density (47% and 48%, respectively), immunosuppression (37% and 45%, respectively). Mood and behavioral change were noted by 56% of CIDP and 37% of gMG respondents, particularly mood swings, irritability, mania, and sleep disorders.
When asked how they balanced the risk for and benefit of corticosteroids, more than 80% of CIDP specialists reported personally monitoring for corticosteroid-related toxicity, and 42% reported they collaborated with the patient’s primary care provider. However, fewer than 10% reported ordering lab tests. Among neurologists treating gMG, 84% said they typically monitor corticosteroid toxicity independently, while 41% reported doing so in collaboration with primary care providers.
Two thirds of CIDP respondents and 53% of gMG respondents reported using guidelines to make clinical decisions on monitoring toxicity, and 34% of gMG respondents actually endorsed using the Guideline for Systematic Surveillance of Steroid Safety, which does not exist.
‘A Big Issue’ in Neurology
Commenting on the results, Said R. Beydoun, MD, professor and division chief, Neuromuscular Medicine, Department of Neurology at Keck Medicine of University of Southern California, Los Angeles, said steroid toxicity is “a big issue” in neurology.
These patients can be on chronic therapy, and they aren’t really monitored for osteoporosis or other complications, he said, adding that neurologists aren’t always taking the necessary precautions to prevent steroid toxicity.
Beydoun estimated that about half of neurologists are not adequately familiar with balancing the efficacy of corticosteroids versus in toxicity.
“Objective improvement, either on the functional scale or the muscle impairment scale — that’s really response treatment. Whereas adverse effects of a treatment are something separate. The patient may be improving but also maybe developing other complications from the treatment,” he said.
Also commenting, Ghazala Hayat, MD, professor of neurology and director of neuromuscular and clinical neurophysiology services at Saint Louis University in St. Louis, said there is a clear need for more education.
“I always say prednisone is our best friend initially, and then it becomes the worst enemy. If you don’t see lots of neuromuscular patients, you might not know even how to recognize toxicity or how to taper. Or the opposite to that, if you taper too quickly, patients relapse.”
The study was funded by argenx. Wolfe reported serving on advisory boards for Alexion, argenx, UCB, and Johnson & Johnson. Neelam Goyal, MD, is a consultant/advisor for Alexion, argenx, Amgen, Janssen, Lycia Therapeutics, and UCB and has received grant support from argenx. Beydoun reported receiving research support and consulting and speaking fees from Healey Center, Amylyx, AB Science, Sanofi, Janssen, Genentech, Regeneron, UCB, Abcuro argenx, Alnylam, AstraZeneca, Amylyx, CSL Behring, Grifols, Takeda, Octapharma, UCB, and Janssen. Hayat reported speaker and advisory roles with argenx, Alexion, and MTPA.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — , results of a US survey showed.
For both MG and CIDP specialists, uncertainty around corticosteroid dosing, duration, and toxicity underscores the need for more guidance, the investigators noted. Over 85% of respondents indicated that a tool for systematically monitoring corticosteroid toxicity would be valuable.
The results indicate “a lack of knowledge by this pool of neurologists about the guidelines and what they contain,” said study investigator Gil Wolfe, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York.
Clearer guidance on how to administer corticosteroids and manage toxicities in patients with gMG and CIDP “would be welcomed by neurologists and have potential for benefit to patient care,” the team noted.
The findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Lack of Knowledge
Although guidelines for both CIDP and gMG recommend corticosteroids as first-line treatment and emphasize using the lowest effective dose to control symptoms, they do not include specific recommendations on dosing, duration, or toxicity monitoring, the researchers noted.
Despite this, a large proportion of survey respondents reported using guidelines to make clinical decisions on monitoring toxicity, with up to a third actually endorsing a guideline that doesn’t exist.
The cross-sectional, online survey was deployed in November and December 2023 and included 200 US neurologists. Of these, 99 answered questions on CIDP, and 101 answered similar questions on gMG.
To participate in the survey, respondents had to be board-certified neurologists, practicing for at least 2 years post-residency, and have treated or consulted on at least three patients with CIDP or 10 patients with gMG in the past year who were on a corticosteroid dose of at least 10 mg daily for 1 month or more.
CIDP respondents had been practicing a mean of 18.1 years since residency and were board certified in neuromuscular (20%), electrodiagnostic medicine/clinical neurophysiology (21%), and pediatric neurology (8%). Two thirds of them accepted referrals from other neurologists.
The gMG respondents had been practicing a mean of 20.5 years since residency and were board certified in neuromuscular (45%), electrodiagnostic medicine/clinical neurophysiology (35%), and pediatric neurology (17%). A total of 72% accepted referrals from other neurologists.
Respondents estimated that about 60% of their patients with gMG and 58% of patients with CIDP were being treated with corticosteroids, with gMG and CIDP respondents reporting a mean of 26.4 and 15.6 patients, respectively, meeting the study’s dosing criteria.
Appropriate Dosing
When asked what chronic, long-term (≥ 6 months) corticosteroid dose they considered safe in terms of minimizing adverse events, 43% of CIDP respondents and 51% of gMG respondents considered corticosteroid doses of 10 mg/d or less (prednisone equivalent) well tolerated; additionally, 32% and 31%, respectively, considered 20-40 mg/d well tolerated. Moreover, they said only about half of their patients would be able to taper to less than 10 mg/d in less than 6 months.
“Studies suggest safety is not seen until patients are on doses at 5 mg/d or less,” Wolfe said. “There is not enough appreciation that doses at levels we once considered safe really do pose significant risk,” he added.
“With the increasing number of treatment options in MG and to a lesser extent in CIDP, we need to do all we can to use corticosteroids as judiciously as possible and be aware of side effects our patients may not even report unless we make a pointed effort to ask about them.”
Familiarity with corticosteroid toxicities was more common among gMG respondents, of whom 77% reported being very/extremely familiar, than among 55% of CIDP respondents. Appetite/weight gain was reported among the most common adverse effects (AEs) associated with long-term CS use (reported by 68% of CIDP and 58% of gMG respondents). Other common AEs reported were insulin resistance (53% of CIDP and 50% of gMG respondents), decreased bone density (47% and 48%, respectively), immunosuppression (37% and 45%, respectively). Mood and behavioral change were noted by 56% of CIDP and 37% of gMG respondents, particularly mood swings, irritability, mania, and sleep disorders.
When asked how they balanced the risk for and benefit of corticosteroids, more than 80% of CIDP specialists reported personally monitoring for corticosteroid-related toxicity, and 42% reported they collaborated with the patient’s primary care provider. However, fewer than 10% reported ordering lab tests. Among neurologists treating gMG, 84% said they typically monitor corticosteroid toxicity independently, while 41% reported doing so in collaboration with primary care providers.
Two thirds of CIDP respondents and 53% of gMG respondents reported using guidelines to make clinical decisions on monitoring toxicity, and 34% of gMG respondents actually endorsed using the Guideline for Systematic Surveillance of Steroid Safety, which does not exist.
‘A Big Issue’ in Neurology
Commenting on the results, Said R. Beydoun, MD, professor and division chief, Neuromuscular Medicine, Department of Neurology at Keck Medicine of University of Southern California, Los Angeles, said steroid toxicity is “a big issue” in neurology.
These patients can be on chronic therapy, and they aren’t really monitored for osteoporosis or other complications, he said, adding that neurologists aren’t always taking the necessary precautions to prevent steroid toxicity.
Beydoun estimated that about half of neurologists are not adequately familiar with balancing the efficacy of corticosteroids versus in toxicity.
“Objective improvement, either on the functional scale or the muscle impairment scale — that’s really response treatment. Whereas adverse effects of a treatment are something separate. The patient may be improving but also maybe developing other complications from the treatment,” he said.
Also commenting, Ghazala Hayat, MD, professor of neurology and director of neuromuscular and clinical neurophysiology services at Saint Louis University in St. Louis, said there is a clear need for more education.
“I always say prednisone is our best friend initially, and then it becomes the worst enemy. If you don’t see lots of neuromuscular patients, you might not know even how to recognize toxicity or how to taper. Or the opposite to that, if you taper too quickly, patients relapse.”
The study was funded by argenx. Wolfe reported serving on advisory boards for Alexion, argenx, UCB, and Johnson & Johnson. Neelam Goyal, MD, is a consultant/advisor for Alexion, argenx, Amgen, Janssen, Lycia Therapeutics, and UCB and has received grant support from argenx. Beydoun reported receiving research support and consulting and speaking fees from Healey Center, Amylyx, AB Science, Sanofi, Janssen, Genentech, Regeneron, UCB, Abcuro argenx, Alnylam, AstraZeneca, Amylyx, CSL Behring, Grifols, Takeda, Octapharma, UCB, and Janssen. Hayat reported speaker and advisory roles with argenx, Alexion, and MTPA.
A version of this article appeared on Medscape.com.
FROM AANEM 2024
Veterans Affairs Hailed as a ‘Bright Spot’ in ALS Care
SAVANNAH, GEORGIA — , said one expert.
In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”
Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.
“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.”
Multidisciplinary vs Interdisciplinary
Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.
In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.
The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.
Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.
Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.
She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
Better Together
A recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.
“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.
“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.
Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.
Howard and Schellenberg reported no disclosures.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — , said one expert.
In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”
Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.
“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.”
Multidisciplinary vs Interdisciplinary
Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.
In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.
The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.
Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.
Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.
She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
Better Together
A recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.
“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.
“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.
Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.
Howard and Schellenberg reported no disclosures.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — , said one expert.
In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”
Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.
“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.”
Multidisciplinary vs Interdisciplinary
Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.
In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.
The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.
Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.
Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.
She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
Better Together
A recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.
“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.
“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.
Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.
Howard and Schellenberg reported no disclosures.
A version of this article appeared on Medscape.com.
FROM AANEM 2024
Digital Tool May Help Neurologists Assess Steroid Toxicity
SAVANNAH, GEORGIA —
The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.
“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.
The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Rapid Evidence of Toxicity
The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.
The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.
Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.
As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.
The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
Clinical Application
The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.
In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.
“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.
Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.
The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.
However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.
She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.
“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”
For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.
Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA —
The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.
“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.
The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Rapid Evidence of Toxicity
The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.
The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.
Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.
As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.
The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
Clinical Application
The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.
In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.
“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.
Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.
The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.
However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.
She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.
“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”
For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.
Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA —
The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.
“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.
The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Rapid Evidence of Toxicity
The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.
The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.
Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.
As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.
The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
Clinical Application
The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.
In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.
“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.
Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.
The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.
However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.
She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.
“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”
For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.
Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
A version of this article appeared on Medscape.com.
FROM AANEM 2024
Multi-Refractory MM: After Immunotherapy, What?
Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.
“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.
“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.
Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.
A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.
The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.
As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.
Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
CELMoDs Active After CAR T-Cell Therapy
Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.
These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.
There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.
However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.
It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*
Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.
“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.
This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
Recycling MM Therapies Deserves Consideration
In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.
Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.
Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.
This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.
“Better T-cell assays may help,” he said.
Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.
*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
A version of this article appeared on Medscape.com.
Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.
“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.
“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.
Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.
A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.
The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.
As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.
Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
CELMoDs Active After CAR T-Cell Therapy
Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.
These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.
There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.
However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.
It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*
Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.
“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.
This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
Recycling MM Therapies Deserves Consideration
In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.
Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.
Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.
This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.
“Better T-cell assays may help,” he said.
Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.
*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
A version of this article appeared on Medscape.com.
Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.
“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.
“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.
Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.
A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.
The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.
As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.
Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
CELMoDs Active After CAR T-Cell Therapy
Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.
These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.
There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.
However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.
It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*
Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.
“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.
This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
Recycling MM Therapies Deserves Consideration
In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.
Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.
Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.
This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.
“Better T-cell assays may help,” he said.
Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.
*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
A version of this article appeared on Medscape.com.
Lymphoma Debate: CAR T Not a Clear Winner
Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.
“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
Targeted Therapies Still Relevant to Advanced FL
Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.
“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible.
Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution.
The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited.
“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”
In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio.
BsAbs Vie With CAR T Cells in Advanced FL
Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both.
There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals.
“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.
“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery.
The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients.
In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment.
“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said.
No Data to Compare BsAbs and CAR T-Cells Directly
Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.
“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.
“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.
For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.
“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.
Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.
Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve.
“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.
Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
A version of this article appeared on Medscape.com.
Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.
“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
Targeted Therapies Still Relevant to Advanced FL
Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.
“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible.
Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution.
The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited.
“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”
In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio.
BsAbs Vie With CAR T Cells in Advanced FL
Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both.
There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals.
“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.
“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery.
The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients.
In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment.
“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said.
No Data to Compare BsAbs and CAR T-Cells Directly
Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.
“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.
“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.
For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.
“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.
Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.
Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve.
“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.
Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
A version of this article appeared on Medscape.com.
Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.
“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
Targeted Therapies Still Relevant to Advanced FL
Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.
“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible.
Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution.
The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited.
“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”
In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio.
BsAbs Vie With CAR T Cells in Advanced FL
Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both.
There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals.
“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.
“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery.
The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients.
In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment.
“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said.
No Data to Compare BsAbs and CAR T-Cells Directly
Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.
“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.
“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.
For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.
“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.
Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.
Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve.
“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.
Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
A version of this article appeared on Medscape.com.