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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Myeloma: Isa-KRd Induction Shows High MRD Responses
“We found that this induction induced exceptionally high response and minimal residual disease (MRD) negativity rates,” said first author Aurore Perrot, MD, PhD, an associate professor of hematology at the University of Toulouse in France, in presenting the findings at the annual meeting of the International Myeloma Society (IMS).
“These rates are the highest reported to date regarding MRD negativity,” she said.
The results from a first interim analysis offer encouraging groundwork in the trial that is investigating the tailoring of subsequent therapeutic choices in patients with newly diagnosed MM based on MRD status after six cycles of induction therapy.
In the standard treatment regimen of induction therapy followed by up-front autologous stem cell transplant (ASCT), the use of ever-improving quadruplet regimens is bolstering prognoses, while the role of up-front ASCT continues to be debated, Perrot explained. She noted that no prospective trials have compared up-front transplant vs no transplant following a quadruplet regimen.
In reporting on the initial findings from the induction phase of the phase 3 IFM 2020-02 MIDAS study, Perrot described results among 791 transplant-eligible patients with newly diagnosed MM and a median age of 59 who were enrolled at 72 centers between December 2021 and July 2023.
The patients were treated with six cycles of 28 days of the Isa-KRd regimen, consisting of isatuximab 10 mg/kg (weekly for 4 weeks then biweekly), carfilzomib 20 mg/m2 on day 1 cycle 1, then 56 mg/m2 (days 1, 8, and 15), lenalidomide 25 mg/d (from day 1 to day 21), and dexamethasone at 40 mg/wk.
Overall, MM was classified as International Staging System (ISS) III in 120 patients (15%) and revised-ISS III in 76 (10%) patients.
Of 757 patients undergoing cytogenetics, 8% were considered high risk on the basis of a linear predictor score > 1, while the t(11;14) translocation, a chromosomal abnormality, was present in 26% of patients.
Extramedullary disease was present in five patients, while 53 (7%) had circulating plasma cells.
All 791 patients initiated Isa-KRd induction, and most (766, 97%) had at least one peripheral stem cell mobilization course, with 761 having at least one apheresis. The median number of CD34+ cells collected was 7.106/kg.
The peripheral stem cells collected allowed for potential tandem transplants in 719 patients. In total, 757 patients completed six cycles of Isa-KRd, with an overall response rate of 95%.
In the intent-to-treat (ITT) population, a very good partial response or better was achieved in 92% of patients following induction, with a rate of 99% in the per-protocol [PP] population.
Of 751 patients in the post-induction ITT population, the MRD negativity rates were 63% at the threshold of 10−5 and 47% at the threshold of 10−6, with corresponding rates of 66% and 50%, respectively, in the PP population.
The rates of near-complete response and complete response were 64% and 66% in the ITT population, and 69% and 71% in the PP population.
Of note, no significant differences were observed in prognostic subgroups, with a trend for a higher MRD negative rate among poorer prognostic groups, Perrot said.
However, notable variability was observed in terms of MRD negativity at 10−5 after induction among some cytogenic groups, with an MRD negativity rate as high as 81% among patients with the t(4;14) translocation vs 62% among those without the abnormality (P = .002), while it was only 40% among patients with the t(11;14) translocation vs 64% without (P < .0001).
“This is the first time we have observed this correlation between the MRD negativity and these cytogenetic subgroups,” Perrot noted.
“For the moment, we are not saying that patients with the t(11;14) translocation have a poor prognosis,” she added. “But just that the early assessment of MRD shows the lower negativity rates.”
Safety
Seven patients experienced disease progression and five died during induction, with one dying from disease progression, two deaths related to cardiac adverse events (AEs), and two related to other AEs.
In terms of safety, the most common grade 3-4 AEs were neutropenia (25%), thrombocytopenia (5%), and infections (7%).
Peripheral neuropathy was reported among 13% of patients at any grade, and less than 1% grade 3-4.
“Our findings confirm that six cycles of Isa-KRd induce exceptionally high response and MRD negativity rates, not only at a sensitivity of 10−5 but also at 10−6,” Perrot said.
She noted that, in comparison, the MRD negativity rate at 10−5 in the related CASSIOPEIA, GRIFFIN, and IsKia trials were 35%, 22%, and 45%, respectively.
“A longer follow-up is needed to better interpret the significance of achieving MRD negativity in patients with different cytogenetic abnormalities,” Perrot added.
“Importantly, the Isa-KRd induction ensures successful stem cell collection, with no new safety signals,” she said.
The Isa-KRd regimen is not yet approved, hence only used in clinical trials, but Perrot told this publication the current evidence should help change that.
“The IsKia trial is comparing KRd and Isa-KRd, and Sanofi should try to approve the combo,” she said. “We hope the Midas data will support this approval.”
Questions Aplenty Moving Ahead
While the results are just the first from the ongoing trial, interest in the study and its design is high, Joseph Mikhael, MD, chief medical officer of the International Myeloma Foundation, told this publication.
“To have a large trial algorithm that is based on response and in particular MRD is novel and reflects the power of MRD in myeloma,” said Mikhael, a professor of applied cancer research and drug discovery at the Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.
“Although the results are preliminary, these kinds of trials can inform our approach to MRD testing and may result in more personalized and effective treatments for patients,” he said. “This may include the potential to de-escalate or even stop therapies that have historically been given for longer or provide more intense therapies for patients with inadequate response.”
“We know the biology of myeloma is ‘one size fits all’, so the design of our trials should reflect that heterogeneity.”
Further commenting on the research, the meeting discussant Sagar Lonial, MD, professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Professor in Cancer at the Winship Cancer Institute of Emory University, Atlanta, Georgia, offered cautious optimism.
Referencing the tale of Midas in Greek mythology as having a “be careful what you wish for” lesson, Lonial pondered that, likewise, a question that may be considered regarding MRD is “whether this is in fact a gift — or could this be a curse that’s going to get us into trouble at some point down the road. I don’t know the answer.”
Some cautionary lessons include prior research indicating that patients with high-risk disease may achieve a complete remission early — but they lose remission earlier down the road, he noted.
Other considerations as the research moves forward: “Recognizing that MRD may in fact be more important than genetics — which is a premise of the current trial,” Lonial pondered. “Does MRD override genetics, or do they travel together?”
The study is ongoing, with future results expected in terms of ASCT vs no ASCT for patients with high and low risk, as well as single vs tandem ASCT.
The trial received financial support from Amgen, Bristol-Myers Squibb, and Sanofi. Perrot reported ties with Amgen, Bristol Myers Squibb, and Sanofi. Mikhael disclosed ties with Amgen, Bristol Myers Squibb, and Sanofi. Lonial reported relationships with Celgene, Bristol-Myers Squibb, Amgen, and Sanofi.
A version of this article first appeared on Medscape.com.
“We found that this induction induced exceptionally high response and minimal residual disease (MRD) negativity rates,” said first author Aurore Perrot, MD, PhD, an associate professor of hematology at the University of Toulouse in France, in presenting the findings at the annual meeting of the International Myeloma Society (IMS).
“These rates are the highest reported to date regarding MRD negativity,” she said.
The results from a first interim analysis offer encouraging groundwork in the trial that is investigating the tailoring of subsequent therapeutic choices in patients with newly diagnosed MM based on MRD status after six cycles of induction therapy.
In the standard treatment regimen of induction therapy followed by up-front autologous stem cell transplant (ASCT), the use of ever-improving quadruplet regimens is bolstering prognoses, while the role of up-front ASCT continues to be debated, Perrot explained. She noted that no prospective trials have compared up-front transplant vs no transplant following a quadruplet regimen.
In reporting on the initial findings from the induction phase of the phase 3 IFM 2020-02 MIDAS study, Perrot described results among 791 transplant-eligible patients with newly diagnosed MM and a median age of 59 who were enrolled at 72 centers between December 2021 and July 2023.
The patients were treated with six cycles of 28 days of the Isa-KRd regimen, consisting of isatuximab 10 mg/kg (weekly for 4 weeks then biweekly), carfilzomib 20 mg/m2 on day 1 cycle 1, then 56 mg/m2 (days 1, 8, and 15), lenalidomide 25 mg/d (from day 1 to day 21), and dexamethasone at 40 mg/wk.
Overall, MM was classified as International Staging System (ISS) III in 120 patients (15%) and revised-ISS III in 76 (10%) patients.
Of 757 patients undergoing cytogenetics, 8% were considered high risk on the basis of a linear predictor score > 1, while the t(11;14) translocation, a chromosomal abnormality, was present in 26% of patients.
Extramedullary disease was present in five patients, while 53 (7%) had circulating plasma cells.
All 791 patients initiated Isa-KRd induction, and most (766, 97%) had at least one peripheral stem cell mobilization course, with 761 having at least one apheresis. The median number of CD34+ cells collected was 7.106/kg.
The peripheral stem cells collected allowed for potential tandem transplants in 719 patients. In total, 757 patients completed six cycles of Isa-KRd, with an overall response rate of 95%.
In the intent-to-treat (ITT) population, a very good partial response or better was achieved in 92% of patients following induction, with a rate of 99% in the per-protocol [PP] population.
Of 751 patients in the post-induction ITT population, the MRD negativity rates were 63% at the threshold of 10−5 and 47% at the threshold of 10−6, with corresponding rates of 66% and 50%, respectively, in the PP population.
The rates of near-complete response and complete response were 64% and 66% in the ITT population, and 69% and 71% in the PP population.
Of note, no significant differences were observed in prognostic subgroups, with a trend for a higher MRD negative rate among poorer prognostic groups, Perrot said.
However, notable variability was observed in terms of MRD negativity at 10−5 after induction among some cytogenic groups, with an MRD negativity rate as high as 81% among patients with the t(4;14) translocation vs 62% among those without the abnormality (P = .002), while it was only 40% among patients with the t(11;14) translocation vs 64% without (P < .0001).
“This is the first time we have observed this correlation between the MRD negativity and these cytogenetic subgroups,” Perrot noted.
“For the moment, we are not saying that patients with the t(11;14) translocation have a poor prognosis,” she added. “But just that the early assessment of MRD shows the lower negativity rates.”
Safety
Seven patients experienced disease progression and five died during induction, with one dying from disease progression, two deaths related to cardiac adverse events (AEs), and two related to other AEs.
In terms of safety, the most common grade 3-4 AEs were neutropenia (25%), thrombocytopenia (5%), and infections (7%).
Peripheral neuropathy was reported among 13% of patients at any grade, and less than 1% grade 3-4.
“Our findings confirm that six cycles of Isa-KRd induce exceptionally high response and MRD negativity rates, not only at a sensitivity of 10−5 but also at 10−6,” Perrot said.
She noted that, in comparison, the MRD negativity rate at 10−5 in the related CASSIOPEIA, GRIFFIN, and IsKia trials were 35%, 22%, and 45%, respectively.
“A longer follow-up is needed to better interpret the significance of achieving MRD negativity in patients with different cytogenetic abnormalities,” Perrot added.
“Importantly, the Isa-KRd induction ensures successful stem cell collection, with no new safety signals,” she said.
The Isa-KRd regimen is not yet approved, hence only used in clinical trials, but Perrot told this publication the current evidence should help change that.
“The IsKia trial is comparing KRd and Isa-KRd, and Sanofi should try to approve the combo,” she said. “We hope the Midas data will support this approval.”
Questions Aplenty Moving Ahead
While the results are just the first from the ongoing trial, interest in the study and its design is high, Joseph Mikhael, MD, chief medical officer of the International Myeloma Foundation, told this publication.
“To have a large trial algorithm that is based on response and in particular MRD is novel and reflects the power of MRD in myeloma,” said Mikhael, a professor of applied cancer research and drug discovery at the Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.
“Although the results are preliminary, these kinds of trials can inform our approach to MRD testing and may result in more personalized and effective treatments for patients,” he said. “This may include the potential to de-escalate or even stop therapies that have historically been given for longer or provide more intense therapies for patients with inadequate response.”
“We know the biology of myeloma is ‘one size fits all’, so the design of our trials should reflect that heterogeneity.”
Further commenting on the research, the meeting discussant Sagar Lonial, MD, professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Professor in Cancer at the Winship Cancer Institute of Emory University, Atlanta, Georgia, offered cautious optimism.
Referencing the tale of Midas in Greek mythology as having a “be careful what you wish for” lesson, Lonial pondered that, likewise, a question that may be considered regarding MRD is “whether this is in fact a gift — or could this be a curse that’s going to get us into trouble at some point down the road. I don’t know the answer.”
Some cautionary lessons include prior research indicating that patients with high-risk disease may achieve a complete remission early — but they lose remission earlier down the road, he noted.
Other considerations as the research moves forward: “Recognizing that MRD may in fact be more important than genetics — which is a premise of the current trial,” Lonial pondered. “Does MRD override genetics, or do they travel together?”
The study is ongoing, with future results expected in terms of ASCT vs no ASCT for patients with high and low risk, as well as single vs tandem ASCT.
The trial received financial support from Amgen, Bristol-Myers Squibb, and Sanofi. Perrot reported ties with Amgen, Bristol Myers Squibb, and Sanofi. Mikhael disclosed ties with Amgen, Bristol Myers Squibb, and Sanofi. Lonial reported relationships with Celgene, Bristol-Myers Squibb, Amgen, and Sanofi.
A version of this article first appeared on Medscape.com.
“We found that this induction induced exceptionally high response and minimal residual disease (MRD) negativity rates,” said first author Aurore Perrot, MD, PhD, an associate professor of hematology at the University of Toulouse in France, in presenting the findings at the annual meeting of the International Myeloma Society (IMS).
“These rates are the highest reported to date regarding MRD negativity,” she said.
The results from a first interim analysis offer encouraging groundwork in the trial that is investigating the tailoring of subsequent therapeutic choices in patients with newly diagnosed MM based on MRD status after six cycles of induction therapy.
In the standard treatment regimen of induction therapy followed by up-front autologous stem cell transplant (ASCT), the use of ever-improving quadruplet regimens is bolstering prognoses, while the role of up-front ASCT continues to be debated, Perrot explained. She noted that no prospective trials have compared up-front transplant vs no transplant following a quadruplet regimen.
In reporting on the initial findings from the induction phase of the phase 3 IFM 2020-02 MIDAS study, Perrot described results among 791 transplant-eligible patients with newly diagnosed MM and a median age of 59 who were enrolled at 72 centers between December 2021 and July 2023.
The patients were treated with six cycles of 28 days of the Isa-KRd regimen, consisting of isatuximab 10 mg/kg (weekly for 4 weeks then biweekly), carfilzomib 20 mg/m2 on day 1 cycle 1, then 56 mg/m2 (days 1, 8, and 15), lenalidomide 25 mg/d (from day 1 to day 21), and dexamethasone at 40 mg/wk.
Overall, MM was classified as International Staging System (ISS) III in 120 patients (15%) and revised-ISS III in 76 (10%) patients.
Of 757 patients undergoing cytogenetics, 8% were considered high risk on the basis of a linear predictor score > 1, while the t(11;14) translocation, a chromosomal abnormality, was present in 26% of patients.
Extramedullary disease was present in five patients, while 53 (7%) had circulating plasma cells.
All 791 patients initiated Isa-KRd induction, and most (766, 97%) had at least one peripheral stem cell mobilization course, with 761 having at least one apheresis. The median number of CD34+ cells collected was 7.106/kg.
The peripheral stem cells collected allowed for potential tandem transplants in 719 patients. In total, 757 patients completed six cycles of Isa-KRd, with an overall response rate of 95%.
In the intent-to-treat (ITT) population, a very good partial response or better was achieved in 92% of patients following induction, with a rate of 99% in the per-protocol [PP] population.
Of 751 patients in the post-induction ITT population, the MRD negativity rates were 63% at the threshold of 10−5 and 47% at the threshold of 10−6, with corresponding rates of 66% and 50%, respectively, in the PP population.
The rates of near-complete response and complete response were 64% and 66% in the ITT population, and 69% and 71% in the PP population.
Of note, no significant differences were observed in prognostic subgroups, with a trend for a higher MRD negative rate among poorer prognostic groups, Perrot said.
However, notable variability was observed in terms of MRD negativity at 10−5 after induction among some cytogenic groups, with an MRD negativity rate as high as 81% among patients with the t(4;14) translocation vs 62% among those without the abnormality (P = .002), while it was only 40% among patients with the t(11;14) translocation vs 64% without (P < .0001).
“This is the first time we have observed this correlation between the MRD negativity and these cytogenetic subgroups,” Perrot noted.
“For the moment, we are not saying that patients with the t(11;14) translocation have a poor prognosis,” she added. “But just that the early assessment of MRD shows the lower negativity rates.”
Safety
Seven patients experienced disease progression and five died during induction, with one dying from disease progression, two deaths related to cardiac adverse events (AEs), and two related to other AEs.
In terms of safety, the most common grade 3-4 AEs were neutropenia (25%), thrombocytopenia (5%), and infections (7%).
Peripheral neuropathy was reported among 13% of patients at any grade, and less than 1% grade 3-4.
“Our findings confirm that six cycles of Isa-KRd induce exceptionally high response and MRD negativity rates, not only at a sensitivity of 10−5 but also at 10−6,” Perrot said.
She noted that, in comparison, the MRD negativity rate at 10−5 in the related CASSIOPEIA, GRIFFIN, and IsKia trials were 35%, 22%, and 45%, respectively.
“A longer follow-up is needed to better interpret the significance of achieving MRD negativity in patients with different cytogenetic abnormalities,” Perrot added.
“Importantly, the Isa-KRd induction ensures successful stem cell collection, with no new safety signals,” she said.
The Isa-KRd regimen is not yet approved, hence only used in clinical trials, but Perrot told this publication the current evidence should help change that.
“The IsKia trial is comparing KRd and Isa-KRd, and Sanofi should try to approve the combo,” she said. “We hope the Midas data will support this approval.”
Questions Aplenty Moving Ahead
While the results are just the first from the ongoing trial, interest in the study and its design is high, Joseph Mikhael, MD, chief medical officer of the International Myeloma Foundation, told this publication.
“To have a large trial algorithm that is based on response and in particular MRD is novel and reflects the power of MRD in myeloma,” said Mikhael, a professor of applied cancer research and drug discovery at the Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.
“Although the results are preliminary, these kinds of trials can inform our approach to MRD testing and may result in more personalized and effective treatments for patients,” he said. “This may include the potential to de-escalate or even stop therapies that have historically been given for longer or provide more intense therapies for patients with inadequate response.”
“We know the biology of myeloma is ‘one size fits all’, so the design of our trials should reflect that heterogeneity.”
Further commenting on the research, the meeting discussant Sagar Lonial, MD, professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Professor in Cancer at the Winship Cancer Institute of Emory University, Atlanta, Georgia, offered cautious optimism.
Referencing the tale of Midas in Greek mythology as having a “be careful what you wish for” lesson, Lonial pondered that, likewise, a question that may be considered regarding MRD is “whether this is in fact a gift — or could this be a curse that’s going to get us into trouble at some point down the road. I don’t know the answer.”
Some cautionary lessons include prior research indicating that patients with high-risk disease may achieve a complete remission early — but they lose remission earlier down the road, he noted.
Other considerations as the research moves forward: “Recognizing that MRD may in fact be more important than genetics — which is a premise of the current trial,” Lonial pondered. “Does MRD override genetics, or do they travel together?”
The study is ongoing, with future results expected in terms of ASCT vs no ASCT for patients with high and low risk, as well as single vs tandem ASCT.
The trial received financial support from Amgen, Bristol-Myers Squibb, and Sanofi. Perrot reported ties with Amgen, Bristol Myers Squibb, and Sanofi. Mikhael disclosed ties with Amgen, Bristol Myers Squibb, and Sanofi. Lonial reported relationships with Celgene, Bristol-Myers Squibb, Amgen, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM IMS 2024
ILD Linked to Poorer Outcomes in Pulmonary Embolism
BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.
Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.
The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.
The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).
Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).
In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.
“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.
He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.
Yuan and Rali disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.
Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.
The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.
The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).
Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).
In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.
“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.
He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.
Yuan and Rali disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — Patients with pulmonary embolism (PE) who also present with interstitial lung disease (ILD) have worse outcomes with respect to in-hospital mortality, length of hospital stay, hospital cost, and all-cause readmission, according to results from a new retrospective analysis.
Unfortunately, there’s not a whole lot of evidence out there to really demonstrate it,” Leah Yuan, MD, said during a presentation of the results at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The question is complicated by the nebulous nature of ILD, which includes a diverse set of diseases and etiologies, and different levels of inflammation and fibrosis. It has been employed in the Pulmonary Embolism Severity Index but counts for only 10 points out of 210. “If you look at ILD and PE outcomes, there’s nothing really out there [in the literature],” Yuan said in an interview. She is a resident physician at Cook County Health and Hospitals System.
The new study suggested that ILD could have an important influence and perhaps should have greater weight in risk stratification of patients with PE, she said. “We looked at all-cause readmissions and we looked at in-hospital mortality, [both] of which are significant for increased odds ratio. One thing that I’m very curious to see is whether there is increased PE readmissions [associated with ILD], which is something that we couldn’t find to be significant in our study,” said Yuan.
The researchers used data from hospitalizations for PE drawn from the Nationwide Readmissions Database in 2019, using International Classification of Diseases, Tenth Revision, codes to identify admissions. Among a total of 105,133 patients admitted for PE, 158 patients also had ILD. The mean age was 63.6 years for those without ILD (SD, 0.1) and 66.5 years for those with ILD (SD, 1.3).
Admission with ILD was associated with all-cause readmission (odds ratio [OR], 4.12; P < .01), in-hospital mortality (OR, 2.17; P = .01), a longer length of stay (+2.07 days; P < .01), and higher hospitalization charges (+$22,627; P < .01).
In the Q&A period after the presentation, Parth Rali, MD, professor of thoracic medicine and surgery at Temple University, Philadelphia, suggested phenotyping patients to better understand the location of the PE in relation to the ILD. “It may not fall into your classic PE classification. It may just depend on where the clot is in relationship to the interstitial lung disease. I think that’s where the field is going to evolve,” he later said in an interview.
“What is interesting is that patients with interstitial lung disease have a lot of fibrotic disease, and they do not need to have a large clot burden to make them sick. An example [is someone] who has undergone a lung transplant evaluation, and if their right lung is completely diseased from interstitial lung disease and if they get a big blood clot on the right side, it doesn’t affect them because the lung is already fibrotic, so the clot doesn’t matter. If they get a small clot [in the left lung], even though if you look at the standard PE classification they may qualify as a low-risk PE or even as an intermediate-low-risk PE, they are much sicker because that’s the functioning part of the lung,” said Rali.
He advised physicians to pay close attention to the location of PEs in relation to fibrotic tissue in patients with ILD. A PE in healthy lung tissue could have an outsized effect on hemodynamics, whereas a PE in fibrotic tissue may be clinically insignificant and not require treatment. “So it goes both ways: You don’t overtreat and you don’t undertreat,” Rali said.
Yuan and Rali disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
CHEST 2024
Use of SGLT2 Inhibitors Associated With Better Survival in PAH
BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.
“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).
At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).
The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.
Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.
Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.
Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.
The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.
“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).
At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).
The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.
Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.
Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.
Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.
The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
BOSTON — The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors is associated with reduced short- and long-term mortality among patients with pulmonary arterial hypertension (PAH), according to results from a new propensity score–matched analysis.
“There are a lot of new studies that show benefits [of SGLT2 inhibitors] in heart failure, in [chronic kidney disease], and of course, in diabetes. There are studies that show that SGLT2 inhibitors can have an impact on inflammatory cascades, fibrosis, and vascular remodeling in general. Together, all this data triggered this idea for me, and that’s when I decided to conduct further studies,” said Irakli Lemonjava, MD, who presented the study at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.
The researchers drew data on 125,634 adult patients from the TriNetX database who were diagnosed with PAH after January 1, 2013. They used propensity score matching to account for demographic characteristics and 10 organ system disorders to compare patients with exposure to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin; n = 6238) with those without such exposure (n = 6243).
At 1 year, 8.1% of patients taking SGLT2 inhibitors had died, compared with 15.5% of patients not taking SGLT2 inhibitors (risk reduction [RR], 0.52; P < .0001). The values were 13% and 22.5% (RR, 0.579; P < .0001) at 3 years and 14.6% and 25% at 5 years (RR, 0.583; P < .0001).
The study generated discussion during the Q&A period following the talk. One audience member asked if the group was able to access patients both inside and outside the United States. “Because I wonder if access to GLP2 inhibitors is actually a surrogate marker for access to other medications,” the questioner said.
Although the finding is intriguing, it shouldn’t change clinical practice, according to Lemonjava. “I don’t think we can make any changes based on what I shared today. Our purpose was to trigger the question. I think the numbers are so impressive that it will trigger more studies. I think if in the future it’s demonstrated by clinical trials that [SGLT2 inhibitors are beneficial], it will not be a problem to prescribe for someone with pulmonary arterial hypertension because they do not have many side effects,” he said. Lemonjava is a resident physician at Jefferson Einstein Philadelphia Hospital, Philadelphia.
Session co-moderator said Syed Rehan Quadery, MD, praised the study but emphasized the remaining uncertainty. “It’s an excellent proof of concept study. More trials need to [be done] on it, and we don’t understand the mechanism of action in which it improves survival in patients with pulmonary artery hypertension. The majority of the patients with pulmonary hypertension are much older and they have comorbidities, including cardiovascular risk factors, and maybe that is one of the ways in which this drug helps. Plus, there are multiple mechanisms in which it may be working, including anti-inflammatory as well as antiproliferative mechanisms through inhibiting the Notch-3 signaling pathway,” said Quadery, who is a consultant respiratory physician at National Pulmonary Hypertension Unit, Dublin, Ireland.
Quadery and his co-moderator Zeenat Safdar, MD, both noted that SGLT2 inhibitors have already been demonstrated to improve outcomes in heart failure. “[SGLT2 inhibition] improves survival, it decreases hospitalization, it improves morbidity and mortality. There are a lot of things that can be shown in different [animal or in vitro] models. In humans, we actually don’t know exactly how it works, but we know that it does. If it works in left heart failure, it also [could] work in right heart failure,” said Safdar, who is the director of the Houston Methodist Lung Center, Houston Methodist Hospital, Houston.
The study was independently supported. Lemonjava, Quadery, and Safdar reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CHEST 2024
Adding Short-term ADT to High-Dose Radiotherapy Benefits Some Prostate Cancers
according to results of the phase 3 GETUG 14 trial.
The 5-year disease-free survival rate was 84% in patients who received short-term ADT plus radiotherapy, compared with 76% in those who received radiotherapy alone.
In addition, short-term ADT with high-dose radiotherapy didn’t increase genitourinary or gastrointestinal toxicities, said Nicolas Demogeot, MD, with the Cancer Institute of Lorraine, Vandœuvre-lès-Nancy, France, who presented the results at the annual meeting of the American Society for Radiation Oncology (ASTRO).
Adding short-term ADT to standard-dose radiotherapy has been shown to improve all clinical outcomes, Dr. Demogeot noted, but few trials have tested it with high-dose radiotherapy. GETUG 14 was designed to do just that.
The multicenter, randomized, phase 3 trial enrolled 376 patients with intermediate- or high-risk localized prostate cancer who had PSA levels under 30 ng/mL and no clinical involvement of the seminal vesicles.
Patients were randomly allocated to high-dose radiotherapy (80 Gy) alone or high-dose radiotherapy plus monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months prior to radiotherapy.
Disease-free survival was the primary endpoint. Secondary endpoints were overall survival, biochemical failure, metastasis failure, toxicity, and quality of life.
The modified intention-to-treat cohort included 191 patients in the radiotherapy-only group and 179 in the short-term ADT plus radiotherapy group. The two groups were well balanced. In both, patients ranged in age from 64 to 73 years; about two thirds had intermediate-risk disease; 70% received three-dimensional conformal radiotherapy, and 30% received intensity-modulated radiotherapy.
Overall, adding short-term ADT to high-dose radiotherapy was associated with a 36% relative improvement in 5-year disease-free survival (84% vs 76% with radiotherapy alone, hazard ratio [HR], 0.64; P = .02).
In subgroup analyses, intermediate-risk patients who received short-term ADT with high-dose radiotherapy demonstrated a significant improvement in disease-free survival (87% vs 74% with radiotherapy alone; HR, 0.55; P = .02). However, there was no significant disease-free survival benefit with short-term ADT with high-dose radiotherapy in high-risk patients (79% vs 75%; HR, 0.76; P = .40).
On multivariable analysis, short-term ADT with high-dose radiotherapy was associated with significant disease-free survival benefits (HR, 0.66; P = .038).
Patients who received short-term ADT with high-dose radiotherapy were significantly less likely to experience biochemical failure (10% vs 21%; HR, 0.45; P = .001), but there was no significant difference in metastasis failure (HR, 0.5; P = .09) or overall survival (HR, 1.22; P = .54).
As for adverse events, the two groups did not demonstrate significant differences in the proportions of early or late grade 2 or higher gastrointestinal or genitourinary toxicities.
Patients in the short-term ADT with high-dose radiotherapy group did experience a greater frequency of early grade 2 or higher erectile dysfunction (31% vs 6%; P < .001), but not late grade 2 or higher erectile dysfunction (63% vs 61%; P = .89).
Limitations of the study include a low power to detect differences between intermediate- and high-risk patients and the short follow-up period.
The GETUG 14 trial “confirms that short-term ADT improves disease-free survival when combined with dose-escalated radiation therapy for intermediate-risk prostate cancer,” Mark A. Hallman, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was not involved in the study, said in an interview. “However, there was not a similar benefit among the smaller subpopulation with high-risk disease.”
Outside expert Amar Kishan, MD, radiation oncologist, UCLA Jonsson Comprehensive Cancer Center, agreed, adding that “it is also reassuring to see no increase in genitourinary or gastrointestinal toxicity and no longer-term impact on erectile dysfunction.”
The GETUG-14 trial was supported by the French Ministry of Health and Ipsen. Dr. Demogeot has disclosed relationships with Ipsen, Janssen, Accord Healthcare, Astellas, and Bayer. Dr. Hallman had no relevant disclosures. Dr. Kishan has disclosed relationships with Boston Scientific, Janssen, Varian Medical Systems, ViewRay, and POINT Biopharma.
A version of this article first appeared on Medscape.com.
according to results of the phase 3 GETUG 14 trial.
The 5-year disease-free survival rate was 84% in patients who received short-term ADT plus radiotherapy, compared with 76% in those who received radiotherapy alone.
In addition, short-term ADT with high-dose radiotherapy didn’t increase genitourinary or gastrointestinal toxicities, said Nicolas Demogeot, MD, with the Cancer Institute of Lorraine, Vandœuvre-lès-Nancy, France, who presented the results at the annual meeting of the American Society for Radiation Oncology (ASTRO).
Adding short-term ADT to standard-dose radiotherapy has been shown to improve all clinical outcomes, Dr. Demogeot noted, but few trials have tested it with high-dose radiotherapy. GETUG 14 was designed to do just that.
The multicenter, randomized, phase 3 trial enrolled 376 patients with intermediate- or high-risk localized prostate cancer who had PSA levels under 30 ng/mL and no clinical involvement of the seminal vesicles.
Patients were randomly allocated to high-dose radiotherapy (80 Gy) alone or high-dose radiotherapy plus monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months prior to radiotherapy.
Disease-free survival was the primary endpoint. Secondary endpoints were overall survival, biochemical failure, metastasis failure, toxicity, and quality of life.
The modified intention-to-treat cohort included 191 patients in the radiotherapy-only group and 179 in the short-term ADT plus radiotherapy group. The two groups were well balanced. In both, patients ranged in age from 64 to 73 years; about two thirds had intermediate-risk disease; 70% received three-dimensional conformal radiotherapy, and 30% received intensity-modulated radiotherapy.
Overall, adding short-term ADT to high-dose radiotherapy was associated with a 36% relative improvement in 5-year disease-free survival (84% vs 76% with radiotherapy alone, hazard ratio [HR], 0.64; P = .02).
In subgroup analyses, intermediate-risk patients who received short-term ADT with high-dose radiotherapy demonstrated a significant improvement in disease-free survival (87% vs 74% with radiotherapy alone; HR, 0.55; P = .02). However, there was no significant disease-free survival benefit with short-term ADT with high-dose radiotherapy in high-risk patients (79% vs 75%; HR, 0.76; P = .40).
On multivariable analysis, short-term ADT with high-dose radiotherapy was associated with significant disease-free survival benefits (HR, 0.66; P = .038).
Patients who received short-term ADT with high-dose radiotherapy were significantly less likely to experience biochemical failure (10% vs 21%; HR, 0.45; P = .001), but there was no significant difference in metastasis failure (HR, 0.5; P = .09) or overall survival (HR, 1.22; P = .54).
As for adverse events, the two groups did not demonstrate significant differences in the proportions of early or late grade 2 or higher gastrointestinal or genitourinary toxicities.
Patients in the short-term ADT with high-dose radiotherapy group did experience a greater frequency of early grade 2 or higher erectile dysfunction (31% vs 6%; P < .001), but not late grade 2 or higher erectile dysfunction (63% vs 61%; P = .89).
Limitations of the study include a low power to detect differences between intermediate- and high-risk patients and the short follow-up period.
The GETUG 14 trial “confirms that short-term ADT improves disease-free survival when combined with dose-escalated radiation therapy for intermediate-risk prostate cancer,” Mark A. Hallman, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was not involved in the study, said in an interview. “However, there was not a similar benefit among the smaller subpopulation with high-risk disease.”
Outside expert Amar Kishan, MD, radiation oncologist, UCLA Jonsson Comprehensive Cancer Center, agreed, adding that “it is also reassuring to see no increase in genitourinary or gastrointestinal toxicity and no longer-term impact on erectile dysfunction.”
The GETUG-14 trial was supported by the French Ministry of Health and Ipsen. Dr. Demogeot has disclosed relationships with Ipsen, Janssen, Accord Healthcare, Astellas, and Bayer. Dr. Hallman had no relevant disclosures. Dr. Kishan has disclosed relationships with Boston Scientific, Janssen, Varian Medical Systems, ViewRay, and POINT Biopharma.
A version of this article first appeared on Medscape.com.
according to results of the phase 3 GETUG 14 trial.
The 5-year disease-free survival rate was 84% in patients who received short-term ADT plus radiotherapy, compared with 76% in those who received radiotherapy alone.
In addition, short-term ADT with high-dose radiotherapy didn’t increase genitourinary or gastrointestinal toxicities, said Nicolas Demogeot, MD, with the Cancer Institute of Lorraine, Vandœuvre-lès-Nancy, France, who presented the results at the annual meeting of the American Society for Radiation Oncology (ASTRO).
Adding short-term ADT to standard-dose radiotherapy has been shown to improve all clinical outcomes, Dr. Demogeot noted, but few trials have tested it with high-dose radiotherapy. GETUG 14 was designed to do just that.
The multicenter, randomized, phase 3 trial enrolled 376 patients with intermediate- or high-risk localized prostate cancer who had PSA levels under 30 ng/mL and no clinical involvement of the seminal vesicles.
Patients were randomly allocated to high-dose radiotherapy (80 Gy) alone or high-dose radiotherapy plus monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months prior to radiotherapy.
Disease-free survival was the primary endpoint. Secondary endpoints were overall survival, biochemical failure, metastasis failure, toxicity, and quality of life.
The modified intention-to-treat cohort included 191 patients in the radiotherapy-only group and 179 in the short-term ADT plus radiotherapy group. The two groups were well balanced. In both, patients ranged in age from 64 to 73 years; about two thirds had intermediate-risk disease; 70% received three-dimensional conformal radiotherapy, and 30% received intensity-modulated radiotherapy.
Overall, adding short-term ADT to high-dose radiotherapy was associated with a 36% relative improvement in 5-year disease-free survival (84% vs 76% with radiotherapy alone, hazard ratio [HR], 0.64; P = .02).
In subgroup analyses, intermediate-risk patients who received short-term ADT with high-dose radiotherapy demonstrated a significant improvement in disease-free survival (87% vs 74% with radiotherapy alone; HR, 0.55; P = .02). However, there was no significant disease-free survival benefit with short-term ADT with high-dose radiotherapy in high-risk patients (79% vs 75%; HR, 0.76; P = .40).
On multivariable analysis, short-term ADT with high-dose radiotherapy was associated with significant disease-free survival benefits (HR, 0.66; P = .038).
Patients who received short-term ADT with high-dose radiotherapy were significantly less likely to experience biochemical failure (10% vs 21%; HR, 0.45; P = .001), but there was no significant difference in metastasis failure (HR, 0.5; P = .09) or overall survival (HR, 1.22; P = .54).
As for adverse events, the two groups did not demonstrate significant differences in the proportions of early or late grade 2 or higher gastrointestinal or genitourinary toxicities.
Patients in the short-term ADT with high-dose radiotherapy group did experience a greater frequency of early grade 2 or higher erectile dysfunction (31% vs 6%; P < .001), but not late grade 2 or higher erectile dysfunction (63% vs 61%; P = .89).
Limitations of the study include a low power to detect differences between intermediate- and high-risk patients and the short follow-up period.
The GETUG 14 trial “confirms that short-term ADT improves disease-free survival when combined with dose-escalated radiation therapy for intermediate-risk prostate cancer,” Mark A. Hallman, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, who was not involved in the study, said in an interview. “However, there was not a similar benefit among the smaller subpopulation with high-risk disease.”
Outside expert Amar Kishan, MD, radiation oncologist, UCLA Jonsson Comprehensive Cancer Center, agreed, adding that “it is also reassuring to see no increase in genitourinary or gastrointestinal toxicity and no longer-term impact on erectile dysfunction.”
The GETUG-14 trial was supported by the French Ministry of Health and Ipsen. Dr. Demogeot has disclosed relationships with Ipsen, Janssen, Accord Healthcare, Astellas, and Bayer. Dr. Hallman had no relevant disclosures. Dr. Kishan has disclosed relationships with Boston Scientific, Janssen, Varian Medical Systems, ViewRay, and POINT Biopharma.
A version of this article first appeared on Medscape.com.
FROM ASTRO 2024
Mycosis Fungoides: Measured Approach Key to Treatment
HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.
Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”
Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
When Close Follow-Up Is Advised
According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)
According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”
Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”
Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
UVB Phototherapy Effective
For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”
Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.
For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.
Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.
Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
Radiation An Option in Some Cases
Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”
Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.
A version of this article first appeared on Medscape.com.
HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.
Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”
Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
When Close Follow-Up Is Advised
According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)
According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”
Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”
Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
UVB Phototherapy Effective
For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”
Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.
For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.
Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.
Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
Radiation An Option in Some Cases
Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”
Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.
A version of this article first appeared on Medscape.com.
HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.
Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”
Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
When Close Follow-Up Is Advised
According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)
According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”
Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”
Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
UVB Phototherapy Effective
For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”
Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.
For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.
Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.
Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
Radiation An Option in Some Cases
Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”
Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.
A version of this article first appeared on Medscape.com.
FROM PDA 2024
Isatuximab Quadruplet Approval Could Change the Landscape for Treating Myeloma
The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.
The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.
Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”
Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.
So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?
“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”
Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.
However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?
“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”
She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”
“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.
Patient preference and access are also important considerations, as is cost, he noted.
Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.
“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
How Will This Combination Be Integrated Into Daily Clinical Practice?
“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.
Dr. Mohty added that the multiple myeloma story is changing and evolving.
“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.
For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.
“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”
Both the IMROZ study and the EMJ article were funded by Sanofi.
Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
A version of this article appeared on Medscape.com.
The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.
The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.
Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”
Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.
So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?
“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”
Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.
However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?
“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”
She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”
“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.
Patient preference and access are also important considerations, as is cost, he noted.
Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.
“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
How Will This Combination Be Integrated Into Daily Clinical Practice?
“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.
Dr. Mohty added that the multiple myeloma story is changing and evolving.
“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.
For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.
“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”
Both the IMROZ study and the EMJ article were funded by Sanofi.
Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
A version of this article appeared on Medscape.com.
The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.
The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.
Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”
Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.
So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?
“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”
Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.
However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?
“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”
She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”
“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.
Patient preference and access are also important considerations, as is cost, he noted.
Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.
“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
How Will This Combination Be Integrated Into Daily Clinical Practice?
“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.
Dr. Mohty added that the multiple myeloma story is changing and evolving.
“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.
For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.
“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”
Both the IMROZ study and the EMJ article were funded by Sanofi.
Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
A version of this article appeared on Medscape.com.
FROM IMS 2024
Is Wildfire Smoke More Toxic Than General Air Pollution?
Wildfire-related air pollution in Europe kills more than non-wildfire air pollution. As climate change exacerbates the frequency and violence of wildfires, researchers are studying the health implications of mitigation methods such as prescribed fires.
Presenting at the annual congress of the European Respiratory Society (ERS), Cathryn Tonne, PhD, an environmental epidemiologist at the Instituto de Salud Global de Barcelona, Spain, said wildfire-related PM2.5 is more toxic than general PM2.5, leading to significantly higher mortality rates.
Prescribed, controlled fires have been employed worldwide to reduce the chance of uncontrolled, catastrophic fires. However, researchers wonder whether the techniques reduce the overall fire-related PM2.5 or add up to it. “Prescribed fire increases ecosystem resilience and can reduce the risk of catastrophic wildfire,” said Jason Sacks, MPH, an epidemiologist in the Center for Public Health and Environmental Assessment in the Office of Research and Development at the Environmental Protection Agency (EPA), at the congress. “But it also leads to poorer air quality and health impacts, and we still don’t know what this means at a regional scale.”
Wildfire Pollution Kills More Than Other Air Pollution
Researchers at the Instituto de Salud Global de Barcelona used a large dataset of daily mortality data from 32 European countries collected through the EARLY-ADAPT project. They utilized the SILAM model to derive daily average concentrations of wildfire-related PM2.5, non-fire PM2.5, and total PM2.5 levels. They also employed GEOSTAT population grids at a 1-km resolution to calculate the attributable number of deaths across different regions, specifically focusing on data from 2006, 2011, and 2018.
The data analysis indicated that the relative risk per unit of PM2.5 is substantially larger for wildfire-related PM2.5, compared with non-fire PM2.5. “We essentially assume that wildfire smoke PM2.5 has the same toxicity as total PM2.5, but it’s increasingly clear that’s likely not the case,” Dr. Tonne said, presenting the study.
When employing exposure-response functions (ERFs) specific to wildfire smoke, researchers found that the attributable deaths from all causes of wildfire PM2.5 were approximately 10 times larger than those calculated using total PM2.5 exposure estimates. Dr. Tonne explained that this stark difference highlights the critical need for tailored ERFs that accurately reflect the unique health risks posed by wildfire smoke.
“Respiratory mortality usually has the strongest relative risks, and we’re seeing that in this study as well,” Dr. Tonne said. “Wildfire smoke seems to operate through quite immediate mechanisms, likely through inflammation and oxidative stress.”
One significant challenge of the study was the lack of uniform spatial resolution across all countries involved in the analysis. This inconsistency may affect how accurately mortality estimates can be attributed to specific PM2.5 sources. Additionally, the study had limited statistical power for generating age- and sex-specific mortality estimates, which could obscure important demographic differences in vulnerability to wildfire smoke exposure. The analysis was also constrained to data available only up to 2020, thereby excluding critical wildfire events from subsequent years, such as those in 2022 and 2023, which may have further elucidated the health impacts of wildfire smoke in Europe.
Fires Prescription
Prescribed fires or controlled burns are intentional fires set by land managers under carefully managed conditions.
Historically, many forested areas have been subjected to fire suppression practices, which allow combustible materials like dry leaves, twigs, and shrubs to accumulate over time. This buildup leads to a higher likelihood of severe, uncontrollable wildfires. Prescribed fires can reduce these fuel loads and improve the health and resilience of ecosystems.
They release fewer pollutants and emissions than the large-scale, unmanageable wildfires they help prevent because they happen at lower temperatures. But they still introduce pollutants in the air that can negatively affect nearby communities’ health.
People with preexisting respiratory conditions, such as asthma or chronic obstructive pulmonary disease (COPD), are particularly vulnerable to smoke, which can trigger health issues like breathing difficulties, coughing, and eye irritation. The cumulative impact of increased burns raises concerns about long-term air quality, especially in densely populated areas. “We need to understand if we’re actually tipping the scale to having less wildfire smoke or just increasing the total amount of smoke.”
Mitigation strategies include accurately picking the right timing and weather conditions to determine when and where to conduct controlled burns and effective and timely communication to inform local communities about upcoming burns, the potential for smoke exposure, and how to protect themselves.
There is a growing need to improve public messaging around prescribed fires, Mr. Sacks said, because often the message communicated is oversimplified, such as “there will be smoke, but don’t worry. But that’s not the message we want to convey, especially for people with asthma or COPD.”
Instead, he said public health agencies should provide clearer, science-based guidance on the risks for smoke exposure and practical steps people can take to reduce their risk.
What Can Doctors Do?
Chris Carlsten, MD, director of the Centre for Lung Health and professor and head of the Respiratory Medicine Division at the University of British Columbia, Vancouver, Canada, told this news organization that determining whether an exacerbation of a respiratory condition is caused by fire exposure or other factors, such as viral infections, is complex because both can trigger similar responses and may complement each other. “It’s very difficult for any individual to know whether, when they’re having an exacerbation of asthma or COPD, that’s due to the fire,” he said. Fire smoke also increases infection risks, further complicating diagnosis.
Dr. Carlsten suggested that physicians could recommend preventative use of inhalers for at-risk patients when wildfires occur rather than waiting for symptoms to worsen. “That is a really interesting idea that could be practical.” Still, he advises caution, stressing that patients should consult their providers because not all may react well to increased inhaler use.
He also highlighted a significant shift in the healthcare landscape, noting that traditionally, the focus has been on the cardiovascular impacts of pollution, particularly traffic-related pollution. However, as wildfire smoke becomes a growing issue, the focus is shifting back to respiratory problems, with profound implications for healthcare resources, budgets, and drug approvals based on the burden of respiratory disease. “Fire smoke is becoming more of a problem. This swing back to respiratory has huge implications for healthcare systems and respiratory disease burden.”
Mr. Sacks and Dr. Carlsten reported no relevant financial relationships. The study presented by Dr. Tonne received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No. 101057131.
A version of this article first appeared on Medscape.com.
Wildfire-related air pollution in Europe kills more than non-wildfire air pollution. As climate change exacerbates the frequency and violence of wildfires, researchers are studying the health implications of mitigation methods such as prescribed fires.
Presenting at the annual congress of the European Respiratory Society (ERS), Cathryn Tonne, PhD, an environmental epidemiologist at the Instituto de Salud Global de Barcelona, Spain, said wildfire-related PM2.5 is more toxic than general PM2.5, leading to significantly higher mortality rates.
Prescribed, controlled fires have been employed worldwide to reduce the chance of uncontrolled, catastrophic fires. However, researchers wonder whether the techniques reduce the overall fire-related PM2.5 or add up to it. “Prescribed fire increases ecosystem resilience and can reduce the risk of catastrophic wildfire,” said Jason Sacks, MPH, an epidemiologist in the Center for Public Health and Environmental Assessment in the Office of Research and Development at the Environmental Protection Agency (EPA), at the congress. “But it also leads to poorer air quality and health impacts, and we still don’t know what this means at a regional scale.”
Wildfire Pollution Kills More Than Other Air Pollution
Researchers at the Instituto de Salud Global de Barcelona used a large dataset of daily mortality data from 32 European countries collected through the EARLY-ADAPT project. They utilized the SILAM model to derive daily average concentrations of wildfire-related PM2.5, non-fire PM2.5, and total PM2.5 levels. They also employed GEOSTAT population grids at a 1-km resolution to calculate the attributable number of deaths across different regions, specifically focusing on data from 2006, 2011, and 2018.
The data analysis indicated that the relative risk per unit of PM2.5 is substantially larger for wildfire-related PM2.5, compared with non-fire PM2.5. “We essentially assume that wildfire smoke PM2.5 has the same toxicity as total PM2.5, but it’s increasingly clear that’s likely not the case,” Dr. Tonne said, presenting the study.
When employing exposure-response functions (ERFs) specific to wildfire smoke, researchers found that the attributable deaths from all causes of wildfire PM2.5 were approximately 10 times larger than those calculated using total PM2.5 exposure estimates. Dr. Tonne explained that this stark difference highlights the critical need for tailored ERFs that accurately reflect the unique health risks posed by wildfire smoke.
“Respiratory mortality usually has the strongest relative risks, and we’re seeing that in this study as well,” Dr. Tonne said. “Wildfire smoke seems to operate through quite immediate mechanisms, likely through inflammation and oxidative stress.”
One significant challenge of the study was the lack of uniform spatial resolution across all countries involved in the analysis. This inconsistency may affect how accurately mortality estimates can be attributed to specific PM2.5 sources. Additionally, the study had limited statistical power for generating age- and sex-specific mortality estimates, which could obscure important demographic differences in vulnerability to wildfire smoke exposure. The analysis was also constrained to data available only up to 2020, thereby excluding critical wildfire events from subsequent years, such as those in 2022 and 2023, which may have further elucidated the health impacts of wildfire smoke in Europe.
Fires Prescription
Prescribed fires or controlled burns are intentional fires set by land managers under carefully managed conditions.
Historically, many forested areas have been subjected to fire suppression practices, which allow combustible materials like dry leaves, twigs, and shrubs to accumulate over time. This buildup leads to a higher likelihood of severe, uncontrollable wildfires. Prescribed fires can reduce these fuel loads and improve the health and resilience of ecosystems.
They release fewer pollutants and emissions than the large-scale, unmanageable wildfires they help prevent because they happen at lower temperatures. But they still introduce pollutants in the air that can negatively affect nearby communities’ health.
People with preexisting respiratory conditions, such as asthma or chronic obstructive pulmonary disease (COPD), are particularly vulnerable to smoke, which can trigger health issues like breathing difficulties, coughing, and eye irritation. The cumulative impact of increased burns raises concerns about long-term air quality, especially in densely populated areas. “We need to understand if we’re actually tipping the scale to having less wildfire smoke or just increasing the total amount of smoke.”
Mitigation strategies include accurately picking the right timing and weather conditions to determine when and where to conduct controlled burns and effective and timely communication to inform local communities about upcoming burns, the potential for smoke exposure, and how to protect themselves.
There is a growing need to improve public messaging around prescribed fires, Mr. Sacks said, because often the message communicated is oversimplified, such as “there will be smoke, but don’t worry. But that’s not the message we want to convey, especially for people with asthma or COPD.”
Instead, he said public health agencies should provide clearer, science-based guidance on the risks for smoke exposure and practical steps people can take to reduce their risk.
What Can Doctors Do?
Chris Carlsten, MD, director of the Centre for Lung Health and professor and head of the Respiratory Medicine Division at the University of British Columbia, Vancouver, Canada, told this news organization that determining whether an exacerbation of a respiratory condition is caused by fire exposure or other factors, such as viral infections, is complex because both can trigger similar responses and may complement each other. “It’s very difficult for any individual to know whether, when they’re having an exacerbation of asthma or COPD, that’s due to the fire,” he said. Fire smoke also increases infection risks, further complicating diagnosis.
Dr. Carlsten suggested that physicians could recommend preventative use of inhalers for at-risk patients when wildfires occur rather than waiting for symptoms to worsen. “That is a really interesting idea that could be practical.” Still, he advises caution, stressing that patients should consult their providers because not all may react well to increased inhaler use.
He also highlighted a significant shift in the healthcare landscape, noting that traditionally, the focus has been on the cardiovascular impacts of pollution, particularly traffic-related pollution. However, as wildfire smoke becomes a growing issue, the focus is shifting back to respiratory problems, with profound implications for healthcare resources, budgets, and drug approvals based on the burden of respiratory disease. “Fire smoke is becoming more of a problem. This swing back to respiratory has huge implications for healthcare systems and respiratory disease burden.”
Mr. Sacks and Dr. Carlsten reported no relevant financial relationships. The study presented by Dr. Tonne received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No. 101057131.
A version of this article first appeared on Medscape.com.
Wildfire-related air pollution in Europe kills more than non-wildfire air pollution. As climate change exacerbates the frequency and violence of wildfires, researchers are studying the health implications of mitigation methods such as prescribed fires.
Presenting at the annual congress of the European Respiratory Society (ERS), Cathryn Tonne, PhD, an environmental epidemiologist at the Instituto de Salud Global de Barcelona, Spain, said wildfire-related PM2.5 is more toxic than general PM2.5, leading to significantly higher mortality rates.
Prescribed, controlled fires have been employed worldwide to reduce the chance of uncontrolled, catastrophic fires. However, researchers wonder whether the techniques reduce the overall fire-related PM2.5 or add up to it. “Prescribed fire increases ecosystem resilience and can reduce the risk of catastrophic wildfire,” said Jason Sacks, MPH, an epidemiologist in the Center for Public Health and Environmental Assessment in the Office of Research and Development at the Environmental Protection Agency (EPA), at the congress. “But it also leads to poorer air quality and health impacts, and we still don’t know what this means at a regional scale.”
Wildfire Pollution Kills More Than Other Air Pollution
Researchers at the Instituto de Salud Global de Barcelona used a large dataset of daily mortality data from 32 European countries collected through the EARLY-ADAPT project. They utilized the SILAM model to derive daily average concentrations of wildfire-related PM2.5, non-fire PM2.5, and total PM2.5 levels. They also employed GEOSTAT population grids at a 1-km resolution to calculate the attributable number of deaths across different regions, specifically focusing on data from 2006, 2011, and 2018.
The data analysis indicated that the relative risk per unit of PM2.5 is substantially larger for wildfire-related PM2.5, compared with non-fire PM2.5. “We essentially assume that wildfire smoke PM2.5 has the same toxicity as total PM2.5, but it’s increasingly clear that’s likely not the case,” Dr. Tonne said, presenting the study.
When employing exposure-response functions (ERFs) specific to wildfire smoke, researchers found that the attributable deaths from all causes of wildfire PM2.5 were approximately 10 times larger than those calculated using total PM2.5 exposure estimates. Dr. Tonne explained that this stark difference highlights the critical need for tailored ERFs that accurately reflect the unique health risks posed by wildfire smoke.
“Respiratory mortality usually has the strongest relative risks, and we’re seeing that in this study as well,” Dr. Tonne said. “Wildfire smoke seems to operate through quite immediate mechanisms, likely through inflammation and oxidative stress.”
One significant challenge of the study was the lack of uniform spatial resolution across all countries involved in the analysis. This inconsistency may affect how accurately mortality estimates can be attributed to specific PM2.5 sources. Additionally, the study had limited statistical power for generating age- and sex-specific mortality estimates, which could obscure important demographic differences in vulnerability to wildfire smoke exposure. The analysis was also constrained to data available only up to 2020, thereby excluding critical wildfire events from subsequent years, such as those in 2022 and 2023, which may have further elucidated the health impacts of wildfire smoke in Europe.
Fires Prescription
Prescribed fires or controlled burns are intentional fires set by land managers under carefully managed conditions.
Historically, many forested areas have been subjected to fire suppression practices, which allow combustible materials like dry leaves, twigs, and shrubs to accumulate over time. This buildup leads to a higher likelihood of severe, uncontrollable wildfires. Prescribed fires can reduce these fuel loads and improve the health and resilience of ecosystems.
They release fewer pollutants and emissions than the large-scale, unmanageable wildfires they help prevent because they happen at lower temperatures. But they still introduce pollutants in the air that can negatively affect nearby communities’ health.
People with preexisting respiratory conditions, such as asthma or chronic obstructive pulmonary disease (COPD), are particularly vulnerable to smoke, which can trigger health issues like breathing difficulties, coughing, and eye irritation. The cumulative impact of increased burns raises concerns about long-term air quality, especially in densely populated areas. “We need to understand if we’re actually tipping the scale to having less wildfire smoke or just increasing the total amount of smoke.”
Mitigation strategies include accurately picking the right timing and weather conditions to determine when and where to conduct controlled burns and effective and timely communication to inform local communities about upcoming burns, the potential for smoke exposure, and how to protect themselves.
There is a growing need to improve public messaging around prescribed fires, Mr. Sacks said, because often the message communicated is oversimplified, such as “there will be smoke, but don’t worry. But that’s not the message we want to convey, especially for people with asthma or COPD.”
Instead, he said public health agencies should provide clearer, science-based guidance on the risks for smoke exposure and practical steps people can take to reduce their risk.
What Can Doctors Do?
Chris Carlsten, MD, director of the Centre for Lung Health and professor and head of the Respiratory Medicine Division at the University of British Columbia, Vancouver, Canada, told this news organization that determining whether an exacerbation of a respiratory condition is caused by fire exposure or other factors, such as viral infections, is complex because both can trigger similar responses and may complement each other. “It’s very difficult for any individual to know whether, when they’re having an exacerbation of asthma or COPD, that’s due to the fire,” he said. Fire smoke also increases infection risks, further complicating diagnosis.
Dr. Carlsten suggested that physicians could recommend preventative use of inhalers for at-risk patients when wildfires occur rather than waiting for symptoms to worsen. “That is a really interesting idea that could be practical.” Still, he advises caution, stressing that patients should consult their providers because not all may react well to increased inhaler use.
He also highlighted a significant shift in the healthcare landscape, noting that traditionally, the focus has been on the cardiovascular impacts of pollution, particularly traffic-related pollution. However, as wildfire smoke becomes a growing issue, the focus is shifting back to respiratory problems, with profound implications for healthcare resources, budgets, and drug approvals based on the burden of respiratory disease. “Fire smoke is becoming more of a problem. This swing back to respiratory has huge implications for healthcare systems and respiratory disease burden.”
Mr. Sacks and Dr. Carlsten reported no relevant financial relationships. The study presented by Dr. Tonne received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No. 101057131.
A version of this article first appeared on Medscape.com.
FROM ERS 2024
Caregiver Surveys on Firearms, Suicide Offer Pediatricians Prevention Opportunities
ORLANDO, FLORIDA — , according to researchers who presented their findings at the American Academy of Pediatrics (AAP) 2024 National Conference.
An estimated 4.6 million US homes with children have firearms that are loaded and unlocked, a risk factor for youth suicide, yet only about half of parents of suicidal children had been screened for gun ownership in the hospital even as most would be receptive to both firearm screening and counseling, found one study in Texas.
In another study in Colorado, nearly all firearm owners believed that securely storing guns reduces the risk for firearm injury or death, but owners were less likely than non-owners to believe suicide is preventable or that removing a gun from the home reduces the risk for injury or death.
“Previous studies have shown that when pediatricians discuss the importance of armed safe storage guidance with families, families are actually more likely to go home and store firearms safely — storing them locked, unloaded, and separate from the ammunition,” said study author Taylor Rosenbaum, MD, a former pediatric fellow at Baylor College of Medicine/Texas Children’s Hospital in Houston and now an assistant professor at Children’s Hospital University of Miami. “However, previous studies have also shown that pediatricians really are not discussing firearm safe storage with our patients and their families, and we see this both in the outpatient setting, but especially in the inpatient setting for youth suicides, which have risen since 2020 and now are the second leading cause of death for those who are 10-24 years old in the United States.”
Firearm Safety Is a Necessary Conversation
The leading cause of death among children and teens aged 1-19 years is actually firearms, which are also the most fatal method for suicide. While only 4% of all suicide attempts in youth are fatal, 90% of those attempted with a firearm are fatal, Dr. Rosenbaum said. In addition, she said, 80% of the guns used in attempted suicide by children and teens belonged to a family member, and an estimated 70% of firearm-related suicides in youth can be prevented with safe storage of guns.
“This really gives us, as pediatricians, something actionable to do during these hospitalizations” for suicidal ideation or attempts, Dr. Rosenbaum said. “We know that when pediatricians discuss the importance of firearm safe storage guidance with families, they’re more likely to store their firearm safely,” Dr. Rosenbaum said. “We also know that families are not being screened for firearm ownership, that caregivers of youth who are in the hospital for suicidal thoughts or actions want their healthcare team to be screening for firearms, to be giving them information on how to safely secure their firearms, and to be providing free firearm blocks.”
Nathan Boonstra, MD, a general pediatrician at Blank Children’s Hospital, Des Moines, Iowa, said these findings are encouraging in terms of the opportunity pediatricians have.
“There is so much politicization around even basic firearm safety that pediatricians might shy away from the topic, but this research is reassuring that parents are receptive to our advice on safe gun storage,” said Dr. Boonstra, who was not involved in any of this presented research. “It’s especially important for pediatricians to address home firearms when their patient has a history of suicidal ideation or an attempt.”
Reducing the Risk
The Colorado findings similarly reinforce the opportunity physicians have to help caregivers reduce suicide risk, according to Maya Haasz, MD, an associate professor of pediatrics and emergency medicine at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.
“Only 60% of firearm owners believed that removing firearms from the home in times of mental health crisis can decrease the risk of suicide,” she said. “These findings are really concerning, but what we found on the flip side was that 93% of firearm owners actually believe that secure storage can overall decrease the risk for firearm injury and death. So overall, we are underestimating the risk for suicide in our community, and we’re also underestimating our ability to prevent it.”
That presents an opportunity, Dr. Haasz said, “to educate families both about the preventability of suicide but also to have specific strategies, like secure storage and temporary removable requirements from the home, that can prevent suicide.”
Dr. Boonstra found it “disheartening that so many children live in a house with an unlocked and even loaded firearm when the evidence is so clear that this is a significant risk factor for youth suicide,” he said. “It’s also disheartening, though not too surprising, that families with a firearm are less likely to think that youth suicide can be prevented.”
Survey Results
Dr. Rosenbaum’s team conducted the survey in Houston with caregivers whose children were 8-21 years old and hospitalized for suicidal ideation or attempts at a large children’s hospital and two nearby community hospitals between June 2023 and May 2024. The respondents were 46% White and 23% Black, and 47% of the population were Hispanic, all but three of whom were not gun owners.
Among 244 potential participants, only 150 were eligible and approached, and 100 of these completed the surveys, including 26% firearm owners and 68% non-owners. Most of the youth (74%) were aged 14-17 years, and about three in four respondents were their mothers. Only half of the respondents (51%) said the healthcare provider had asked them whether they owned a gun.
One of the key findings Dr. Rosenbaum highlighted was the receptiveness of firearm-owning caregivers to advice from healthcare providers about ownership. If the healthcare team advised parents not to have any guns in the home for the safety of their child with self-arm, 58% of the firearm owners would follow the advice and 27% would consider it, with none saying they would be offended by it.
Among the firearm owners, 81% said their guns were safely secured where they did not believe their child could access it, which meant one in five youth had unsecured access to firearms. Most of the gun owners (77%), like the non-owners (70%), were “not at all worried” about their child getting ahold of a gun in the home, though 11.5% of the firearm owners were “very worried” about it. Interestingly, more gun owners (19%) were very worried about their children accessing a gun outside their home, a concern shared by 37% of non-owners. Nearly twice as many gun owners (46%) as non-owners (25%) were not at all worried about their child getting a gun outside the home.
The vast majority of respondents — 88% of gun owners and 91% of non-owners — felt it was “very important for the healthcare team to ask parents of children with suicidal ideation/attempts about firearms in the home.” Similarly, high proportions believed it was important for the healthcare team to counsel those parents on safe gun storage. Although only 69% of firearm owners believed it was important to distribute firearm locks in the hospital, 81% would be interested in receiving a free one. Significantly more of the non-owners (80%; P = .02) believed free lock distribution was important, and 72% of non-owners would also be interested in one.
About half the respondents (55%) preferred to hear firearm counseling one-on-one from a provider, whereas 31% would like written information and 27% would be interested in a video. In terms of what information parents preferred to receive, a little over half of owners (54%) and non-owners (56%) were interested in how or when (50% and 40%, respectively) to discuss the topic with their child. Only about a third (35% owners and 37% non-owners) wanted information on how to discuss the topic with the parents of their child’s friends.
The survey’s biggest limitations after its small size were the selection bias of those willing to complete the survey and potential response bias from the self-reported data.
The study of Colorado caregivers, just published in Pediatrics, surveyed 512 Colorado caregivers in April-May 2023 to learn about their beliefs and perceptions regarding firearms, firearm storage and risk, and youth suicide (2024 Oct 1;154[4]:e2024066930. doi: 10.1542/peds.2024-066930). Just over half the respondents (52%) had grown up in a household with firearms, and 44% currently lived in a household with a gun. The sample was 43% men and 88% White, predominantly non-Hispanic (75%), with 11% living in rural areas and 19% who currently or previously served in the military. Most (79%) had a child age 12 or younger in the home.
Only about one in four caregivers (24%) correctly answered that suicide is the leading cause of firearm death in Colorado, with similar rates of correct responses among both firearm owners and non-firearm owners. Both groups were also similarly likely (64% overall) to be concerned about youth suicide in their community, though those from homes with firearms were less likely to be concerned about youth suicide in their own family (28%) than those from homes without firearms (39%; P = .013).
In addition, caregivers from homes with versus without firearms were considerably less likely to believe suicide can be prevented (48% vs 69%) and were less likely to believe that temporarily removing a firearm from the home reduces the risk for gun injury or death (60% vs 78%; P < .001 for both comparisons).
Firearm owners were also much less likely than non-owners to believe keeping a gun in the home makes it more dangerous (7% vs 29%) and over twice as likely to think keeping a firearm makes their home safer (52% vs 22%; P < .001). The vast majority of respondents (89%) believed secure storage of guns reduces the risk for injury or death, though the response was higher for firearm owners (93%) than for non-owners (86%; P < .001).
“Our finding that most firearm owners believe that secure firearm storage is protective against firearm injury is a promising messaging strategy,” the authors wrote. “It presents a preventive education opportunity for adults living with children who have mental health concerns, who may benefit most from secure in-home storage and/or temporary and voluntary storage of firearms away from home.”
Firearm Injuries
A separate study at the AAP conference underscored the devastating impact of firearm injuries even among those who survive, whether self-inflicted or not, and the potential for reducing healthcare treatment and costs from effective prevention efforts. A national analysis of pediatric inpatient data from 2017 to 2020 calculated how much greater the burden of healthcare treatment and costs is for firearm injuries of any kind compared with penetrating traumas and blunt traumas.
“As a surgical resident, I have seen these patients who make it into the trauma bed that we are then faced to care for,” said Colleen Nofi, DO, PhD, MBA, a general surgery resident at Cohen Children’s Medical Center at Northwell Health in New York. “Anecdotally, we understand that the devastation and injury caused by bullets far outweighs the injuries caused by other trauma mechanisms,” but the actual calculation of the burden hasn’t been studied.
Among 6615 firearm injuries, 9787 penetrating traumas and 66,003 blunt traumas examined from the National Inpatient Sample Healthcare Cost and Utilization Project Database, 11% of firearm traumas required a transfusion of red blood cells, compared with 1.4% of penetrating traumas and 3% of blunt traumas (P < .001). Patients with firearm injuries also had a longer length of stay — 10.8 days compared with 8.3 for patients with penetrating trauma and 9.8 for those with blunt trauma — and significantly higher rates of CPR, pericardiotomy, chest tube, exploratory laparotomy and/or thoracotomy, colorectal surgery, small bowel surgery, ostomy formation, splenectomy, hepatic resection, tracheostomy, and feeding tube placement.
Pulmonary complications were higher for firearm injuries (4.9%) than for penetrating trauma (0.6%) or blunt trauma (2.9%), and septicemia rates were also higher (1.7% vs 0.2% and 1%, respectively). Cardiac, neurologic, and urinary complications were also significantly and substantially higher for firearm injuries, 6.9% of which resulted in death compared with 0.2% of penetrating traumas and 1.2% of blunt traumas.
The costs from firearm injuries were also significantly higher than the costs from other traumas; “firearm injury remained independently predictive of greater hospital costs, even when controlling for injury severity as well as age, sex, race, insurance, region, hospital type, and household income.
“These findings underscore the urgent need for targeted prevention, supportive measures, and resource allocation to mitigate the devastating impact of firearm injuries on children and healthcare systems alike,” Dr. Nofi said.
The Colorado study was funded by the Colorado Department of Public Health and Environment and a National Institutes of Health grant to Dr. Haasz. The Texas study and the one from Northwell Health did not note any external funding. Dr. Haasz, Dr. Rosenbaum, Dr. Boonstra, and Dr. Nofi had no disclosures.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — , according to researchers who presented their findings at the American Academy of Pediatrics (AAP) 2024 National Conference.
An estimated 4.6 million US homes with children have firearms that are loaded and unlocked, a risk factor for youth suicide, yet only about half of parents of suicidal children had been screened for gun ownership in the hospital even as most would be receptive to both firearm screening and counseling, found one study in Texas.
In another study in Colorado, nearly all firearm owners believed that securely storing guns reduces the risk for firearm injury or death, but owners were less likely than non-owners to believe suicide is preventable or that removing a gun from the home reduces the risk for injury or death.
“Previous studies have shown that when pediatricians discuss the importance of armed safe storage guidance with families, families are actually more likely to go home and store firearms safely — storing them locked, unloaded, and separate from the ammunition,” said study author Taylor Rosenbaum, MD, a former pediatric fellow at Baylor College of Medicine/Texas Children’s Hospital in Houston and now an assistant professor at Children’s Hospital University of Miami. “However, previous studies have also shown that pediatricians really are not discussing firearm safe storage with our patients and their families, and we see this both in the outpatient setting, but especially in the inpatient setting for youth suicides, which have risen since 2020 and now are the second leading cause of death for those who are 10-24 years old in the United States.”
Firearm Safety Is a Necessary Conversation
The leading cause of death among children and teens aged 1-19 years is actually firearms, which are also the most fatal method for suicide. While only 4% of all suicide attempts in youth are fatal, 90% of those attempted with a firearm are fatal, Dr. Rosenbaum said. In addition, she said, 80% of the guns used in attempted suicide by children and teens belonged to a family member, and an estimated 70% of firearm-related suicides in youth can be prevented with safe storage of guns.
“This really gives us, as pediatricians, something actionable to do during these hospitalizations” for suicidal ideation or attempts, Dr. Rosenbaum said. “We know that when pediatricians discuss the importance of firearm safe storage guidance with families, they’re more likely to store their firearm safely,” Dr. Rosenbaum said. “We also know that families are not being screened for firearm ownership, that caregivers of youth who are in the hospital for suicidal thoughts or actions want their healthcare team to be screening for firearms, to be giving them information on how to safely secure their firearms, and to be providing free firearm blocks.”
Nathan Boonstra, MD, a general pediatrician at Blank Children’s Hospital, Des Moines, Iowa, said these findings are encouraging in terms of the opportunity pediatricians have.
“There is so much politicization around even basic firearm safety that pediatricians might shy away from the topic, but this research is reassuring that parents are receptive to our advice on safe gun storage,” said Dr. Boonstra, who was not involved in any of this presented research. “It’s especially important for pediatricians to address home firearms when their patient has a history of suicidal ideation or an attempt.”
Reducing the Risk
The Colorado findings similarly reinforce the opportunity physicians have to help caregivers reduce suicide risk, according to Maya Haasz, MD, an associate professor of pediatrics and emergency medicine at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.
“Only 60% of firearm owners believed that removing firearms from the home in times of mental health crisis can decrease the risk of suicide,” she said. “These findings are really concerning, but what we found on the flip side was that 93% of firearm owners actually believe that secure storage can overall decrease the risk for firearm injury and death. So overall, we are underestimating the risk for suicide in our community, and we’re also underestimating our ability to prevent it.”
That presents an opportunity, Dr. Haasz said, “to educate families both about the preventability of suicide but also to have specific strategies, like secure storage and temporary removable requirements from the home, that can prevent suicide.”
Dr. Boonstra found it “disheartening that so many children live in a house with an unlocked and even loaded firearm when the evidence is so clear that this is a significant risk factor for youth suicide,” he said. “It’s also disheartening, though not too surprising, that families with a firearm are less likely to think that youth suicide can be prevented.”
Survey Results
Dr. Rosenbaum’s team conducted the survey in Houston with caregivers whose children were 8-21 years old and hospitalized for suicidal ideation or attempts at a large children’s hospital and two nearby community hospitals between June 2023 and May 2024. The respondents were 46% White and 23% Black, and 47% of the population were Hispanic, all but three of whom were not gun owners.
Among 244 potential participants, only 150 were eligible and approached, and 100 of these completed the surveys, including 26% firearm owners and 68% non-owners. Most of the youth (74%) were aged 14-17 years, and about three in four respondents were their mothers. Only half of the respondents (51%) said the healthcare provider had asked them whether they owned a gun.
One of the key findings Dr. Rosenbaum highlighted was the receptiveness of firearm-owning caregivers to advice from healthcare providers about ownership. If the healthcare team advised parents not to have any guns in the home for the safety of their child with self-arm, 58% of the firearm owners would follow the advice and 27% would consider it, with none saying they would be offended by it.
Among the firearm owners, 81% said their guns were safely secured where they did not believe their child could access it, which meant one in five youth had unsecured access to firearms. Most of the gun owners (77%), like the non-owners (70%), were “not at all worried” about their child getting ahold of a gun in the home, though 11.5% of the firearm owners were “very worried” about it. Interestingly, more gun owners (19%) were very worried about their children accessing a gun outside their home, a concern shared by 37% of non-owners. Nearly twice as many gun owners (46%) as non-owners (25%) were not at all worried about their child getting a gun outside the home.
The vast majority of respondents — 88% of gun owners and 91% of non-owners — felt it was “very important for the healthcare team to ask parents of children with suicidal ideation/attempts about firearms in the home.” Similarly, high proportions believed it was important for the healthcare team to counsel those parents on safe gun storage. Although only 69% of firearm owners believed it was important to distribute firearm locks in the hospital, 81% would be interested in receiving a free one. Significantly more of the non-owners (80%; P = .02) believed free lock distribution was important, and 72% of non-owners would also be interested in one.
About half the respondents (55%) preferred to hear firearm counseling one-on-one from a provider, whereas 31% would like written information and 27% would be interested in a video. In terms of what information parents preferred to receive, a little over half of owners (54%) and non-owners (56%) were interested in how or when (50% and 40%, respectively) to discuss the topic with their child. Only about a third (35% owners and 37% non-owners) wanted information on how to discuss the topic with the parents of their child’s friends.
The survey’s biggest limitations after its small size were the selection bias of those willing to complete the survey and potential response bias from the self-reported data.
The study of Colorado caregivers, just published in Pediatrics, surveyed 512 Colorado caregivers in April-May 2023 to learn about their beliefs and perceptions regarding firearms, firearm storage and risk, and youth suicide (2024 Oct 1;154[4]:e2024066930. doi: 10.1542/peds.2024-066930). Just over half the respondents (52%) had grown up in a household with firearms, and 44% currently lived in a household with a gun. The sample was 43% men and 88% White, predominantly non-Hispanic (75%), with 11% living in rural areas and 19% who currently or previously served in the military. Most (79%) had a child age 12 or younger in the home.
Only about one in four caregivers (24%) correctly answered that suicide is the leading cause of firearm death in Colorado, with similar rates of correct responses among both firearm owners and non-firearm owners. Both groups were also similarly likely (64% overall) to be concerned about youth suicide in their community, though those from homes with firearms were less likely to be concerned about youth suicide in their own family (28%) than those from homes without firearms (39%; P = .013).
In addition, caregivers from homes with versus without firearms were considerably less likely to believe suicide can be prevented (48% vs 69%) and were less likely to believe that temporarily removing a firearm from the home reduces the risk for gun injury or death (60% vs 78%; P < .001 for both comparisons).
Firearm owners were also much less likely than non-owners to believe keeping a gun in the home makes it more dangerous (7% vs 29%) and over twice as likely to think keeping a firearm makes their home safer (52% vs 22%; P < .001). The vast majority of respondents (89%) believed secure storage of guns reduces the risk for injury or death, though the response was higher for firearm owners (93%) than for non-owners (86%; P < .001).
“Our finding that most firearm owners believe that secure firearm storage is protective against firearm injury is a promising messaging strategy,” the authors wrote. “It presents a preventive education opportunity for adults living with children who have mental health concerns, who may benefit most from secure in-home storage and/or temporary and voluntary storage of firearms away from home.”
Firearm Injuries
A separate study at the AAP conference underscored the devastating impact of firearm injuries even among those who survive, whether self-inflicted or not, and the potential for reducing healthcare treatment and costs from effective prevention efforts. A national analysis of pediatric inpatient data from 2017 to 2020 calculated how much greater the burden of healthcare treatment and costs is for firearm injuries of any kind compared with penetrating traumas and blunt traumas.
“As a surgical resident, I have seen these patients who make it into the trauma bed that we are then faced to care for,” said Colleen Nofi, DO, PhD, MBA, a general surgery resident at Cohen Children’s Medical Center at Northwell Health in New York. “Anecdotally, we understand that the devastation and injury caused by bullets far outweighs the injuries caused by other trauma mechanisms,” but the actual calculation of the burden hasn’t been studied.
Among 6615 firearm injuries, 9787 penetrating traumas and 66,003 blunt traumas examined from the National Inpatient Sample Healthcare Cost and Utilization Project Database, 11% of firearm traumas required a transfusion of red blood cells, compared with 1.4% of penetrating traumas and 3% of blunt traumas (P < .001). Patients with firearm injuries also had a longer length of stay — 10.8 days compared with 8.3 for patients with penetrating trauma and 9.8 for those with blunt trauma — and significantly higher rates of CPR, pericardiotomy, chest tube, exploratory laparotomy and/or thoracotomy, colorectal surgery, small bowel surgery, ostomy formation, splenectomy, hepatic resection, tracheostomy, and feeding tube placement.
Pulmonary complications were higher for firearm injuries (4.9%) than for penetrating trauma (0.6%) or blunt trauma (2.9%), and septicemia rates were also higher (1.7% vs 0.2% and 1%, respectively). Cardiac, neurologic, and urinary complications were also significantly and substantially higher for firearm injuries, 6.9% of which resulted in death compared with 0.2% of penetrating traumas and 1.2% of blunt traumas.
The costs from firearm injuries were also significantly higher than the costs from other traumas; “firearm injury remained independently predictive of greater hospital costs, even when controlling for injury severity as well as age, sex, race, insurance, region, hospital type, and household income.
“These findings underscore the urgent need for targeted prevention, supportive measures, and resource allocation to mitigate the devastating impact of firearm injuries on children and healthcare systems alike,” Dr. Nofi said.
The Colorado study was funded by the Colorado Department of Public Health and Environment and a National Institutes of Health grant to Dr. Haasz. The Texas study and the one from Northwell Health did not note any external funding. Dr. Haasz, Dr. Rosenbaum, Dr. Boonstra, and Dr. Nofi had no disclosures.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — , according to researchers who presented their findings at the American Academy of Pediatrics (AAP) 2024 National Conference.
An estimated 4.6 million US homes with children have firearms that are loaded and unlocked, a risk factor for youth suicide, yet only about half of parents of suicidal children had been screened for gun ownership in the hospital even as most would be receptive to both firearm screening and counseling, found one study in Texas.
In another study in Colorado, nearly all firearm owners believed that securely storing guns reduces the risk for firearm injury or death, but owners were less likely than non-owners to believe suicide is preventable or that removing a gun from the home reduces the risk for injury or death.
“Previous studies have shown that when pediatricians discuss the importance of armed safe storage guidance with families, families are actually more likely to go home and store firearms safely — storing them locked, unloaded, and separate from the ammunition,” said study author Taylor Rosenbaum, MD, a former pediatric fellow at Baylor College of Medicine/Texas Children’s Hospital in Houston and now an assistant professor at Children’s Hospital University of Miami. “However, previous studies have also shown that pediatricians really are not discussing firearm safe storage with our patients and their families, and we see this both in the outpatient setting, but especially in the inpatient setting for youth suicides, which have risen since 2020 and now are the second leading cause of death for those who are 10-24 years old in the United States.”
Firearm Safety Is a Necessary Conversation
The leading cause of death among children and teens aged 1-19 years is actually firearms, which are also the most fatal method for suicide. While only 4% of all suicide attempts in youth are fatal, 90% of those attempted with a firearm are fatal, Dr. Rosenbaum said. In addition, she said, 80% of the guns used in attempted suicide by children and teens belonged to a family member, and an estimated 70% of firearm-related suicides in youth can be prevented with safe storage of guns.
“This really gives us, as pediatricians, something actionable to do during these hospitalizations” for suicidal ideation or attempts, Dr. Rosenbaum said. “We know that when pediatricians discuss the importance of firearm safe storage guidance with families, they’re more likely to store their firearm safely,” Dr. Rosenbaum said. “We also know that families are not being screened for firearm ownership, that caregivers of youth who are in the hospital for suicidal thoughts or actions want their healthcare team to be screening for firearms, to be giving them information on how to safely secure their firearms, and to be providing free firearm blocks.”
Nathan Boonstra, MD, a general pediatrician at Blank Children’s Hospital, Des Moines, Iowa, said these findings are encouraging in terms of the opportunity pediatricians have.
“There is so much politicization around even basic firearm safety that pediatricians might shy away from the topic, but this research is reassuring that parents are receptive to our advice on safe gun storage,” said Dr. Boonstra, who was not involved in any of this presented research. “It’s especially important for pediatricians to address home firearms when their patient has a history of suicidal ideation or an attempt.”
Reducing the Risk
The Colorado findings similarly reinforce the opportunity physicians have to help caregivers reduce suicide risk, according to Maya Haasz, MD, an associate professor of pediatrics and emergency medicine at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.
“Only 60% of firearm owners believed that removing firearms from the home in times of mental health crisis can decrease the risk of suicide,” she said. “These findings are really concerning, but what we found on the flip side was that 93% of firearm owners actually believe that secure storage can overall decrease the risk for firearm injury and death. So overall, we are underestimating the risk for suicide in our community, and we’re also underestimating our ability to prevent it.”
That presents an opportunity, Dr. Haasz said, “to educate families both about the preventability of suicide but also to have specific strategies, like secure storage and temporary removable requirements from the home, that can prevent suicide.”
Dr. Boonstra found it “disheartening that so many children live in a house with an unlocked and even loaded firearm when the evidence is so clear that this is a significant risk factor for youth suicide,” he said. “It’s also disheartening, though not too surprising, that families with a firearm are less likely to think that youth suicide can be prevented.”
Survey Results
Dr. Rosenbaum’s team conducted the survey in Houston with caregivers whose children were 8-21 years old and hospitalized for suicidal ideation or attempts at a large children’s hospital and two nearby community hospitals between June 2023 and May 2024. The respondents were 46% White and 23% Black, and 47% of the population were Hispanic, all but three of whom were not gun owners.
Among 244 potential participants, only 150 were eligible and approached, and 100 of these completed the surveys, including 26% firearm owners and 68% non-owners. Most of the youth (74%) were aged 14-17 years, and about three in four respondents were their mothers. Only half of the respondents (51%) said the healthcare provider had asked them whether they owned a gun.
One of the key findings Dr. Rosenbaum highlighted was the receptiveness of firearm-owning caregivers to advice from healthcare providers about ownership. If the healthcare team advised parents not to have any guns in the home for the safety of their child with self-arm, 58% of the firearm owners would follow the advice and 27% would consider it, with none saying they would be offended by it.
Among the firearm owners, 81% said their guns were safely secured where they did not believe their child could access it, which meant one in five youth had unsecured access to firearms. Most of the gun owners (77%), like the non-owners (70%), were “not at all worried” about their child getting ahold of a gun in the home, though 11.5% of the firearm owners were “very worried” about it. Interestingly, more gun owners (19%) were very worried about their children accessing a gun outside their home, a concern shared by 37% of non-owners. Nearly twice as many gun owners (46%) as non-owners (25%) were not at all worried about their child getting a gun outside the home.
The vast majority of respondents — 88% of gun owners and 91% of non-owners — felt it was “very important for the healthcare team to ask parents of children with suicidal ideation/attempts about firearms in the home.” Similarly, high proportions believed it was important for the healthcare team to counsel those parents on safe gun storage. Although only 69% of firearm owners believed it was important to distribute firearm locks in the hospital, 81% would be interested in receiving a free one. Significantly more of the non-owners (80%; P = .02) believed free lock distribution was important, and 72% of non-owners would also be interested in one.
About half the respondents (55%) preferred to hear firearm counseling one-on-one from a provider, whereas 31% would like written information and 27% would be interested in a video. In terms of what information parents preferred to receive, a little over half of owners (54%) and non-owners (56%) were interested in how or when (50% and 40%, respectively) to discuss the topic with their child. Only about a third (35% owners and 37% non-owners) wanted information on how to discuss the topic with the parents of their child’s friends.
The survey’s biggest limitations after its small size were the selection bias of those willing to complete the survey and potential response bias from the self-reported data.
The study of Colorado caregivers, just published in Pediatrics, surveyed 512 Colorado caregivers in April-May 2023 to learn about their beliefs and perceptions regarding firearms, firearm storage and risk, and youth suicide (2024 Oct 1;154[4]:e2024066930. doi: 10.1542/peds.2024-066930). Just over half the respondents (52%) had grown up in a household with firearms, and 44% currently lived in a household with a gun. The sample was 43% men and 88% White, predominantly non-Hispanic (75%), with 11% living in rural areas and 19% who currently or previously served in the military. Most (79%) had a child age 12 or younger in the home.
Only about one in four caregivers (24%) correctly answered that suicide is the leading cause of firearm death in Colorado, with similar rates of correct responses among both firearm owners and non-firearm owners. Both groups were also similarly likely (64% overall) to be concerned about youth suicide in their community, though those from homes with firearms were less likely to be concerned about youth suicide in their own family (28%) than those from homes without firearms (39%; P = .013).
In addition, caregivers from homes with versus without firearms were considerably less likely to believe suicide can be prevented (48% vs 69%) and were less likely to believe that temporarily removing a firearm from the home reduces the risk for gun injury or death (60% vs 78%; P < .001 for both comparisons).
Firearm owners were also much less likely than non-owners to believe keeping a gun in the home makes it more dangerous (7% vs 29%) and over twice as likely to think keeping a firearm makes their home safer (52% vs 22%; P < .001). The vast majority of respondents (89%) believed secure storage of guns reduces the risk for injury or death, though the response was higher for firearm owners (93%) than for non-owners (86%; P < .001).
“Our finding that most firearm owners believe that secure firearm storage is protective against firearm injury is a promising messaging strategy,” the authors wrote. “It presents a preventive education opportunity for adults living with children who have mental health concerns, who may benefit most from secure in-home storage and/or temporary and voluntary storage of firearms away from home.”
Firearm Injuries
A separate study at the AAP conference underscored the devastating impact of firearm injuries even among those who survive, whether self-inflicted or not, and the potential for reducing healthcare treatment and costs from effective prevention efforts. A national analysis of pediatric inpatient data from 2017 to 2020 calculated how much greater the burden of healthcare treatment and costs is for firearm injuries of any kind compared with penetrating traumas and blunt traumas.
“As a surgical resident, I have seen these patients who make it into the trauma bed that we are then faced to care for,” said Colleen Nofi, DO, PhD, MBA, a general surgery resident at Cohen Children’s Medical Center at Northwell Health in New York. “Anecdotally, we understand that the devastation and injury caused by bullets far outweighs the injuries caused by other trauma mechanisms,” but the actual calculation of the burden hasn’t been studied.
Among 6615 firearm injuries, 9787 penetrating traumas and 66,003 blunt traumas examined from the National Inpatient Sample Healthcare Cost and Utilization Project Database, 11% of firearm traumas required a transfusion of red blood cells, compared with 1.4% of penetrating traumas and 3% of blunt traumas (P < .001). Patients with firearm injuries also had a longer length of stay — 10.8 days compared with 8.3 for patients with penetrating trauma and 9.8 for those with blunt trauma — and significantly higher rates of CPR, pericardiotomy, chest tube, exploratory laparotomy and/or thoracotomy, colorectal surgery, small bowel surgery, ostomy formation, splenectomy, hepatic resection, tracheostomy, and feeding tube placement.
Pulmonary complications were higher for firearm injuries (4.9%) than for penetrating trauma (0.6%) or blunt trauma (2.9%), and septicemia rates were also higher (1.7% vs 0.2% and 1%, respectively). Cardiac, neurologic, and urinary complications were also significantly and substantially higher for firearm injuries, 6.9% of which resulted in death compared with 0.2% of penetrating traumas and 1.2% of blunt traumas.
The costs from firearm injuries were also significantly higher than the costs from other traumas; “firearm injury remained independently predictive of greater hospital costs, even when controlling for injury severity as well as age, sex, race, insurance, region, hospital type, and household income.
“These findings underscore the urgent need for targeted prevention, supportive measures, and resource allocation to mitigate the devastating impact of firearm injuries on children and healthcare systems alike,” Dr. Nofi said.
The Colorado study was funded by the Colorado Department of Public Health and Environment and a National Institutes of Health grant to Dr. Haasz. The Texas study and the one from Northwell Health did not note any external funding. Dr. Haasz, Dr. Rosenbaum, Dr. Boonstra, and Dr. Nofi had no disclosures.
A version of this article appeared on Medscape.com.
From AAP 2024
Detecting Type 2 Diabetes Through Voice: How Does It Work?
An international study, Colive Voice, presented at the European Association for the Study of Diabetes (EASD) 2024 conference, shows that These results “open up possibilities for developing a first-line, noninvasive, and rapid screening tool for T2D, feasible with just a few seconds of voice recording on a smartphone or during consultations,” explained the study’s principal investigator Guy Fagherazzi, PhD, a diabetes epidemiologist at the Luxembourg Institute of Health, in an interview with this news organization.
How did the idea of detecting diabetes through voice come about?
During the COVID-19 pandemic, we began analyzing voice recordings from patients with chronic diseases. We wanted to find solutions to assess people’s health remotely, without physical contact. We quickly realized that this approach could be extended to other diseases. Because my main research focus has always been diabetes, I looked into how voice characteristics might correlate with diabetes. Previous studies had indicated that patients with diabetes have distinct voices compared with the general population, and this insight formed the starting point.
What mechanism could explain why patients with T2D have different voice characteristics?
It’s challenging to pinpoint a single factor that would explain why patients with T2D have different voices from those without diabetes. Several factors are involved.
Some biological mechanisms, especially those affecting the vascular system, influence symptoms in people with metabolic diseases such as diabetes. For example, people with T2D have more frequent cardiorespiratory fatigue. Obesity and overweight are also key factors, as these conditions can slightly alter vocal parameters compared with people of normal weight. Hypertension, common in patients with T2D, adds to the complexity.
Neurologic complications can affect the nerves and muscles involved in voice production, particularly the vocal cords.
Therefore, respiratory fatigue, neuropathies, and other conditions such as dehydration and gastric acid reflux, which are more common in patients with diabetes, can contribute to differences in voice.
These differences might not be noticeable to the human ear. That’s why we often don’t notice the link between voice and diabetes. However, technological advancements in signal processing and artificial intelligence allow us to extract a large amount of information from these subtle variations. By analyzing these small differences, we can detect diabetes with a reasonable degree of accuracy.
In your study, you mention that voice tone can indicate diabetic status. Could you elaborate?
Yes, voice tone can be affected, though it’s a complex, multidimensional phenomenon.
Patients who have had diabetes for 5-10 years, or longer, tend to have a rougher voice than those without diabetes of the same age and gender. In our study, we were able to extract many voice characteristics from the raw audio signal, which is why it’s difficult to isolate one specific factor that stands out.
Is there a difference in voice changes between patients with well-managed diabetes and those whose disease is uncontrolled?
The roughness of the voice tends to increase with the duration of diabetes. It’s more noticeable in people with poorly controlled diabetes. Our hypothesis, based on the results we presented at the EASD conference, is that fluctuations in blood sugar levels, both hypo- and hyperglycemia, may cause short-term changes in the voice. There are also many subtle, rapid changes that could potentially be detected, though we haven’t confirmed this yet. We’re currently conducting additional studies to explore this.
Why did you ask participants to read a passage from the Universal Declaration of Human Rights?
We used a highly standardized approach. Participants completed several recordings, including holding the sound “Aaaaaa” for as long as possible in one breath. They also read a passage, which helps us better distinguish between patients with and those without diabetes. This method works slightly better than other sounds typically used for analyzing diseases. We chose this particular text in the participant’s native language because it’s neutral and doesn’t trigger emotional fluctuations. Because Colive Voice is an international, multilingual study, we use official translations in various languages.
Your research focuses on T2D. Do you plan to study type 1 diabetes (T1D) as well?
We believe that individuals with T1D also exhibit voice changes over time. However, our current focus is on T2D because our goal is to develop large-scale screening methods. T1D, typically diagnosed in childhood, requires different screening approaches. For now, our research mainly involves adults.
Were there any gender differences in the accuracy of your voice analysis?
Yes, voice studies generally show that women have different vocal signatures from men, partly owing to hormonal fluctuations that affect pitch and tone. Detecting differences between healthy individuals and those with diabetes can sometimes be more challenging in women, depending on the condition. In our study, we achieved about 70% accuracy for women compared with 75% for men.
The EASD results focused on a US-based population. When can we expect data from France?
We started with the US because we could quickly gather a large number of patients. Now, we’re expanding to global and language-specific analyses. French data are certainly a priority, and we’re working on it. We encourage people to participate — it takes only 20 minutes and contributes to innovative research on noninvasive diabetes detection. Participants can sign up at www.colivevoice.org
Dr. Fagherazzi heads the Deep Digital Phenotyping laboratory and the Department of Precision Health at the Luxembourg Institute of Health. His research focuses on integrating new technologies and digital data into diabetes research. He has declared no relevant financial relationships.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
An international study, Colive Voice, presented at the European Association for the Study of Diabetes (EASD) 2024 conference, shows that These results “open up possibilities for developing a first-line, noninvasive, and rapid screening tool for T2D, feasible with just a few seconds of voice recording on a smartphone or during consultations,” explained the study’s principal investigator Guy Fagherazzi, PhD, a diabetes epidemiologist at the Luxembourg Institute of Health, in an interview with this news organization.
How did the idea of detecting diabetes through voice come about?
During the COVID-19 pandemic, we began analyzing voice recordings from patients with chronic diseases. We wanted to find solutions to assess people’s health remotely, without physical contact. We quickly realized that this approach could be extended to other diseases. Because my main research focus has always been diabetes, I looked into how voice characteristics might correlate with diabetes. Previous studies had indicated that patients with diabetes have distinct voices compared with the general population, and this insight formed the starting point.
What mechanism could explain why patients with T2D have different voice characteristics?
It’s challenging to pinpoint a single factor that would explain why patients with T2D have different voices from those without diabetes. Several factors are involved.
Some biological mechanisms, especially those affecting the vascular system, influence symptoms in people with metabolic diseases such as diabetes. For example, people with T2D have more frequent cardiorespiratory fatigue. Obesity and overweight are also key factors, as these conditions can slightly alter vocal parameters compared with people of normal weight. Hypertension, common in patients with T2D, adds to the complexity.
Neurologic complications can affect the nerves and muscles involved in voice production, particularly the vocal cords.
Therefore, respiratory fatigue, neuropathies, and other conditions such as dehydration and gastric acid reflux, which are more common in patients with diabetes, can contribute to differences in voice.
These differences might not be noticeable to the human ear. That’s why we often don’t notice the link between voice and diabetes. However, technological advancements in signal processing and artificial intelligence allow us to extract a large amount of information from these subtle variations. By analyzing these small differences, we can detect diabetes with a reasonable degree of accuracy.
In your study, you mention that voice tone can indicate diabetic status. Could you elaborate?
Yes, voice tone can be affected, though it’s a complex, multidimensional phenomenon.
Patients who have had diabetes for 5-10 years, or longer, tend to have a rougher voice than those without diabetes of the same age and gender. In our study, we were able to extract many voice characteristics from the raw audio signal, which is why it’s difficult to isolate one specific factor that stands out.
Is there a difference in voice changes between patients with well-managed diabetes and those whose disease is uncontrolled?
The roughness of the voice tends to increase with the duration of diabetes. It’s more noticeable in people with poorly controlled diabetes. Our hypothesis, based on the results we presented at the EASD conference, is that fluctuations in blood sugar levels, both hypo- and hyperglycemia, may cause short-term changes in the voice. There are also many subtle, rapid changes that could potentially be detected, though we haven’t confirmed this yet. We’re currently conducting additional studies to explore this.
Why did you ask participants to read a passage from the Universal Declaration of Human Rights?
We used a highly standardized approach. Participants completed several recordings, including holding the sound “Aaaaaa” for as long as possible in one breath. They also read a passage, which helps us better distinguish between patients with and those without diabetes. This method works slightly better than other sounds typically used for analyzing diseases. We chose this particular text in the participant’s native language because it’s neutral and doesn’t trigger emotional fluctuations. Because Colive Voice is an international, multilingual study, we use official translations in various languages.
Your research focuses on T2D. Do you plan to study type 1 diabetes (T1D) as well?
We believe that individuals with T1D also exhibit voice changes over time. However, our current focus is on T2D because our goal is to develop large-scale screening methods. T1D, typically diagnosed in childhood, requires different screening approaches. For now, our research mainly involves adults.
Were there any gender differences in the accuracy of your voice analysis?
Yes, voice studies generally show that women have different vocal signatures from men, partly owing to hormonal fluctuations that affect pitch and tone. Detecting differences between healthy individuals and those with diabetes can sometimes be more challenging in women, depending on the condition. In our study, we achieved about 70% accuracy for women compared with 75% for men.
The EASD results focused on a US-based population. When can we expect data from France?
We started with the US because we could quickly gather a large number of patients. Now, we’re expanding to global and language-specific analyses. French data are certainly a priority, and we’re working on it. We encourage people to participate — it takes only 20 minutes and contributes to innovative research on noninvasive diabetes detection. Participants can sign up at www.colivevoice.org
Dr. Fagherazzi heads the Deep Digital Phenotyping laboratory and the Department of Precision Health at the Luxembourg Institute of Health. His research focuses on integrating new technologies and digital data into diabetes research. He has declared no relevant financial relationships.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
An international study, Colive Voice, presented at the European Association for the Study of Diabetes (EASD) 2024 conference, shows that These results “open up possibilities for developing a first-line, noninvasive, and rapid screening tool for T2D, feasible with just a few seconds of voice recording on a smartphone or during consultations,” explained the study’s principal investigator Guy Fagherazzi, PhD, a diabetes epidemiologist at the Luxembourg Institute of Health, in an interview with this news organization.
How did the idea of detecting diabetes through voice come about?
During the COVID-19 pandemic, we began analyzing voice recordings from patients with chronic diseases. We wanted to find solutions to assess people’s health remotely, without physical contact. We quickly realized that this approach could be extended to other diseases. Because my main research focus has always been diabetes, I looked into how voice characteristics might correlate with diabetes. Previous studies had indicated that patients with diabetes have distinct voices compared with the general population, and this insight formed the starting point.
What mechanism could explain why patients with T2D have different voice characteristics?
It’s challenging to pinpoint a single factor that would explain why patients with T2D have different voices from those without diabetes. Several factors are involved.
Some biological mechanisms, especially those affecting the vascular system, influence symptoms in people with metabolic diseases such as diabetes. For example, people with T2D have more frequent cardiorespiratory fatigue. Obesity and overweight are also key factors, as these conditions can slightly alter vocal parameters compared with people of normal weight. Hypertension, common in patients with T2D, adds to the complexity.
Neurologic complications can affect the nerves and muscles involved in voice production, particularly the vocal cords.
Therefore, respiratory fatigue, neuropathies, and other conditions such as dehydration and gastric acid reflux, which are more common in patients with diabetes, can contribute to differences in voice.
These differences might not be noticeable to the human ear. That’s why we often don’t notice the link between voice and diabetes. However, technological advancements in signal processing and artificial intelligence allow us to extract a large amount of information from these subtle variations. By analyzing these small differences, we can detect diabetes with a reasonable degree of accuracy.
In your study, you mention that voice tone can indicate diabetic status. Could you elaborate?
Yes, voice tone can be affected, though it’s a complex, multidimensional phenomenon.
Patients who have had diabetes for 5-10 years, or longer, tend to have a rougher voice than those without diabetes of the same age and gender. In our study, we were able to extract many voice characteristics from the raw audio signal, which is why it’s difficult to isolate one specific factor that stands out.
Is there a difference in voice changes between patients with well-managed diabetes and those whose disease is uncontrolled?
The roughness of the voice tends to increase with the duration of diabetes. It’s more noticeable in people with poorly controlled diabetes. Our hypothesis, based on the results we presented at the EASD conference, is that fluctuations in blood sugar levels, both hypo- and hyperglycemia, may cause short-term changes in the voice. There are also many subtle, rapid changes that could potentially be detected, though we haven’t confirmed this yet. We’re currently conducting additional studies to explore this.
Why did you ask participants to read a passage from the Universal Declaration of Human Rights?
We used a highly standardized approach. Participants completed several recordings, including holding the sound “Aaaaaa” for as long as possible in one breath. They also read a passage, which helps us better distinguish between patients with and those without diabetes. This method works slightly better than other sounds typically used for analyzing diseases. We chose this particular text in the participant’s native language because it’s neutral and doesn’t trigger emotional fluctuations. Because Colive Voice is an international, multilingual study, we use official translations in various languages.
Your research focuses on T2D. Do you plan to study type 1 diabetes (T1D) as well?
We believe that individuals with T1D also exhibit voice changes over time. However, our current focus is on T2D because our goal is to develop large-scale screening methods. T1D, typically diagnosed in childhood, requires different screening approaches. For now, our research mainly involves adults.
Were there any gender differences in the accuracy of your voice analysis?
Yes, voice studies generally show that women have different vocal signatures from men, partly owing to hormonal fluctuations that affect pitch and tone. Detecting differences between healthy individuals and those with diabetes can sometimes be more challenging in women, depending on the condition. In our study, we achieved about 70% accuracy for women compared with 75% for men.
The EASD results focused on a US-based population. When can we expect data from France?
We started with the US because we could quickly gather a large number of patients. Now, we’re expanding to global and language-specific analyses. French data are certainly a priority, and we’re working on it. We encourage people to participate — it takes only 20 minutes and contributes to innovative research on noninvasive diabetes detection. Participants can sign up at www.colivevoice.org
Dr. Fagherazzi heads the Deep Digital Phenotyping laboratory and the Department of Precision Health at the Luxembourg Institute of Health. His research focuses on integrating new technologies and digital data into diabetes research. He has declared no relevant financial relationships.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
FROM EASD 2024
Which Medication Is Best? VA Genetic Tests May Have the Answer
The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.
The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.
Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”
The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.
For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.
Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.
Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.
In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine.
Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.
Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.
The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.
A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.
The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”
Bates reported that she had no disclosures.
The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.
The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.
Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”
The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.
For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.
Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.
Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.
In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine.
Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.
Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.
The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.
A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.
The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”
Bates reported that she had no disclosures.
The US Department of Veterans Affairs (VA) now has a permanent pharmacogenomics service that provides genetic tests to give clinicians insight into the best medication options for their patients.
The tests, which have no extra cost, are available to all veterans, said pharmacist Jill S. Bates, PharmD, MS, executive director of the VA National Pharmacogenomics Program, who spoke in an interview and a presentation at the annual meeting of the Association of VA Hematology/Oncology.
Genetic testing is “a tool that can help optimize care that we provide for veterans,” she said. “Pharmacogenomics is additional information to help the clinician make a decision. We know that most veterans—greater than 90%—carry a variant in a pharmacogenomics gene that is actionable.”
The genetic tests can provide insight into the optimal medication for multiple conditions such as mental illness, gastrointestinal disorders, cancer, pain, and heart disease. According to a 2019 analysis of over 6 years of data, more than half of the VA patient population used medications whose efficacy may have been affected by detectable genetic variants.
For instance, Bates said tests can let clinicians know whether patients are susceptible to statin-associated muscle adverse effects if they take simvastatin, the cholesterol medication. An estimated 25.6% of the VA population has this variant.
Elsewhere on the cardiac front, an estimated 58.3% of the VA population has a genetic variant that increases sensitivity to the blood thinner warfarin.
Testing could help psychiatrists determine whether certain medications should not be prescribed—or should be prescribed at lower doses—in patients who’ve had adverse reactions to antidepressants, Bates said.
In cancer, Bates said, genetic testing can identify patients who have a genetic variant that boosts toxicity from fluoropyrimidine chemotherapy treatments, which include capecitabine, floxuridine, and fluorouracil. Meanwhile, an estimated 0.9% will have no reaction or limited reaction to capecitabine and fluorouracil, and 4.8% will have hypersensitivity to carbamazepine and oxcarbazepine.
Tests can also identify a genetic variant that can lead to poor metabolism of the chemotherapy drug irinotecan, which is used to treat colon cancer. “In those patients, you’d want to reduce the dose by 20%,” Bates said. In other cases, alternate drugs may be the best strategy to address genetic variations.
Prior to 2019, clinicians had to order pharmacogenomic tests outside of the VA system, according to Bates. That year, a donation from Sanford Health brought VA pharmacogenomics to 40 pilot sites. Since then, more than 88,000 tests have been performed.
The VA has now made its pharmacogenomic program permanent, Bates said. As of early September, testing was available at 139 VA sites and is coming soon to 4 more. It’s not available at another 23 sites that are scattered across the country.
A tool in the VA electronic health record now reminds clinicians about the availability of genetic testing and allows them to order tests. However, testing isn’t available for patients who have had liver transplants or certain bone marrow transplants.
The VA is working on developing decision-making tools to help clinicians determine when the tests are appropriate, Bates said. It typically takes 2 to 3 weeks to get results, she said, adding that external laboratories provide results. “We eventually would like to bring in all pharmacogenomics testing to be conducted within the VA enterprise.”
Bates reported that she had no disclosures.