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T-ALL: Cranial Radiotherapy Yields Little Benefit
“Overall, comparison of these cohorts provides a strong indication that CRT provides minimal benefit to patients with CNS-3 disease at diagnosis,” first author Ajay Vora, MD, a consultant hematologist with Great Ormond Street Hospital, in London, and his colleagues report in a research letter published recently in Blood Advances.
“Given the high rates of neurocognitive impairment and secondary CNS malignancies, we believe strong consideration should be given to eliminating CRT in first-line treatment for all patients with T-ALL,” they wrote.
More aggressive than B-cell ALL, T-ALL is characterized by a higher likelihood of infiltration of the CNS at diagnosis, which increases the risk of relapse after treatment.
Until recently, treatment of T-ALL long entailed CNS-directed therapy using prophylactic CRT. Now, however, due to the risks of significant toxicity, including neurocognitive defects and secondary cancers, CRT is usually either omitted or limited to key subgroups, such as those with CNS-3 disease. As an alternative, intrathecal chemotherapy is used, the authors explain.
In a 2023 study evaluating the consecutive Children’s Oncology Group (COG) AALL0434 and AALL1231 phase 3 trials of 2,164 patients with T-ALL, patients with CNS-3 at diagnosis were found to have worse outcomes, compared with CNS-1 and 2.
Importantly, the outcomes in both of those two trials were similar, despite the use of CRT in more than 90% of patients in the AALL0434 trial--but in only 10% of patients AALL1231 trial (mainly those with CNS-3 and at high-risk). These outcomes suggested that CRT can safely be eliminated for CNS-1 and 2 patients.
With CRT used in both trials among patients with CNS-3, conclusions about eliminating CRT among those patients could not be drawn. However, with other large groups (including the Dutch Childhood Oncology Group), eliminating CRT in the frontline treatment of all patients with T-ALL, including those with CNS-3, is what Dr. Vora and colleagues sought to further investigate.
For the current study, they evaluated outcomes in the UKALL2003 and UKALL2011 trials conducted by the UK National Cancer Research Institute, in which CRT was eliminated for all patients — including those with CNS-3 — and compared them with the COG AALL0434 and AALL1231 trials.
In the UK trials, involving 665 patients with T-ALL aged 1 to 24, treatment included a dexamethasone-based backbone chemotherapy consisting of a 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation, interim maintenance, delayed intensification, and maintenance therapy, with the treatment stratified based on morphological early response and minimal residual disease at the end of induction.
While the UKALL2003 trial initially recommended CRT for patients with CNS-3, that practice ended in 2009, and CNS-directed therapy subsequently consisted of intrathecal methotrexate (MTX) at regular intervals throughout treatment. Additional weekly intrathecal MTX treatments were recommended throughout induction for patients with CNS-3.
In the UKALL2011 trial, the weekly intrathecal MTX treatments were recommended for patients with CNS-2, as well as CNS-3.
Overall, among those with CNS data available, 557 patients had CNS-1 (87.4%), 44 CNS-2 (6.9%), and 36 CNS-3 (5.7%).
For the outcomes of 4-year cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) in the combined cohort of the 2 UK trials, there were no significant differences between CNS-1, 2 or 3 groups.
Specifically, the mean rates of 4-year CIR in the CNS-1, 2, and 3 groups were 13.6%, 25.9% and 24.6%, respectively (P = .241); mean EFS rates were 82.9%, 74.1% and 77.8% (P = .623), and OS rates were 88.6%, 80.9% and 91.8%, (P = .453).
“Most importantly, outcomes are not significantly different for the patients with CNS-3, despite omission of CRT in the UK cohort,” the authors underscored.
Comparatively, in the cohort of the 2 COG trials, there were significant differences based on CNS status for 4-year CIR (P = .0002); EFS (P = .0004) and OS (P = .005).
The 4-year relapse rates among those with CNS-3 in the UK cohort were slightly higher compared with those in the COG cohort (24.6% UK vs 17.9%, COG). However, the difference did not translate to poorer long-term survival in the UK cohort (91.8% vs 82.7%, respectively).
Those findings are consistent with a previous meta-analysis that Dr. Vora and his colleagues conducted of more than 16,000 patients with mainly B-cell ALL, which showed that CRT reduced the risk of isolated and combined CNS relapse in patients with CNS-3. However, that risk had no impact on EFS and OS.
Of note, patients in the UK cohort with CNS-2 had worse outcomes compared with the COG group, with double the rate of relapse and lower EFS and OS. However, the authors speculate that factors including a lower proportion of patients with CNS-2 in the UK cohort and differences in methodologies may explain those different outcomes and may preclude their generalizability to other groups.
Overall, “these findings corroborate those of earlier studies that CRT has marginal, if any benefit, for any sub-group of ALL, especially as part of contemporary treatment,” Dr. Vora said in an interview.
In terms of therapies that do appear to make a difference in the treatment of CNS-3, Dr. Vora noted that the addition of nelarabine in the COG AALL0434 trial showed “remarkable benefit” in the CNS-3 group, with a 93.1% rate of disease-free survival in those patients versus 70.2% without nelarabine.
Importantly, those patients did also receive CRT. However, Dr. Vora and colleagues underscore that “the improvement is impressive and raises the question of whether nelarabine would have a similar beneficial effect in the absence of CRT.”
In an editorial published with the COG trials, Josep-Maria Ribera, MD, of the Josep Carreras Leukemia Research Institute, in Barcelona, Spain, agrees that “better approaches clearly are needed to treat CNS-3 T-ALL, especially if omission of CRT is a priority.”
Noting the improvements observed with nelarabine, as well as Capizzi escalating-dose methotrexate (C-MTX), and dexamethasone in reducing the risk of CNS relapse, he speculates that “it is possible that the additional use of C-MTX and induction dexamethasone could eliminate the need for CRT in these patients.”
The authors and Dr. Ribera had no disclosures to report.
“Overall, comparison of these cohorts provides a strong indication that CRT provides minimal benefit to patients with CNS-3 disease at diagnosis,” first author Ajay Vora, MD, a consultant hematologist with Great Ormond Street Hospital, in London, and his colleagues report in a research letter published recently in Blood Advances.
“Given the high rates of neurocognitive impairment and secondary CNS malignancies, we believe strong consideration should be given to eliminating CRT in first-line treatment for all patients with T-ALL,” they wrote.
More aggressive than B-cell ALL, T-ALL is characterized by a higher likelihood of infiltration of the CNS at diagnosis, which increases the risk of relapse after treatment.
Until recently, treatment of T-ALL long entailed CNS-directed therapy using prophylactic CRT. Now, however, due to the risks of significant toxicity, including neurocognitive defects and secondary cancers, CRT is usually either omitted or limited to key subgroups, such as those with CNS-3 disease. As an alternative, intrathecal chemotherapy is used, the authors explain.
In a 2023 study evaluating the consecutive Children’s Oncology Group (COG) AALL0434 and AALL1231 phase 3 trials of 2,164 patients with T-ALL, patients with CNS-3 at diagnosis were found to have worse outcomes, compared with CNS-1 and 2.
Importantly, the outcomes in both of those two trials were similar, despite the use of CRT in more than 90% of patients in the AALL0434 trial--but in only 10% of patients AALL1231 trial (mainly those with CNS-3 and at high-risk). These outcomes suggested that CRT can safely be eliminated for CNS-1 and 2 patients.
With CRT used in both trials among patients with CNS-3, conclusions about eliminating CRT among those patients could not be drawn. However, with other large groups (including the Dutch Childhood Oncology Group), eliminating CRT in the frontline treatment of all patients with T-ALL, including those with CNS-3, is what Dr. Vora and colleagues sought to further investigate.
For the current study, they evaluated outcomes in the UKALL2003 and UKALL2011 trials conducted by the UK National Cancer Research Institute, in which CRT was eliminated for all patients — including those with CNS-3 — and compared them with the COG AALL0434 and AALL1231 trials.
In the UK trials, involving 665 patients with T-ALL aged 1 to 24, treatment included a dexamethasone-based backbone chemotherapy consisting of a 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation, interim maintenance, delayed intensification, and maintenance therapy, with the treatment stratified based on morphological early response and minimal residual disease at the end of induction.
While the UKALL2003 trial initially recommended CRT for patients with CNS-3, that practice ended in 2009, and CNS-directed therapy subsequently consisted of intrathecal methotrexate (MTX) at regular intervals throughout treatment. Additional weekly intrathecal MTX treatments were recommended throughout induction for patients with CNS-3.
In the UKALL2011 trial, the weekly intrathecal MTX treatments were recommended for patients with CNS-2, as well as CNS-3.
Overall, among those with CNS data available, 557 patients had CNS-1 (87.4%), 44 CNS-2 (6.9%), and 36 CNS-3 (5.7%).
For the outcomes of 4-year cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) in the combined cohort of the 2 UK trials, there were no significant differences between CNS-1, 2 or 3 groups.
Specifically, the mean rates of 4-year CIR in the CNS-1, 2, and 3 groups were 13.6%, 25.9% and 24.6%, respectively (P = .241); mean EFS rates were 82.9%, 74.1% and 77.8% (P = .623), and OS rates were 88.6%, 80.9% and 91.8%, (P = .453).
“Most importantly, outcomes are not significantly different for the patients with CNS-3, despite omission of CRT in the UK cohort,” the authors underscored.
Comparatively, in the cohort of the 2 COG trials, there were significant differences based on CNS status for 4-year CIR (P = .0002); EFS (P = .0004) and OS (P = .005).
The 4-year relapse rates among those with CNS-3 in the UK cohort were slightly higher compared with those in the COG cohort (24.6% UK vs 17.9%, COG). However, the difference did not translate to poorer long-term survival in the UK cohort (91.8% vs 82.7%, respectively).
Those findings are consistent with a previous meta-analysis that Dr. Vora and his colleagues conducted of more than 16,000 patients with mainly B-cell ALL, which showed that CRT reduced the risk of isolated and combined CNS relapse in patients with CNS-3. However, that risk had no impact on EFS and OS.
Of note, patients in the UK cohort with CNS-2 had worse outcomes compared with the COG group, with double the rate of relapse and lower EFS and OS. However, the authors speculate that factors including a lower proportion of patients with CNS-2 in the UK cohort and differences in methodologies may explain those different outcomes and may preclude their generalizability to other groups.
Overall, “these findings corroborate those of earlier studies that CRT has marginal, if any benefit, for any sub-group of ALL, especially as part of contemporary treatment,” Dr. Vora said in an interview.
In terms of therapies that do appear to make a difference in the treatment of CNS-3, Dr. Vora noted that the addition of nelarabine in the COG AALL0434 trial showed “remarkable benefit” in the CNS-3 group, with a 93.1% rate of disease-free survival in those patients versus 70.2% without nelarabine.
Importantly, those patients did also receive CRT. However, Dr. Vora and colleagues underscore that “the improvement is impressive and raises the question of whether nelarabine would have a similar beneficial effect in the absence of CRT.”
In an editorial published with the COG trials, Josep-Maria Ribera, MD, of the Josep Carreras Leukemia Research Institute, in Barcelona, Spain, agrees that “better approaches clearly are needed to treat CNS-3 T-ALL, especially if omission of CRT is a priority.”
Noting the improvements observed with nelarabine, as well as Capizzi escalating-dose methotrexate (C-MTX), and dexamethasone in reducing the risk of CNS relapse, he speculates that “it is possible that the additional use of C-MTX and induction dexamethasone could eliminate the need for CRT in these patients.”
The authors and Dr. Ribera had no disclosures to report.
“Overall, comparison of these cohorts provides a strong indication that CRT provides minimal benefit to patients with CNS-3 disease at diagnosis,” first author Ajay Vora, MD, a consultant hematologist with Great Ormond Street Hospital, in London, and his colleagues report in a research letter published recently in Blood Advances.
“Given the high rates of neurocognitive impairment and secondary CNS malignancies, we believe strong consideration should be given to eliminating CRT in first-line treatment for all patients with T-ALL,” they wrote.
More aggressive than B-cell ALL, T-ALL is characterized by a higher likelihood of infiltration of the CNS at diagnosis, which increases the risk of relapse after treatment.
Until recently, treatment of T-ALL long entailed CNS-directed therapy using prophylactic CRT. Now, however, due to the risks of significant toxicity, including neurocognitive defects and secondary cancers, CRT is usually either omitted or limited to key subgroups, such as those with CNS-3 disease. As an alternative, intrathecal chemotherapy is used, the authors explain.
In a 2023 study evaluating the consecutive Children’s Oncology Group (COG) AALL0434 and AALL1231 phase 3 trials of 2,164 patients with T-ALL, patients with CNS-3 at diagnosis were found to have worse outcomes, compared with CNS-1 and 2.
Importantly, the outcomes in both of those two trials were similar, despite the use of CRT in more than 90% of patients in the AALL0434 trial--but in only 10% of patients AALL1231 trial (mainly those with CNS-3 and at high-risk). These outcomes suggested that CRT can safely be eliminated for CNS-1 and 2 patients.
With CRT used in both trials among patients with CNS-3, conclusions about eliminating CRT among those patients could not be drawn. However, with other large groups (including the Dutch Childhood Oncology Group), eliminating CRT in the frontline treatment of all patients with T-ALL, including those with CNS-3, is what Dr. Vora and colleagues sought to further investigate.
For the current study, they evaluated outcomes in the UKALL2003 and UKALL2011 trials conducted by the UK National Cancer Research Institute, in which CRT was eliminated for all patients — including those with CNS-3 — and compared them with the COG AALL0434 and AALL1231 trials.
In the UK trials, involving 665 patients with T-ALL aged 1 to 24, treatment included a dexamethasone-based backbone chemotherapy consisting of a 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation, interim maintenance, delayed intensification, and maintenance therapy, with the treatment stratified based on morphological early response and minimal residual disease at the end of induction.
While the UKALL2003 trial initially recommended CRT for patients with CNS-3, that practice ended in 2009, and CNS-directed therapy subsequently consisted of intrathecal methotrexate (MTX) at regular intervals throughout treatment. Additional weekly intrathecal MTX treatments were recommended throughout induction for patients with CNS-3.
In the UKALL2011 trial, the weekly intrathecal MTX treatments were recommended for patients with CNS-2, as well as CNS-3.
Overall, among those with CNS data available, 557 patients had CNS-1 (87.4%), 44 CNS-2 (6.9%), and 36 CNS-3 (5.7%).
For the outcomes of 4-year cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) in the combined cohort of the 2 UK trials, there were no significant differences between CNS-1, 2 or 3 groups.
Specifically, the mean rates of 4-year CIR in the CNS-1, 2, and 3 groups were 13.6%, 25.9% and 24.6%, respectively (P = .241); mean EFS rates were 82.9%, 74.1% and 77.8% (P = .623), and OS rates were 88.6%, 80.9% and 91.8%, (P = .453).
“Most importantly, outcomes are not significantly different for the patients with CNS-3, despite omission of CRT in the UK cohort,” the authors underscored.
Comparatively, in the cohort of the 2 COG trials, there were significant differences based on CNS status for 4-year CIR (P = .0002); EFS (P = .0004) and OS (P = .005).
The 4-year relapse rates among those with CNS-3 in the UK cohort were slightly higher compared with those in the COG cohort (24.6% UK vs 17.9%, COG). However, the difference did not translate to poorer long-term survival in the UK cohort (91.8% vs 82.7%, respectively).
Those findings are consistent with a previous meta-analysis that Dr. Vora and his colleagues conducted of more than 16,000 patients with mainly B-cell ALL, which showed that CRT reduced the risk of isolated and combined CNS relapse in patients with CNS-3. However, that risk had no impact on EFS and OS.
Of note, patients in the UK cohort with CNS-2 had worse outcomes compared with the COG group, with double the rate of relapse and lower EFS and OS. However, the authors speculate that factors including a lower proportion of patients with CNS-2 in the UK cohort and differences in methodologies may explain those different outcomes and may preclude their generalizability to other groups.
Overall, “these findings corroborate those of earlier studies that CRT has marginal, if any benefit, for any sub-group of ALL, especially as part of contemporary treatment,” Dr. Vora said in an interview.
In terms of therapies that do appear to make a difference in the treatment of CNS-3, Dr. Vora noted that the addition of nelarabine in the COG AALL0434 trial showed “remarkable benefit” in the CNS-3 group, with a 93.1% rate of disease-free survival in those patients versus 70.2% without nelarabine.
Importantly, those patients did also receive CRT. However, Dr. Vora and colleagues underscore that “the improvement is impressive and raises the question of whether nelarabine would have a similar beneficial effect in the absence of CRT.”
In an editorial published with the COG trials, Josep-Maria Ribera, MD, of the Josep Carreras Leukemia Research Institute, in Barcelona, Spain, agrees that “better approaches clearly are needed to treat CNS-3 T-ALL, especially if omission of CRT is a priority.”
Noting the improvements observed with nelarabine, as well as Capizzi escalating-dose methotrexate (C-MTX), and dexamethasone in reducing the risk of CNS relapse, he speculates that “it is possible that the additional use of C-MTX and induction dexamethasone could eliminate the need for CRT in these patients.”
The authors and Dr. Ribera had no disclosures to report.
FROM BLOOD ADVANCES
Researchers Uncover Nanoplastics in Water Bottles
Using an advanced microscopic technique, American researchers have detected 100,000 nanoplastic molecules per liter of water in plastic bottles. Because of their small size, these particles can enter the bloodstream, cells, and the brain, thus posing potential health risks. The study, recently published in the Proceedings of the National Academy of Sciences, raises concerns about the impact of these nanoparticles.
An Unknown Realm
Formed as plastics break down into increasingly small pieces, these particles are consumed by humans and other organisms, with unknown effects on health and ecosystems. Whereas macroplastics have been found in various organs, including the lungs and liver, the study marks a unique exploration into the world of nanoplastics.
Concerns about nanoplastic presence in humans intensified when a 2018 study revealed contamination signs in 93% of 259 examined bottles from nine countries.
The novelty of this research lies in its focus, using a refined spectrometry method, on the poorly understood world of nanoplastics, which derive from the decomposition of microplastics. For the first time, American researchers, including biophysicists and chemists, counted and identified these tiny particles in bottled water. On average, they found around 240,000 detectable plastic fragments per liter, which is 10-100 times more than previous estimates based on larger sizes.
Microplastics are defined as fragments ranging from 5 mm to 1 µm, whereas nanoplastics, particles < 1 µm, are measured in billionths of a meter.
In contrast to microplastics, nanoplastics are so small that they can traverse the intestines and lungs and move directly into the bloodstream, reaching organs such as the heart or brain or even the fetus via the placenta.
“This was previously an obscure, unexplored area. Toxicity studies could only speculate about what was in there,” said Beizhan Yan, PhD, coauthor of the study and environmental chemist at the Lamont–Doherty Earth Observatory of Columbia University, New York. “This study opens a window for us to observe a world we were not exposed to before.”
90% Nanoplastics Found
The new study employed a technique called stimulated Raman scattering microscopy, which was invented by study coauthor Wei Min, a biophysicist at Columbia. This method involves probing samples simultaneously with two lasers tuned to resonate specific molecules.
Researchers tested three bottled water brands that are popular in the United States, analyzing plastic particles up to 100 nm in size. They identified 110,000-370,000 plastic particles per liter. About 90% were nanoplastics — which are invisible by standard imaging techniques — and the rest were microplastics. The study also identified the seven plastics involved.
The most common is polyamide, a type of nylon, likely from plastic filters purportedly used to purify water before bottling. Next is polyethylene terephthalate, which is commonly used for water bottles and other food containers. Researchers also found other common plastics, including polystyrene, polyvinyl chloride, and methyl methacrylate, used in various industrial processes.
Not Size But Quantity
What’s more concerning is that the seven types of plastics accounted for only about 10% of all nanoparticles found in the samples. Researchers have no idea about the composition of the remaining 90%. If these are all nanoparticles, their number could reach tens of millions per liter, representing the complex composition of seemingly simple water samples, as noted by the authors.
Researchers now plan to expand beyond bottled water, exploring the vast realm of nanoplastics. They emphasize that, in terms of mass, nanoplastics are far smaller than microplastics, but “it’s not about size. It’s about the numbers as smaller things can easily penetrate us.”
The team aims to study tap water, which also contains microplastics but in much smaller proportions than bottled water.
This article was translated from the Medscape French edition.
Using an advanced microscopic technique, American researchers have detected 100,000 nanoplastic molecules per liter of water in plastic bottles. Because of their small size, these particles can enter the bloodstream, cells, and the brain, thus posing potential health risks. The study, recently published in the Proceedings of the National Academy of Sciences, raises concerns about the impact of these nanoparticles.
An Unknown Realm
Formed as plastics break down into increasingly small pieces, these particles are consumed by humans and other organisms, with unknown effects on health and ecosystems. Whereas macroplastics have been found in various organs, including the lungs and liver, the study marks a unique exploration into the world of nanoplastics.
Concerns about nanoplastic presence in humans intensified when a 2018 study revealed contamination signs in 93% of 259 examined bottles from nine countries.
The novelty of this research lies in its focus, using a refined spectrometry method, on the poorly understood world of nanoplastics, which derive from the decomposition of microplastics. For the first time, American researchers, including biophysicists and chemists, counted and identified these tiny particles in bottled water. On average, they found around 240,000 detectable plastic fragments per liter, which is 10-100 times more than previous estimates based on larger sizes.
Microplastics are defined as fragments ranging from 5 mm to 1 µm, whereas nanoplastics, particles < 1 µm, are measured in billionths of a meter.
In contrast to microplastics, nanoplastics are so small that they can traverse the intestines and lungs and move directly into the bloodstream, reaching organs such as the heart or brain or even the fetus via the placenta.
“This was previously an obscure, unexplored area. Toxicity studies could only speculate about what was in there,” said Beizhan Yan, PhD, coauthor of the study and environmental chemist at the Lamont–Doherty Earth Observatory of Columbia University, New York. “This study opens a window for us to observe a world we were not exposed to before.”
90% Nanoplastics Found
The new study employed a technique called stimulated Raman scattering microscopy, which was invented by study coauthor Wei Min, a biophysicist at Columbia. This method involves probing samples simultaneously with two lasers tuned to resonate specific molecules.
Researchers tested three bottled water brands that are popular in the United States, analyzing plastic particles up to 100 nm in size. They identified 110,000-370,000 plastic particles per liter. About 90% were nanoplastics — which are invisible by standard imaging techniques — and the rest were microplastics. The study also identified the seven plastics involved.
The most common is polyamide, a type of nylon, likely from plastic filters purportedly used to purify water before bottling. Next is polyethylene terephthalate, which is commonly used for water bottles and other food containers. Researchers also found other common plastics, including polystyrene, polyvinyl chloride, and methyl methacrylate, used in various industrial processes.
Not Size But Quantity
What’s more concerning is that the seven types of plastics accounted for only about 10% of all nanoparticles found in the samples. Researchers have no idea about the composition of the remaining 90%. If these are all nanoparticles, their number could reach tens of millions per liter, representing the complex composition of seemingly simple water samples, as noted by the authors.
Researchers now plan to expand beyond bottled water, exploring the vast realm of nanoplastics. They emphasize that, in terms of mass, nanoplastics are far smaller than microplastics, but “it’s not about size. It’s about the numbers as smaller things can easily penetrate us.”
The team aims to study tap water, which also contains microplastics but in much smaller proportions than bottled water.
This article was translated from the Medscape French edition.
Using an advanced microscopic technique, American researchers have detected 100,000 nanoplastic molecules per liter of water in plastic bottles. Because of their small size, these particles can enter the bloodstream, cells, and the brain, thus posing potential health risks. The study, recently published in the Proceedings of the National Academy of Sciences, raises concerns about the impact of these nanoparticles.
An Unknown Realm
Formed as plastics break down into increasingly small pieces, these particles are consumed by humans and other organisms, with unknown effects on health and ecosystems. Whereas macroplastics have been found in various organs, including the lungs and liver, the study marks a unique exploration into the world of nanoplastics.
Concerns about nanoplastic presence in humans intensified when a 2018 study revealed contamination signs in 93% of 259 examined bottles from nine countries.
The novelty of this research lies in its focus, using a refined spectrometry method, on the poorly understood world of nanoplastics, which derive from the decomposition of microplastics. For the first time, American researchers, including biophysicists and chemists, counted and identified these tiny particles in bottled water. On average, they found around 240,000 detectable plastic fragments per liter, which is 10-100 times more than previous estimates based on larger sizes.
Microplastics are defined as fragments ranging from 5 mm to 1 µm, whereas nanoplastics, particles < 1 µm, are measured in billionths of a meter.
In contrast to microplastics, nanoplastics are so small that they can traverse the intestines and lungs and move directly into the bloodstream, reaching organs such as the heart or brain or even the fetus via the placenta.
“This was previously an obscure, unexplored area. Toxicity studies could only speculate about what was in there,” said Beizhan Yan, PhD, coauthor of the study and environmental chemist at the Lamont–Doherty Earth Observatory of Columbia University, New York. “This study opens a window for us to observe a world we were not exposed to before.”
90% Nanoplastics Found
The new study employed a technique called stimulated Raman scattering microscopy, which was invented by study coauthor Wei Min, a biophysicist at Columbia. This method involves probing samples simultaneously with two lasers tuned to resonate specific molecules.
Researchers tested three bottled water brands that are popular in the United States, analyzing plastic particles up to 100 nm in size. They identified 110,000-370,000 plastic particles per liter. About 90% were nanoplastics — which are invisible by standard imaging techniques — and the rest were microplastics. The study also identified the seven plastics involved.
The most common is polyamide, a type of nylon, likely from plastic filters purportedly used to purify water before bottling. Next is polyethylene terephthalate, which is commonly used for water bottles and other food containers. Researchers also found other common plastics, including polystyrene, polyvinyl chloride, and methyl methacrylate, used in various industrial processes.
Not Size But Quantity
What’s more concerning is that the seven types of plastics accounted for only about 10% of all nanoparticles found in the samples. Researchers have no idea about the composition of the remaining 90%. If these are all nanoparticles, their number could reach tens of millions per liter, representing the complex composition of seemingly simple water samples, as noted by the authors.
Researchers now plan to expand beyond bottled water, exploring the vast realm of nanoplastics. They emphasize that, in terms of mass, nanoplastics are far smaller than microplastics, but “it’s not about size. It’s about the numbers as smaller things can easily penetrate us.”
The team aims to study tap water, which also contains microplastics but in much smaller proportions than bottled water.
This article was translated from the Medscape French edition.
FROM THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
Oncologists Sound the Alarm About Rise of White Bagging
For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.
Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.
On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.
That is why Dr. DiPersio’s cancer center does not allow white bagging.
And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.
“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.
In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”
Increasingly, white bagging mandates are becoming harder for practices to avoid.
In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.
A 2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.
This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
White Bagging: Who Benefits?
At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.
Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.
Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).
Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.
Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.
A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.
For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.
White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.
Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.
When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
Dangerous to Patients?
On the safety front, proponents of white bagging say the process is safe and efficient.
Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.
In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.
However, oncologists argue that white bagging can be dangerous.
With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.
White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.
Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.
Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.
“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”
When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.
“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
More Legislation to Prevent Bagging
As white bagging mandates from insurance companies ramp up, more practices and states are banning it.
In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.
At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.
Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.
When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.
“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”
Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.
At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.
Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.
“That is a difficult position to put oncologists in,” she said.
A version of this article appeared on Medscape.com.
For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.
Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.
On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.
That is why Dr. DiPersio’s cancer center does not allow white bagging.
And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.
“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.
In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”
Increasingly, white bagging mandates are becoming harder for practices to avoid.
In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.
A 2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.
This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
White Bagging: Who Benefits?
At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.
Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.
Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).
Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.
Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.
A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.
For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.
White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.
Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.
When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
Dangerous to Patients?
On the safety front, proponents of white bagging say the process is safe and efficient.
Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.
In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.
However, oncologists argue that white bagging can be dangerous.
With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.
White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.
Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.
Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.
“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”
When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.
“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
More Legislation to Prevent Bagging
As white bagging mandates from insurance companies ramp up, more practices and states are banning it.
In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.
At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.
Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.
When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.
“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”
Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.
At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.
Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.
“That is a difficult position to put oncologists in,” she said.
A version of this article appeared on Medscape.com.
For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.
Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.
On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.
That is why Dr. DiPersio’s cancer center does not allow white bagging.
And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.
“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.
In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”
Increasingly, white bagging mandates are becoming harder for practices to avoid.
In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.
A 2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.
This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
White Bagging: Who Benefits?
At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.
Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.
Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).
Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.
Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.
A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.
For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.
White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.
Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.
When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
Dangerous to Patients?
On the safety front, proponents of white bagging say the process is safe and efficient.
Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.
In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.
However, oncologists argue that white bagging can be dangerous.
With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.
White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.
Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.
Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.
“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”
When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.
“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
More Legislation to Prevent Bagging
As white bagging mandates from insurance companies ramp up, more practices and states are banning it.
In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.
At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.
Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.
When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.
“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”
Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.
At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.
Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.
“That is a difficult position to put oncologists in,” she said.
A version of this article appeared on Medscape.com.
CRISPR-Based Gene Therapy Earns Beta Thalassemia Approval
The approval, which comes more than 2 months ahead of a target action date of March 30, marks the second for the landmark therapy. The FDA greenlit the CRISPR gene therapy to treat sickle cell disease last December.
The autologous, ex vivo, CRISPR/Cas9 gene-edited therapy from Vertex and CRISPR Therapeutics is the first to use the gene-editing tool CRISPR.
The transfusion-dependent beta thalassemia approval is based on data from pivotal studies showing “consistent and durable response to treatment” in 52 patients who received an infusion and followed for up to 4 years. Treatment conferred transfusion independence in patients with transfusion-dependent beta thalassemia, according to a press release from Vertex late last year.
Vertex noted in a new press statement that expanded approval means about 1000 patients aged 12 years or older will be eligible for the one-time treatment for this indication.
Exa-cel requires administration at authorized treatment centers experienced in stem cell transplantation.
The therapy, which has a list price of $2.2 million in the United States, should be available initially at nine authorized treatment centers early this year, with more to come, according to Vertex.
A version of this article appeared on Medscape.com.
The approval, which comes more than 2 months ahead of a target action date of March 30, marks the second for the landmark therapy. The FDA greenlit the CRISPR gene therapy to treat sickle cell disease last December.
The autologous, ex vivo, CRISPR/Cas9 gene-edited therapy from Vertex and CRISPR Therapeutics is the first to use the gene-editing tool CRISPR.
The transfusion-dependent beta thalassemia approval is based on data from pivotal studies showing “consistent and durable response to treatment” in 52 patients who received an infusion and followed for up to 4 years. Treatment conferred transfusion independence in patients with transfusion-dependent beta thalassemia, according to a press release from Vertex late last year.
Vertex noted in a new press statement that expanded approval means about 1000 patients aged 12 years or older will be eligible for the one-time treatment for this indication.
Exa-cel requires administration at authorized treatment centers experienced in stem cell transplantation.
The therapy, which has a list price of $2.2 million in the United States, should be available initially at nine authorized treatment centers early this year, with more to come, according to Vertex.
A version of this article appeared on Medscape.com.
The approval, which comes more than 2 months ahead of a target action date of March 30, marks the second for the landmark therapy. The FDA greenlit the CRISPR gene therapy to treat sickle cell disease last December.
The autologous, ex vivo, CRISPR/Cas9 gene-edited therapy from Vertex and CRISPR Therapeutics is the first to use the gene-editing tool CRISPR.
The transfusion-dependent beta thalassemia approval is based on data from pivotal studies showing “consistent and durable response to treatment” in 52 patients who received an infusion and followed for up to 4 years. Treatment conferred transfusion independence in patients with transfusion-dependent beta thalassemia, according to a press release from Vertex late last year.
Vertex noted in a new press statement that expanded approval means about 1000 patients aged 12 years or older will be eligible for the one-time treatment for this indication.
Exa-cel requires administration at authorized treatment centers experienced in stem cell transplantation.
The therapy, which has a list price of $2.2 million in the United States, should be available initially at nine authorized treatment centers early this year, with more to come, according to Vertex.
A version of this article appeared on Medscape.com.
New Federal Rule for Prior Authorizations a ‘Major Win’ for Patients, Doctors
Physicians groups on January 17 hailed a new federal rule requiring health insurers to streamline and disclose more information about their prior authorization processes, saying it will improve patient care and reduce doctors’ administrative burden.
Health insurers participating in federal programs, including Medicare Advantage and Medicaid, must now respond to expedited prior authorization requests within 72 hours and other requests within 7 days under the long-awaited final rule, released on January 17 by the Centers for Medicare & Medicaid Services (CMS).
Insurers also must include their reasons for denying a prior authorization request and will be required to publicly release data on denial and approval rates for medical treatment. They’ll also need to give patients more information about their decisions to deny care. Insurers must comply with some of the rule’s provisions by January 2026 and others by January 2027.
The final rule “is an important step forward” toward the Medical Group Management Association’s goal of reducing the overall volume of prior authorization requests, said Anders Gilberg, the group’s senior vice president for government affairs, in a statement.
“Only then will medical groups find meaningful reprieve from these onerous, ill-intentioned administrative requirements that dangerously impede patient care,” Mr. Gilberg said.
Health insurers have long lobbied against increased regulation of prior authorization, arguing that it’s needed to rein in healthcare costs and prevent unnecessary treatment.
“We appreciate CMS’s announcement of enforcement discretion that will permit plans to use one standard, rather than mixing and matching, to reduce costs and speed implementation,” said America’s Health Insurance Plans, an insurers’ lobbying group, in an unsigned statement. “However, we must remember that the CMS rule is only half the picture; the Office of the Coordinator for Health Information Technology (ONC) should swiftly require vendors to build electronic prior authorization capabilities into the electronic health record so that providers can do their part, or plans will build a bridge to nowhere.”
The rule comes as health insurers have increasingly been criticized for onerous and time-consuming prior authorization procedures that physicians say unfairly delay or deny the medical treatment that their patients need. With federal legislation to rein in prior authorization overuse at a standstill, 30 states have introduced their own bills to address the problem. Regulators and lawsuits also have called attention to insurers’ increasing use of artificial intelligence and algorithms to deny claims without human review.
“Family physicians know firsthand how prior authorizations divert valuable time and resources away from direct patient care. We also know that these types of administrative requirements are driving physicians away from the workforce and worsening physician shortages,” said Steven P. Furr, MD, president of the American Academy of Family Physicians, in a statement praising the new rule.
Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, called the final rule “ a major win” for patients and physicians, adding that its requirements for health insurers to integrate their prior authorization procedures into physicians’ electronic health records systems will also help make “the current time-consuming, manual workflow” more efficient.
A version of this article first appeared on Medscape.com.
Physicians groups on January 17 hailed a new federal rule requiring health insurers to streamline and disclose more information about their prior authorization processes, saying it will improve patient care and reduce doctors’ administrative burden.
Health insurers participating in federal programs, including Medicare Advantage and Medicaid, must now respond to expedited prior authorization requests within 72 hours and other requests within 7 days under the long-awaited final rule, released on January 17 by the Centers for Medicare & Medicaid Services (CMS).
Insurers also must include their reasons for denying a prior authorization request and will be required to publicly release data on denial and approval rates for medical treatment. They’ll also need to give patients more information about their decisions to deny care. Insurers must comply with some of the rule’s provisions by January 2026 and others by January 2027.
The final rule “is an important step forward” toward the Medical Group Management Association’s goal of reducing the overall volume of prior authorization requests, said Anders Gilberg, the group’s senior vice president for government affairs, in a statement.
“Only then will medical groups find meaningful reprieve from these onerous, ill-intentioned administrative requirements that dangerously impede patient care,” Mr. Gilberg said.
Health insurers have long lobbied against increased regulation of prior authorization, arguing that it’s needed to rein in healthcare costs and prevent unnecessary treatment.
“We appreciate CMS’s announcement of enforcement discretion that will permit plans to use one standard, rather than mixing and matching, to reduce costs and speed implementation,” said America’s Health Insurance Plans, an insurers’ lobbying group, in an unsigned statement. “However, we must remember that the CMS rule is only half the picture; the Office of the Coordinator for Health Information Technology (ONC) should swiftly require vendors to build electronic prior authorization capabilities into the electronic health record so that providers can do their part, or plans will build a bridge to nowhere.”
The rule comes as health insurers have increasingly been criticized for onerous and time-consuming prior authorization procedures that physicians say unfairly delay or deny the medical treatment that their patients need. With federal legislation to rein in prior authorization overuse at a standstill, 30 states have introduced their own bills to address the problem. Regulators and lawsuits also have called attention to insurers’ increasing use of artificial intelligence and algorithms to deny claims without human review.
“Family physicians know firsthand how prior authorizations divert valuable time and resources away from direct patient care. We also know that these types of administrative requirements are driving physicians away from the workforce and worsening physician shortages,” said Steven P. Furr, MD, president of the American Academy of Family Physicians, in a statement praising the new rule.
Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, called the final rule “ a major win” for patients and physicians, adding that its requirements for health insurers to integrate their prior authorization procedures into physicians’ electronic health records systems will also help make “the current time-consuming, manual workflow” more efficient.
A version of this article first appeared on Medscape.com.
Physicians groups on January 17 hailed a new federal rule requiring health insurers to streamline and disclose more information about their prior authorization processes, saying it will improve patient care and reduce doctors’ administrative burden.
Health insurers participating in federal programs, including Medicare Advantage and Medicaid, must now respond to expedited prior authorization requests within 72 hours and other requests within 7 days under the long-awaited final rule, released on January 17 by the Centers for Medicare & Medicaid Services (CMS).
Insurers also must include their reasons for denying a prior authorization request and will be required to publicly release data on denial and approval rates for medical treatment. They’ll also need to give patients more information about their decisions to deny care. Insurers must comply with some of the rule’s provisions by January 2026 and others by January 2027.
The final rule “is an important step forward” toward the Medical Group Management Association’s goal of reducing the overall volume of prior authorization requests, said Anders Gilberg, the group’s senior vice president for government affairs, in a statement.
“Only then will medical groups find meaningful reprieve from these onerous, ill-intentioned administrative requirements that dangerously impede patient care,” Mr. Gilberg said.
Health insurers have long lobbied against increased regulation of prior authorization, arguing that it’s needed to rein in healthcare costs and prevent unnecessary treatment.
“We appreciate CMS’s announcement of enforcement discretion that will permit plans to use one standard, rather than mixing and matching, to reduce costs and speed implementation,” said America’s Health Insurance Plans, an insurers’ lobbying group, in an unsigned statement. “However, we must remember that the CMS rule is only half the picture; the Office of the Coordinator for Health Information Technology (ONC) should swiftly require vendors to build electronic prior authorization capabilities into the electronic health record so that providers can do their part, or plans will build a bridge to nowhere.”
The rule comes as health insurers have increasingly been criticized for onerous and time-consuming prior authorization procedures that physicians say unfairly delay or deny the medical treatment that their patients need. With federal legislation to rein in prior authorization overuse at a standstill, 30 states have introduced their own bills to address the problem. Regulators and lawsuits also have called attention to insurers’ increasing use of artificial intelligence and algorithms to deny claims without human review.
“Family physicians know firsthand how prior authorizations divert valuable time and resources away from direct patient care. We also know that these types of administrative requirements are driving physicians away from the workforce and worsening physician shortages,” said Steven P. Furr, MD, president of the American Academy of Family Physicians, in a statement praising the new rule.
Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, called the final rule “ a major win” for patients and physicians, adding that its requirements for health insurers to integrate their prior authorization procedures into physicians’ electronic health records systems will also help make “the current time-consuming, manual workflow” more efficient.
A version of this article first appeared on Medscape.com.
Panel Recommends Small Bump in 2025 Medicare Physician Pay
An influential panel is seeking an increase in Medicare’s 2025 payments for clinicians, adding to pressure on Congress to reconsider how the largest US purchaser of health services pays for office visits and related care of the nation’s older citizens and those with disabilities.
The Medicare Payment Advisory Commission (MedPAC) on Thursday voted unanimously in favor of a two-part recommendation on changes to the 2025 physician fee schedule:
- An increase in the base rate equal to half of the projected change in the Medicare Economic Index (MEI). Recent estimates have projected a 2.6% increase in MEI for 2025, which is intended to show how inflation affects the costs of running a medical practice.
- The creation of a safety-net add-on payment under the physician fee schedule to cover care of people with low incomes.
These recommendations echo the calls MedPAC made in a 2023 report to Congress.
Lawmakers and the Centers for Medicare and Medicaid Services (CMS) rely on MedPAC’s work in deciding how much to pay for services. About 1.3 million clinicians bill Medicare for their work, including about 670,000 physicians.
Thursday’s MedPAC vote comes amid continuing uncertainty about how much the federal government will actually pay clinicians this year through the physician fee schedule.
There are serious efforts underway to undo cuts already demanded by previously passed federal law. In an email, Rep. Larry Buchson, MD, (R-IN) said he remains committed to “eliminating the full 3.37% cut this year while also working toward a permanent solution to halt the downward spiral of physician reimbursement.”
“The Medicare payment cut to physicians will impede patients’ access to care and further accelerate the current path toward consolidation, physician burnout, and closure of medical practices,” Buchson told this news organization. “It’s past time that Congress provides much needed and deserved stability for America’s doctors.”
Congress this month is attempting to complete overdue budget legislation needed to fund federal operations for fiscal 2024, which began October 1, 2023. The pending expiration of a short-term stopgap continuing resolution could provide a vehicle that could also carry legislation that would address the physician fee schedule.
In a Thursday statement, Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, commended MedPAC for its recommendations and urged lawmakers to act.
“Long-term reforms from Congress are overdue to close the unsustainable gap between what Medicare pays physicians and the actual costs of delivering high-quality care,” Dr. Ehrenfeld said. “When adjusted for inflation in practice costs, Medicare physician pay declined 26% from 2001 to 2023.”
Continual Struggles
Congress has struggled for years in its attempts to set Medicare payments for office visits and other services covered by the physician fee schedule. A 1990s budget law set the stage for what proved to be untenable reductions in payment through the sustainable growth rate mechanism.
Between 2003 through April 2014, lawmakers passed “doc-fix” legislation 17 times to block the slated cuts, according to the Congressional Research Service. In 2015, Congress passed an intended overhaul of the physician fee schedule through the Medicare Access and CHIP Reauthorization Act (MACRA). As part of this law, Congress eliminated a base automatic inflation adjuster for the physician fee schedule.
In recent years, Congress has acted repeatedly to address MACRA’s mandates for flat base pay. MedPAC and members of both parties in Congress have called for a broad new look at how Medicare pays physicians.
At Thursday’s meeting, MedPAC member Lawrence Casalino, MD, PhD, MPH, noted that the struggles to keep up with inflation and the “unpredictability of what the payment rates are going to be from year to year really do affect physician morale.”
A version of this article appeared on Medscape.com.
An influential panel is seeking an increase in Medicare’s 2025 payments for clinicians, adding to pressure on Congress to reconsider how the largest US purchaser of health services pays for office visits and related care of the nation’s older citizens and those with disabilities.
The Medicare Payment Advisory Commission (MedPAC) on Thursday voted unanimously in favor of a two-part recommendation on changes to the 2025 physician fee schedule:
- An increase in the base rate equal to half of the projected change in the Medicare Economic Index (MEI). Recent estimates have projected a 2.6% increase in MEI for 2025, which is intended to show how inflation affects the costs of running a medical practice.
- The creation of a safety-net add-on payment under the physician fee schedule to cover care of people with low incomes.
These recommendations echo the calls MedPAC made in a 2023 report to Congress.
Lawmakers and the Centers for Medicare and Medicaid Services (CMS) rely on MedPAC’s work in deciding how much to pay for services. About 1.3 million clinicians bill Medicare for their work, including about 670,000 physicians.
Thursday’s MedPAC vote comes amid continuing uncertainty about how much the federal government will actually pay clinicians this year through the physician fee schedule.
There are serious efforts underway to undo cuts already demanded by previously passed federal law. In an email, Rep. Larry Buchson, MD, (R-IN) said he remains committed to “eliminating the full 3.37% cut this year while also working toward a permanent solution to halt the downward spiral of physician reimbursement.”
“The Medicare payment cut to physicians will impede patients’ access to care and further accelerate the current path toward consolidation, physician burnout, and closure of medical practices,” Buchson told this news organization. “It’s past time that Congress provides much needed and deserved stability for America’s doctors.”
Congress this month is attempting to complete overdue budget legislation needed to fund federal operations for fiscal 2024, which began October 1, 2023. The pending expiration of a short-term stopgap continuing resolution could provide a vehicle that could also carry legislation that would address the physician fee schedule.
In a Thursday statement, Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, commended MedPAC for its recommendations and urged lawmakers to act.
“Long-term reforms from Congress are overdue to close the unsustainable gap between what Medicare pays physicians and the actual costs of delivering high-quality care,” Dr. Ehrenfeld said. “When adjusted for inflation in practice costs, Medicare physician pay declined 26% from 2001 to 2023.”
Continual Struggles
Congress has struggled for years in its attempts to set Medicare payments for office visits and other services covered by the physician fee schedule. A 1990s budget law set the stage for what proved to be untenable reductions in payment through the sustainable growth rate mechanism.
Between 2003 through April 2014, lawmakers passed “doc-fix” legislation 17 times to block the slated cuts, according to the Congressional Research Service. In 2015, Congress passed an intended overhaul of the physician fee schedule through the Medicare Access and CHIP Reauthorization Act (MACRA). As part of this law, Congress eliminated a base automatic inflation adjuster for the physician fee schedule.
In recent years, Congress has acted repeatedly to address MACRA’s mandates for flat base pay. MedPAC and members of both parties in Congress have called for a broad new look at how Medicare pays physicians.
At Thursday’s meeting, MedPAC member Lawrence Casalino, MD, PhD, MPH, noted that the struggles to keep up with inflation and the “unpredictability of what the payment rates are going to be from year to year really do affect physician morale.”
A version of this article appeared on Medscape.com.
An influential panel is seeking an increase in Medicare’s 2025 payments for clinicians, adding to pressure on Congress to reconsider how the largest US purchaser of health services pays for office visits and related care of the nation’s older citizens and those with disabilities.
The Medicare Payment Advisory Commission (MedPAC) on Thursday voted unanimously in favor of a two-part recommendation on changes to the 2025 physician fee schedule:
- An increase in the base rate equal to half of the projected change in the Medicare Economic Index (MEI). Recent estimates have projected a 2.6% increase in MEI for 2025, which is intended to show how inflation affects the costs of running a medical practice.
- The creation of a safety-net add-on payment under the physician fee schedule to cover care of people with low incomes.
These recommendations echo the calls MedPAC made in a 2023 report to Congress.
Lawmakers and the Centers for Medicare and Medicaid Services (CMS) rely on MedPAC’s work in deciding how much to pay for services. About 1.3 million clinicians bill Medicare for their work, including about 670,000 physicians.
Thursday’s MedPAC vote comes amid continuing uncertainty about how much the federal government will actually pay clinicians this year through the physician fee schedule.
There are serious efforts underway to undo cuts already demanded by previously passed federal law. In an email, Rep. Larry Buchson, MD, (R-IN) said he remains committed to “eliminating the full 3.37% cut this year while also working toward a permanent solution to halt the downward spiral of physician reimbursement.”
“The Medicare payment cut to physicians will impede patients’ access to care and further accelerate the current path toward consolidation, physician burnout, and closure of medical practices,” Buchson told this news organization. “It’s past time that Congress provides much needed and deserved stability for America’s doctors.”
Congress this month is attempting to complete overdue budget legislation needed to fund federal operations for fiscal 2024, which began October 1, 2023. The pending expiration of a short-term stopgap continuing resolution could provide a vehicle that could also carry legislation that would address the physician fee schedule.
In a Thursday statement, Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, commended MedPAC for its recommendations and urged lawmakers to act.
“Long-term reforms from Congress are overdue to close the unsustainable gap between what Medicare pays physicians and the actual costs of delivering high-quality care,” Dr. Ehrenfeld said. “When adjusted for inflation in practice costs, Medicare physician pay declined 26% from 2001 to 2023.”
Continual Struggles
Congress has struggled for years in its attempts to set Medicare payments for office visits and other services covered by the physician fee schedule. A 1990s budget law set the stage for what proved to be untenable reductions in payment through the sustainable growth rate mechanism.
Between 2003 through April 2014, lawmakers passed “doc-fix” legislation 17 times to block the slated cuts, according to the Congressional Research Service. In 2015, Congress passed an intended overhaul of the physician fee schedule through the Medicare Access and CHIP Reauthorization Act (MACRA). As part of this law, Congress eliminated a base automatic inflation adjuster for the physician fee schedule.
In recent years, Congress has acted repeatedly to address MACRA’s mandates for flat base pay. MedPAC and members of both parties in Congress have called for a broad new look at how Medicare pays physicians.
At Thursday’s meeting, MedPAC member Lawrence Casalino, MD, PhD, MPH, noted that the struggles to keep up with inflation and the “unpredictability of what the payment rates are going to be from year to year really do affect physician morale.”
A version of this article appeared on Medscape.com.
Yes, Patients Are Getting More Complicated
This transcript has been edited for clarity.
The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.
Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”
But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?
Right?
It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.
I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.
Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?
And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.
Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.
Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success.
Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?
There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.
Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”
But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?
Right?
It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.
I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.
Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?
And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.
Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.
Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success.
Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?
There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.
Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”
But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?
Right?
It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.
I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.
Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?
And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.
Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.
Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success.
Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?
There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
ALL: ASH Draws Up Tx Guidelines For Patients 15-39
At the crux of the matter is the unusual nature of ALL, said University of Chicago leukemia specialist Wendy Stock, MD, in a presentation at the annual meeting of the American Society of Hematology in December 2023. The disease is both rare and unique since it spans the entire lifetime from infancy to old age, she said.
The guidelines will focus on adolescents and young adults, which the National Cancer Institute defines as those aged 15-39. For these patients, “treatment is administered by the whole gamut of practitioners in the world of hematology, from pediatricians to adult hematologist/oncologists, which provides unique challenges in terms of understanding and access to care,” Dr. Stock said.
As she explained, ALL “is the bread and butter of pediatric oncology, but in the world of adult hematology-oncology, many patients are treated in small-practice settings where there have been very few uniform approaches available to the treating practitioners,” she said. “There’s not going to ever be the ability to get every — or even the majority — of adults into those big academic centers.”
Meanwhile, research from around the world has highlighted major mortality gaps between pediatric and adult care in ALL. “This has been our huge challenge: Is it the treatment approach? Is it the disease biology, the patient biology, the doctors who treat these diseases? Is it the geographic location where they’re treated? Well, we now know that, of course, it’s probably all of the above, and a lot more than that.”
In light of the need for guidance in ALL treatment, it will be crucial to disseminate data and recommendations via the guidelines, she said.
In 2021, ASH members approved the development of new clinical practice guidelines for this population. The process so far has been difficult, said pediatric oncologist Sumit Gupta, MD, PhD, of the Hospital for Sick Children in Toronto, Ontario, at the ASH presentation.
“At one point,” Dr. Gupta recalled, “someone on our methodology team said this was the most challenging systematic review and guideline creation that they’d ever worked on, which is not what you want to hear as a co-chair.”
One major challenge for the guideline drafters is to balance ALL research findings that cover only certain ages, Dr. Gupta said. A study, for example, may only include patients up to age 21 or over age 35, making it difficult to decide how it fits into a larger evidence base for adolescents and young adults.
“We don’t always have perfect evidence. But we’re trying to take all of that and translate it into a formalized systematic review,” he said. “This is tricky for any guideline. But ALL poses a particular challenge because of how the evidence base is spread out.”
Another challenge is figuring out how to review psychosocial interventions in ALL. They are obviously crucial, he said. But should guidelines only take into account strategies that were tested in ALL? Or should they look at a wider perspective and encompass research into non–ALL-specific approaches?
In terms of guidance about frontline treatment, the guideline developers are focusing on several topics, said University of Rochester hematologist/oncologist Kristen O’Dwyer, MD, at the ASH presentation. These include: Should adolescents and young adults receive pediatric or adult regimens? Where do targeted therapy, immunotherapy, steroids, allogeneic stem cell transplants, and central nervous system (CNS) prophylaxis fit in?
“Finally, there are a series of questions that are addressing the toxicity prevention and management that go along with these intensive chemotherapy regimens,” she said.
On one front, there’s a “knowledge gap” about the value of stem cell transplant vs pediatric-inspired chemotherapy as postremission therapies, Dr. O’Dwyer said, because there are no direct comparisons. What to do? “There are retrospective comparisons that are emerging along with population-level analysis, single-arm observational studies that suggest that a pediatric-based chemotherapy approach is superior with similar relapse rates and less treatment-related mortality,” she said.
ASH expects to release a draft of its ALL guidelines for adolescents and young adults later this year and publish final recommendations in late 2024 or early 2025.
Dr. Stock, Dr. Gupta, and Dr. O’Dwyer have no disclosures.
At the crux of the matter is the unusual nature of ALL, said University of Chicago leukemia specialist Wendy Stock, MD, in a presentation at the annual meeting of the American Society of Hematology in December 2023. The disease is both rare and unique since it spans the entire lifetime from infancy to old age, she said.
The guidelines will focus on adolescents and young adults, which the National Cancer Institute defines as those aged 15-39. For these patients, “treatment is administered by the whole gamut of practitioners in the world of hematology, from pediatricians to adult hematologist/oncologists, which provides unique challenges in terms of understanding and access to care,” Dr. Stock said.
As she explained, ALL “is the bread and butter of pediatric oncology, but in the world of adult hematology-oncology, many patients are treated in small-practice settings where there have been very few uniform approaches available to the treating practitioners,” she said. “There’s not going to ever be the ability to get every — or even the majority — of adults into those big academic centers.”
Meanwhile, research from around the world has highlighted major mortality gaps between pediatric and adult care in ALL. “This has been our huge challenge: Is it the treatment approach? Is it the disease biology, the patient biology, the doctors who treat these diseases? Is it the geographic location where they’re treated? Well, we now know that, of course, it’s probably all of the above, and a lot more than that.”
In light of the need for guidance in ALL treatment, it will be crucial to disseminate data and recommendations via the guidelines, she said.
In 2021, ASH members approved the development of new clinical practice guidelines for this population. The process so far has been difficult, said pediatric oncologist Sumit Gupta, MD, PhD, of the Hospital for Sick Children in Toronto, Ontario, at the ASH presentation.
“At one point,” Dr. Gupta recalled, “someone on our methodology team said this was the most challenging systematic review and guideline creation that they’d ever worked on, which is not what you want to hear as a co-chair.”
One major challenge for the guideline drafters is to balance ALL research findings that cover only certain ages, Dr. Gupta said. A study, for example, may only include patients up to age 21 or over age 35, making it difficult to decide how it fits into a larger evidence base for adolescents and young adults.
“We don’t always have perfect evidence. But we’re trying to take all of that and translate it into a formalized systematic review,” he said. “This is tricky for any guideline. But ALL poses a particular challenge because of how the evidence base is spread out.”
Another challenge is figuring out how to review psychosocial interventions in ALL. They are obviously crucial, he said. But should guidelines only take into account strategies that were tested in ALL? Or should they look at a wider perspective and encompass research into non–ALL-specific approaches?
In terms of guidance about frontline treatment, the guideline developers are focusing on several topics, said University of Rochester hematologist/oncologist Kristen O’Dwyer, MD, at the ASH presentation. These include: Should adolescents and young adults receive pediatric or adult regimens? Where do targeted therapy, immunotherapy, steroids, allogeneic stem cell transplants, and central nervous system (CNS) prophylaxis fit in?
“Finally, there are a series of questions that are addressing the toxicity prevention and management that go along with these intensive chemotherapy regimens,” she said.
On one front, there’s a “knowledge gap” about the value of stem cell transplant vs pediatric-inspired chemotherapy as postremission therapies, Dr. O’Dwyer said, because there are no direct comparisons. What to do? “There are retrospective comparisons that are emerging along with population-level analysis, single-arm observational studies that suggest that a pediatric-based chemotherapy approach is superior with similar relapse rates and less treatment-related mortality,” she said.
ASH expects to release a draft of its ALL guidelines for adolescents and young adults later this year and publish final recommendations in late 2024 or early 2025.
Dr. Stock, Dr. Gupta, and Dr. O’Dwyer have no disclosures.
At the crux of the matter is the unusual nature of ALL, said University of Chicago leukemia specialist Wendy Stock, MD, in a presentation at the annual meeting of the American Society of Hematology in December 2023. The disease is both rare and unique since it spans the entire lifetime from infancy to old age, she said.
The guidelines will focus on adolescents and young adults, which the National Cancer Institute defines as those aged 15-39. For these patients, “treatment is administered by the whole gamut of practitioners in the world of hematology, from pediatricians to adult hematologist/oncologists, which provides unique challenges in terms of understanding and access to care,” Dr. Stock said.
As she explained, ALL “is the bread and butter of pediatric oncology, but in the world of adult hematology-oncology, many patients are treated in small-practice settings where there have been very few uniform approaches available to the treating practitioners,” she said. “There’s not going to ever be the ability to get every — or even the majority — of adults into those big academic centers.”
Meanwhile, research from around the world has highlighted major mortality gaps between pediatric and adult care in ALL. “This has been our huge challenge: Is it the treatment approach? Is it the disease biology, the patient biology, the doctors who treat these diseases? Is it the geographic location where they’re treated? Well, we now know that, of course, it’s probably all of the above, and a lot more than that.”
In light of the need for guidance in ALL treatment, it will be crucial to disseminate data and recommendations via the guidelines, she said.
In 2021, ASH members approved the development of new clinical practice guidelines for this population. The process so far has been difficult, said pediatric oncologist Sumit Gupta, MD, PhD, of the Hospital for Sick Children in Toronto, Ontario, at the ASH presentation.
“At one point,” Dr. Gupta recalled, “someone on our methodology team said this was the most challenging systematic review and guideline creation that they’d ever worked on, which is not what you want to hear as a co-chair.”
One major challenge for the guideline drafters is to balance ALL research findings that cover only certain ages, Dr. Gupta said. A study, for example, may only include patients up to age 21 or over age 35, making it difficult to decide how it fits into a larger evidence base for adolescents and young adults.
“We don’t always have perfect evidence. But we’re trying to take all of that and translate it into a formalized systematic review,” he said. “This is tricky for any guideline. But ALL poses a particular challenge because of how the evidence base is spread out.”
Another challenge is figuring out how to review psychosocial interventions in ALL. They are obviously crucial, he said. But should guidelines only take into account strategies that were tested in ALL? Or should they look at a wider perspective and encompass research into non–ALL-specific approaches?
In terms of guidance about frontline treatment, the guideline developers are focusing on several topics, said University of Rochester hematologist/oncologist Kristen O’Dwyer, MD, at the ASH presentation. These include: Should adolescents and young adults receive pediatric or adult regimens? Where do targeted therapy, immunotherapy, steroids, allogeneic stem cell transplants, and central nervous system (CNS) prophylaxis fit in?
“Finally, there are a series of questions that are addressing the toxicity prevention and management that go along with these intensive chemotherapy regimens,” she said.
On one front, there’s a “knowledge gap” about the value of stem cell transplant vs pediatric-inspired chemotherapy as postremission therapies, Dr. O’Dwyer said, because there are no direct comparisons. What to do? “There are retrospective comparisons that are emerging along with population-level analysis, single-arm observational studies that suggest that a pediatric-based chemotherapy approach is superior with similar relapse rates and less treatment-related mortality,” she said.
ASH expects to release a draft of its ALL guidelines for adolescents and young adults later this year and publish final recommendations in late 2024 or early 2025.
Dr. Stock, Dr. Gupta, and Dr. O’Dwyer have no disclosures.
FROM ASH 2023
ALL mortality gains bypass older adults
From 1999 to 2020, age-adjusted mortality rates for patients with ALL aged 55 and up didn’t change, oncologist-hematologist Jamie L. Koprivnikar, MD, of New Jersey’s Hackensack University Medical Center, reported at the annual meeting of the American Society of Hematology. The rates were 10.8 per 1 million in 1999 and 10.6 per 1 million in 2020.
By contrast, the mortality rates for children aged 0-15 improved from 3.5 per 1 million in 1999 to 2.2 per 1 million in 2020.
“The findings were particularly surprising and disappointing to me,” Dr. Koprivnikar said in an interview. “My overall sense is that we’ve really improved our outcomes of treating patients with ALL and are making great strides forward, moving away from so much chemotherapy and toward more kinds of immunotherapies and targeted therapies. So we need to understand what’s driving this.”
According to Dr. Koprivnikar, ALL is more common in children than adults. However, “even though the majority of cases tend to occur in children, we know that the majority of deaths are actually in the adult patient population,” she said.
One challenge for treatment is that therapies that work well in the pediatric population aren’t as effective in adults, she said. ALL is biologically different in adults in some ways, she added, and older patients may have more comorbidities. “It ends up being a really complicated story with all of these different factors playing into the complexity.”
For the new study, Dr. Koprivnikar and colleagues analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database. They found that 17,238 people died from ALL between 1999 and 2020. There were no significant differences in terms of gender, race, and region.
The study authors noted that mortality rates didn’t change despite medical advances in ALL such as blinatumomab, inotuzumab, and targeted tyrosine kinase inhibitor-based therapy. It’s unclear if the treatments have made it to the older-adult setting yet, Dr. Koprivnikar said.
There may be problems with access due to socioeconomic factors as well, she said. “ALL is actually more common among those of Hispanic heritage, and we don’t completely understand that.”
Marlise R. Luskin, MD, a leukemia specialist at Dana-Farber Cancer Institute, Boston, said in an interview that the study “is a reminder that clinical trial outcomes are limited — specifically trial results that often emphasize early results and report on a select population of older patients who generally are socially resourced and physically and mentally more fit.”
Dr. Luskin added that the study reports on outcomes through 2020, including years when newer regimens were not broadly disseminated outside of clinical trials.
Moving forward, she said, “this report suggests we need to continue to develop novel approaches and understand long-term outcomes as well as ‘real world’ outcomes. A similar study should be repeated again in 3-5 years as novel regimens become standard. We hope to see improvements.”
No study funding was reported. Dr. Koprivnikar disclosed consulting relationships with Alexion, GSK, Novartis, and Apellis. Other authors reported no disclosures. Dr. Luskin disclosed ties with Pfizer, Novartis, Jazz, Kite, and AbbVie.
From 1999 to 2020, age-adjusted mortality rates for patients with ALL aged 55 and up didn’t change, oncologist-hematologist Jamie L. Koprivnikar, MD, of New Jersey’s Hackensack University Medical Center, reported at the annual meeting of the American Society of Hematology. The rates were 10.8 per 1 million in 1999 and 10.6 per 1 million in 2020.
By contrast, the mortality rates for children aged 0-15 improved from 3.5 per 1 million in 1999 to 2.2 per 1 million in 2020.
“The findings were particularly surprising and disappointing to me,” Dr. Koprivnikar said in an interview. “My overall sense is that we’ve really improved our outcomes of treating patients with ALL and are making great strides forward, moving away from so much chemotherapy and toward more kinds of immunotherapies and targeted therapies. So we need to understand what’s driving this.”
According to Dr. Koprivnikar, ALL is more common in children than adults. However, “even though the majority of cases tend to occur in children, we know that the majority of deaths are actually in the adult patient population,” she said.
One challenge for treatment is that therapies that work well in the pediatric population aren’t as effective in adults, she said. ALL is biologically different in adults in some ways, she added, and older patients may have more comorbidities. “It ends up being a really complicated story with all of these different factors playing into the complexity.”
For the new study, Dr. Koprivnikar and colleagues analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database. They found that 17,238 people died from ALL between 1999 and 2020. There were no significant differences in terms of gender, race, and region.
The study authors noted that mortality rates didn’t change despite medical advances in ALL such as blinatumomab, inotuzumab, and targeted tyrosine kinase inhibitor-based therapy. It’s unclear if the treatments have made it to the older-adult setting yet, Dr. Koprivnikar said.
There may be problems with access due to socioeconomic factors as well, she said. “ALL is actually more common among those of Hispanic heritage, and we don’t completely understand that.”
Marlise R. Luskin, MD, a leukemia specialist at Dana-Farber Cancer Institute, Boston, said in an interview that the study “is a reminder that clinical trial outcomes are limited — specifically trial results that often emphasize early results and report on a select population of older patients who generally are socially resourced and physically and mentally more fit.”
Dr. Luskin added that the study reports on outcomes through 2020, including years when newer regimens were not broadly disseminated outside of clinical trials.
Moving forward, she said, “this report suggests we need to continue to develop novel approaches and understand long-term outcomes as well as ‘real world’ outcomes. A similar study should be repeated again in 3-5 years as novel regimens become standard. We hope to see improvements.”
No study funding was reported. Dr. Koprivnikar disclosed consulting relationships with Alexion, GSK, Novartis, and Apellis. Other authors reported no disclosures. Dr. Luskin disclosed ties with Pfizer, Novartis, Jazz, Kite, and AbbVie.
From 1999 to 2020, age-adjusted mortality rates for patients with ALL aged 55 and up didn’t change, oncologist-hematologist Jamie L. Koprivnikar, MD, of New Jersey’s Hackensack University Medical Center, reported at the annual meeting of the American Society of Hematology. The rates were 10.8 per 1 million in 1999 and 10.6 per 1 million in 2020.
By contrast, the mortality rates for children aged 0-15 improved from 3.5 per 1 million in 1999 to 2.2 per 1 million in 2020.
“The findings were particularly surprising and disappointing to me,” Dr. Koprivnikar said in an interview. “My overall sense is that we’ve really improved our outcomes of treating patients with ALL and are making great strides forward, moving away from so much chemotherapy and toward more kinds of immunotherapies and targeted therapies. So we need to understand what’s driving this.”
According to Dr. Koprivnikar, ALL is more common in children than adults. However, “even though the majority of cases tend to occur in children, we know that the majority of deaths are actually in the adult patient population,” she said.
One challenge for treatment is that therapies that work well in the pediatric population aren’t as effective in adults, she said. ALL is biologically different in adults in some ways, she added, and older patients may have more comorbidities. “It ends up being a really complicated story with all of these different factors playing into the complexity.”
For the new study, Dr. Koprivnikar and colleagues analyzed death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database. They found that 17,238 people died from ALL between 1999 and 2020. There were no significant differences in terms of gender, race, and region.
The study authors noted that mortality rates didn’t change despite medical advances in ALL such as blinatumomab, inotuzumab, and targeted tyrosine kinase inhibitor-based therapy. It’s unclear if the treatments have made it to the older-adult setting yet, Dr. Koprivnikar said.
There may be problems with access due to socioeconomic factors as well, she said. “ALL is actually more common among those of Hispanic heritage, and we don’t completely understand that.”
Marlise R. Luskin, MD, a leukemia specialist at Dana-Farber Cancer Institute, Boston, said in an interview that the study “is a reminder that clinical trial outcomes are limited — specifically trial results that often emphasize early results and report on a select population of older patients who generally are socially resourced and physically and mentally more fit.”
Dr. Luskin added that the study reports on outcomes through 2020, including years when newer regimens were not broadly disseminated outside of clinical trials.
Moving forward, she said, “this report suggests we need to continue to develop novel approaches and understand long-term outcomes as well as ‘real world’ outcomes. A similar study should be repeated again in 3-5 years as novel regimens become standard. We hope to see improvements.”
No study funding was reported. Dr. Koprivnikar disclosed consulting relationships with Alexion, GSK, Novartis, and Apellis. Other authors reported no disclosures. Dr. Luskin disclosed ties with Pfizer, Novartis, Jazz, Kite, and AbbVie.
FROM ASH 2023
New Multiple Myeloma Staging Systems Outperform the Standard
.
The findings should encourage greater use of these newer staging systems in routine clinical practice, first author Manni Mohyuddin, MD, said during a presentation at the American Society of Hematology annual meeting.
Dr. Mohyuddin and his colleagues retrospectively compared the standard Revised International Staging System (R-ISS) with two newer systems, the Second Revision of the R-ISS (R2-ISS) and the Mayo Additive Staging System (MASS), using real-world data from nearly 500 patients with newly diagnosed multiple myeloma.
The R-ISS, the most common multiple myeloma staging system, incorporates a range of prognostic features, including high-risk genetic markers assessed using fluorescence in situ hybridization as well as levels of lactate dehydrogenase, albumin, and beta-2 microglobulin, explained Dr. Mohyuddin, assistant professor at the Huntsman Cancer Institute, University of Utah, Salt Lake City.
R2-ISS and MASS include additional factors that reflect experts’ growing understanding of multiple myeloma. Specifically, the systems also evaluate a gain of chromosome 1q, in which patients have an extra copy of chromosome 1q, as well as the additive effects of multiple high-risk cytogenetic abnormalities, both of which indicate worse prognosis in multiple myeloma, Dr. Mohyuddin said in an interview.
To compare the three staging systems, the investigators used information on newly diagnosed patients in the Flatiron Health EHR–derived deidentified database, which includes data from cancer clinics across the United States. Patients were followed from first-line treatment initiation until death, the end of the study period, or last recorded activity.
The patients from the database had a median age of 70 years, and most had not received a transplant. The most common cytogenetic abnormality was gain 1q, present in about one third of patients.
Given that the R2-ISS originated from patients in clinical trials, Dr. Mohyuddin noted the importance of assessing how the system would perform in a real-world setting.
Of the 497 patients in the analysis, the R-ISS staging system classified 24% as stage I, 63% as stage II, and 13% as stage III. Overall survival differed across these R-ISS stages, indicating the system was prognostic for survival. Median overall survival was not reached for those with stage I disease, was 62.9 months for those with stage II disease, and 37.6 months for those with stage III disease.
Because the R-ISS doesn’t consider the additive effect of multiple cytogenetic abnormalities, many patients end up in the R-ISS stage II category but ultimately may have vastly different outcomes, Dr. Mohyuddin said.
The R2-ISS includes four risk categories, which provide more granularity to the stage II classification: Stage I is low risk, stage II is low-intermediate, stage III is intermediate, and stage IV is high risk. Using this staging system, 20% of patients were stage I, 25% were stage II, 46% were stage III, and 9% were stage IV.
The R2-ISS was also prognostic for survival, which generally worsened from stage I to stage IV: Median overall survival was not reached in stage I patients, was 69.3 months for stage II, 50.0 months for stage III, and 50.6 months for stage IV patients. However, Dr. Mohyuddin noted that there was some overlap in the survival curves for stages I and II and for stages III and IV.
When applying MASS, 34% of patients were categorized as stage I, 35% as stage II, and 31% as stage III disease. This system was prognostic for survival as well, with median overall survival of 76.9 months for stage I, 61.2 months for stage II, and 45.0 months for stage III.
With R2-ISS, many of those in R-ISS stage II are moved into stage I and III. With MASS, the R-ISS stage II patients are more evenly distributed across stages I, II, and III.
In other words, “we show that both these newer staging systems basically recategorize patients into different stages,” essentially “decreasing the number of people in the large, ambiguous (R-ISS) stage II category,” said Dr. Mohyuddin.
Dr. Mohyuddin and colleagues also evaluated the staging systems in fully adjusted analyses that controlled for age, race/ethnicity, sex, practice type, and diagnosis year.
Using R2-ISS, stage I patients had a similar risk for death compared with stage II patients (hazard ratio [HR], 1.2). Compared with stage I patients, stage III and IV patients had comparable risks for death, both about 2.5-fold higher than in those with stage I disease (HR, 2.4 and 2.6, respectively).
Compared with stage I MASS patients, those with stage II had a twofold higher risk for death (HR, 2.0), and those with stage III had an almost threefold higher risk (HR, 2.7).
Although no system considers all factors associated with myeloma outcomes, R2-ISS and MASS do offer a benefit over R-ISS, Dr. Mohyuddin said.
He added that the R2-ISS and MASS are similar from a statistical standpoint, but he gave MASS a slight edge for use in clinical practice.
MASS “more cleanly demarcated [patients] into prognostic subsets,” plus it is “a little easier to remember by heart,” he explained. MASS also puts more emphasis on the presence of multiple high-risk cytogenetic abnormalities, which is a worse prognostic in this era of quadruplet therapy for multiple myeloma, he added.
Because the study largely took place in an era when triplet therapy dominated, “we would be curious to see, with longer follow-up and more use of quadruplets, how these staging systems would perform,” he said.
Despite the benefits of these newer staging systems, many factors play a role in multiple myeloma outcomes, Dr. Mohyuddin explained. Staging systems are “only a piece of the puzzle.”
Dr. Mohyuddin reported having no financial interests to disclose.
A version of this article appeared on Medscape.com.
.
The findings should encourage greater use of these newer staging systems in routine clinical practice, first author Manni Mohyuddin, MD, said during a presentation at the American Society of Hematology annual meeting.
Dr. Mohyuddin and his colleagues retrospectively compared the standard Revised International Staging System (R-ISS) with two newer systems, the Second Revision of the R-ISS (R2-ISS) and the Mayo Additive Staging System (MASS), using real-world data from nearly 500 patients with newly diagnosed multiple myeloma.
The R-ISS, the most common multiple myeloma staging system, incorporates a range of prognostic features, including high-risk genetic markers assessed using fluorescence in situ hybridization as well as levels of lactate dehydrogenase, albumin, and beta-2 microglobulin, explained Dr. Mohyuddin, assistant professor at the Huntsman Cancer Institute, University of Utah, Salt Lake City.
R2-ISS and MASS include additional factors that reflect experts’ growing understanding of multiple myeloma. Specifically, the systems also evaluate a gain of chromosome 1q, in which patients have an extra copy of chromosome 1q, as well as the additive effects of multiple high-risk cytogenetic abnormalities, both of which indicate worse prognosis in multiple myeloma, Dr. Mohyuddin said in an interview.
To compare the three staging systems, the investigators used information on newly diagnosed patients in the Flatiron Health EHR–derived deidentified database, which includes data from cancer clinics across the United States. Patients were followed from first-line treatment initiation until death, the end of the study period, or last recorded activity.
The patients from the database had a median age of 70 years, and most had not received a transplant. The most common cytogenetic abnormality was gain 1q, present in about one third of patients.
Given that the R2-ISS originated from patients in clinical trials, Dr. Mohyuddin noted the importance of assessing how the system would perform in a real-world setting.
Of the 497 patients in the analysis, the R-ISS staging system classified 24% as stage I, 63% as stage II, and 13% as stage III. Overall survival differed across these R-ISS stages, indicating the system was prognostic for survival. Median overall survival was not reached for those with stage I disease, was 62.9 months for those with stage II disease, and 37.6 months for those with stage III disease.
Because the R-ISS doesn’t consider the additive effect of multiple cytogenetic abnormalities, many patients end up in the R-ISS stage II category but ultimately may have vastly different outcomes, Dr. Mohyuddin said.
The R2-ISS includes four risk categories, which provide more granularity to the stage II classification: Stage I is low risk, stage II is low-intermediate, stage III is intermediate, and stage IV is high risk. Using this staging system, 20% of patients were stage I, 25% were stage II, 46% were stage III, and 9% were stage IV.
The R2-ISS was also prognostic for survival, which generally worsened from stage I to stage IV: Median overall survival was not reached in stage I patients, was 69.3 months for stage II, 50.0 months for stage III, and 50.6 months for stage IV patients. However, Dr. Mohyuddin noted that there was some overlap in the survival curves for stages I and II and for stages III and IV.
When applying MASS, 34% of patients were categorized as stage I, 35% as stage II, and 31% as stage III disease. This system was prognostic for survival as well, with median overall survival of 76.9 months for stage I, 61.2 months for stage II, and 45.0 months for stage III.
With R2-ISS, many of those in R-ISS stage II are moved into stage I and III. With MASS, the R-ISS stage II patients are more evenly distributed across stages I, II, and III.
In other words, “we show that both these newer staging systems basically recategorize patients into different stages,” essentially “decreasing the number of people in the large, ambiguous (R-ISS) stage II category,” said Dr. Mohyuddin.
Dr. Mohyuddin and colleagues also evaluated the staging systems in fully adjusted analyses that controlled for age, race/ethnicity, sex, practice type, and diagnosis year.
Using R2-ISS, stage I patients had a similar risk for death compared with stage II patients (hazard ratio [HR], 1.2). Compared with stage I patients, stage III and IV patients had comparable risks for death, both about 2.5-fold higher than in those with stage I disease (HR, 2.4 and 2.6, respectively).
Compared with stage I MASS patients, those with stage II had a twofold higher risk for death (HR, 2.0), and those with stage III had an almost threefold higher risk (HR, 2.7).
Although no system considers all factors associated with myeloma outcomes, R2-ISS and MASS do offer a benefit over R-ISS, Dr. Mohyuddin said.
He added that the R2-ISS and MASS are similar from a statistical standpoint, but he gave MASS a slight edge for use in clinical practice.
MASS “more cleanly demarcated [patients] into prognostic subsets,” plus it is “a little easier to remember by heart,” he explained. MASS also puts more emphasis on the presence of multiple high-risk cytogenetic abnormalities, which is a worse prognostic in this era of quadruplet therapy for multiple myeloma, he added.
Because the study largely took place in an era when triplet therapy dominated, “we would be curious to see, with longer follow-up and more use of quadruplets, how these staging systems would perform,” he said.
Despite the benefits of these newer staging systems, many factors play a role in multiple myeloma outcomes, Dr. Mohyuddin explained. Staging systems are “only a piece of the puzzle.”
Dr. Mohyuddin reported having no financial interests to disclose.
A version of this article appeared on Medscape.com.
.
The findings should encourage greater use of these newer staging systems in routine clinical practice, first author Manni Mohyuddin, MD, said during a presentation at the American Society of Hematology annual meeting.
Dr. Mohyuddin and his colleagues retrospectively compared the standard Revised International Staging System (R-ISS) with two newer systems, the Second Revision of the R-ISS (R2-ISS) and the Mayo Additive Staging System (MASS), using real-world data from nearly 500 patients with newly diagnosed multiple myeloma.
The R-ISS, the most common multiple myeloma staging system, incorporates a range of prognostic features, including high-risk genetic markers assessed using fluorescence in situ hybridization as well as levels of lactate dehydrogenase, albumin, and beta-2 microglobulin, explained Dr. Mohyuddin, assistant professor at the Huntsman Cancer Institute, University of Utah, Salt Lake City.
R2-ISS and MASS include additional factors that reflect experts’ growing understanding of multiple myeloma. Specifically, the systems also evaluate a gain of chromosome 1q, in which patients have an extra copy of chromosome 1q, as well as the additive effects of multiple high-risk cytogenetic abnormalities, both of which indicate worse prognosis in multiple myeloma, Dr. Mohyuddin said in an interview.
To compare the three staging systems, the investigators used information on newly diagnosed patients in the Flatiron Health EHR–derived deidentified database, which includes data from cancer clinics across the United States. Patients were followed from first-line treatment initiation until death, the end of the study period, or last recorded activity.
The patients from the database had a median age of 70 years, and most had not received a transplant. The most common cytogenetic abnormality was gain 1q, present in about one third of patients.
Given that the R2-ISS originated from patients in clinical trials, Dr. Mohyuddin noted the importance of assessing how the system would perform in a real-world setting.
Of the 497 patients in the analysis, the R-ISS staging system classified 24% as stage I, 63% as stage II, and 13% as stage III. Overall survival differed across these R-ISS stages, indicating the system was prognostic for survival. Median overall survival was not reached for those with stage I disease, was 62.9 months for those with stage II disease, and 37.6 months for those with stage III disease.
Because the R-ISS doesn’t consider the additive effect of multiple cytogenetic abnormalities, many patients end up in the R-ISS stage II category but ultimately may have vastly different outcomes, Dr. Mohyuddin said.
The R2-ISS includes four risk categories, which provide more granularity to the stage II classification: Stage I is low risk, stage II is low-intermediate, stage III is intermediate, and stage IV is high risk. Using this staging system, 20% of patients were stage I, 25% were stage II, 46% were stage III, and 9% were stage IV.
The R2-ISS was also prognostic for survival, which generally worsened from stage I to stage IV: Median overall survival was not reached in stage I patients, was 69.3 months for stage II, 50.0 months for stage III, and 50.6 months for stage IV patients. However, Dr. Mohyuddin noted that there was some overlap in the survival curves for stages I and II and for stages III and IV.
When applying MASS, 34% of patients were categorized as stage I, 35% as stage II, and 31% as stage III disease. This system was prognostic for survival as well, with median overall survival of 76.9 months for stage I, 61.2 months for stage II, and 45.0 months for stage III.
With R2-ISS, many of those in R-ISS stage II are moved into stage I and III. With MASS, the R-ISS stage II patients are more evenly distributed across stages I, II, and III.
In other words, “we show that both these newer staging systems basically recategorize patients into different stages,” essentially “decreasing the number of people in the large, ambiguous (R-ISS) stage II category,” said Dr. Mohyuddin.
Dr. Mohyuddin and colleagues also evaluated the staging systems in fully adjusted analyses that controlled for age, race/ethnicity, sex, practice type, and diagnosis year.
Using R2-ISS, stage I patients had a similar risk for death compared with stage II patients (hazard ratio [HR], 1.2). Compared with stage I patients, stage III and IV patients had comparable risks for death, both about 2.5-fold higher than in those with stage I disease (HR, 2.4 and 2.6, respectively).
Compared with stage I MASS patients, those with stage II had a twofold higher risk for death (HR, 2.0), and those with stage III had an almost threefold higher risk (HR, 2.7).
Although no system considers all factors associated with myeloma outcomes, R2-ISS and MASS do offer a benefit over R-ISS, Dr. Mohyuddin said.
He added that the R2-ISS and MASS are similar from a statistical standpoint, but he gave MASS a slight edge for use in clinical practice.
MASS “more cleanly demarcated [patients] into prognostic subsets,” plus it is “a little easier to remember by heart,” he explained. MASS also puts more emphasis on the presence of multiple high-risk cytogenetic abnormalities, which is a worse prognostic in this era of quadruplet therapy for multiple myeloma, he added.
Because the study largely took place in an era when triplet therapy dominated, “we would be curious to see, with longer follow-up and more use of quadruplets, how these staging systems would perform,” he said.
Despite the benefits of these newer staging systems, many factors play a role in multiple myeloma outcomes, Dr. Mohyuddin explained. Staging systems are “only a piece of the puzzle.”
Dr. Mohyuddin reported having no financial interests to disclose.
A version of this article appeared on Medscape.com.
FROM ASH 2023