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CAR T cells can produce durable remissions
Credit: Penn Medicine
In a small study, 90% of children and adults with relapsed or refractory acute lymphoblastic leukemia (ALL) achieved remission after receiving CTL019, a chimeric antigen receptor (CAR) T-cell therapy.
Seven of these 27 patients ultimately relapsed, and 5 went on to receive additional therapy, including stem cell transplant.
Still, 15 of these heavily pretreated patients remained in remission at a median of 7 months of follow-up and did not require further treatment.
“[Patients] had relapsed as many as 4 times, including 60% whose cancers came back even after stem cell transplants,” said Stephan Grupp, MD, PhD, of the Children’s Hospital of Philadelphia in Pennsylvania.
“Their cancers were so aggressive they had no treatment options left. The durable responses we have observed with CTL019 therapy are unprecedented.”
Dr Grupp and his colleagues reported these results in NEJM. The new data build on preliminary findings presented at the 2013 ASH Annual Meeting and the 2012 ASH Annual Meeting.
CTL019 cells are a patient’s own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.
In all, 30 patients received CTL019, including 25 children and young adults (ages 5 to 22) and 5 adults (ages 26 to 60). Three patients had primary refractory disease, 5 had relapsed once, and 22 patients had relapsed 2 or more times. Eighteen patients had received an allogeneic stem cell transplant.
Twenty-seven patients achieved a complete remission after an infusion of CTL019. Nineteen patients remain in remission, 15 of whom received CTL019 alone. Follow-up ranged from 1.4 months to 24 months.
Tests in patients who experienced complete remissions showed that their normal B cells had been eliminated along with their tumors. The researchers noted that persistent absence of normal B cells following CTL019 treatment indicates continued activity of the CAR T cells.
“Our results support that CTL019 can produce long-lasting remissions for certain heavily pretreated ALL patients without further therapy,” said Noelle Frey, MD, of the University of Pennsylvania in Philadelphia.
However, 5 patients did seek additional therapy, 3 of whom proceeded to allogeneic stem cell transplants while in remission.
Seven patients relapsed, between 6 weeks and 8.5 months after their infusions, including 3 whose cancers returned as CD19-negative leukemia that would not have been targeted by CTL019.
At 6 months, the overall survival rate was 78%, and the event-free survival rate was 67%.
All of the patients experienced cytokine release syndrome (CRS) within a few days of receiving CTL019, but they all fully recovered.
Twenty-two patients experienced mild to moderate CRS, which included varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain. Eight patients developed severe CRS, which required treatment for low blood pressure and breathing difficulties.
Nine patients were treated with tocilizumab, an immunosuppressant that inhibits the effects of the inflammatory cytokine IL-6, which have been found to spike during the most robust phase of the CAR T cells’ expansion in the body. Six patients also received short courses of steroids to combat CRS symptoms.
CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. In July, the US Food and Drug Administration granted CTL019 breakthrough therapy designation for the treatment of relapsed and refractory adult and pediatric ALL.
The first multicenter trial of CTL019 recently opened in the US, and additional multisite trials are expected to begin by the end of the year. 
Credit: Penn Medicine
In a small study, 90% of children and adults with relapsed or refractory acute lymphoblastic leukemia (ALL) achieved remission after receiving CTL019, a chimeric antigen receptor (CAR) T-cell therapy.
Seven of these 27 patients ultimately relapsed, and 5 went on to receive additional therapy, including stem cell transplant.
Still, 15 of these heavily pretreated patients remained in remission at a median of 7 months of follow-up and did not require further treatment.
“[Patients] had relapsed as many as 4 times, including 60% whose cancers came back even after stem cell transplants,” said Stephan Grupp, MD, PhD, of the Children’s Hospital of Philadelphia in Pennsylvania.
“Their cancers were so aggressive they had no treatment options left. The durable responses we have observed with CTL019 therapy are unprecedented.”
Dr Grupp and his colleagues reported these results in NEJM. The new data build on preliminary findings presented at the 2013 ASH Annual Meeting and the 2012 ASH Annual Meeting.
CTL019 cells are a patient’s own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.
In all, 30 patients received CTL019, including 25 children and young adults (ages 5 to 22) and 5 adults (ages 26 to 60). Three patients had primary refractory disease, 5 had relapsed once, and 22 patients had relapsed 2 or more times. Eighteen patients had received an allogeneic stem cell transplant.
Twenty-seven patients achieved a complete remission after an infusion of CTL019. Nineteen patients remain in remission, 15 of whom received CTL019 alone. Follow-up ranged from 1.4 months to 24 months.
Tests in patients who experienced complete remissions showed that their normal B cells had been eliminated along with their tumors. The researchers noted that persistent absence of normal B cells following CTL019 treatment indicates continued activity of the CAR T cells.
“Our results support that CTL019 can produce long-lasting remissions for certain heavily pretreated ALL patients without further therapy,” said Noelle Frey, MD, of the University of Pennsylvania in Philadelphia.
However, 5 patients did seek additional therapy, 3 of whom proceeded to allogeneic stem cell transplants while in remission.
Seven patients relapsed, between 6 weeks and 8.5 months after their infusions, including 3 whose cancers returned as CD19-negative leukemia that would not have been targeted by CTL019.
At 6 months, the overall survival rate was 78%, and the event-free survival rate was 67%.
All of the patients experienced cytokine release syndrome (CRS) within a few days of receiving CTL019, but they all fully recovered.
Twenty-two patients experienced mild to moderate CRS, which included varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain. Eight patients developed severe CRS, which required treatment for low blood pressure and breathing difficulties.
Nine patients were treated with tocilizumab, an immunosuppressant that inhibits the effects of the inflammatory cytokine IL-6, which have been found to spike during the most robust phase of the CAR T cells’ expansion in the body. Six patients also received short courses of steroids to combat CRS symptoms.
CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. In July, the US Food and Drug Administration granted CTL019 breakthrough therapy designation for the treatment of relapsed and refractory adult and pediatric ALL.
The first multicenter trial of CTL019 recently opened in the US, and additional multisite trials are expected to begin by the end of the year.
Credit: Penn Medicine
In a small study, 90% of children and adults with relapsed or refractory acute lymphoblastic leukemia (ALL) achieved remission after receiving CTL019, a chimeric antigen receptor (CAR) T-cell therapy.
Seven of these 27 patients ultimately relapsed, and 5 went on to receive additional therapy, including stem cell transplant.
Still, 15 of these heavily pretreated patients remained in remission at a median of 7 months of follow-up and did not require further treatment.
“[Patients] had relapsed as many as 4 times, including 60% whose cancers came back even after stem cell transplants,” said Stephan Grupp, MD, PhD, of the Children’s Hospital of Philadelphia in Pennsylvania.
“Their cancers were so aggressive they had no treatment options left. The durable responses we have observed with CTL019 therapy are unprecedented.”
Dr Grupp and his colleagues reported these results in NEJM. The new data build on preliminary findings presented at the 2013 ASH Annual Meeting and the 2012 ASH Annual Meeting.
CTL019 cells are a patient’s own T cells genetically engineered to express an anti-CD19 scFv coupled to CD3ζ signaling and 4-1BB co-stimulatory domains. The cells are activated and expanded ex vivo with anti-CD3 and anti-CD28 beads, then infused into patients.
In all, 30 patients received CTL019, including 25 children and young adults (ages 5 to 22) and 5 adults (ages 26 to 60). Three patients had primary refractory disease, 5 had relapsed once, and 22 patients had relapsed 2 or more times. Eighteen patients had received an allogeneic stem cell transplant.
Twenty-seven patients achieved a complete remission after an infusion of CTL019. Nineteen patients remain in remission, 15 of whom received CTL019 alone. Follow-up ranged from 1.4 months to 24 months.
Tests in patients who experienced complete remissions showed that their normal B cells had been eliminated along with their tumors. The researchers noted that persistent absence of normal B cells following CTL019 treatment indicates continued activity of the CAR T cells.
“Our results support that CTL019 can produce long-lasting remissions for certain heavily pretreated ALL patients without further therapy,” said Noelle Frey, MD, of the University of Pennsylvania in Philadelphia.
However, 5 patients did seek additional therapy, 3 of whom proceeded to allogeneic stem cell transplants while in remission.
Seven patients relapsed, between 6 weeks and 8.5 months after their infusions, including 3 whose cancers returned as CD19-negative leukemia that would not have been targeted by CTL019.
At 6 months, the overall survival rate was 78%, and the event-free survival rate was 67%.
All of the patients experienced cytokine release syndrome (CRS) within a few days of receiving CTL019, but they all fully recovered.
Twenty-two patients experienced mild to moderate CRS, which included varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain. Eight patients developed severe CRS, which required treatment for low blood pressure and breathing difficulties.
Nine patients were treated with tocilizumab, an immunosuppressant that inhibits the effects of the inflammatory cytokine IL-6, which have been found to spike during the most robust phase of the CAR T cells’ expansion in the body. Six patients also received short courses of steroids to combat CRS symptoms.
CTL019 was invented at The University of Pennsylvania but has been licensed to Novartis. In July, the US Food and Drug Administration granted CTL019 breakthrough therapy designation for the treatment of relapsed and refractory adult and pediatric ALL.
The first multicenter trial of CTL019 recently opened in the US, and additional multisite trials are expected to begin by the end of the year.
NICE doesn’t support pomalidomide for MM
Credit: CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide
(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).
NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.
Furthermore, the drug did not offer enough of a benefit to justify its high price.
“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.
Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”
The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.
The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.
The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.
When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.
The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.
The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.
Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.
Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Credit: CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide
(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).
NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.
Furthermore, the drug did not offer enough of a benefit to justify its high price.
“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.
Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”
The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.
The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.
The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.
When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.
The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.
The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.
Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.
Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Credit: CDC
The UK’s National Institute for Health and Care Excellence (NICE) has issued a preliminary draft guidance rejecting the use of pomalidomide
(Imnovid) to treat patients with relapsed or refractory multiple myeloma (MM).
NICE said the drug’s maker, Celgene, did not provide sufficient evidence of pomalidomide’s effectiveness as compared to current treatment.
Furthermore, the drug did not offer enough of a benefit to justify its high price.
“We are disappointed not to be able to recommend pomalidomide in this preliminary guidance, but the analyses submitted by Celgene, the company that makes the drug, did not show how well the drug works compared to the other treatments available,” said Sir Andrew Dillon, NICE chief executive.
Specifically, NICE said it cannot recommend pomalidomide in combination with dexamethasone for treating relapsed and refractory MM in adults who have had at least 2 prior treatments, including lenalidomide and bortezomib, and whose disease has progressed on their last therapy.
A committee advising NICE concluded that, because of the design of the MM-003 study, the extent of the benefits associated with pomalidomide was uncertain. In addition, the MM-003 results were of limited value in comparing pomalidomide with “established practice without pomalidomide.”
The recommended dose of pomalidomide is 4 mg once daily, taken on days 1 to 21 of repeated 28-day cycles. Treatment should continue until disease progression.
The price of a pack (21 tablets) of 1 mg, 2 mg, 3 mg, or 4 mg tablets is £8884 (excluding value-added tax). Costs may vary in different settings because of negotiated procurement discounts.
The cost per quality-adjusted life-year (QALY) gained presented by Celgene was over £50,000 compared with bortezomib.
The committee heard from a clinical expert that, although there is no standard of care for people with relapsed or refractory MM, bendamustine was likely to be the most commonly used therapy in this setting in England.
When comparing pomalidomide with bendamustine plus thalidomide and dexamethasone, all costs per QALYs presented were over £70,000.
The committee was not persuaded that the estimates of the extension to life were robust, objective, or plausible based on the company’s economic modeling. It therefore concluded that pomalidomide did not fulfill the criteria for being a life-extending, end-of-life treatment.
The committee further concluded that, even if pomalidomide fulfilled these criteria, the weight that would have to be placed on the QALYs would be too high for pomalidomide to be considered a cost-effective use of National Health Service resources.
Consultees, including the manufacturer, healthcare professionals, and members of the public are now able to comment on these preliminary recommendations.
Until a final guidance is issued, National Health Service bodies should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Amoeba could help fight cancers
Experiments in a soil-dwelling amoeba have provided insight that could help us treat cancers characterized by PTEN mutations, researchers have reported in PLOS ONE.
The team discovered that this amoeba has two genes that function like the human tumor suppressor PTEN.
And increasing expression of one of these genes compensated for a mutation in the other gene.
If the same method works in humans with mutated PTEN, this finding could have implications for a range of cancers.
PTEN mutations are thought to be involved in nearly half of all leukemia cases, 40% of breast cancer cases, and up to 70% of prostate cancer cases.
“If you look at tumors across the board . . . , you find that PTEN is the most generally mutated gene, and, when you mutate PTEN in mice, you cause tumors,” said study author David Soll, PhD, of the University of Iowa in Iowa City.
He and his colleagues found that the amoeba Dictyostelium discoideum has the gene ptenA, which mutates similarly to the human PTEN gene and causes behavioral defects in the cell.
They also found a close relative of ptenA in the amoeba, called lpten, that performs the same functions of ptenA but to a lesser degree.
The researchers hypothesized that ramping up the presence of lpten could compensate for the mutated ptenA.
They tested this theory by placing lpten in a plasmid behind a powerful promoter designed to overexpress the gene. They then introduced the super-charged lpten into a cell with the mutated ptenA gene.
The team found that the overexpressed lpten gene fully compensated for all of the defects in the ptenA mutant.
If this method works in human cells, it could lead to a new way to treat cancers, the researchers said. They are now aiming to identify a drug that would activate the promoter for one of PTEN’s close relatives.
Once a patient is diagnosed with cancer caused by a PTEN mutation, the patient could take the drug, overexpress the PTEN replacement gene, and potentially stop cancer in its tracks, Dr Soll said.
This research has also led Dr Soll and his colleagues to study other human genes that may be able to step in for the mutated PTEN gene and perform the same tumor-suppressing role. The team is currently studying 2 close relatives of PTEN.
“And nature might have put them there just for that; that’s the curious thing,” Dr Soll said. “Somewhere, there may be a backup system, what we call ‘redundancy,’ that might be the basis for better identifying tumors and possibly creating cancer-fighting drugs. You have another gene which might be able to step in for the broken gene to keep things normal, and that’s what we’re playing with here. It’s very sophisticated.”
Experiments in a soil-dwelling amoeba have provided insight that could help us treat cancers characterized by PTEN mutations, researchers have reported in PLOS ONE.
The team discovered that this amoeba has two genes that function like the human tumor suppressor PTEN.
And increasing expression of one of these genes compensated for a mutation in the other gene.
If the same method works in humans with mutated PTEN, this finding could have implications for a range of cancers.
PTEN mutations are thought to be involved in nearly half of all leukemia cases, 40% of breast cancer cases, and up to 70% of prostate cancer cases.
“If you look at tumors across the board . . . , you find that PTEN is the most generally mutated gene, and, when you mutate PTEN in mice, you cause tumors,” said study author David Soll, PhD, of the University of Iowa in Iowa City.
He and his colleagues found that the amoeba Dictyostelium discoideum has the gene ptenA, which mutates similarly to the human PTEN gene and causes behavioral defects in the cell.
They also found a close relative of ptenA in the amoeba, called lpten, that performs the same functions of ptenA but to a lesser degree.
The researchers hypothesized that ramping up the presence of lpten could compensate for the mutated ptenA.
They tested this theory by placing lpten in a plasmid behind a powerful promoter designed to overexpress the gene. They then introduced the super-charged lpten into a cell with the mutated ptenA gene.
The team found that the overexpressed lpten gene fully compensated for all of the defects in the ptenA mutant.
If this method works in human cells, it could lead to a new way to treat cancers, the researchers said. They are now aiming to identify a drug that would activate the promoter for one of PTEN’s close relatives.
Once a patient is diagnosed with cancer caused by a PTEN mutation, the patient could take the drug, overexpress the PTEN replacement gene, and potentially stop cancer in its tracks, Dr Soll said.
This research has also led Dr Soll and his colleagues to study other human genes that may be able to step in for the mutated PTEN gene and perform the same tumor-suppressing role. The team is currently studying 2 close relatives of PTEN.
“And nature might have put them there just for that; that’s the curious thing,” Dr Soll said. “Somewhere, there may be a backup system, what we call ‘redundancy,’ that might be the basis for better identifying tumors and possibly creating cancer-fighting drugs. You have another gene which might be able to step in for the broken gene to keep things normal, and that’s what we’re playing with here. It’s very sophisticated.”
Experiments in a soil-dwelling amoeba have provided insight that could help us treat cancers characterized by PTEN mutations, researchers have reported in PLOS ONE.
The team discovered that this amoeba has two genes that function like the human tumor suppressor PTEN.
And increasing expression of one of these genes compensated for a mutation in the other gene.
If the same method works in humans with mutated PTEN, this finding could have implications for a range of cancers.
PTEN mutations are thought to be involved in nearly half of all leukemia cases, 40% of breast cancer cases, and up to 70% of prostate cancer cases.
“If you look at tumors across the board . . . , you find that PTEN is the most generally mutated gene, and, when you mutate PTEN in mice, you cause tumors,” said study author David Soll, PhD, of the University of Iowa in Iowa City.
He and his colleagues found that the amoeba Dictyostelium discoideum has the gene ptenA, which mutates similarly to the human PTEN gene and causes behavioral defects in the cell.
They also found a close relative of ptenA in the amoeba, called lpten, that performs the same functions of ptenA but to a lesser degree.
The researchers hypothesized that ramping up the presence of lpten could compensate for the mutated ptenA.
They tested this theory by placing lpten in a plasmid behind a powerful promoter designed to overexpress the gene. They then introduced the super-charged lpten into a cell with the mutated ptenA gene.
The team found that the overexpressed lpten gene fully compensated for all of the defects in the ptenA mutant.
If this method works in human cells, it could lead to a new way to treat cancers, the researchers said. They are now aiming to identify a drug that would activate the promoter for one of PTEN’s close relatives.
Once a patient is diagnosed with cancer caused by a PTEN mutation, the patient could take the drug, overexpress the PTEN replacement gene, and potentially stop cancer in its tracks, Dr Soll said.
This research has also led Dr Soll and his colleagues to study other human genes that may be able to step in for the mutated PTEN gene and perform the same tumor-suppressing role. The team is currently studying 2 close relatives of PTEN.
“And nature might have put them there just for that; that’s the curious thing,” Dr Soll said. “Somewhere, there may be a backup system, what we call ‘redundancy,’ that might be the basis for better identifying tumors and possibly creating cancer-fighting drugs. You have another gene which might be able to step in for the broken gene to keep things normal, and that’s what we’re playing with here. It’s very sophisticated.”
Malpractice reform may not reduce ‘defensive medicine’
Credit: CDC
Making it more difficult for patients to sue physicians for medical malpractice may not reduce the amount of “defensive medicine” physicians
practice, new research suggests.
Investigators studied patient records in 3 states that raised the standard for malpractice in the emergency room to gross negligence.
And they found that strong new legal protections did not significantly reduce the use of common defensive medicine practices or the cost of care.
The team detailed these findings in NEJM.
“Our findings suggest that malpractice reform may have less effect on costs than has been projected by conventional wisdom,” said lead study author Daniel A. Waxman, MD, PhD, of RAND Health in Santa Monica, California.
“Physicians say they order unnecessary tests strictly out of fear of being sued, but our results suggest the story is more complicated.”
The investigators evaluated the results of malpractice reform in 3 states—Georgia, Texas, and South Carolina.
About a decade ago, these states changed the legal malpractice standard for emergency care to gross negligence. The higher standard means plaintiffs must prove that doctors consciously disregarded the need to use reasonable care, knowing full well that their actions were likely to cause serious injury.
“These malpractice reforms have been said to provide virtual immunity against lawsuits,” Dr Waxman noted.
He and his colleagues examined 3.8 million Medicare patient records from 1166 hospital emergency departments spanning the period from 1997 to 2011. They compared care in the 3 reform states, before and after the statutes took effect, to care in neighboring states that did not pass malpractice reform.
The team assessed whether physicians ordered an advanced imaging study (CT or MRI scan), whether the patient was hospitalized after the emergency visit, and total charges for the visit.
Advanced imaging and hospitalization are among the most costly consequences of an emergency room visit, and physicians have identified them as common defensive medicine practices.
The malpractice reform laws had no effect on the use of imaging or the rate of hospitalization following emergency visits.
For 2 of the states, Texas and South Carolina, the law did not appear to cause any reduction in charges. Relative to neighboring states, Georgia saw a drop of 3.6% in average emergency room charges following its 2005 reform.
“This study suggests that, even when the risk of being sued for malpractice decreases, the path of least resistance still may favor resource-intensive care, at least in hospital emergency departments,” Dr Waxman said.
Credit: CDC
Making it more difficult for patients to sue physicians for medical malpractice may not reduce the amount of “defensive medicine” physicians
practice, new research suggests.
Investigators studied patient records in 3 states that raised the standard for malpractice in the emergency room to gross negligence.
And they found that strong new legal protections did not significantly reduce the use of common defensive medicine practices or the cost of care.
The team detailed these findings in NEJM.
“Our findings suggest that malpractice reform may have less effect on costs than has been projected by conventional wisdom,” said lead study author Daniel A. Waxman, MD, PhD, of RAND Health in Santa Monica, California.
“Physicians say they order unnecessary tests strictly out of fear of being sued, but our results suggest the story is more complicated.”
The investigators evaluated the results of malpractice reform in 3 states—Georgia, Texas, and South Carolina.
About a decade ago, these states changed the legal malpractice standard for emergency care to gross negligence. The higher standard means plaintiffs must prove that doctors consciously disregarded the need to use reasonable care, knowing full well that their actions were likely to cause serious injury.
“These malpractice reforms have been said to provide virtual immunity against lawsuits,” Dr Waxman noted.
He and his colleagues examined 3.8 million Medicare patient records from 1166 hospital emergency departments spanning the period from 1997 to 2011. They compared care in the 3 reform states, before and after the statutes took effect, to care in neighboring states that did not pass malpractice reform.
The team assessed whether physicians ordered an advanced imaging study (CT or MRI scan), whether the patient was hospitalized after the emergency visit, and total charges for the visit.
Advanced imaging and hospitalization are among the most costly consequences of an emergency room visit, and physicians have identified them as common defensive medicine practices.
The malpractice reform laws had no effect on the use of imaging or the rate of hospitalization following emergency visits.
For 2 of the states, Texas and South Carolina, the law did not appear to cause any reduction in charges. Relative to neighboring states, Georgia saw a drop of 3.6% in average emergency room charges following its 2005 reform.
“This study suggests that, even when the risk of being sued for malpractice decreases, the path of least resistance still may favor resource-intensive care, at least in hospital emergency departments,” Dr Waxman said.
Credit: CDC
Making it more difficult for patients to sue physicians for medical malpractice may not reduce the amount of “defensive medicine” physicians
practice, new research suggests.
Investigators studied patient records in 3 states that raised the standard for malpractice in the emergency room to gross negligence.
And they found that strong new legal protections did not significantly reduce the use of common defensive medicine practices or the cost of care.
The team detailed these findings in NEJM.
“Our findings suggest that malpractice reform may have less effect on costs than has been projected by conventional wisdom,” said lead study author Daniel A. Waxman, MD, PhD, of RAND Health in Santa Monica, California.
“Physicians say they order unnecessary tests strictly out of fear of being sued, but our results suggest the story is more complicated.”
The investigators evaluated the results of malpractice reform in 3 states—Georgia, Texas, and South Carolina.
About a decade ago, these states changed the legal malpractice standard for emergency care to gross negligence. The higher standard means plaintiffs must prove that doctors consciously disregarded the need to use reasonable care, knowing full well that their actions were likely to cause serious injury.
“These malpractice reforms have been said to provide virtual immunity against lawsuits,” Dr Waxman noted.
He and his colleagues examined 3.8 million Medicare patient records from 1166 hospital emergency departments spanning the period from 1997 to 2011. They compared care in the 3 reform states, before and after the statutes took effect, to care in neighboring states that did not pass malpractice reform.
The team assessed whether physicians ordered an advanced imaging study (CT or MRI scan), whether the patient was hospitalized after the emergency visit, and total charges for the visit.
Advanced imaging and hospitalization are among the most costly consequences of an emergency room visit, and physicians have identified them as common defensive medicine practices.
The malpractice reform laws had no effect on the use of imaging or the rate of hospitalization following emergency visits.
For 2 of the states, Texas and South Carolina, the law did not appear to cause any reduction in charges. Relative to neighboring states, Georgia saw a drop of 3.6% in average emergency room charges following its 2005 reform.
“This study suggests that, even when the risk of being sued for malpractice decreases, the path of least resistance still may favor resource-intensive care, at least in hospital emergency departments,” Dr Waxman said.
Drug can safely target NF-κB pathway in MM
Credit: Rhoda Baer
A new drug can safely target the NF-κB pathway in multiple myeloma (MM), according to research published in Cancer Cell.
The investigators identified an interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM.
They then developed a drug known as DTP3, which disrupts the GADD45β/MKK7 complex, thereby killing MM cells in vitro and in vivo, without harming normal cells.
“Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year,” said study author Guido Franzoso, MD, PhD, of Imperial College London in the UK.
Dr Franzoso and his colleagues knew that NF-κB is overactive in MM and other malignancies, but targeting NF-κB can have detrimental effects on healthy cells. So they looked for target genes downstream of NF-kB that might be responsible for its role in cancers.
By studying cells from MM patients, the investigators identified the protein complex GADD45β/MKK7, which appeared to play a critical role in allowing MM cells to survive.
Searching for a safe way to target the NF-kB pathway, the team screened more than 20,000 molecules and found 2 that disrupted GADD45β/MKK7. Further refinements led to the development of DTP3.
In human MM cells, DTP3 had a similar anticancer potency to that of bortezomib, but with a more than 100-fold higher cancer-cell specificity. DTP3 also retained full therapeutic efficacy in cell lines that were resistant to standard MM treatments.
In mice, DTP3 eradicated MM, with no apparent side effects at the effective doses.
In an orthotopic xenograft model of MM, control mice had a median overall survival of 26 days. But mice treated with DTP3 had a median overall survival that extended past the experimental endpoint on day 161.
“We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically,” Dr Franzoso said.
“The discovery that blocking the GADD45β/MKK7 segment of the NF-kB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma.”
A spinout company, Kesios Therapeutics, was formed to commercialize DTP3 and other drug candidates based on Dr Franzoso’s research, with support from Imperial Innovations, a technology commercialization company focused on developing academic research in the UK.
Credit: Rhoda Baer
A new drug can safely target the NF-κB pathway in multiple myeloma (MM), according to research published in Cancer Cell.
The investigators identified an interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM.
They then developed a drug known as DTP3, which disrupts the GADD45β/MKK7 complex, thereby killing MM cells in vitro and in vivo, without harming normal cells.
“Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year,” said study author Guido Franzoso, MD, PhD, of Imperial College London in the UK.
Dr Franzoso and his colleagues knew that NF-κB is overactive in MM and other malignancies, but targeting NF-κB can have detrimental effects on healthy cells. So they looked for target genes downstream of NF-kB that might be responsible for its role in cancers.
By studying cells from MM patients, the investigators identified the protein complex GADD45β/MKK7, which appeared to play a critical role in allowing MM cells to survive.
Searching for a safe way to target the NF-kB pathway, the team screened more than 20,000 molecules and found 2 that disrupted GADD45β/MKK7. Further refinements led to the development of DTP3.
In human MM cells, DTP3 had a similar anticancer potency to that of bortezomib, but with a more than 100-fold higher cancer-cell specificity. DTP3 also retained full therapeutic efficacy in cell lines that were resistant to standard MM treatments.
In mice, DTP3 eradicated MM, with no apparent side effects at the effective doses.
In an orthotopic xenograft model of MM, control mice had a median overall survival of 26 days. But mice treated with DTP3 had a median overall survival that extended past the experimental endpoint on day 161.
“We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically,” Dr Franzoso said.
“The discovery that blocking the GADD45β/MKK7 segment of the NF-kB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma.”
A spinout company, Kesios Therapeutics, was formed to commercialize DTP3 and other drug candidates based on Dr Franzoso’s research, with support from Imperial Innovations, a technology commercialization company focused on developing academic research in the UK.
Credit: Rhoda Baer
A new drug can safely target the NF-κB pathway in multiple myeloma (MM), according to research published in Cancer Cell.
The investigators identified an interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM.
They then developed a drug known as DTP3, which disrupts the GADD45β/MKK7 complex, thereby killing MM cells in vitro and in vivo, without harming normal cells.
“Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year,” said study author Guido Franzoso, MD, PhD, of Imperial College London in the UK.
Dr Franzoso and his colleagues knew that NF-κB is overactive in MM and other malignancies, but targeting NF-κB can have detrimental effects on healthy cells. So they looked for target genes downstream of NF-kB that might be responsible for its role in cancers.
By studying cells from MM patients, the investigators identified the protein complex GADD45β/MKK7, which appeared to play a critical role in allowing MM cells to survive.
Searching for a safe way to target the NF-kB pathway, the team screened more than 20,000 molecules and found 2 that disrupted GADD45β/MKK7. Further refinements led to the development of DTP3.
In human MM cells, DTP3 had a similar anticancer potency to that of bortezomib, but with a more than 100-fold higher cancer-cell specificity. DTP3 also retained full therapeutic efficacy in cell lines that were resistant to standard MM treatments.
In mice, DTP3 eradicated MM, with no apparent side effects at the effective doses.
In an orthotopic xenograft model of MM, control mice had a median overall survival of 26 days. But mice treated with DTP3 had a median overall survival that extended past the experimental endpoint on day 161.
“We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically,” Dr Franzoso said.
“The discovery that blocking the GADD45β/MKK7 segment of the NF-kB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma.”
A spinout company, Kesios Therapeutics, was formed to commercialize DTP3 and other drug candidates based on Dr Franzoso’s research, with support from Imperial Innovations, a technology commercialization company focused on developing academic research in the UK.
VTE is ‘major contributor’ to global disease burden
Credit: Andre E.X. Brown
Results of a systematic review suggest venous thromboembolism (VTE) has a high disease burden throughout the world, regardless of a country’s income.
Researchers reviewed the literature to quantify the global disease burden of VTE.
And they found that VTE associated with hospitalization was the leading cause of disability-adjusted life-years (DALYs) lost in low- and middle-income countries. It was the second most common cause of DALYs lost in high-income countries.
“Venous thromboembolism in hospitalized patients was responsible for more years lost due to ill-health than hospital-acquired pneumonia, catheter-related blood stream infections, and side effects from drugs,” said study author Gary Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City.
Dr Raskob and his colleagues reported these results in the Journal of Thrombosis & Haemostasis.
The team reviewed 8702 studies on VTE and found that studies from western Europe, North America, Australia, and southern Latin America (Argentina) yielded consistent results.
The annual incidence of VTE ranged from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 VTEs per 1000 people among those 70 years of age or older.
Only two studies were designed to evaluate the prevalence of VTE, and both were conducted using US data. In one study, researchers investigated the prevalence of VTE from 2002 to 2006 using a health insurance claims database of 12.7 million individuals.
VTE occurred in 3.2 enrollees per 1000 in 2002 and 4.2 per 1000 in 2006. In 2006, the prevalence of VTE was 13.8 per 1000 in enrollees age 65 and older and 2.3 per 1000 in those younger than 65 years of age.
The other study designed to assess VTE prevalence in the US showed that prevalence was highest in African American males, followed by Caucasian males, Caucasian females, and African American females. Hispanic individuals of both sexes had the lowest prevalence rates.
Two studies were designed to evaluate VTE disease burden in terms of DALYs. The strongest of these included data from a literature review and epidemiologic studies commissioned by the WHO.
The study showed that VTE occurred in 3.3 of 100 hospitalizations in high-income countries and 3.0 of 100 hospitalizations in low-income and middle-income countries. The estimated annual cases of VTE were 3.9 million and 6.0 million, respectively.
VTE was the leading cause of hospital-related DALYs lost overall. It was responsible for a third (7681) of the 22,644 DALYs.
The researchers concluded that VTE causes a major burden of disease across low-income, middle-income, and high-income countries. However, more detailed data on the global burden of VTE is needed.
Credit: Andre E.X. Brown
Results of a systematic review suggest venous thromboembolism (VTE) has a high disease burden throughout the world, regardless of a country’s income.
Researchers reviewed the literature to quantify the global disease burden of VTE.
And they found that VTE associated with hospitalization was the leading cause of disability-adjusted life-years (DALYs) lost in low- and middle-income countries. It was the second most common cause of DALYs lost in high-income countries.
“Venous thromboembolism in hospitalized patients was responsible for more years lost due to ill-health than hospital-acquired pneumonia, catheter-related blood stream infections, and side effects from drugs,” said study author Gary Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City.
Dr Raskob and his colleagues reported these results in the Journal of Thrombosis & Haemostasis.
The team reviewed 8702 studies on VTE and found that studies from western Europe, North America, Australia, and southern Latin America (Argentina) yielded consistent results.
The annual incidence of VTE ranged from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 VTEs per 1000 people among those 70 years of age or older.
Only two studies were designed to evaluate the prevalence of VTE, and both were conducted using US data. In one study, researchers investigated the prevalence of VTE from 2002 to 2006 using a health insurance claims database of 12.7 million individuals.
VTE occurred in 3.2 enrollees per 1000 in 2002 and 4.2 per 1000 in 2006. In 2006, the prevalence of VTE was 13.8 per 1000 in enrollees age 65 and older and 2.3 per 1000 in those younger than 65 years of age.
The other study designed to assess VTE prevalence in the US showed that prevalence was highest in African American males, followed by Caucasian males, Caucasian females, and African American females. Hispanic individuals of both sexes had the lowest prevalence rates.
Two studies were designed to evaluate VTE disease burden in terms of DALYs. The strongest of these included data from a literature review and epidemiologic studies commissioned by the WHO.
The study showed that VTE occurred in 3.3 of 100 hospitalizations in high-income countries and 3.0 of 100 hospitalizations in low-income and middle-income countries. The estimated annual cases of VTE were 3.9 million and 6.0 million, respectively.
VTE was the leading cause of hospital-related DALYs lost overall. It was responsible for a third (7681) of the 22,644 DALYs.
The researchers concluded that VTE causes a major burden of disease across low-income, middle-income, and high-income countries. However, more detailed data on the global burden of VTE is needed.
Credit: Andre E.X. Brown
Results of a systematic review suggest venous thromboembolism (VTE) has a high disease burden throughout the world, regardless of a country’s income.
Researchers reviewed the literature to quantify the global disease burden of VTE.
And they found that VTE associated with hospitalization was the leading cause of disability-adjusted life-years (DALYs) lost in low- and middle-income countries. It was the second most common cause of DALYs lost in high-income countries.
“Venous thromboembolism in hospitalized patients was responsible for more years lost due to ill-health than hospital-acquired pneumonia, catheter-related blood stream infections, and side effects from drugs,” said study author Gary Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City.
Dr Raskob and his colleagues reported these results in the Journal of Thrombosis & Haemostasis.
The team reviewed 8702 studies on VTE and found that studies from western Europe, North America, Australia, and southern Latin America (Argentina) yielded consistent results.
The annual incidence of VTE ranged from 0.75 to 2.69 per 1000 individuals in the population. The incidence increased to between 2 and 7 VTEs per 1000 people among those 70 years of age or older.
Only two studies were designed to evaluate the prevalence of VTE, and both were conducted using US data. In one study, researchers investigated the prevalence of VTE from 2002 to 2006 using a health insurance claims database of 12.7 million individuals.
VTE occurred in 3.2 enrollees per 1000 in 2002 and 4.2 per 1000 in 2006. In 2006, the prevalence of VTE was 13.8 per 1000 in enrollees age 65 and older and 2.3 per 1000 in those younger than 65 years of age.
The other study designed to assess VTE prevalence in the US showed that prevalence was highest in African American males, followed by Caucasian males, Caucasian females, and African American females. Hispanic individuals of both sexes had the lowest prevalence rates.
Two studies were designed to evaluate VTE disease burden in terms of DALYs. The strongest of these included data from a literature review and epidemiologic studies commissioned by the WHO.
The study showed that VTE occurred in 3.3 of 100 hospitalizations in high-income countries and 3.0 of 100 hospitalizations in low-income and middle-income countries. The estimated annual cases of VTE were 3.9 million and 6.0 million, respectively.
VTE was the leading cause of hospital-related DALYs lost overall. It was responsible for a third (7681) of the 22,644 DALYs.
The researchers concluded that VTE causes a major burden of disease across low-income, middle-income, and high-income countries. However, more detailed data on the global burden of VTE is needed.
Study reveals potential strategy for treating leukemia
The protein kinases Cdk4 and Cdk6 may determine the incidence and aggressiveness of leukemia, according to preclinical research.
The study showed that Cdk4 and Cdk6 cooperate to promote hematopoietic tumor development in mice.
And inhibiting Cdk4 and Cdk6 simultaneously proved a more effective method of fighting leukemia than inhibiting either protein alone.
The researchers recounted these findings in Blood.
“Cdk4/6 inhibitors used in cancer treatment don’t differentiate between the two molecules,” said study author Marcos Malumbres, PhD, of the Spanish National Cancer Research Centre (CNIO).
“The effectiveness of blocking both proteins at once has not been demonstrated to date.”
To get a wider perspective on this issue, Dr Malumbres and his colleagues designed genetically modified mice carrying active Cdk4, active Cdk6, or both versions of the active proteins.
The researchers found that simultaneous activation of both proteins promoted tumor growth in the mice, leading to more aggressive tumors and an increased risk of developing leukemia.
The team also found an explanation for why the simultaneous activation of Cdk4 and Cdk6 leads to such aggressive tumors.
Under normal conditions, Cdk4 and Cdk6 are inhibited by p16INK4A proteins. But when both Cdk4 and Cdk6 are present at high levels, p16INK4A proteins are unable to act as a retaining wall, leading to uncontrolled tumor growth.
“The assumption to date has been that these molecules act independently of each other,” Dr Malumbres said. “However, our recent findings now suggest that the combined inhibitors could be a more effective cancer treatment.”
“The clinical success of these compounds depends on the appropriate selection of patients. Our findings could help us to understand the molecular basis underpinning the success of these inhibitors, thereby contributing to the development of novel and more effective drugs.”
The protein kinases Cdk4 and Cdk6 may determine the incidence and aggressiveness of leukemia, according to preclinical research.
The study showed that Cdk4 and Cdk6 cooperate to promote hematopoietic tumor development in mice.
And inhibiting Cdk4 and Cdk6 simultaneously proved a more effective method of fighting leukemia than inhibiting either protein alone.
The researchers recounted these findings in Blood.
“Cdk4/6 inhibitors used in cancer treatment don’t differentiate between the two molecules,” said study author Marcos Malumbres, PhD, of the Spanish National Cancer Research Centre (CNIO).
“The effectiveness of blocking both proteins at once has not been demonstrated to date.”
To get a wider perspective on this issue, Dr Malumbres and his colleagues designed genetically modified mice carrying active Cdk4, active Cdk6, or both versions of the active proteins.
The researchers found that simultaneous activation of both proteins promoted tumor growth in the mice, leading to more aggressive tumors and an increased risk of developing leukemia.
The team also found an explanation for why the simultaneous activation of Cdk4 and Cdk6 leads to such aggressive tumors.
Under normal conditions, Cdk4 and Cdk6 are inhibited by p16INK4A proteins. But when both Cdk4 and Cdk6 are present at high levels, p16INK4A proteins are unable to act as a retaining wall, leading to uncontrolled tumor growth.
“The assumption to date has been that these molecules act independently of each other,” Dr Malumbres said. “However, our recent findings now suggest that the combined inhibitors could be a more effective cancer treatment.”
“The clinical success of these compounds depends on the appropriate selection of patients. Our findings could help us to understand the molecular basis underpinning the success of these inhibitors, thereby contributing to the development of novel and more effective drugs.”
The protein kinases Cdk4 and Cdk6 may determine the incidence and aggressiveness of leukemia, according to preclinical research.
The study showed that Cdk4 and Cdk6 cooperate to promote hematopoietic tumor development in mice.
And inhibiting Cdk4 and Cdk6 simultaneously proved a more effective method of fighting leukemia than inhibiting either protein alone.
The researchers recounted these findings in Blood.
“Cdk4/6 inhibitors used in cancer treatment don’t differentiate between the two molecules,” said study author Marcos Malumbres, PhD, of the Spanish National Cancer Research Centre (CNIO).
“The effectiveness of blocking both proteins at once has not been demonstrated to date.”
To get a wider perspective on this issue, Dr Malumbres and his colleagues designed genetically modified mice carrying active Cdk4, active Cdk6, or both versions of the active proteins.
The researchers found that simultaneous activation of both proteins promoted tumor growth in the mice, leading to more aggressive tumors and an increased risk of developing leukemia.
The team also found an explanation for why the simultaneous activation of Cdk4 and Cdk6 leads to such aggressive tumors.
Under normal conditions, Cdk4 and Cdk6 are inhibited by p16INK4A proteins. But when both Cdk4 and Cdk6 are present at high levels, p16INK4A proteins are unable to act as a retaining wall, leading to uncontrolled tumor growth.
“The assumption to date has been that these molecules act independently of each other,” Dr Malumbres said. “However, our recent findings now suggest that the combined inhibitors could be a more effective cancer treatment.”
“The clinical success of these compounds depends on the appropriate selection of patients. Our findings could help us to understand the molecular basis underpinning the success of these inhibitors, thereby contributing to the development of novel and more effective drugs.”
How being a parent affects advanced cancer patients
Credit: Vera Kratochvil
BOSTON—Having dependent children may motivate advanced cancer patients to pursue more aggressive treatment, a pilot study indicates.
Parental status was an important factor in treatment decision-making for most of the 42 patients studied.
A majority of patients said being a parent motivated them to pursue life-extending treatments, although some patients mentioned the importance of staying close to their families to receive treatment and retaining the ability to function as a parent.
This research was released in a presscast in advance of ASCO’s 2014 Quality Care Symposium, which is scheduled to take place October 17-18 at the Boston Marriott Copley Place. The research is set to be presented as abstract 65.*
Researchers interviewed 42 patients with metastatic cancer who have children younger than 18 years of age. The patients had an average age of 44.
When asked how having children influenced their treatment decisions, 64% of patients said being a parent motivated them to pursue life-extending treatments, largely out of a desire to have more time with their children. However, 24% of patients said being a parent did not influence their treatment decisions.
Twenty-four percent of respondents identified preserving parental functioning as a treatment priority. They didn’t want side effects interfering with their or their children’s daily lives.
And 12% of patients mentioned the importance of receiving treatment close to their families, rather than traveling for a second opinion or pursuing treatment that might require long hospital stays.
Fifty-two percent of patients indicated an interest in using hospice services. Others were specifically interested in institutional rather than home hospice care, due to a desire to protect their children from the dying experience.
Fifty-nine percent of patients reported an interest in receiving palliative care concurrent with their cancer treatment, although several patients seemed to conflate palliative care with end-of-life care.
“Numerous psychosocial factors influence patients’ decisions about cancer treatment,” said lead study author Devon Check, a PhD student at the University of North Carolina at Chapel Hill.
“It’s important for patients with dependent children to discuss their treatment priorities with their oncologist, who may not know, for example, how important it is for a patient with children to preserve their functioning at home.”
“We hope that our study can help oncologists engage patients with children in shared decision-making and promote alignment of the treatment plan with the patients’ priorities, including family responsibilities.”
Although this study included patients with a range of physical functioning and a variety of cancer types, the findings may not generalize to other patient groups.
The researchers are planning a larger study to explore the associations between parental status, parenting concerns, and decision-making about treatment for advanced cancer.
*Some of the data presented differ from data in the abstract.
Credit: Vera Kratochvil
BOSTON—Having dependent children may motivate advanced cancer patients to pursue more aggressive treatment, a pilot study indicates.
Parental status was an important factor in treatment decision-making for most of the 42 patients studied.
A majority of patients said being a parent motivated them to pursue life-extending treatments, although some patients mentioned the importance of staying close to their families to receive treatment and retaining the ability to function as a parent.
This research was released in a presscast in advance of ASCO’s 2014 Quality Care Symposium, which is scheduled to take place October 17-18 at the Boston Marriott Copley Place. The research is set to be presented as abstract 65.*
Researchers interviewed 42 patients with metastatic cancer who have children younger than 18 years of age. The patients had an average age of 44.
When asked how having children influenced their treatment decisions, 64% of patients said being a parent motivated them to pursue life-extending treatments, largely out of a desire to have more time with their children. However, 24% of patients said being a parent did not influence their treatment decisions.
Twenty-four percent of respondents identified preserving parental functioning as a treatment priority. They didn’t want side effects interfering with their or their children’s daily lives.
And 12% of patients mentioned the importance of receiving treatment close to their families, rather than traveling for a second opinion or pursuing treatment that might require long hospital stays.
Fifty-two percent of patients indicated an interest in using hospice services. Others were specifically interested in institutional rather than home hospice care, due to a desire to protect their children from the dying experience.
Fifty-nine percent of patients reported an interest in receiving palliative care concurrent with their cancer treatment, although several patients seemed to conflate palliative care with end-of-life care.
“Numerous psychosocial factors influence patients’ decisions about cancer treatment,” said lead study author Devon Check, a PhD student at the University of North Carolina at Chapel Hill.
“It’s important for patients with dependent children to discuss their treatment priorities with their oncologist, who may not know, for example, how important it is for a patient with children to preserve their functioning at home.”
“We hope that our study can help oncologists engage patients with children in shared decision-making and promote alignment of the treatment plan with the patients’ priorities, including family responsibilities.”
Although this study included patients with a range of physical functioning and a variety of cancer types, the findings may not generalize to other patient groups.
The researchers are planning a larger study to explore the associations between parental status, parenting concerns, and decision-making about treatment for advanced cancer.
*Some of the data presented differ from data in the abstract.
Credit: Vera Kratochvil
BOSTON—Having dependent children may motivate advanced cancer patients to pursue more aggressive treatment, a pilot study indicates.
Parental status was an important factor in treatment decision-making for most of the 42 patients studied.
A majority of patients said being a parent motivated them to pursue life-extending treatments, although some patients mentioned the importance of staying close to their families to receive treatment and retaining the ability to function as a parent.
This research was released in a presscast in advance of ASCO’s 2014 Quality Care Symposium, which is scheduled to take place October 17-18 at the Boston Marriott Copley Place. The research is set to be presented as abstract 65.*
Researchers interviewed 42 patients with metastatic cancer who have children younger than 18 years of age. The patients had an average age of 44.
When asked how having children influenced their treatment decisions, 64% of patients said being a parent motivated them to pursue life-extending treatments, largely out of a desire to have more time with their children. However, 24% of patients said being a parent did not influence their treatment decisions.
Twenty-four percent of respondents identified preserving parental functioning as a treatment priority. They didn’t want side effects interfering with their or their children’s daily lives.
And 12% of patients mentioned the importance of receiving treatment close to their families, rather than traveling for a second opinion or pursuing treatment that might require long hospital stays.
Fifty-two percent of patients indicated an interest in using hospice services. Others were specifically interested in institutional rather than home hospice care, due to a desire to protect their children from the dying experience.
Fifty-nine percent of patients reported an interest in receiving palliative care concurrent with their cancer treatment, although several patients seemed to conflate palliative care with end-of-life care.
“Numerous psychosocial factors influence patients’ decisions about cancer treatment,” said lead study author Devon Check, a PhD student at the University of North Carolina at Chapel Hill.
“It’s important for patients with dependent children to discuss their treatment priorities with their oncologist, who may not know, for example, how important it is for a patient with children to preserve their functioning at home.”
“We hope that our study can help oncologists engage patients with children in shared decision-making and promote alignment of the treatment plan with the patients’ priorities, including family responsibilities.”
Although this study included patients with a range of physical functioning and a variety of cancer types, the findings may not generalize to other patient groups.
The researchers are planning a larger study to explore the associations between parental status, parenting concerns, and decision-making about treatment for advanced cancer.
*Some of the data presented differ from data in the abstract.
CAR T cells serve as bridge to HSCT in ALL
Credit: Charles Haymond
An anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can elicit complete responses (CRs) in heavily pretreated patients with acute lymphoblastic leukemia (ALL), results of a phase 1 trial suggest.
More than half of the 21 patients enrolled achieved a CR, and most of those patients went on to hematopoietic stem cell transplant (HSCT).
All 10 patients who underwent HSCT remain leukemia-free at a median follow-up of 10 months.
The CAR T cells did prompt some serious adverse effects, but all effects were fully reversible.
Crystal L. Mackall, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues reported these results in The Lancet.
The phase 1 study enrolled patients ages 1 to 30 years who had relapsed or refractory ALL or non-Hodgkin lymphoma. Twenty patients had B-cell ALL, and 1 had diffuse large B-cell lymphoma (DLBCL). All of the patients had been heavily pretreated, and 8 had received a prior HSCT.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by a single infusion of CAR T cells: either 1×10⁶ CAR-transduced T cells per kg or 3×10⁶ CAR-transduced T cells per kg.
The CAR T cells were produced from each patient’s own peripheral blood mononuclear cells, modified using a gammaretroviral vector encoding the CAR, as well as a CD28 costimulatory moiety. After the dose-escalation phase, an expansion cohort was treated at the maximum-tolerated dose.
Twenty-one patients were enrolled and infused, but 2 of them did not receive the prescribed dose of CAR T cells, as the assigned dose could not be generated. The maximum-tolerated dose was 1×10⁶ CAR T cells per kg.
All toxicities were fully reversible. The most common non-hematologic grade 3 adverse events were fever (n=9), hypokalemia (n=9), fever and neutropenia (n=8), and cytokine release syndrome (n=3). Grade 4 cytokine release syndrome occurred in 3 patients.
At day 28, 12 patients had achieved a minimal residual disease (MRD)-negative CR. One patient had an MRD-positive CR, 1 had an MRD-positive CR with incomplete count recovery, and 3 patients had stable disease. Four patients, including the one with DLBCL, progressed.
Ten of the patients with an MRD-negative CR subsequently underwent HSCT, and all 10 remained disease-free with a median follow-up of 10 months.
“The results show that this treatment is feasible in many patients with ALL and can eradicate chemoresistant disease with an acceptable toxicity profile,” said Gary Schiller, MD, of the University of California, Los Angeles, who was not involved in this study.
“Further, the findings demonstrate substantially higher response rates than seen in the literature for the most recently approved agent for refractory ALL. CD19-CAR therapy represents a potentially important new tool to address the urgent need for new treatment modalities in these patients.”
Researchers previously reported positive results with this therapy in patients with chemotherapy-refractory DLBCL.
Credit: Charles Haymond
An anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can elicit complete responses (CRs) in heavily pretreated patients with acute lymphoblastic leukemia (ALL), results of a phase 1 trial suggest.
More than half of the 21 patients enrolled achieved a CR, and most of those patients went on to hematopoietic stem cell transplant (HSCT).
All 10 patients who underwent HSCT remain leukemia-free at a median follow-up of 10 months.
The CAR T cells did prompt some serious adverse effects, but all effects were fully reversible.
Crystal L. Mackall, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues reported these results in The Lancet.
The phase 1 study enrolled patients ages 1 to 30 years who had relapsed or refractory ALL or non-Hodgkin lymphoma. Twenty patients had B-cell ALL, and 1 had diffuse large B-cell lymphoma (DLBCL). All of the patients had been heavily pretreated, and 8 had received a prior HSCT.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by a single infusion of CAR T cells: either 1×10⁶ CAR-transduced T cells per kg or 3×10⁶ CAR-transduced T cells per kg.
The CAR T cells were produced from each patient’s own peripheral blood mononuclear cells, modified using a gammaretroviral vector encoding the CAR, as well as a CD28 costimulatory moiety. After the dose-escalation phase, an expansion cohort was treated at the maximum-tolerated dose.
Twenty-one patients were enrolled and infused, but 2 of them did not receive the prescribed dose of CAR T cells, as the assigned dose could not be generated. The maximum-tolerated dose was 1×10⁶ CAR T cells per kg.
All toxicities were fully reversible. The most common non-hematologic grade 3 adverse events were fever (n=9), hypokalemia (n=9), fever and neutropenia (n=8), and cytokine release syndrome (n=3). Grade 4 cytokine release syndrome occurred in 3 patients.
At day 28, 12 patients had achieved a minimal residual disease (MRD)-negative CR. One patient had an MRD-positive CR, 1 had an MRD-positive CR with incomplete count recovery, and 3 patients had stable disease. Four patients, including the one with DLBCL, progressed.
Ten of the patients with an MRD-negative CR subsequently underwent HSCT, and all 10 remained disease-free with a median follow-up of 10 months.
“The results show that this treatment is feasible in many patients with ALL and can eradicate chemoresistant disease with an acceptable toxicity profile,” said Gary Schiller, MD, of the University of California, Los Angeles, who was not involved in this study.
“Further, the findings demonstrate substantially higher response rates than seen in the literature for the most recently approved agent for refractory ALL. CD19-CAR therapy represents a potentially important new tool to address the urgent need for new treatment modalities in these patients.”
Researchers previously reported positive results with this therapy in patients with chemotherapy-refractory DLBCL.
Credit: Charles Haymond
An anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can elicit complete responses (CRs) in heavily pretreated patients with acute lymphoblastic leukemia (ALL), results of a phase 1 trial suggest.
More than half of the 21 patients enrolled achieved a CR, and most of those patients went on to hematopoietic stem cell transplant (HSCT).
All 10 patients who underwent HSCT remain leukemia-free at a median follow-up of 10 months.
The CAR T cells did prompt some serious adverse effects, but all effects were fully reversible.
Crystal L. Mackall, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues reported these results in The Lancet.
The phase 1 study enrolled patients ages 1 to 30 years who had relapsed or refractory ALL or non-Hodgkin lymphoma. Twenty patients had B-cell ALL, and 1 had diffuse large B-cell lymphoma (DLBCL). All of the patients had been heavily pretreated, and 8 had received a prior HSCT.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by a single infusion of CAR T cells: either 1×10⁶ CAR-transduced T cells per kg or 3×10⁶ CAR-transduced T cells per kg.
The CAR T cells were produced from each patient’s own peripheral blood mononuclear cells, modified using a gammaretroviral vector encoding the CAR, as well as a CD28 costimulatory moiety. After the dose-escalation phase, an expansion cohort was treated at the maximum-tolerated dose.
Twenty-one patients were enrolled and infused, but 2 of them did not receive the prescribed dose of CAR T cells, as the assigned dose could not be generated. The maximum-tolerated dose was 1×10⁶ CAR T cells per kg.
All toxicities were fully reversible. The most common non-hematologic grade 3 adverse events were fever (n=9), hypokalemia (n=9), fever and neutropenia (n=8), and cytokine release syndrome (n=3). Grade 4 cytokine release syndrome occurred in 3 patients.
At day 28, 12 patients had achieved a minimal residual disease (MRD)-negative CR. One patient had an MRD-positive CR, 1 had an MRD-positive CR with incomplete count recovery, and 3 patients had stable disease. Four patients, including the one with DLBCL, progressed.
Ten of the patients with an MRD-negative CR subsequently underwent HSCT, and all 10 remained disease-free with a median follow-up of 10 months.
“The results show that this treatment is feasible in many patients with ALL and can eradicate chemoresistant disease with an acceptable toxicity profile,” said Gary Schiller, MD, of the University of California, Los Angeles, who was not involved in this study.
“Further, the findings demonstrate substantially higher response rates than seen in the literature for the most recently approved agent for refractory ALL. CD19-CAR therapy represents a potentially important new tool to address the urgent need for new treatment modalities in these patients.”
Researchers previously reported positive results with this therapy in patients with chemotherapy-refractory DLBCL.
Coating repels blood and bacteria
to form a blood clot
Credit: James Weaver
Researchers have developed a coating that can prevent blood and bacteria from adhering to the surface of medical devices.
The coating repelled blood from more than 20 medically relevant substrates, suppressed biofilm formation, and prevented coagulation in an animal model for at least 8 hours.
The researchers believe this technology could reduce the use of anticoagulants and help prevent thrombotic occlusion and biofouling of medical devices.
The idea for the coating evolved from a surface technology known as “slippery liquid-infused porous surfaces (SLIPS),” which was developed by Joanna Aizenberg, PhD, of Harvard University’s Wyss Institute for Biologically Inspired Engineering.
Inspired by the slippery surface of the carnivorous pitcher plant, which enables the plant to capture insects, SLIPS can repel nearly any material. The liquid layer on the surface provides a barrier to everything from ice to crude oil and blood.
“Traditional SLIPS uses porous, textured surface substrates to immobilize the liquid layer, whereas medical surfaces are mostly flat and smooth,” Dr Aizenberg said. “So we further adapted our approach by capitalizing on the natural roughness of chemically modified surfaces of medical devices.”
She and her colleagues described this work in Nature Biotechnology.
The researchers developed a super-repellent coating that can be adhered to existing, approved medical devices. In a 2-step surface-coating process, they chemically attached a monolayer of perfluorocarbon, which is similar to Teflon.
Then, they added a layer of liquid perfluorocarbon, which is widely used in medicine for applications such as liquid ventilation for infants with breathing challenges, blood substitution, and eye surgery. The team calls the tethered perfluorocarbon plus the liquid layer a “tethered-liquid perfluorocarbon surface (TLP)”.
TLP worked seamlessly when coated on more than 20 different medical surfaces, including plastics, glasses, and metals.
The researchers also implanted medical-grade tubing and catheters coated with TLP in large blood vessels in pigs, and the coating prevented blood from clotting for at least 8 hours without the use of anticoagulants.
TLP-treated medical tubing was stored for more than a year under normal temperature and humidity conditions and still prevented clot formation, repelling fibrin and platelets.
The TLP surface remained stable under the full range of clinically relevant physiological shear stresses, or rates of blood flow seen in catheters and central lines, all the way up to dialysis machines.
When the bacteria Pseudomonas aeruginosa were grown in TLP-coated medical tubing for more than 6 weeks, less than 1 in a billion bacteria were able to adhere. Central lines coated with TLP significantly reduced sepsis from central-line associated bloodstream infections.
Out of curiosity, the researchers even tested a TLP-coated surface with a gecko, whose footpads contain hair-like structures with tremendous adhesive strength. And the gecko was unable to hold on.
“We were wonderfully surprised by how well the TLP coating worked, particularly in vivo without heparin,” said Anna Waterhouse, PhD, of the Wyss Institute.
“Usually, the blood will start to clot within an hour in the extracorporeal circuit, so our experiments really demonstrate the clinical relevance of this new coating.”
to form a blood clot
Credit: James Weaver
Researchers have developed a coating that can prevent blood and bacteria from adhering to the surface of medical devices.
The coating repelled blood from more than 20 medically relevant substrates, suppressed biofilm formation, and prevented coagulation in an animal model for at least 8 hours.
The researchers believe this technology could reduce the use of anticoagulants and help prevent thrombotic occlusion and biofouling of medical devices.
The idea for the coating evolved from a surface technology known as “slippery liquid-infused porous surfaces (SLIPS),” which was developed by Joanna Aizenberg, PhD, of Harvard University’s Wyss Institute for Biologically Inspired Engineering.
Inspired by the slippery surface of the carnivorous pitcher plant, which enables the plant to capture insects, SLIPS can repel nearly any material. The liquid layer on the surface provides a barrier to everything from ice to crude oil and blood.
“Traditional SLIPS uses porous, textured surface substrates to immobilize the liquid layer, whereas medical surfaces are mostly flat and smooth,” Dr Aizenberg said. “So we further adapted our approach by capitalizing on the natural roughness of chemically modified surfaces of medical devices.”
She and her colleagues described this work in Nature Biotechnology.
The researchers developed a super-repellent coating that can be adhered to existing, approved medical devices. In a 2-step surface-coating process, they chemically attached a monolayer of perfluorocarbon, which is similar to Teflon.
Then, they added a layer of liquid perfluorocarbon, which is widely used in medicine for applications such as liquid ventilation for infants with breathing challenges, blood substitution, and eye surgery. The team calls the tethered perfluorocarbon plus the liquid layer a “tethered-liquid perfluorocarbon surface (TLP)”.
TLP worked seamlessly when coated on more than 20 different medical surfaces, including plastics, glasses, and metals.
The researchers also implanted medical-grade tubing and catheters coated with TLP in large blood vessels in pigs, and the coating prevented blood from clotting for at least 8 hours without the use of anticoagulants.
TLP-treated medical tubing was stored for more than a year under normal temperature and humidity conditions and still prevented clot formation, repelling fibrin and platelets.
The TLP surface remained stable under the full range of clinically relevant physiological shear stresses, or rates of blood flow seen in catheters and central lines, all the way up to dialysis machines.
When the bacteria Pseudomonas aeruginosa were grown in TLP-coated medical tubing for more than 6 weeks, less than 1 in a billion bacteria were able to adhere. Central lines coated with TLP significantly reduced sepsis from central-line associated bloodstream infections.
Out of curiosity, the researchers even tested a TLP-coated surface with a gecko, whose footpads contain hair-like structures with tremendous adhesive strength. And the gecko was unable to hold on.
“We were wonderfully surprised by how well the TLP coating worked, particularly in vivo without heparin,” said Anna Waterhouse, PhD, of the Wyss Institute.
“Usually, the blood will start to clot within an hour in the extracorporeal circuit, so our experiments really demonstrate the clinical relevance of this new coating.”
to form a blood clot
Credit: James Weaver
Researchers have developed a coating that can prevent blood and bacteria from adhering to the surface of medical devices.
The coating repelled blood from more than 20 medically relevant substrates, suppressed biofilm formation, and prevented coagulation in an animal model for at least 8 hours.
The researchers believe this technology could reduce the use of anticoagulants and help prevent thrombotic occlusion and biofouling of medical devices.
The idea for the coating evolved from a surface technology known as “slippery liquid-infused porous surfaces (SLIPS),” which was developed by Joanna Aizenberg, PhD, of Harvard University’s Wyss Institute for Biologically Inspired Engineering.
Inspired by the slippery surface of the carnivorous pitcher plant, which enables the plant to capture insects, SLIPS can repel nearly any material. The liquid layer on the surface provides a barrier to everything from ice to crude oil and blood.
“Traditional SLIPS uses porous, textured surface substrates to immobilize the liquid layer, whereas medical surfaces are mostly flat and smooth,” Dr Aizenberg said. “So we further adapted our approach by capitalizing on the natural roughness of chemically modified surfaces of medical devices.”
She and her colleagues described this work in Nature Biotechnology.
The researchers developed a super-repellent coating that can be adhered to existing, approved medical devices. In a 2-step surface-coating process, they chemically attached a monolayer of perfluorocarbon, which is similar to Teflon.
Then, they added a layer of liquid perfluorocarbon, which is widely used in medicine for applications such as liquid ventilation for infants with breathing challenges, blood substitution, and eye surgery. The team calls the tethered perfluorocarbon plus the liquid layer a “tethered-liquid perfluorocarbon surface (TLP)”.
TLP worked seamlessly when coated on more than 20 different medical surfaces, including plastics, glasses, and metals.
The researchers also implanted medical-grade tubing and catheters coated with TLP in large blood vessels in pigs, and the coating prevented blood from clotting for at least 8 hours without the use of anticoagulants.
TLP-treated medical tubing was stored for more than a year under normal temperature and humidity conditions and still prevented clot formation, repelling fibrin and platelets.
The TLP surface remained stable under the full range of clinically relevant physiological shear stresses, or rates of blood flow seen in catheters and central lines, all the way up to dialysis machines.
When the bacteria Pseudomonas aeruginosa were grown in TLP-coated medical tubing for more than 6 weeks, less than 1 in a billion bacteria were able to adhere. Central lines coated with TLP significantly reduced sepsis from central-line associated bloodstream infections.
Out of curiosity, the researchers even tested a TLP-coated surface with a gecko, whose footpads contain hair-like structures with tremendous adhesive strength. And the gecko was unable to hold on.
“We were wonderfully surprised by how well the TLP coating worked, particularly in vivo without heparin,” said Anna Waterhouse, PhD, of the Wyss Institute.
“Usually, the blood will start to clot within an hour in the extracorporeal circuit, so our experiments really demonstrate the clinical relevance of this new coating.”