MADRID – With some genetic sleight-of-hand, investigators hope to mimic a rare, naturally occurring mutation that protects some patients with beta-thalassemia or sickle-cell disease (SCD) from becoming symptomatic.

Although human studies have yet to begin, investigators in a biotech company report that they can use CRISPR/Cas9 gene editing to recreate the rare condition known as hereditary persistence of fetal hemoglobin, or HPFH, which causes some patients with SCD or beta-thalassemia to continue to produce the fully functional fetal rather than adult form of hemoglobin into adulthood.

Neil Osterweil/Frontline Medical News

The company plans to submit a clinical trial application in 2017, and start clinical trials in 2018, Dr. Lundberg said.

At a media briefing where he discussed his research prior to his presentation of data in a symposium, Dr. Lundberg said that to date they have worked only with mouse models and with cells from healthy donors.

Neil Osterweil/Frontline Medical News

MADRID – With some genetic sleight-of-hand, investigators hope to mimic a rare, naturally occurring mutation that protects some patients with beta-thalassemia or sickle-cell disease (SCD) from becoming symptomatic.

Although human studies have yet to begin, investigators in a biotech company report that they can use CRISPR/Cas9 gene editing to recreate the rare condition known as hereditary persistence of fetal hemoglobin, or HPFH, which causes some patients with SCD or beta-thalassemia to continue to produce the fully functional fetal rather than adult form of hemoglobin into adulthood.

Neil Osterweil/Frontline Medical News

The company plans to submit a clinical trial application in 2017, and start clinical trials in 2018, Dr. Lundberg said.

At a media briefing where he discussed his research prior to his presentation of data in a symposium, Dr. Lundberg said that to date they have worked only with mouse models and with cells from healthy donors.

Neil Osterweil/Frontline Medical News

MADRID – With some genetic sleight-of-hand, investigators hope to mimic a rare, naturally occurring mutation that protects some patients with beta-thalassemia or sickle-cell disease (SCD) from becoming symptomatic.

Although human studies have yet to begin, investigators in a biotech company report that they can use CRISPR/Cas9 gene editing to recreate the rare condition known as hereditary persistence of fetal hemoglobin, or HPFH, which causes some patients with SCD or beta-thalassemia to continue to produce the fully functional fetal rather than adult form of hemoglobin into adulthood.

Neil Osterweil/Frontline Medical News

The company plans to submit a clinical trial application in 2017, and start clinical trials in 2018, Dr. Lundberg said.

At a media briefing where he discussed his research prior to his presentation of data in a symposium, Dr. Lundberg said that to date they have worked only with mouse models and with cells from healthy donors.

Neil Osterweil/Frontline Medical News

SAN DIEGO – In an industry-funded phase II trial, researchers say they’ve shown for the first time that oral basal insulin tablets can safely decrease plasma glucose in patients with type 2 diabetes (T2DM).

“Oral basal insulin appears safe and efficacious in insulin-naive patients with type 2 [diabetes] insufficiently controlled with medications. It improves glycemic control to a similar extent as does glargine,” said study lead author Leona Plum-Mörschel, MD, CEO of the German clinical research organization Profil Mainz, in an oral presentation at the scientific sessions of the American Diabetes Association. A statement from Novo Nordisk, the maker of the investigational medication, says the company discontinued development of the product due to its low bioavailability and concerns about the costs of producing it.

According to Dr. Plum-Mörschel, researchers have been searching for an oral insulin treatment for almost a century without success.

In the new phase IIa study, researchers tested a basal insulin analog tablet called OI338GT. It uses a technology platform called Gipet by Merrion Pharmaceuticals that aims to boost the absorption of injectable drugs when they are given in oral form.

Researchers recruited 50 insulin-naive patients with T2DM (mean age 61 ± 7 years, mean BMI 30.5 ± 3.7 kg/m²) whose diabetes wasn’t properly controlled by metformin by itself or in conjunction with other drugs. All had hemoglobin A_1c (HbA1c) levels between 7% and 10%.

The patients were randomly assigned (1:1) to the investigational oral medication or subcutaneous insulin glargine (IGlar). They took the drugs once a day for 8 weeks in addition to their existing drug regimen.

The researchers increased the doses on a weekly basis with a goal of reaching fasting plasma glucose (FPG) of 80-126 mg/dL. Daily doses of the investigational drug (nmol/kg) began at a mean 30 ± 11 and reached 114 ± 51 by the end of the study; daily mean doses of IGlar (U/kg) began at 0.11 ± 0.03 and ended at 0.33 ± 0.15.

Both medications boosted glycemic control at about the same level, the researchers report, based on levels of FPG, HbA_1c, and fructosamine levels at 8 weeks.

Mean FPG levels (mg/dL), the primary endpoint, declined in investigational medication and IGlar from 175 ± 50 and 164 ± 31, respectively, at baseline to 129 ± 33 and 121 ± 17, respectively, at end of treatment. The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.

In a post hoc analysis, mean HbA_1c levels declined from 8.1 ± 0.6% and 8.2 ± 0.8% at baseline in investigational medication and IGlar, respectively, to 7.3 ± 0.8% and 7.1 ± 0.6%, respectively. The treatment difference (investigational medication – IGlar) was 0.30% [–0.03;0.63], 95% CI, P = .0774.

In another post hoc analysis, mean fructosamine levels (micromol/L) dipped from 275 ± 44 and 273 ± 50 in investigational medication and IGlar, respectively, to 235 ± 45 and 223 ± 34, respectively. The treatment difference (investigational medication – IGlar)

was 9.6 micromol/L [–11.7;30.9], 95% CI, P = .3700. None of the patients reported severe hypoglycemia. In the investigational group, 6 subjects suffered 7 events of hypoglycemia that emerged or worsened during treatment; 11 events occurred in 6 subjects in the IGlar group. Researchers report similar levels of adverse events in both groups: 31 in 15 patients treated with the investigational drug and 37 in 17 patients treated with IGlar.

“After termination of treatment, plasma glucose rebounded to baseline levels within a couple of weeks,” Dr. Plum-Mörschel said.

Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.

SAN DIEGO – In an industry-funded phase II trial, researchers say they’ve shown for the first time that oral basal insulin tablets can safely decrease plasma glucose in patients with type 2 diabetes (T2DM).

“Oral basal insulin appears safe and efficacious in insulin-naive patients with type 2 [diabetes] insufficiently controlled with medications. It improves glycemic control to a similar extent as does glargine,” said study lead author Leona Plum-Mörschel, MD, CEO of the German clinical research organization Profil Mainz, in an oral presentation at the scientific sessions of the American Diabetes Association. A statement from Novo Nordisk, the maker of the investigational medication, says the company discontinued development of the product due to its low bioavailability and concerns about the costs of producing it.

According to Dr. Plum-Mörschel, researchers have been searching for an oral insulin treatment for almost a century without success.

In the new phase IIa study, researchers tested a basal insulin analog tablet called OI338GT. It uses a technology platform called Gipet by Merrion Pharmaceuticals that aims to boost the absorption of injectable drugs when they are given in oral form.

Researchers recruited 50 insulin-naive patients with T2DM (mean age 61 ± 7 years, mean BMI 30.5 ± 3.7 kg/m²) whose diabetes wasn’t properly controlled by metformin by itself or in conjunction with other drugs. All had hemoglobin A_1c (HbA1c) levels between 7% and 10%.

The patients were randomly assigned (1:1) to the investigational oral medication or subcutaneous insulin glargine (IGlar). They took the drugs once a day for 8 weeks in addition to their existing drug regimen.

The researchers increased the doses on a weekly basis with a goal of reaching fasting plasma glucose (FPG) of 80-126 mg/dL. Daily doses of the investigational drug (nmol/kg) began at a mean 30 ± 11 and reached 114 ± 51 by the end of the study; daily mean doses of IGlar (U/kg) began at 0.11 ± 0.03 and ended at 0.33 ± 0.15.

Both medications boosted glycemic control at about the same level, the researchers report, based on levels of FPG, HbA_1c, and fructosamine levels at 8 weeks.

Mean FPG levels (mg/dL), the primary endpoint, declined in investigational medication and IGlar from 175 ± 50 and 164 ± 31, respectively, at baseline to 129 ± 33 and 121 ± 17, respectively, at end of treatment. The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.

In a post hoc analysis, mean HbA_1c levels declined from 8.1 ± 0.6% and 8.2 ± 0.8% at baseline in investigational medication and IGlar, respectively, to 7.3 ± 0.8% and 7.1 ± 0.6%, respectively. The treatment difference (investigational medication – IGlar) was 0.30% [–0.03;0.63], 95% CI, P = .0774.

In another post hoc analysis, mean fructosamine levels (micromol/L) dipped from 275 ± 44 and 273 ± 50 in investigational medication and IGlar, respectively, to 235 ± 45 and 223 ± 34, respectively. The treatment difference (investigational medication – IGlar)

was 9.6 micromol/L [–11.7;30.9], 95% CI, P = .3700. None of the patients reported severe hypoglycemia. In the investigational group, 6 subjects suffered 7 events of hypoglycemia that emerged or worsened during treatment; 11 events occurred in 6 subjects in the IGlar group. Researchers report similar levels of adverse events in both groups: 31 in 15 patients treated with the investigational drug and 37 in 17 patients treated with IGlar.

“After termination of treatment, plasma glucose rebounded to baseline levels within a couple of weeks,” Dr. Plum-Mörschel said.

Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.

SAN DIEGO – In an industry-funded phase II trial, researchers say they’ve shown for the first time that oral basal insulin tablets can safely decrease plasma glucose in patients with type 2 diabetes (T2DM).

“Oral basal insulin appears safe and efficacious in insulin-naive patients with type 2 [diabetes] insufficiently controlled with medications. It improves glycemic control to a similar extent as does glargine,” said study lead author Leona Plum-Mörschel, MD, CEO of the German clinical research organization Profil Mainz, in an oral presentation at the scientific sessions of the American Diabetes Association. A statement from Novo Nordisk, the maker of the investigational medication, says the company discontinued development of the product due to its low bioavailability and concerns about the costs of producing it.

According to Dr. Plum-Mörschel, researchers have been searching for an oral insulin treatment for almost a century without success.

In the new phase IIa study, researchers tested a basal insulin analog tablet called OI338GT. It uses a technology platform called Gipet by Merrion Pharmaceuticals that aims to boost the absorption of injectable drugs when they are given in oral form.

Researchers recruited 50 insulin-naive patients with T2DM (mean age 61 ± 7 years, mean BMI 30.5 ± 3.7 kg/m²) whose diabetes wasn’t properly controlled by metformin by itself or in conjunction with other drugs. All had hemoglobin A_1c (HbA1c) levels between 7% and 10%.

The patients were randomly assigned (1:1) to the investigational oral medication or subcutaneous insulin glargine (IGlar). They took the drugs once a day for 8 weeks in addition to their existing drug regimen.

The researchers increased the doses on a weekly basis with a goal of reaching fasting plasma glucose (FPG) of 80-126 mg/dL. Daily doses of the investigational drug (nmol/kg) began at a mean 30 ± 11 and reached 114 ± 51 by the end of the study; daily mean doses of IGlar (U/kg) began at 0.11 ± 0.03 and ended at 0.33 ± 0.15.

Both medications boosted glycemic control at about the same level, the researchers report, based on levels of FPG, HbA_1c, and fructosamine levels at 8 weeks.

Mean FPG levels (mg/dL), the primary endpoint, declined in investigational medication and IGlar from 175 ± 50 and 164 ± 31, respectively, at baseline to 129 ± 33 and 121 ± 17, respectively, at end of treatment. The treatment difference (investigational medication – IGlar) was 5.2 mg/dL [–8.8;19.1], 95% CI, P = .4567.

In a post hoc analysis, mean HbA_1c levels declined from 8.1 ± 0.6% and 8.2 ± 0.8% at baseline in investigational medication and IGlar, respectively, to 7.3 ± 0.8% and 7.1 ± 0.6%, respectively. The treatment difference (investigational medication – IGlar) was 0.30% [–0.03;0.63], 95% CI, P = .0774.

In another post hoc analysis, mean fructosamine levels (micromol/L) dipped from 275 ± 44 and 273 ± 50 in investigational medication and IGlar, respectively, to 235 ± 45 and 223 ± 34, respectively. The treatment difference (investigational medication – IGlar)

was 9.6 micromol/L [–11.7;30.9], 95% CI, P = .3700. None of the patients reported severe hypoglycemia. In the investigational group, 6 subjects suffered 7 events of hypoglycemia that emerged or worsened during treatment; 11 events occurred in 6 subjects in the IGlar group. Researchers report similar levels of adverse events in both groups: 31 in 15 patients treated with the investigational drug and 37 in 17 patients treated with IGlar.

“After termination of treatment, plasma glucose rebounded to baseline levels within a couple of weeks,” Dr. Plum-Mörschel said.

Novo Nordisk funded the trial. Dr. Plum-Mörschel reports no disclosures.

Image by Peter H. Seeberger

Progress is being made in the battle against malaria. From engineering a mosquito-killing fungus to discovering new anti-malaria targets, scientists are making advances on multiple malaria fronts.

And US aid to combat malaria is having a positive impact on reducing childhood mortality in 19 sub-Saharan countries.  A few of the recent developments are described here.

Genetic engineering

Scientists developed a genetic technique that disrupts the heme synthesis pathway in Plasmodium berghei parasites, which could be an effective way to target Plasmodium parasites in the liver.

Heme synthesis is essential for P berghei development in mosquitoes that transmit the parasite between rodent hosts. However, the pathway is not essential during a later stage of the parasite’s development in the bloodstream.

So researchers produced P berghei parasites capable of expressing the FC gene. The FC (ferrochelatase) gene allows P berghei to produce heme. The parasites could develop properly in mosquitoes, but produced some FC-deficient parasites once they infected mouse liver cells.

FC-deficient parasites were unable to complete their liver development phase.

The team says this approach would be prophylactic, since malaria symptoms aren't apparent until the parasite leaves the liver and begins its bloodstream phase.

The team published its findings in PLOS Pathogens.

Mosquito-killing fungi

 In a report that sounds almost like a science fiction story, researchers genetically engineered a fungus to kill mosquitoes by producing spider and scorpion toxins.

They suggest this method could serve as a highly effective biological control mechanism to fight malaria-carrying mosquitoes.

The researchers isolated genes that express neurotoxins from the venom of scorpions and spiders. They then engineered the genes into the fungus's DNA.

The researchers used the fungus Metarhizium pingshaensei, which is a natural killer of mosquitoes.

The fungus was originally isolated from a mosquito and previous evidence suggests it is specific to disease-carrying mosquito species, including Anopheles gambiae and Aedes aegypti.

When spores of the fungus contact a mosquito's body, the spores germinate and penetrate the insect's exoskeleton, eventually killing the insect host from the inside out.

And the most potent fungal strains, Brian Lovett, a graduate student at the University of Maryland in College Park, explained, “are able to kill mosquitoes with a single spore."

He added that the fungi also stop mosquitoes from blood feeding. Taken together, this means “that our fungal strains are capable of preventing transmission of disease by more than 90 percent of mosquitoes after just 5 days."

The fungus is specific to mosquitoes and does not pose a risk to humans. The study results also suggest the fungus is safe for honeybees and other insects.

The researchers plan to expand on-the-ground testing in Burkina Faso.

For more on this mosquito-killing approach, see their study published in Scientific Reports.

Potential new target

Researchers have described a new protein, the transcription factor PfAP2-I, which they say may turn out to be an effective target to combat drug-resistant malaria parasites.

PfAP2-I regulates genes involved with the parasite's invasion of red blood cells. This is a critical part of the parasite's 3-stage life cycle that could be targeted by new anti-malarial drugs.

“Most multi-celled organisms have hundreds of these regulators,” said lead author Manuel Llinás, PhD, of Penn State University in State College, Pennsylvania, “but it turns out, so far as we can recognize, the [Plasmodium] parasite has a single family of transcription factors called Apicomplexan AP2 proteins. One of these transcription factors is PfAP2-I."

PfAP2-I is the first known regulator of invasion genes in Plasmodium falciparum.

The new study also indicates that PfAP2-I likely recruits another protein, Bromodomain Protein 1 (PfBDP1), which was previously shown to be involved in the invasion of red blood cells.

The two proteins may work together to regulate gene transcription during this critical stage of infection.

For more on this potential new target, see their study published in Cell Host & Microbe.

Parasite diversity

 Not all malaria infections result in life-threatening anemia and organ failure, and so a research team led by Matthew B. B. McCall, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, set out to determine why.

They exposed 23 healthy human volunteers to sets of 5 mosquitoes carrying the NF54, NF135.C10, or NF166.C8 isolates of P falciparum.

All volunteers developed parasitemia, were treated with anti-malarial drugs, and recovered, although some strains caused more severe symptoms.

The investigators found that 3 geographic and genetically diverse forms of the parasite each demonstrated a distinct ability to infect liver cells.

They also observed the degree of infection in human liver cells growing in culture was closely correlated with parasite loads in the bloodstream.

The investigators believe the variability among parasite types suggests that malaria vaccines should use multiple strains.

In addition, the infectivity of different parasite strains could vary in populations previously exposed to malaria.

For more details on parasite diversity, see the team’s findings in Science Translational Medicine.

Malaria test

A new malaria test can diagnose malaria faster and more reliably than current methods, according to a report in the NL Times.

The new test uses an algorithm that can diagnose malaria at a rate of 120 blood tests per hour.  It is 97% accurate.

Rather than search for the parasite itself in blood samples, the new test analyzes the effect the infection has on the blood, such as shape and density of red blood cells, hemoglobin level, and 27 other parameters simultaneously.

The developers won the European Inventor Award for the rapid malaria test, which will be further developed by Siemens.

Aid to combat malaria

The US malaria initiative in 19 sub-Saharan African countries has contributed to a 16% reduction in the annual risk of mortality for children under 5 years, according to a new study published in PLOS Medicine.

Thirteen sub-Saharan countries did not receive funding from the initiative, which allowed researchers to compare and analyze the impact of the intervention.

Because the study may have had confounding variables that were not measured, however, the results could not be definitively interpreted as causal evidence of the reduction in child mortality rates.

However, they do indicate an association between the receipt of funding and mortality.

The funding went to support malaria prevention technologies, such as insecticide-treated nets and indoor residual spraying.

The authors believe further investment in these interventions “may translate to additional lives saved, reduced household financial burdens associated with caring for ill household members and lost wages, and less strain on health systems associated with treating malaria cases.”

Countries that received funding included: Angola, Benin, Congo DRC, Ethiopia, Ghana, Guinea, Kenya, Liberia, Madagascar, Malawi, Mali, Mozambique, Nigeria, Rwanda, Senegal, Tanzania, Uganda, Zambia, and Zimbabwe.

Comparison countries include: Burkina Faso, Burundi, Cameroon, Chad, Congo, Cote d’Ivoire, Gabon, Namibia, Niger, Sierra Leone, Swaziland, The Gambia, and Togo. 

Image by Peter H. Seeberger

Progress is being made in the battle against malaria. From engineering a mosquito-killing fungus to discovering new anti-malaria targets, scientists are making advances on multiple malaria fronts.

And US aid to combat malaria is having a positive impact on reducing childhood mortality in 19 sub-Saharan countries.  A few of the recent developments are described here.

Genetic engineering

Scientists developed a genetic technique that disrupts the heme synthesis pathway in Plasmodium berghei parasites, which could be an effective way to target Plasmodium parasites in the liver.

Heme synthesis is essential for P berghei development in mosquitoes that transmit the parasite between rodent hosts. However, the pathway is not essential during a later stage of the parasite’s development in the bloodstream.

So researchers produced P berghei parasites capable of expressing the FC gene. The FC (ferrochelatase) gene allows P berghei to produce heme. The parasites could develop properly in mosquitoes, but produced some FC-deficient parasites once they infected mouse liver cells.

FC-deficient parasites were unable to complete their liver development phase.

The team says this approach would be prophylactic, since malaria symptoms aren't apparent until the parasite leaves the liver and begins its bloodstream phase.

The team published its findings in PLOS Pathogens.

Mosquito-killing fungi

 In a report that sounds almost like a science fiction story, researchers genetically engineered a fungus to kill mosquitoes by producing spider and scorpion toxins.

They suggest this method could serve as a highly effective biological control mechanism to fight malaria-carrying mosquitoes.

The researchers isolated genes that express neurotoxins from the venom of scorpions and spiders. They then engineered the genes into the fungus's DNA.

The researchers used the fungus Metarhizium pingshaensei, which is a natural killer of mosquitoes.

The fungus was originally isolated from a mosquito and previous evidence suggests it is specific to disease-carrying mosquito species, including Anopheles gambiae and Aedes aegypti.

When spores of the fungus contact a mosquito's body, the spores germinate and penetrate the insect's exoskeleton, eventually killing the insect host from the inside out.

And the most potent fungal strains, Brian Lovett, a graduate student at the University of Maryland in College Park, explained, “are able to kill mosquitoes with a single spore."

He added that the fungi also stop mosquitoes from blood feeding. Taken together, this means “that our fungal strains are capable of preventing transmission of disease by more than 90 percent of mosquitoes after just 5 days."

The fungus is specific to mosquitoes and does not pose a risk to humans. The study results also suggest the fungus is safe for honeybees and other insects.

The researchers plan to expand on-the-ground testing in Burkina Faso.

For more on this mosquito-killing approach, see their study published in Scientific Reports.

Potential new target

Researchers have described a new protein, the transcription factor PfAP2-I, which they say may turn out to be an effective target to combat drug-resistant malaria parasites.

PfAP2-I regulates genes involved with the parasite's invasion of red blood cells. This is a critical part of the parasite's 3-stage life cycle that could be targeted by new anti-malarial drugs.

“Most multi-celled organisms have hundreds of these regulators,” said lead author Manuel Llinás, PhD, of Penn State University in State College, Pennsylvania, “but it turns out, so far as we can recognize, the [Plasmodium] parasite has a single family of transcription factors called Apicomplexan AP2 proteins. One of these transcription factors is PfAP2-I."

PfAP2-I is the first known regulator of invasion genes in Plasmodium falciparum.

The new study also indicates that PfAP2-I likely recruits another protein, Bromodomain Protein 1 (PfBDP1), which was previously shown to be involved in the invasion of red blood cells.

The two proteins may work together to regulate gene transcription during this critical stage of infection.

For more on this potential new target, see their study published in Cell Host & Microbe.

Parasite diversity

 Not all malaria infections result in life-threatening anemia and organ failure, and so a research team led by Matthew B. B. McCall, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, set out to determine why.

They exposed 23 healthy human volunteers to sets of 5 mosquitoes carrying the NF54, NF135.C10, or NF166.C8 isolates of P falciparum.

All volunteers developed parasitemia, were treated with anti-malarial drugs, and recovered, although some strains caused more severe symptoms.

The investigators found that 3 geographic and genetically diverse forms of the parasite each demonstrated a distinct ability to infect liver cells.

They also observed the degree of infection in human liver cells growing in culture was closely correlated with parasite loads in the bloodstream.

The investigators believe the variability among parasite types suggests that malaria vaccines should use multiple strains.

In addition, the infectivity of different parasite strains could vary in populations previously exposed to malaria.

For more details on parasite diversity, see the team’s findings in Science Translational Medicine.

Malaria test

A new malaria test can diagnose malaria faster and more reliably than current methods, according to a report in the NL Times.

The new test uses an algorithm that can diagnose malaria at a rate of 120 blood tests per hour.  It is 97% accurate.

Rather than search for the parasite itself in blood samples, the new test analyzes the effect the infection has on the blood, such as shape and density of red blood cells, hemoglobin level, and 27 other parameters simultaneously.

The developers won the European Inventor Award for the rapid malaria test, which will be further developed by Siemens.

Aid to combat malaria

The US malaria initiative in 19 sub-Saharan African countries has contributed to a 16% reduction in the annual risk of mortality for children under 5 years, according to a new study published in PLOS Medicine.

Thirteen sub-Saharan countries did not receive funding from the initiative, which allowed researchers to compare and analyze the impact of the intervention.

Because the study may have had confounding variables that were not measured, however, the results could not be definitively interpreted as causal evidence of the reduction in child mortality rates.

However, they do indicate an association between the receipt of funding and mortality.

The funding went to support malaria prevention technologies, such as insecticide-treated nets and indoor residual spraying.

The authors believe further investment in these interventions “may translate to additional lives saved, reduced household financial burdens associated with caring for ill household members and lost wages, and less strain on health systems associated with treating malaria cases.”

Countries that received funding included: Angola, Benin, Congo DRC, Ethiopia, Ghana, Guinea, Kenya, Liberia, Madagascar, Malawi, Mali, Mozambique, Nigeria, Rwanda, Senegal, Tanzania, Uganda, Zambia, and Zimbabwe.

Comparison countries include: Burkina Faso, Burundi, Cameroon, Chad, Congo, Cote d’Ivoire, Gabon, Namibia, Niger, Sierra Leone, Swaziland, The Gambia, and Togo. 

Image by Peter H. Seeberger

Progress is being made in the battle against malaria. From engineering a mosquito-killing fungus to discovering new anti-malaria targets, scientists are making advances on multiple malaria fronts.

And US aid to combat malaria is having a positive impact on reducing childhood mortality in 19 sub-Saharan countries.  A few of the recent developments are described here.

Genetic engineering

Scientists developed a genetic technique that disrupts the heme synthesis pathway in Plasmodium berghei parasites, which could be an effective way to target Plasmodium parasites in the liver.

Heme synthesis is essential for P berghei development in mosquitoes that transmit the parasite between rodent hosts. However, the pathway is not essential during a later stage of the parasite’s development in the bloodstream.

So researchers produced P berghei parasites capable of expressing the FC gene. The FC (ferrochelatase) gene allows P berghei to produce heme. The parasites could develop properly in mosquitoes, but produced some FC-deficient parasites once they infected mouse liver cells.

FC-deficient parasites were unable to complete their liver development phase.

The team says this approach would be prophylactic, since malaria symptoms aren't apparent until the parasite leaves the liver and begins its bloodstream phase.

The team published its findings in PLOS Pathogens.

Mosquito-killing fungi

 In a report that sounds almost like a science fiction story, researchers genetically engineered a fungus to kill mosquitoes by producing spider and scorpion toxins.

They suggest this method could serve as a highly effective biological control mechanism to fight malaria-carrying mosquitoes.

The researchers isolated genes that express neurotoxins from the venom of scorpions and spiders. They then engineered the genes into the fungus's DNA.

The researchers used the fungus Metarhizium pingshaensei, which is a natural killer of mosquitoes.

The fungus was originally isolated from a mosquito and previous evidence suggests it is specific to disease-carrying mosquito species, including Anopheles gambiae and Aedes aegypti.

When spores of the fungus contact a mosquito's body, the spores germinate and penetrate the insect's exoskeleton, eventually killing the insect host from the inside out.

And the most potent fungal strains, Brian Lovett, a graduate student at the University of Maryland in College Park, explained, “are able to kill mosquitoes with a single spore."

He added that the fungi also stop mosquitoes from blood feeding. Taken together, this means “that our fungal strains are capable of preventing transmission of disease by more than 90 percent of mosquitoes after just 5 days."

The fungus is specific to mosquitoes and does not pose a risk to humans. The study results also suggest the fungus is safe for honeybees and other insects.

The researchers plan to expand on-the-ground testing in Burkina Faso.

For more on this mosquito-killing approach, see their study published in Scientific Reports.

Potential new target

Researchers have described a new protein, the transcription factor PfAP2-I, which they say may turn out to be an effective target to combat drug-resistant malaria parasites.

PfAP2-I regulates genes involved with the parasite's invasion of red blood cells. This is a critical part of the parasite's 3-stage life cycle that could be targeted by new anti-malarial drugs.

“Most multi-celled organisms have hundreds of these regulators,” said lead author Manuel Llinás, PhD, of Penn State University in State College, Pennsylvania, “but it turns out, so far as we can recognize, the [Plasmodium] parasite has a single family of transcription factors called Apicomplexan AP2 proteins. One of these transcription factors is PfAP2-I."

PfAP2-I is the first known regulator of invasion genes in Plasmodium falciparum.

The new study also indicates that PfAP2-I likely recruits another protein, Bromodomain Protein 1 (PfBDP1), which was previously shown to be involved in the invasion of red blood cells.

The two proteins may work together to regulate gene transcription during this critical stage of infection.

For more on this potential new target, see their study published in Cell Host & Microbe.

Parasite diversity

 Not all malaria infections result in life-threatening anemia and organ failure, and so a research team led by Matthew B. B. McCall, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, set out to determine why.

They exposed 23 healthy human volunteers to sets of 5 mosquitoes carrying the NF54, NF135.C10, or NF166.C8 isolates of P falciparum.

All volunteers developed parasitemia, were treated with anti-malarial drugs, and recovered, although some strains caused more severe symptoms.

The investigators found that 3 geographic and genetically diverse forms of the parasite each demonstrated a distinct ability to infect liver cells.

They also observed the degree of infection in human liver cells growing in culture was closely correlated with parasite loads in the bloodstream.

The investigators believe the variability among parasite types suggests that malaria vaccines should use multiple strains.

In addition, the infectivity of different parasite strains could vary in populations previously exposed to malaria.

For more details on parasite diversity, see the team’s findings in Science Translational Medicine.

Malaria test

A new malaria test can diagnose malaria faster and more reliably than current methods, according to a report in the NL Times.

The new test uses an algorithm that can diagnose malaria at a rate of 120 blood tests per hour.  It is 97% accurate.

Rather than search for the parasite itself in blood samples, the new test analyzes the effect the infection has on the blood, such as shape and density of red blood cells, hemoglobin level, and 27 other parameters simultaneously.

The developers won the European Inventor Award for the rapid malaria test, which will be further developed by Siemens.

Aid to combat malaria

The US malaria initiative in 19 sub-Saharan African countries has contributed to a 16% reduction in the annual risk of mortality for children under 5 years, according to a new study published in PLOS Medicine.

Thirteen sub-Saharan countries did not receive funding from the initiative, which allowed researchers to compare and analyze the impact of the intervention.

Because the study may have had confounding variables that were not measured, however, the results could not be definitively interpreted as causal evidence of the reduction in child mortality rates.

However, they do indicate an association between the receipt of funding and mortality.

The funding went to support malaria prevention technologies, such as insecticide-treated nets and indoor residual spraying.

The authors believe further investment in these interventions “may translate to additional lives saved, reduced household financial burdens associated with caring for ill household members and lost wages, and less strain on health systems associated with treating malaria cases.”

Countries that received funding included: Angola, Benin, Congo DRC, Ethiopia, Ghana, Guinea, Kenya, Liberia, Madagascar, Malawi, Mali, Mozambique, Nigeria, Rwanda, Senegal, Tanzania, Uganda, Zambia, and Zimbabwe.

Comparison countries include: Burkina Faso, Burundi, Cameroon, Chad, Congo, Cote d’Ivoire, Gabon, Namibia, Niger, Sierra Leone, Swaziland, The Gambia, and Togo. 

MADRID – Abatacept doesn’t appear to increase the risk of opportunistic infections among patients with rheumatoid arthritis, Kevin Winthrop, MD, reported at the European Congress of Rheumatology.

After reviewing all of the extant safety data on the drug – all of its clinical trial and open-label study data, and case reports of abatacept-associated adverse events – Dr. Winthrop concluded that infections, including tuberculosis, fungal overgrowth, herpes simplex and herpes zoster, occur either with similar frequency or less often than among those taking placebo.

“In fact, there is a sense that abatacept is actually safer,” than some other disease-modifying antirheumatic drugs,” said Dr. Winthrop, an infectious disease specialist at Oregon Health and Science University, Portland. However, there are few data comparing safety among the agents – something he said should be examined in more detail.

His review encompassed 16 clinical trials comprising 7,044 patients who took the drug (21,330 patient/years of abatacept exposure) and 1,485 patients who took placebo. He conducted two analyses: one for opportunistic bacterial and fungal infections, and one for herpes simplex and herpes zoster.

The first analysis found 45 opportunistic bacterial or fungal infections among those taking abatacept – an incidence rate of 0.21/ 100 person-years. There were seven such infections in the placebo group – an incidence rate of 0.56/100 person-years. This difference was statistically significant.

In the abatacept cohort, there were two cases of bronchopulmonary aspergilliosis (IR 0.01) and three fungal eye infections (IR 0.01). There was also one case of gastrointestinal candidiasis; one fungal esophagitis; one cryptococcal meningitis; two pneumonias (one pseudomonal and one caused by Pneumocystis jirovecii); and two cases of respiratory monoliasis. All of these infections had an incidence rate of less than 0.01/100 person-years.

There were 17 tuberculosis cases (IR 0.08/100 person-years). Three cases were latent. Six of the cases were pulmonary and five were extrapulmonary. Two cases were unspecified. All occurred in regions with high or moderate endemic tuberculosis levels.

A meta-regression analysis examined the risk of opportunistic infections in the patients taken from the placebo-controlled clinical trials only (2,653 abatacept, 1,485 placebo). The estimated frequency of an opportunistic infection was 0.15% among those taking the drug and 0.48% among those taking placebo.

The herpes analysis examined the placebo-controlled clinical trial population as well. There were 57 cases of herpes simplex (IR 2.5/100 person-years) among those taking abatacept and 22 among those taking placebo (IR 1.8/100 person-years). The difference was not statistically significant.

There were 44 cases of herpes zoster among those taking abatacept (IR 1.9/100 person-years) and 21 among those taking placebo (IR 1.7/100 person-years).

“Basically, I think what we’re seeing here is a whole lot of nothing,” Dr. Winthrop said.

Dr. Winthrop has been a consultant for Pfizer, AbbVie, Bristol-Myers Squibb, UCB Pharma, Roche/Genentech, Amgen, Galapagos, and Eli Lilly.

[email protected]

On Twitter @Alz_gal

MADRID – Abatacept doesn’t appear to increase the risk of opportunistic infections among patients with rheumatoid arthritis, Kevin Winthrop, MD, reported at the European Congress of Rheumatology.

After reviewing all of the extant safety data on the drug – all of its clinical trial and open-label study data, and case reports of abatacept-associated adverse events – Dr. Winthrop concluded that infections, including tuberculosis, fungal overgrowth, herpes simplex and herpes zoster, occur either with similar frequency or less often than among those taking placebo.

“In fact, there is a sense that abatacept is actually safer,” than some other disease-modifying antirheumatic drugs,” said Dr. Winthrop, an infectious disease specialist at Oregon Health and Science University, Portland. However, there are few data comparing safety among the agents – something he said should be examined in more detail.

His review encompassed 16 clinical trials comprising 7,044 patients who took the drug (21,330 patient/years of abatacept exposure) and 1,485 patients who took placebo. He conducted two analyses: one for opportunistic bacterial and fungal infections, and one for herpes simplex and herpes zoster.

The first analysis found 45 opportunistic bacterial or fungal infections among those taking abatacept – an incidence rate of 0.21/ 100 person-years. There were seven such infections in the placebo group – an incidence rate of 0.56/100 person-years. This difference was statistically significant.

In the abatacept cohort, there were two cases of bronchopulmonary aspergilliosis (IR 0.01) and three fungal eye infections (IR 0.01). There was also one case of gastrointestinal candidiasis; one fungal esophagitis; one cryptococcal meningitis; two pneumonias (one pseudomonal and one caused by Pneumocystis jirovecii); and two cases of respiratory monoliasis. All of these infections had an incidence rate of less than 0.01/100 person-years.

There were 17 tuberculosis cases (IR 0.08/100 person-years). Three cases were latent. Six of the cases were pulmonary and five were extrapulmonary. Two cases were unspecified. All occurred in regions with high or moderate endemic tuberculosis levels.

A meta-regression analysis examined the risk of opportunistic infections in the patients taken from the placebo-controlled clinical trials only (2,653 abatacept, 1,485 placebo). The estimated frequency of an opportunistic infection was 0.15% among those taking the drug and 0.48% among those taking placebo.

The herpes analysis examined the placebo-controlled clinical trial population as well. There were 57 cases of herpes simplex (IR 2.5/100 person-years) among those taking abatacept and 22 among those taking placebo (IR 1.8/100 person-years). The difference was not statistically significant.

There were 44 cases of herpes zoster among those taking abatacept (IR 1.9/100 person-years) and 21 among those taking placebo (IR 1.7/100 person-years).

“Basically, I think what we’re seeing here is a whole lot of nothing,” Dr. Winthrop said.

Dr. Winthrop has been a consultant for Pfizer, AbbVie, Bristol-Myers Squibb, UCB Pharma, Roche/Genentech, Amgen, Galapagos, and Eli Lilly.

[email protected]

On Twitter @Alz_gal

MADRID – Abatacept doesn’t appear to increase the risk of opportunistic infections among patients with rheumatoid arthritis, Kevin Winthrop, MD, reported at the European Congress of Rheumatology.

After reviewing all of the extant safety data on the drug – all of its clinical trial and open-label study data, and case reports of abatacept-associated adverse events – Dr. Winthrop concluded that infections, including tuberculosis, fungal overgrowth, herpes simplex and herpes zoster, occur either with similar frequency or less often than among those taking placebo.

“In fact, there is a sense that abatacept is actually safer,” than some other disease-modifying antirheumatic drugs,” said Dr. Winthrop, an infectious disease specialist at Oregon Health and Science University, Portland. However, there are few data comparing safety among the agents – something he said should be examined in more detail.

His review encompassed 16 clinical trials comprising 7,044 patients who took the drug (21,330 patient/years of abatacept exposure) and 1,485 patients who took placebo. He conducted two analyses: one for opportunistic bacterial and fungal infections, and one for herpes simplex and herpes zoster.

The first analysis found 45 opportunistic bacterial or fungal infections among those taking abatacept – an incidence rate of 0.21/ 100 person-years. There were seven such infections in the placebo group – an incidence rate of 0.56/100 person-years. This difference was statistically significant.

In the abatacept cohort, there were two cases of bronchopulmonary aspergilliosis (IR 0.01) and three fungal eye infections (IR 0.01). There was also one case of gastrointestinal candidiasis; one fungal esophagitis; one cryptococcal meningitis; two pneumonias (one pseudomonal and one caused by Pneumocystis jirovecii); and two cases of respiratory monoliasis. All of these infections had an incidence rate of less than 0.01/100 person-years.

There were 17 tuberculosis cases (IR 0.08/100 person-years). Three cases were latent. Six of the cases were pulmonary and five were extrapulmonary. Two cases were unspecified. All occurred in regions with high or moderate endemic tuberculosis levels.

A meta-regression analysis examined the risk of opportunistic infections in the patients taken from the placebo-controlled clinical trials only (2,653 abatacept, 1,485 placebo). The estimated frequency of an opportunistic infection was 0.15% among those taking the drug and 0.48% among those taking placebo.

The herpes analysis examined the placebo-controlled clinical trial population as well. There were 57 cases of herpes simplex (IR 2.5/100 person-years) among those taking abatacept and 22 among those taking placebo (IR 1.8/100 person-years). The difference was not statistically significant.

There were 44 cases of herpes zoster among those taking abatacept (IR 1.9/100 person-years) and 21 among those taking placebo (IR 1.7/100 person-years).

“Basically, I think what we’re seeing here is a whole lot of nothing,” Dr. Winthrop said.

Dr. Winthrop has been a consultant for Pfizer, AbbVie, Bristol-Myers Squibb, UCB Pharma, Roche/Genentech, Amgen, Galapagos, and Eli Lilly.

[email protected]

On Twitter @Alz_gal

Adding the multitargeted kinase inhibitor midostaurin to standard chemotherapy led to significantly longer overall and event-free survival, compared with placebo and standard chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients with FLT3 gene mutations, according to phase III trial results published in the New England Journal of Medicine.*

About 30% of AML patients have mutations to the FLT3 gene – with three-quarters of those internal tandem duplication (ITD) mutations, which involves duplication of between 3 and 100 amino acids in the juxtamembrane region. These mutations are linked with a high relapse rate and poor prognosis, especially when there is a high ratio of these mutations to wild-type FLT3. About 8% of patients with newly diagnosed AML have an FLT3 point mutation in the tyrosine kinase domain (TKD), but the effect of these on prognosis isn’t clear.

In the trial, called RATIFY and conducted at 225 sites in 17 countries, 360 patients were randomized to the midostaurin group and 357* to placebo, and they were treated from 2008 to 2013. In all, 29.8% of patients were “ITD high,” meaning their ITD FLT3 mutation to wild-type FLT3 ratio was higher than 0.7, and 47.6% were “ITD low,” with a mutation-to-wild-type FLT3 ratio of 0.5 to 0.7. A total of 22.6% of patients had TKD mutations.

Patients received standard induction chemotherapy, with daunorubicine and cytarabine, and on days 8 through 21 either 50 mg of midostaurin or placebo orally twice a day. Patients were given an identical second cycle of induction therapy, with midostaurin or placebo, if they showed definitive clinically significant residual leukemia after the first induction treatment.

Those who achieved complete remission after induction were given 4, 28-day cycles of consolidation treatment, with midostaurin or placebo on days 8 through 21. If they stayed in remission after that, they were given maintenance of 12, 28-day cycles of midostaurin or placebo.

They were not required to receive hematopoetic stem cell transplantation (HSCT), but it was performed at investigator discretion.

Midostaurin improved survival but not rates of complete remission as defined in the trial protocol, researchers reported.

The hazard ratio for death in the midostaurin group was 0.78 (95% CI, 0.63 to 0.96; one-sided P = .0009). The 4-year overall survival rate was 51.4% for the midostaurin group and 44.3% for the placebo group. Midostaurin was shown to benefit all mutation subgroups, but with no greater benefit in one group than another.

Patients in the midostaurin group had a 21.6% lower likelihood of having an event, defined as failure to achieve protocol-defined complete remission, relapse or death without relapse.

There was no significant difference between the groups in complete remission, which under protocol had to occur by day 60.

HSCT was performed in 57% of patients – during the first complete remission in 28.1% of the midostaurin group and in 22.7% during the first complete remission in the placebo group. For those who were transplanted after the first complete remission, no treatment effect was seen.

Researchers noted that there was a therapeutic benefit even among patients with ITD mutations but with a low allelic burden, in whom the disease might be due largely to mutations other than FLT3.

“It is possible that the benefit of midostaurin, which is a multitargeted kinase inhibitor, might lie beyond its ability to inhibit FLT3,” possibly through inhibition of KIT, researchers said.

They also noted that as the trial went on, more and more investigators decided to treat patients with hematopoietic stem cell transplantation, based on newly reported data elsewhere. Since midostaurin was discontinued at the time of transplant, that could have limited exposure to the drug and limited its effect.

*CORRECTION 7/5/2017: An earlier version of this article misstated the number of patients in the placebo group as well as where the study originally appeared.

Adding the multitargeted kinase inhibitor midostaurin to standard chemotherapy led to significantly longer overall and event-free survival, compared with placebo and standard chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients with FLT3 gene mutations, according to phase III trial results published in the New England Journal of Medicine.*

About 30% of AML patients have mutations to the FLT3 gene – with three-quarters of those internal tandem duplication (ITD) mutations, which involves duplication of between 3 and 100 amino acids in the juxtamembrane region. These mutations are linked with a high relapse rate and poor prognosis, especially when there is a high ratio of these mutations to wild-type FLT3. About 8% of patients with newly diagnosed AML have an FLT3 point mutation in the tyrosine kinase domain (TKD), but the effect of these on prognosis isn’t clear.

In the trial, called RATIFY and conducted at 225 sites in 17 countries, 360 patients were randomized to the midostaurin group and 357* to placebo, and they were treated from 2008 to 2013. In all, 29.8% of patients were “ITD high,” meaning their ITD FLT3 mutation to wild-type FLT3 ratio was higher than 0.7, and 47.6% were “ITD low,” with a mutation-to-wild-type FLT3 ratio of 0.5 to 0.7. A total of 22.6% of patients had TKD mutations.

Patients received standard induction chemotherapy, with daunorubicine and cytarabine, and on days 8 through 21 either 50 mg of midostaurin or placebo orally twice a day. Patients were given an identical second cycle of induction therapy, with midostaurin or placebo, if they showed definitive clinically significant residual leukemia after the first induction treatment.

Those who achieved complete remission after induction were given 4, 28-day cycles of consolidation treatment, with midostaurin or placebo on days 8 through 21. If they stayed in remission after that, they were given maintenance of 12, 28-day cycles of midostaurin or placebo.

They were not required to receive hematopoetic stem cell transplantation (HSCT), but it was performed at investigator discretion.

Midostaurin improved survival but not rates of complete remission as defined in the trial protocol, researchers reported.

The hazard ratio for death in the midostaurin group was 0.78 (95% CI, 0.63 to 0.96; one-sided P = .0009). The 4-year overall survival rate was 51.4% for the midostaurin group and 44.3% for the placebo group. Midostaurin was shown to benefit all mutation subgroups, but with no greater benefit in one group than another.

Patients in the midostaurin group had a 21.6% lower likelihood of having an event, defined as failure to achieve protocol-defined complete remission, relapse or death without relapse.

There was no significant difference between the groups in complete remission, which under protocol had to occur by day 60.

HSCT was performed in 57% of patients – during the first complete remission in 28.1% of the midostaurin group and in 22.7% during the first complete remission in the placebo group. For those who were transplanted after the first complete remission, no treatment effect was seen.

Researchers noted that there was a therapeutic benefit even among patients with ITD mutations but with a low allelic burden, in whom the disease might be due largely to mutations other than FLT3.

“It is possible that the benefit of midostaurin, which is a multitargeted kinase inhibitor, might lie beyond its ability to inhibit FLT3,” possibly through inhibition of KIT, researchers said.

They also noted that as the trial went on, more and more investigators decided to treat patients with hematopoietic stem cell transplantation, based on newly reported data elsewhere. Since midostaurin was discontinued at the time of transplant, that could have limited exposure to the drug and limited its effect.

*CORRECTION 7/5/2017: An earlier version of this article misstated the number of patients in the placebo group as well as where the study originally appeared.

Adding the multitargeted kinase inhibitor midostaurin to standard chemotherapy led to significantly longer overall and event-free survival, compared with placebo and standard chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients with FLT3 gene mutations, according to phase III trial results published in the New England Journal of Medicine.*

About 30% of AML patients have mutations to the FLT3 gene – with three-quarters of those internal tandem duplication (ITD) mutations, which involves duplication of between 3 and 100 amino acids in the juxtamembrane region. These mutations are linked with a high relapse rate and poor prognosis, especially when there is a high ratio of these mutations to wild-type FLT3. About 8% of patients with newly diagnosed AML have an FLT3 point mutation in the tyrosine kinase domain (TKD), but the effect of these on prognosis isn’t clear.

In the trial, called RATIFY and conducted at 225 sites in 17 countries, 360 patients were randomized to the midostaurin group and 357* to placebo, and they were treated from 2008 to 2013. In all, 29.8% of patients were “ITD high,” meaning their ITD FLT3 mutation to wild-type FLT3 ratio was higher than 0.7, and 47.6% were “ITD low,” with a mutation-to-wild-type FLT3 ratio of 0.5 to 0.7. A total of 22.6% of patients had TKD mutations.

Patients received standard induction chemotherapy, with daunorubicine and cytarabine, and on days 8 through 21 either 50 mg of midostaurin or placebo orally twice a day. Patients were given an identical second cycle of induction therapy, with midostaurin or placebo, if they showed definitive clinically significant residual leukemia after the first induction treatment.

Those who achieved complete remission after induction were given 4, 28-day cycles of consolidation treatment, with midostaurin or placebo on days 8 through 21. If they stayed in remission after that, they were given maintenance of 12, 28-day cycles of midostaurin or placebo.

They were not required to receive hematopoetic stem cell transplantation (HSCT), but it was performed at investigator discretion.

Midostaurin improved survival but not rates of complete remission as defined in the trial protocol, researchers reported.

The hazard ratio for death in the midostaurin group was 0.78 (95% CI, 0.63 to 0.96; one-sided P = .0009). The 4-year overall survival rate was 51.4% for the midostaurin group and 44.3% for the placebo group. Midostaurin was shown to benefit all mutation subgroups, but with no greater benefit in one group than another.

Patients in the midostaurin group had a 21.6% lower likelihood of having an event, defined as failure to achieve protocol-defined complete remission, relapse or death without relapse.

There was no significant difference between the groups in complete remission, which under protocol had to occur by day 60.

HSCT was performed in 57% of patients – during the first complete remission in 28.1% of the midostaurin group and in 22.7% during the first complete remission in the placebo group. For those who were transplanted after the first complete remission, no treatment effect was seen.

Researchers noted that there was a therapeutic benefit even among patients with ITD mutations but with a low allelic burden, in whom the disease might be due largely to mutations other than FLT3.

“It is possible that the benefit of midostaurin, which is a multitargeted kinase inhibitor, might lie beyond its ability to inhibit FLT3,” possibly through inhibition of KIT, researchers said.

They also noted that as the trial went on, more and more investigators decided to treat patients with hematopoietic stem cell transplantation, based on newly reported data elsewhere. Since midostaurin was discontinued at the time of transplant, that could have limited exposure to the drug and limited its effect.

*CORRECTION 7/5/2017: An earlier version of this article misstated the number of patients in the placebo group as well as where the study originally appeared.

MADRID – Talk about versatility: Ibrutinib (Imbruvica), a drug with marked activity against B-cell malignancies, also appears to be a safe and acceptable option for the treatment of patients with chronic graft vs. host disease (cGVHD) for whom frontline therapies have failed.

Among 42 patients in a phase II study with steroid-refractory cGVHD, the overall response rate with ibrutinib was 67%, with one-third of responders having a complete response, reported Iskra Pusic, MD, from Washington University School of Medicine in St. Louis.

Neil Osterweil/Frontline Medical News

Investigators are currently enrolling patients in a double-blind clinical trial comparing ibrutinib or placebo in combination with corticosteroids in patients with newly diagnosed cGVHD, she noted.

The study was supported by Pharmacyclics. Dr. Pusic did not report disclosures.

MADRID – Talk about versatility: Ibrutinib (Imbruvica), a drug with marked activity against B-cell malignancies, also appears to be a safe and acceptable option for the treatment of patients with chronic graft vs. host disease (cGVHD) for whom frontline therapies have failed.

Among 42 patients in a phase II study with steroid-refractory cGVHD, the overall response rate with ibrutinib was 67%, with one-third of responders having a complete response, reported Iskra Pusic, MD, from Washington University School of Medicine in St. Louis.

Neil Osterweil/Frontline Medical News

Investigators are currently enrolling patients in a double-blind clinical trial comparing ibrutinib or placebo in combination with corticosteroids in patients with newly diagnosed cGVHD, she noted.

The study was supported by Pharmacyclics. Dr. Pusic did not report disclosures.

MADRID – Talk about versatility: Ibrutinib (Imbruvica), a drug with marked activity against B-cell malignancies, also appears to be a safe and acceptable option for the treatment of patients with chronic graft vs. host disease (cGVHD) for whom frontline therapies have failed.

Among 42 patients in a phase II study with steroid-refractory cGVHD, the overall response rate with ibrutinib was 67%, with one-third of responders having a complete response, reported Iskra Pusic, MD, from Washington University School of Medicine in St. Louis.

Neil Osterweil/Frontline Medical News

Investigators are currently enrolling patients in a double-blind clinical trial comparing ibrutinib or placebo in combination with corticosteroids in patients with newly diagnosed cGVHD, she noted.

The study was supported by Pharmacyclics. Dr. Pusic did not report disclosures.

MADRID – Aprelimast rapidly improved symptoms for patients with active psoriatic arthritis who were naive to biologics, whether or not they were on background methotrexate.

Response to the phosphodiesterase 4-inhibitor also increased with time, Peter Nash, MD, said at the European Congress of Rheumatology. By 2 weeks, 16% had achieved an ACR20 response. By 24 weeks, that had risen to 43%, and at 52 weeks, was 67%. Many patients responded even better, with 37% achieving an ACR50 response and 21% and ACR70 response by the end of the phase III placebo-controlled trial, said Dr. Nash of the University of Queensland, Brisbane, Australia.

Michele G Sullivan/Frontline Medical News

ACTIVE randomized 229 patients with active psoriatic arthritis (PsA) to either placebo or 30 mg apremilast twice daily. The primary endpoint was ACR20 response at week 16. At that time, patients who had not improved by at least 10% were offered early escape into active therapy.

Patients were a mean of 49 years old, with mean disease duration of 4 years. This is considerably shorter than the duration seen in many PsA trials, Dr. Nash said. It was a reflection of the study requirement that patients have taken no more than one synthetic disease-modifying antirheumatic agent (sDMARD) and no biologics for their disease.

The active and placebo groups separated very early in this study, with 16% of the apremilast group achieving an ACR 20 response by 2 weeks compared to 6% taking placebo. The response curves remained significantly separated throughout the entire study. By the 16-week endpoint, 38% of the active group and 20% of the placebo group had achieved ACR20. At this point, 11 of those taking apremilast asked for early escape and went on open-label apremilast at the same dose; 35 taking placebo were switched to open-label apremilast.

By 24 weeks, the ACR20 responses were 44% in the apremilast group and 25% in the placebo group. That response rate continued to rise over the year of treatment. By week 52, 67% of patients who had been on the study drug since the beginning had an ACR20, 37% an ACR50, and 21% an ACR70 response. ACR response was just as good in patients who were taking background methotrexate as those who were not, Dr. Nash said.

Compared to placebo, apremilast was associated with significantly more improvement on the Disease Activity Score-28 (CRP). Again, the response curves separated significantly by 2 weeks (–0.59 apremilast vs. –0.31 placebo) and continued to separate at 16 weeks (–1.07 vs. –0.39), and 24 weeks (–1.26 vs. –0.76). At 52 weeks, among those who had been initially randomized to apremilast, the mean DAS-28 (CRP) score had changed –1.71 from baseline.

The drug also significantly improved enthesitis relative to placebo, with rapid onset of action that continued to improve by week 24. The adverse event profile was good, Dr. Nash said. There were no opportunistic infections and no reactivations of tuberculosis. Ten in the active group and five in the placebo group withdrew due to an adverse event. Diarrhea and headache were the most common issues. Diarrhea occurred in 11% of the placebo group and 15% of the apremilast group; headache in 4% of the placebo group and 7% of the apremilast group. These were more common in the beginning of the study and tended to resolve with time, Dr. Nash said.

Thirty patients in the study had a history of depression and of these, two had a depression flare that lead to withdrawal from the study. Weight loss of at least 10% occurred in 5% of those taking apremilast.

Celgene sponsored the study. Dr. Nash has received research support from the company.

[email protected]

On Twitter @Alz_gal

MADRID – Aprelimast rapidly improved symptoms for patients with active psoriatic arthritis who were naive to biologics, whether or not they were on background methotrexate.

Response to the phosphodiesterase 4-inhibitor also increased with time, Peter Nash, MD, said at the European Congress of Rheumatology. By 2 weeks, 16% had achieved an ACR20 response. By 24 weeks, that had risen to 43%, and at 52 weeks, was 67%. Many patients responded even better, with 37% achieving an ACR50 response and 21% and ACR70 response by the end of the phase III placebo-controlled trial, said Dr. Nash of the University of Queensland, Brisbane, Australia.

Michele G Sullivan/Frontline Medical News

ACTIVE randomized 229 patients with active psoriatic arthritis (PsA) to either placebo or 30 mg apremilast twice daily. The primary endpoint was ACR20 response at week 16. At that time, patients who had not improved by at least 10% were offered early escape into active therapy.

Patients were a mean of 49 years old, with mean disease duration of 4 years. This is considerably shorter than the duration seen in many PsA trials, Dr. Nash said. It was a reflection of the study requirement that patients have taken no more than one synthetic disease-modifying antirheumatic agent (sDMARD) and no biologics for their disease.

The active and placebo groups separated very early in this study, with 16% of the apremilast group achieving an ACR 20 response by 2 weeks compared to 6% taking placebo. The response curves remained significantly separated throughout the entire study. By the 16-week endpoint, 38% of the active group and 20% of the placebo group had achieved ACR20. At this point, 11 of those taking apremilast asked for early escape and went on open-label apremilast at the same dose; 35 taking placebo were switched to open-label apremilast.

By 24 weeks, the ACR20 responses were 44% in the apremilast group and 25% in the placebo group. That response rate continued to rise over the year of treatment. By week 52, 67% of patients who had been on the study drug since the beginning had an ACR20, 37% an ACR50, and 21% an ACR70 response. ACR response was just as good in patients who were taking background methotrexate as those who were not, Dr. Nash said.

Compared to placebo, apremilast was associated with significantly more improvement on the Disease Activity Score-28 (CRP). Again, the response curves separated significantly by 2 weeks (–0.59 apremilast vs. –0.31 placebo) and continued to separate at 16 weeks (–1.07 vs. –0.39), and 24 weeks (–1.26 vs. –0.76). At 52 weeks, among those who had been initially randomized to apremilast, the mean DAS-28 (CRP) score had changed –1.71 from baseline.

The drug also significantly improved enthesitis relative to placebo, with rapid onset of action that continued to improve by week 24. The adverse event profile was good, Dr. Nash said. There were no opportunistic infections and no reactivations of tuberculosis. Ten in the active group and five in the placebo group withdrew due to an adverse event. Diarrhea and headache were the most common issues. Diarrhea occurred in 11% of the placebo group and 15% of the apremilast group; headache in 4% of the placebo group and 7% of the apremilast group. These were more common in the beginning of the study and tended to resolve with time, Dr. Nash said.

Thirty patients in the study had a history of depression and of these, two had a depression flare that lead to withdrawal from the study. Weight loss of at least 10% occurred in 5% of those taking apremilast.

Celgene sponsored the study. Dr. Nash has received research support from the company.

[email protected]

On Twitter @Alz_gal

MADRID – Aprelimast rapidly improved symptoms for patients with active psoriatic arthritis who were naive to biologics, whether or not they were on background methotrexate.

Response to the phosphodiesterase 4-inhibitor also increased with time, Peter Nash, MD, said at the European Congress of Rheumatology. By 2 weeks, 16% had achieved an ACR20 response. By 24 weeks, that had risen to 43%, and at 52 weeks, was 67%. Many patients responded even better, with 37% achieving an ACR50 response and 21% and ACR70 response by the end of the phase III placebo-controlled trial, said Dr. Nash of the University of Queensland, Brisbane, Australia.

Michele G Sullivan/Frontline Medical News

ACTIVE randomized 229 patients with active psoriatic arthritis (PsA) to either placebo or 30 mg apremilast twice daily. The primary endpoint was ACR20 response at week 16. At that time, patients who had not improved by at least 10% were offered early escape into active therapy.

Patients were a mean of 49 years old, with mean disease duration of 4 years. This is considerably shorter than the duration seen in many PsA trials, Dr. Nash said. It was a reflection of the study requirement that patients have taken no more than one synthetic disease-modifying antirheumatic agent (sDMARD) and no biologics for their disease.

The active and placebo groups separated very early in this study, with 16% of the apremilast group achieving an ACR 20 response by 2 weeks compared to 6% taking placebo. The response curves remained significantly separated throughout the entire study. By the 16-week endpoint, 38% of the active group and 20% of the placebo group had achieved ACR20. At this point, 11 of those taking apremilast asked for early escape and went on open-label apremilast at the same dose; 35 taking placebo were switched to open-label apremilast.

By 24 weeks, the ACR20 responses were 44% in the apremilast group and 25% in the placebo group. That response rate continued to rise over the year of treatment. By week 52, 67% of patients who had been on the study drug since the beginning had an ACR20, 37% an ACR50, and 21% an ACR70 response. ACR response was just as good in patients who were taking background methotrexate as those who were not, Dr. Nash said.

Compared to placebo, apremilast was associated with significantly more improvement on the Disease Activity Score-28 (CRP). Again, the response curves separated significantly by 2 weeks (–0.59 apremilast vs. –0.31 placebo) and continued to separate at 16 weeks (–1.07 vs. –0.39), and 24 weeks (–1.26 vs. –0.76). At 52 weeks, among those who had been initially randomized to apremilast, the mean DAS-28 (CRP) score had changed –1.71 from baseline.

The drug also significantly improved enthesitis relative to placebo, with rapid onset of action that continued to improve by week 24. The adverse event profile was good, Dr. Nash said. There were no opportunistic infections and no reactivations of tuberculosis. Ten in the active group and five in the placebo group withdrew due to an adverse event. Diarrhea and headache were the most common issues. Diarrhea occurred in 11% of the placebo group and 15% of the apremilast group; headache in 4% of the placebo group and 7% of the apremilast group. These were more common in the beginning of the study and tended to resolve with time, Dr. Nash said.

Thirty patients in the study had a history of depression and of these, two had a depression flare that lead to withdrawal from the study. Weight loss of at least 10% occurred in 5% of those taking apremilast.

Celgene sponsored the study. Dr. Nash has received research support from the company.

[email protected]

On Twitter @Alz_gal

SEATTLE – Intraperitoneal ropivacaine decreases postoperative pain and improves functional recovery after laparoscopic colectomy, according to randomized, blinded trial from the Royal Adelaide (Australia) Hospital.

“We recommend routine inclusion of IPLA [intraperitoneal local anesthetic] in the multimodal analgesia component of ERAS [enhanced-recovery-after-surgery] programs for laparoscopic colectomy,” the investigators concluded.

[email protected]

SEATTLE – Intraperitoneal ropivacaine decreases postoperative pain and improves functional recovery after laparoscopic colectomy, according to randomized, blinded trial from the Royal Adelaide (Australia) Hospital.

“We recommend routine inclusion of IPLA [intraperitoneal local anesthetic] in the multimodal analgesia component of ERAS [enhanced-recovery-after-surgery] programs for laparoscopic colectomy,” the investigators concluded.

[email protected]

SEATTLE – Intraperitoneal ropivacaine decreases postoperative pain and improves functional recovery after laparoscopic colectomy, according to randomized, blinded trial from the Royal Adelaide (Australia) Hospital.

“We recommend routine inclusion of IPLA [intraperitoneal local anesthetic] in the multimodal analgesia component of ERAS [enhanced-recovery-after-surgery] programs for laparoscopic colectomy,” the investigators concluded.

[email protected]

MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.

Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.

Neil Osterweil/Frontline Medical News

“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.

Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.

To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.

A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.

After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.

The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.

The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.

Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).

In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.

There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.

In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.

The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.

MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.

Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.

Neil Osterweil/Frontline Medical News

“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.

Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.

To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.

A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.

After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.

The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.

The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.

Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).

In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.

There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.

In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.

The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.

MADRID – Patients with advanced Hodgkin lymphoma who have a metabolic response after the first two cycles of extended-dose(e)BEACOPP can be spared from undergoing more than two additional cycles of the highly intensive and toxic regimen, investigators from the German Hodgkin Study Group (GHSG) contend.

Among 1,005 patients with Hodgkin lymphoma who had negative PET scans after the second cycle of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, prednisone, procarbazine), progression-free survival (PFS) was virtually identical whether patients were randomized to undergo a total of six-to-eight cycles or only four cycles, reported Peter Borchmann, MD, from the University of Cologne, Germany.

Neil Osterweil/Frontline Medical News

“For patients with negative PET-2 after initial treatment with eBEACOPP. Therapy with only two additional cycles of eBEACOPP is very effective, obviously, very safe, very short – it just takes 12 weeks – and it’s affordable,” he said.

“When balancing efficacy and safety, results compare favorably with any other published treatment strategy so far. That’s why we recommend this treatment, PET-guided extended BEACOPP in patients with newly diagnosed, advanced-stage Hodgkin lymphoma,” he added.

Although most patients in the United States with newly diagnosed Hodgkin lymphoma receive ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), BEACOPP is sometimes used for high-risk patients. BEACOPP is associated with considerable toxicities, however, including increased risk of secondary malignancies.

To see whether select patients could be cured with fewer cycles of therapy, the GHSG investigators designed the GHSG HD18 study in which patient with metabolic responses determined by fluorodeoxyglucose-PET after two eBEACOPP cycles were randomized to either two or six-to-eight additional cycles.

A total of 2,101 patients from the ages of 18-60 years with newly diagnosed advanced-stage Hodgkin lymphoma were enrolled from centers in Germany, Switzerland, Austria, the Czech Republic, and the Netherlands.

After the second cycle of therapy, patients underwent fluorodeoxyglucose-PET scans, and those with negative results were then randomized.

The trial was designed and powered for noninferiority of the shortened regimen, with a maximum allowable difference of 6%.

The trial met its primary endpoint and then some. After a median observation time of 53 months, the 5-year PFS rate for patients who received only four cycles was 91.2%, compared with 91.8% for patients who underwent six-to-eight cycles. As shown on a Kaplan-Meier curve, the two lines were superimposable and virtually impossible to tell apart.

Interestingly, 5-year overall survival was significantly better with the shorter, less toxic regimen, at 97.6% vs. 95.4%, respectively, translating into a hazard ratio favoring the shorter regimen of 0.36 (P = .006).

In addition, the four-cycle regimen was associated with fewer severe infections (8% vs 15%), and lower degrees of organ toxicity (8% vs. 18%). In addition, the rate of secondary acute myeloid leukemia or the myelodysplastic syndrome was 0.4% among the 501 patients treated with only four cycles, compared with 1.6% for the 504 patients who received six to eight cycles.

There were no treatment-related deaths among patients who underwent four cycles, compared with six deaths among patients treated with additional cycles.

In an interview, Dr. Borchmann said that the findings are likely to change the standard of care for those centers that use the BEACOPP regimen. He acknowledged that the regimen is highly toxic and requires intensive patient surveillance and management, which may be more practical in Europe where patients generally live closer to major cancer centers than in the more spacious United States.

The study was supported by German Cancer Aid, the Swiss State Secratariate for Education, Research and Innovation, and by Roche Pharma AG. Dr, Borchmann reported having no relevant disclosures.

MADRID – Look before you leap into anticoagulation therapy for older cancer patients, results from a Canadian cohort study suggest.

Among patients 65 and older with cancer and a venous thromboembolic event (VTE) within 6 months of the cancer diagnosis, the 7-day mortality rate from VTE was 0.5%, compared with an 11% rate of death from a major bleeding episode, reported Alejandro Lazo-Langner MD, MSc from Western University in London, Canada.

Neil Osterweil/Frontline Medical News

Neil Osterweil/Frontline Medical News

MADRID – Look before you leap into anticoagulation therapy for older cancer patients, results from a Canadian cohort study suggest.

Among patients 65 and older with cancer and a venous thromboembolic event (VTE) within 6 months of the cancer diagnosis, the 7-day mortality rate from VTE was 0.5%, compared with an 11% rate of death from a major bleeding episode, reported Alejandro Lazo-Langner MD, MSc from Western University in London, Canada.

Neil Osterweil/Frontline Medical News

Neil Osterweil/Frontline Medical News

MADRID – Look before you leap into anticoagulation therapy for older cancer patients, results from a Canadian cohort study suggest.

Among patients 65 and older with cancer and a venous thromboembolic event (VTE) within 6 months of the cancer diagnosis, the 7-day mortality rate from VTE was 0.5%, compared with an 11% rate of death from a major bleeding episode, reported Alejandro Lazo-Langner MD, MSc from Western University in London, Canada.

Neil Osterweil/Frontline Medical News

Neil Osterweil/Frontline Medical News