Hematology Times

Doctor and patient
Photo courtesy of the CDC

A large study has revealed a lower death rate among US patients treated by internationally trained doctors rather than US-trained doctors.

Researchers

analyzed data on more than 1.2 million US hospital admissions and found

a slight but statistically significant difference in 30-day mortality

for patients treated by internationally trained doctors and US-trained

doctors—11.2% and

11.6%, respectively (P<0.001).

These findings were published in The BMJ.

Yusuke Tsugawa, MD, PhD, of Harvard T H Chan School of Public Health in Boston, Massachusetts, and his colleagues conducted this research.

The team wanted to determine whether patient outcomes differ between general internists who graduated from a medical school outside the US and those who graduated from a US medical school.

The researchers analyzed data on the treatment of Medicare beneficiaries (age 65 and older) who were admitted to a hospital with a medical condition from 2011 through 2014. This included 1,215,490 hospital admissions and 44,227 general internists.

The primary outcome was 30-day patient mortality. Secondary outcomes were 30-day readmission rates and costs of care.

Compared with patients treated by US graduates, patients treated by international graduates had slightly more chronic conditions.

After adjusting for factors that could have affected the results (including patient characteristics, physician characteristics, and hospital fixed effects), the researchers found that patients cared for by international graduates had a lower rate of 30-day mortality than patients cared for by US graduates (11.2% and

11.6%, respectively, P<0.001).

The researchers said that for every 250 patients treated by US medical graduates, 1 patient’s life would be saved if the quality of care were equivalent between the international graduates and US graduates.

Thirty-day readmission rates did not differ significantly between the 2 types of graduates—15.4% for international graduates and 15.5% for US graduates (P=0.54).

However, the cost of care per admission was higher for international medical graduates—$1145 vs $1098 (P<0.001).

Further analysis to test the strength of these results made no difference to the overall findings.

One possible explanation for these findings, according to the researchers, is that the current approach for allowing international medical graduates to practice in the US may select for, on average, better physicians.

The team stressed that this is an observational study, so no firm conclusions can be drawn about cause and effect. Nevertheless, they said their findings “should reassure policymakers and the public that our current approach to licensing international medical graduates in the US is sufficiently rigorous to ensure high quality care.”

Doctor and patient
Photo courtesy of the CDC

A large study has revealed a lower death rate among US patients treated by internationally trained doctors rather than US-trained doctors.

Researchers

analyzed data on more than 1.2 million US hospital admissions and found

a slight but statistically significant difference in 30-day mortality

for patients treated by internationally trained doctors and US-trained

doctors—11.2% and

11.6%, respectively (P<0.001).

These findings were published in The BMJ.

Yusuke Tsugawa, MD, PhD, of Harvard T H Chan School of Public Health in Boston, Massachusetts, and his colleagues conducted this research.

The team wanted to determine whether patient outcomes differ between general internists who graduated from a medical school outside the US and those who graduated from a US medical school.

The researchers analyzed data on the treatment of Medicare beneficiaries (age 65 and older) who were admitted to a hospital with a medical condition from 2011 through 2014. This included 1,215,490 hospital admissions and 44,227 general internists.

The primary outcome was 30-day patient mortality. Secondary outcomes were 30-day readmission rates and costs of care.

Compared with patients treated by US graduates, patients treated by international graduates had slightly more chronic conditions.

After adjusting for factors that could have affected the results (including patient characteristics, physician characteristics, and hospital fixed effects), the researchers found that patients cared for by international graduates had a lower rate of 30-day mortality than patients cared for by US graduates (11.2% and

11.6%, respectively, P<0.001).

The researchers said that for every 250 patients treated by US medical graduates, 1 patient’s life would be saved if the quality of care were equivalent between the international graduates and US graduates.

Thirty-day readmission rates did not differ significantly between the 2 types of graduates—15.4% for international graduates and 15.5% for US graduates (P=0.54).

However, the cost of care per admission was higher for international medical graduates—$1145 vs $1098 (P<0.001).

Further analysis to test the strength of these results made no difference to the overall findings.

One possible explanation for these findings, according to the researchers, is that the current approach for allowing international medical graduates to practice in the US may select for, on average, better physicians.

The team stressed that this is an observational study, so no firm conclusions can be drawn about cause and effect. Nevertheless, they said their findings “should reassure policymakers and the public that our current approach to licensing international medical graduates in the US is sufficiently rigorous to ensure high quality care.”

Doctor and patient
Photo courtesy of the CDC

A large study has revealed a lower death rate among US patients treated by internationally trained doctors rather than US-trained doctors.

Researchers

analyzed data on more than 1.2 million US hospital admissions and found

a slight but statistically significant difference in 30-day mortality

for patients treated by internationally trained doctors and US-trained

doctors—11.2% and

11.6%, respectively (P<0.001).

These findings were published in The BMJ.

Yusuke Tsugawa, MD, PhD, of Harvard T H Chan School of Public Health in Boston, Massachusetts, and his colleagues conducted this research.

The team wanted to determine whether patient outcomes differ between general internists who graduated from a medical school outside the US and those who graduated from a US medical school.

The researchers analyzed data on the treatment of Medicare beneficiaries (age 65 and older) who were admitted to a hospital with a medical condition from 2011 through 2014. This included 1,215,490 hospital admissions and 44,227 general internists.

The primary outcome was 30-day patient mortality. Secondary outcomes were 30-day readmission rates and costs of care.

Compared with patients treated by US graduates, patients treated by international graduates had slightly more chronic conditions.

After adjusting for factors that could have affected the results (including patient characteristics, physician characteristics, and hospital fixed effects), the researchers found that patients cared for by international graduates had a lower rate of 30-day mortality than patients cared for by US graduates (11.2% and

11.6%, respectively, P<0.001).

The researchers said that for every 250 patients treated by US medical graduates, 1 patient’s life would be saved if the quality of care were equivalent between the international graduates and US graduates.

Thirty-day readmission rates did not differ significantly between the 2 types of graduates—15.4% for international graduates and 15.5% for US graduates (P=0.54).

However, the cost of care per admission was higher for international medical graduates—$1145 vs $1098 (P<0.001).

Further analysis to test the strength of these results made no difference to the overall findings.

One possible explanation for these findings, according to the researchers, is that the current approach for allowing international medical graduates to practice in the US may select for, on average, better physicians.

The team stressed that this is an observational study, so no firm conclusions can be drawn about cause and effect. Nevertheless, they said their findings “should reassure policymakers and the public that our current approach to licensing international medical graduates in the US is sufficiently rigorous to ensure high quality care.”

Blood sample
Photo by Juan D. Alfonso

A new study suggests that hemoglobin A1c (HbA1c), a biomarker used to measure blood sugar over time, may not perform as accurately among African-Americans with sickle cell trait (SCT) and could be leading to a systemic underestimation of blood sugar control in that population.

Researchers analyzed data from more than 4600 people and found that HbA1c readings were significantly lower in individuals with SCT than in those without it, even after accounting for several possible confounding factors.

The team reported these findings in JAMA. 

“We found that HbA1c was systematically lower in African-Americans with sickle cell trait than those without sickle cell trait, despite similar blood sugar measurements using other tests,” said study author Mary Lacy, a doctoral candidate at the Brown University School of Public Health in Providence, Rhode Island.

“We might be missing an opportunity for diagnosis and treatment of a serious disease.”

Lacy and her co-authors found that using standard clinical HbA1c cutoffs resulted in identifying 40% fewer potential cases of prediabetes and 48% fewer potential cases of diabetes in people with SCT than in people without SCT.

However, when the researchers used other blood glucose measures as the diagnostic criteria, they found no significant difference in the likelihood of diabetes and prediabetes among patients with or without SCT.

The questions the study raises about using HbA1c among SCT carriers matter for treatment as well as diagnosis, said study author Wen-Chih Wu, MD, of Brown University.

“The clinical implications of these results are highly relevant,” Dr Wu said. “For patients with diabetes, HbA1c is often used as a marker of how well they are managing their diabetes, so having an underestimation of their blood sugars is problematic because they might have a false sense of security, thinking they are doing okay when they are not.”

Study details

For this study, the researchers analyzed data from 2 major public health studies—the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). Of the 4620 participants included in the analysis, 367 had SCT.

Among all the patients included in the analysis, HbA1c readings came from either of 2 widely used, clinically accepted assays made by Tosoh Bioscience Inc. that rely on a process called high-performance liquid chromatography.

In addition to those measures, the researchers also compared fasting and 2-hour blood glucose and statistically controlled for demographic and medical factors, such as gender, age, body-mass index, whether diabetes had already been diagnosed, and whether it was being treated.

Study author Gregory Wellenius, ScD, of Brown University, said the study’s scale and breadth allowed for the most definitive comparison to date of HbA1c readings in patients with and without SCT. Two previous, smaller studies had not detected a similar discrepancy.

“The strengths of the study are that it’s the largest sample size ever used, it’s across 2 different studies with somewhat different populations, and it’s a more thorough evaluation than prior studies,” Dr Wellenius said.

While the study showed that HbA1c readings were significantly different between people with and without SCT, it also showed that blood glucose readings were not, suggesting that glucose metabolism is not necessarily different between the 2 groups, as the HbA1c readings alone would suggest.

Implications for practice

The study does not explain why the HbA1c readings differ. While it could be related to the assay method, which is approved by the NGSP (formerly National Glycohemoglobin Standardization Program) for use in patients with SCT, it could also be a consequence of the underlying biology of SCT.

Hypothetically, according to the researchers, if the hemoglobin variant of the trait endows red blood cells with a shorter lifespan, the cells’ hemoglobin would carry less accumulated blood glucose, leading to falsely low HbA1c readings.

“Irrespective of the reason of the underestimation, the underestimation is very real, and clinicians should consider screening for sickle cell trait and account for the difference in HbA1c,” Dr Wu said.

Yet not many people with SCT in the US know they carry the variant, especially those born before routine screenings at birth began, Lacy said.

The researchers therefore recommend that practitioners following African-American patients whose HbA1c levels are within 0.3 percentage points of a diagnostic cutoff also consider using additional blood glucose measures. Current diagnostic thresholds for A1C are ≥5.7% for prediabetes and ≥6.5% for diabetes.

Blood sample
Photo by Juan D. Alfonso

A new study suggests that hemoglobin A1c (HbA1c), a biomarker used to measure blood sugar over time, may not perform as accurately among African-Americans with sickle cell trait (SCT) and could be leading to a systemic underestimation of blood sugar control in that population.

Researchers analyzed data from more than 4600 people and found that HbA1c readings were significantly lower in individuals with SCT than in those without it, even after accounting for several possible confounding factors.

The team reported these findings in JAMA. 

“We found that HbA1c was systematically lower in African-Americans with sickle cell trait than those without sickle cell trait, despite similar blood sugar measurements using other tests,” said study author Mary Lacy, a doctoral candidate at the Brown University School of Public Health in Providence, Rhode Island.

“We might be missing an opportunity for diagnosis and treatment of a serious disease.”

Lacy and her co-authors found that using standard clinical HbA1c cutoffs resulted in identifying 40% fewer potential cases of prediabetes and 48% fewer potential cases of diabetes in people with SCT than in people without SCT.

However, when the researchers used other blood glucose measures as the diagnostic criteria, they found no significant difference in the likelihood of diabetes and prediabetes among patients with or without SCT.

The questions the study raises about using HbA1c among SCT carriers matter for treatment as well as diagnosis, said study author Wen-Chih Wu, MD, of Brown University.

“The clinical implications of these results are highly relevant,” Dr Wu said. “For patients with diabetes, HbA1c is often used as a marker of how well they are managing their diabetes, so having an underestimation of their blood sugars is problematic because they might have a false sense of security, thinking they are doing okay when they are not.”

Study details

For this study, the researchers analyzed data from 2 major public health studies—the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). Of the 4620 participants included in the analysis, 367 had SCT.

Among all the patients included in the analysis, HbA1c readings came from either of 2 widely used, clinically accepted assays made by Tosoh Bioscience Inc. that rely on a process called high-performance liquid chromatography.

In addition to those measures, the researchers also compared fasting and 2-hour blood glucose and statistically controlled for demographic and medical factors, such as gender, age, body-mass index, whether diabetes had already been diagnosed, and whether it was being treated.

Study author Gregory Wellenius, ScD, of Brown University, said the study’s scale and breadth allowed for the most definitive comparison to date of HbA1c readings in patients with and without SCT. Two previous, smaller studies had not detected a similar discrepancy.

“The strengths of the study are that it’s the largest sample size ever used, it’s across 2 different studies with somewhat different populations, and it’s a more thorough evaluation than prior studies,” Dr Wellenius said.

While the study showed that HbA1c readings were significantly different between people with and without SCT, it also showed that blood glucose readings were not, suggesting that glucose metabolism is not necessarily different between the 2 groups, as the HbA1c readings alone would suggest.

Implications for practice

The study does not explain why the HbA1c readings differ. While it could be related to the assay method, which is approved by the NGSP (formerly National Glycohemoglobin Standardization Program) for use in patients with SCT, it could also be a consequence of the underlying biology of SCT.

Hypothetically, according to the researchers, if the hemoglobin variant of the trait endows red blood cells with a shorter lifespan, the cells’ hemoglobin would carry less accumulated blood glucose, leading to falsely low HbA1c readings.

“Irrespective of the reason of the underestimation, the underestimation is very real, and clinicians should consider screening for sickle cell trait and account for the difference in HbA1c,” Dr Wu said.

Yet not many people with SCT in the US know they carry the variant, especially those born before routine screenings at birth began, Lacy said.

The researchers therefore recommend that practitioners following African-American patients whose HbA1c levels are within 0.3 percentage points of a diagnostic cutoff also consider using additional blood glucose measures. Current diagnostic thresholds for A1C are ≥5.7% for prediabetes and ≥6.5% for diabetes.

Blood sample
Photo by Juan D. Alfonso

A new study suggests that hemoglobin A1c (HbA1c), a biomarker used to measure blood sugar over time, may not perform as accurately among African-Americans with sickle cell trait (SCT) and could be leading to a systemic underestimation of blood sugar control in that population.

Researchers analyzed data from more than 4600 people and found that HbA1c readings were significantly lower in individuals with SCT than in those without it, even after accounting for several possible confounding factors.

The team reported these findings in JAMA. 

“We found that HbA1c was systematically lower in African-Americans with sickle cell trait than those without sickle cell trait, despite similar blood sugar measurements using other tests,” said study author Mary Lacy, a doctoral candidate at the Brown University School of Public Health in Providence, Rhode Island.

“We might be missing an opportunity for diagnosis and treatment of a serious disease.”

Lacy and her co-authors found that using standard clinical HbA1c cutoffs resulted in identifying 40% fewer potential cases of prediabetes and 48% fewer potential cases of diabetes in people with SCT than in people without SCT.

However, when the researchers used other blood glucose measures as the diagnostic criteria, they found no significant difference in the likelihood of diabetes and prediabetes among patients with or without SCT.

The questions the study raises about using HbA1c among SCT carriers matter for treatment as well as diagnosis, said study author Wen-Chih Wu, MD, of Brown University.

“The clinical implications of these results are highly relevant,” Dr Wu said. “For patients with diabetes, HbA1c is often used as a marker of how well they are managing their diabetes, so having an underestimation of their blood sugars is problematic because they might have a false sense of security, thinking they are doing okay when they are not.”

Study details

For this study, the researchers analyzed data from 2 major public health studies—the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). Of the 4620 participants included in the analysis, 367 had SCT.

Among all the patients included in the analysis, HbA1c readings came from either of 2 widely used, clinically accepted assays made by Tosoh Bioscience Inc. that rely on a process called high-performance liquid chromatography.

In addition to those measures, the researchers also compared fasting and 2-hour blood glucose and statistically controlled for demographic and medical factors, such as gender, age, body-mass index, whether diabetes had already been diagnosed, and whether it was being treated.

Study author Gregory Wellenius, ScD, of Brown University, said the study’s scale and breadth allowed for the most definitive comparison to date of HbA1c readings in patients with and without SCT. Two previous, smaller studies had not detected a similar discrepancy.

“The strengths of the study are that it’s the largest sample size ever used, it’s across 2 different studies with somewhat different populations, and it’s a more thorough evaluation than prior studies,” Dr Wellenius said.

While the study showed that HbA1c readings were significantly different between people with and without SCT, it also showed that blood glucose readings were not, suggesting that glucose metabolism is not necessarily different between the 2 groups, as the HbA1c readings alone would suggest.

Implications for practice

The study does not explain why the HbA1c readings differ. While it could be related to the assay method, which is approved by the NGSP (formerly National Glycohemoglobin Standardization Program) for use in patients with SCT, it could also be a consequence of the underlying biology of SCT.

Hypothetically, according to the researchers, if the hemoglobin variant of the trait endows red blood cells with a shorter lifespan, the cells’ hemoglobin would carry less accumulated blood glucose, leading to falsely low HbA1c readings.

“Irrespective of the reason of the underestimation, the underestimation is very real, and clinicians should consider screening for sickle cell trait and account for the difference in HbA1c,” Dr Wu said.

Yet not many people with SCT in the US know they carry the variant, especially those born before routine screenings at birth began, Lacy said.

The researchers therefore recommend that practitioners following African-American patients whose HbA1c levels are within 0.3 percentage points of a diagnostic cutoff also consider using additional blood glucose measures. Current diagnostic thresholds for A1C are ≥5.7% for prediabetes and ≥6.5% for diabetes.

Bone marrow harvest
Photo by Chad McNeeley

Researchers have reported a “promising” treatment approach for

refractory, severe aplastic anemia (SAA).

The

regimen consists of nonmyeloablative conditioning, bone marrow

transplants (BMTs) from “alternative” donors, and graft-vs-host disease

(GVHD) prophylaxis.

All 16 SAA patients who received this treatment

achieved engraftment and were completely cleared of disease.

There were 2 cases of acute and chronic GVHD, but they resolved.

All patients were ultimately able to stop immunosuppressive therapy.

Robert Brodsky, MD, of Sidney Kimmel Cancer Center in Baltimore, Maryland, and his colleagues reported these findings in Biology of Blood and Marrow Transplantation.

“Our findings have the potential to greatly widen treatment options for the vast majority of severe aplastic anemia patients,” Dr Brodsky said.

He and his colleagues tested their approach in 16 SAA patients between 11 and 69 years of age. Each of the patients had failed to respond to immunosuppressive therapy and other treatments.

The patients received conditioning with antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation.

They then received BMTs. Thirteen of the donors were haploidentical related, 2 were fully matched unrelated, and 1 was mismatched unrelated.

Three and 4 days after BMT, the patients received cyclophosphamide at 50 mg/kg/day as GVHD prophylaxis. They then received mycophenolate mofetil on days 5 through 35 and tacrolimus from day 5 through 1 year.

The median time to neutrophil recovery (over 1000 × 10³/mm³ for 3 consecutive days) was 19 days (range, 16 to 27). The median time to red cell engraftment was 25 days (range, 2 to 58). And the median time to the last platelet transfusion (to keep platelet counts over 50 × 10³/mm³) was 27.5 days (range, 22 to 108).

At a median follow-up of 21 months (range, 3 to 64), all 16 patients were still alive, disease-free, and no longer required transfusions.

Two patients did develop grade 1/2 acute skin GVHD. They also had mild chronic GVHD of the skin/mouth, which required systemic steroids.

One of these patients was able to come off all immunosuppressive therapy by 15 months, and the other was able to do so by 17 months. All of the other patients stopped immunosuppressive therapy at 1 year.

Ending all therapy related to their disease has been life-changing for these patients, said study author Amy DeZern, MD, also of the Sidney Kimmel Cancer Center.

“It’s like night and day,” she said. “They go from not knowing if they have a future to hoping for what they’d hoped for before they got sick. It’s that transformative.”

Successful BMTs using partially matched donors open up the transplant option to nearly all patients with SAA, especially minority patients, added Dr Brodsky.

“Now, a therapy that used to be available to 25% to 30% of patients with severe aplastic anemia is potentially available to more than 95%,” he said.

Bone marrow harvest
Photo by Chad McNeeley

Researchers have reported a “promising” treatment approach for

refractory, severe aplastic anemia (SAA).

The

regimen consists of nonmyeloablative conditioning, bone marrow

transplants (BMTs) from “alternative” donors, and graft-vs-host disease

(GVHD) prophylaxis.

All 16 SAA patients who received this treatment

achieved engraftment and were completely cleared of disease.

There were 2 cases of acute and chronic GVHD, but they resolved.

All patients were ultimately able to stop immunosuppressive therapy.

Robert Brodsky, MD, of Sidney Kimmel Cancer Center in Baltimore, Maryland, and his colleagues reported these findings in Biology of Blood and Marrow Transplantation.

“Our findings have the potential to greatly widen treatment options for the vast majority of severe aplastic anemia patients,” Dr Brodsky said.

He and his colleagues tested their approach in 16 SAA patients between 11 and 69 years of age. Each of the patients had failed to respond to immunosuppressive therapy and other treatments.

The patients received conditioning with antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation.

They then received BMTs. Thirteen of the donors were haploidentical related, 2 were fully matched unrelated, and 1 was mismatched unrelated.

Three and 4 days after BMT, the patients received cyclophosphamide at 50 mg/kg/day as GVHD prophylaxis. They then received mycophenolate mofetil on days 5 through 35 and tacrolimus from day 5 through 1 year.

The median time to neutrophil recovery (over 1000 × 10³/mm³ for 3 consecutive days) was 19 days (range, 16 to 27). The median time to red cell engraftment was 25 days (range, 2 to 58). And the median time to the last platelet transfusion (to keep platelet counts over 50 × 10³/mm³) was 27.5 days (range, 22 to 108).

At a median follow-up of 21 months (range, 3 to 64), all 16 patients were still alive, disease-free, and no longer required transfusions.

Two patients did develop grade 1/2 acute skin GVHD. They also had mild chronic GVHD of the skin/mouth, which required systemic steroids.

One of these patients was able to come off all immunosuppressive therapy by 15 months, and the other was able to do so by 17 months. All of the other patients stopped immunosuppressive therapy at 1 year.

Ending all therapy related to their disease has been life-changing for these patients, said study author Amy DeZern, MD, also of the Sidney Kimmel Cancer Center.

“It’s like night and day,” she said. “They go from not knowing if they have a future to hoping for what they’d hoped for before they got sick. It’s that transformative.”

Successful BMTs using partially matched donors open up the transplant option to nearly all patients with SAA, especially minority patients, added Dr Brodsky.

“Now, a therapy that used to be available to 25% to 30% of patients with severe aplastic anemia is potentially available to more than 95%,” he said.

Bone marrow harvest
Photo by Chad McNeeley

Researchers have reported a “promising” treatment approach for

refractory, severe aplastic anemia (SAA).

The

regimen consists of nonmyeloablative conditioning, bone marrow

transplants (BMTs) from “alternative” donors, and graft-vs-host disease

(GVHD) prophylaxis.

All 16 SAA patients who received this treatment

achieved engraftment and were completely cleared of disease.

There were 2 cases of acute and chronic GVHD, but they resolved.

All patients were ultimately able to stop immunosuppressive therapy.

Robert Brodsky, MD, of Sidney Kimmel Cancer Center in Baltimore, Maryland, and his colleagues reported these findings in Biology of Blood and Marrow Transplantation.

“Our findings have the potential to greatly widen treatment options for the vast majority of severe aplastic anemia patients,” Dr Brodsky said.

He and his colleagues tested their approach in 16 SAA patients between 11 and 69 years of age. Each of the patients had failed to respond to immunosuppressive therapy and other treatments.

The patients received conditioning with antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation.

They then received BMTs. Thirteen of the donors were haploidentical related, 2 were fully matched unrelated, and 1 was mismatched unrelated.

Three and 4 days after BMT, the patients received cyclophosphamide at 50 mg/kg/day as GVHD prophylaxis. They then received mycophenolate mofetil on days 5 through 35 and tacrolimus from day 5 through 1 year.

The median time to neutrophil recovery (over 1000 × 10³/mm³ for 3 consecutive days) was 19 days (range, 16 to 27). The median time to red cell engraftment was 25 days (range, 2 to 58). And the median time to the last platelet transfusion (to keep platelet counts over 50 × 10³/mm³) was 27.5 days (range, 22 to 108).

At a median follow-up of 21 months (range, 3 to 64), all 16 patients were still alive, disease-free, and no longer required transfusions.

Two patients did develop grade 1/2 acute skin GVHD. They also had mild chronic GVHD of the skin/mouth, which required systemic steroids.

One of these patients was able to come off all immunosuppressive therapy by 15 months, and the other was able to do so by 17 months. All of the other patients stopped immunosuppressive therapy at 1 year.

Ending all therapy related to their disease has been life-changing for these patients, said study author Amy DeZern, MD, also of the Sidney Kimmel Cancer Center.

“It’s like night and day,” she said. “They go from not knowing if they have a future to hoping for what they’d hoped for before they got sick. It’s that transformative.”

Successful BMTs using partially matched donors open up the transplant option to nearly all patients with SAA, especially minority patients, added Dr Brodsky.

“Now, a therapy that used to be available to 25% to 30% of patients with severe aplastic anemia is potentially available to more than 95%,” he said.

Researchers Pin Wang (left)
and Antoine Snijders analyze
blood cells collected from mice
exposed to third-hand smoke.
Photo courtesy of
Marilyn Chung/Berkeley Lab

Exposure to third-hand smoke leads to biological effects on weight and blood cell development, according to preclinical research published in Scientific Reports.

Researchers found that newborn mice housed with smoke-treated cloths for 3 weeks weighed significantly less than mice in a control group.

Moreover, newborn and adult mice exposed to third-hand smoke experienced persistent changes in blood cell counts.

The blood cell count changes are associated with inflammatory and allergic reactions upon exposure to third-hand smoke, the researchers said.

For this study, the team set out to characterize the biological effects of exposure to third-hand smoke by placing 5-square-centimeter pieces of smoke-contaminated cotton cloth in cages with mice.

The researchers then compared smoke-exposed mice to control mice. The team assessed changes to body weight and the hematopoietic system after 3 weeks of exposure (or no exposure) for mice belonging to 2 age groups: birth to 3 weeks (neonatal) and 12 to 15 weeks (young adult).

The results showed that smoke exposure temporarily inhibited weight gain in the neonatal mice. There was no effect on weight gain in the young adult mice.

In addition, smoke exposure produced changes in blood cell populations that persisted over time and were evident in mice from both age groups.

In general, there were lower levels of platelets and specific types of white blood cells in the smoke-exposed mice.

For example, neonatal mice exposed to third-hand smoke had higher levels of eosinophils, female mice had higher levels of neutrophils, males had higher levels of basophils, and all mice had higher levels of B cells.

“Those are all types of white blood cells associated with inflammation and allergic reactions,” said study author Jian-Hua Mao, PhD, of Lawrence Berkeley National Laboratory in Berkeley, California.

“And the effects on blood cell count persisted even after exposure ended. Changes remained at least 14 weeks after exposure ended for the neonatal group and 2 weeks after it ended for the adults.”

The researchers pointed out that they did not study whether the observed biological changes led to specific diseases or other health outcomes, but other studies suggest links to adverse health effects.

“Third-hand smoke is an underappreciated risk factor in health,” said study author Antoine Snijders, PhD, of Lawrence Berkeley National Laboratory.

“It’s clear that more and bigger studies are needed, particularly in humans, so we can support policy decisions on third-hand smoke.”

Researchers Pin Wang (left)
and Antoine Snijders analyze
blood cells collected from mice
exposed to third-hand smoke.
Photo courtesy of
Marilyn Chung/Berkeley Lab

Exposure to third-hand smoke leads to biological effects on weight and blood cell development, according to preclinical research published in Scientific Reports.

Researchers found that newborn mice housed with smoke-treated cloths for 3 weeks weighed significantly less than mice in a control group.

Moreover, newborn and adult mice exposed to third-hand smoke experienced persistent changes in blood cell counts.

The blood cell count changes are associated with inflammatory and allergic reactions upon exposure to third-hand smoke, the researchers said.

For this study, the team set out to characterize the biological effects of exposure to third-hand smoke by placing 5-square-centimeter pieces of smoke-contaminated cotton cloth in cages with mice.

The researchers then compared smoke-exposed mice to control mice. The team assessed changes to body weight and the hematopoietic system after 3 weeks of exposure (or no exposure) for mice belonging to 2 age groups: birth to 3 weeks (neonatal) and 12 to 15 weeks (young adult).

The results showed that smoke exposure temporarily inhibited weight gain in the neonatal mice. There was no effect on weight gain in the young adult mice.

In addition, smoke exposure produced changes in blood cell populations that persisted over time and were evident in mice from both age groups.

In general, there were lower levels of platelets and specific types of white blood cells in the smoke-exposed mice.

For example, neonatal mice exposed to third-hand smoke had higher levels of eosinophils, female mice had higher levels of neutrophils, males had higher levels of basophils, and all mice had higher levels of B cells.

“Those are all types of white blood cells associated with inflammation and allergic reactions,” said study author Jian-Hua Mao, PhD, of Lawrence Berkeley National Laboratory in Berkeley, California.

“And the effects on blood cell count persisted even after exposure ended. Changes remained at least 14 weeks after exposure ended for the neonatal group and 2 weeks after it ended for the adults.”

The researchers pointed out that they did not study whether the observed biological changes led to specific diseases or other health outcomes, but other studies suggest links to adverse health effects.

“Third-hand smoke is an underappreciated risk factor in health,” said study author Antoine Snijders, PhD, of Lawrence Berkeley National Laboratory.

“It’s clear that more and bigger studies are needed, particularly in humans, so we can support policy decisions on third-hand smoke.”

Researchers Pin Wang (left)
and Antoine Snijders analyze
blood cells collected from mice
exposed to third-hand smoke.
Photo courtesy of
Marilyn Chung/Berkeley Lab

Exposure to third-hand smoke leads to biological effects on weight and blood cell development, according to preclinical research published in Scientific Reports.

Researchers found that newborn mice housed with smoke-treated cloths for 3 weeks weighed significantly less than mice in a control group.

Moreover, newborn and adult mice exposed to third-hand smoke experienced persistent changes in blood cell counts.

The blood cell count changes are associated with inflammatory and allergic reactions upon exposure to third-hand smoke, the researchers said.

For this study, the team set out to characterize the biological effects of exposure to third-hand smoke by placing 5-square-centimeter pieces of smoke-contaminated cotton cloth in cages with mice.

The researchers then compared smoke-exposed mice to control mice. The team assessed changes to body weight and the hematopoietic system after 3 weeks of exposure (or no exposure) for mice belonging to 2 age groups: birth to 3 weeks (neonatal) and 12 to 15 weeks (young adult).

The results showed that smoke exposure temporarily inhibited weight gain in the neonatal mice. There was no effect on weight gain in the young adult mice.

In addition, smoke exposure produced changes in blood cell populations that persisted over time and were evident in mice from both age groups.

In general, there were lower levels of platelets and specific types of white blood cells in the smoke-exposed mice.

For example, neonatal mice exposed to third-hand smoke had higher levels of eosinophils, female mice had higher levels of neutrophils, males had higher levels of basophils, and all mice had higher levels of B cells.

“Those are all types of white blood cells associated with inflammation and allergic reactions,” said study author Jian-Hua Mao, PhD, of Lawrence Berkeley National Laboratory in Berkeley, California.

“And the effects on blood cell count persisted even after exposure ended. Changes remained at least 14 weeks after exposure ended for the neonatal group and 2 weeks after it ended for the adults.”

The researchers pointed out that they did not study whether the observed biological changes led to specific diseases or other health outcomes, but other studies suggest links to adverse health effects.

“Third-hand smoke is an underappreciated risk factor in health,” said study author Antoine Snijders, PhD, of Lawrence Berkeley National Laboratory.

“It’s clear that more and bigger studies are needed, particularly in humans, so we can support policy decisions on third-hand smoke.”

Micrograph showing WM

The National Comprehensive Cancer Network® (NCCN) has published a set of

guidelines for patients with

Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL).

This resource describes what WM is and how it develops,

explains testing for WM, and provides information on the treatment of

primary, relapsed, and refractory WM.

NCCN Guidelines for Patients are adaptations of the

NCCN Clinical Practice Guidelines in Oncology.

The NCCN also publishes Quick Guide™ sheets, which are 1-page summaries of key points in the patient guidelines.

Both patient resources are available free of charge at NCCN.org/patients as well as on the NCCN Patient Guides for Cancer mobile app.

“The treatment approach to patients with Waldenström’s macroglobulinemia has significantly changed in the recent years with better understanding of the disease biology and its natural history and availability of new drugs, allowing for a more individualized approach,” said Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota.

“The revised guidelines reflect these changes and will be a valuable guide for patients in shared decision-making with their oncologists.”  

NCCN Guidelines for Patients are based on the same clinical practice guidelines used by healthcare professionals to determine the best way to treat a patient with cancer.

Each resource features expert guidance from US cancer centers designed to help people living with cancer talk to their physicians about the best treatment options for their disease.

The Guidelines for Patients and Quick Guide sheets are written in plain language and include patient-friendly elements, such as “questions to ask your doctor,” a glossary of terms, and medical illustrations of anatomy, tests, and treatment.

NCCN currently offers NCCN Guidelines for Patients covering the following topics: brain, breast, colon esophageal, kidney, non-small cell lung, ovarian, pancreatic, prostate, and stomach cancers; acute lymphoblastic leukemia; adolescents and young adults with cancer; chronic lymphocytic leukemia; chronic myelogenous leukemia; Hodgkin lymphoma; lung cancer screening; malignant pleural mesothelioma; melanoma; multiple myeloma; nausea and vomiting; non-Hodgkin lymphomas; soft tissue sarcoma; and WM/LPL.

Micrograph showing WM

The National Comprehensive Cancer Network® (NCCN) has published a set of

guidelines for patients with

Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL).

This resource describes what WM is and how it develops,

explains testing for WM, and provides information on the treatment of

primary, relapsed, and refractory WM.

NCCN Guidelines for Patients are adaptations of the

NCCN Clinical Practice Guidelines in Oncology.

The NCCN also publishes Quick Guide™ sheets, which are 1-page summaries of key points in the patient guidelines.

Both patient resources are available free of charge at NCCN.org/patients as well as on the NCCN Patient Guides for Cancer mobile app.

“The treatment approach to patients with Waldenström’s macroglobulinemia has significantly changed in the recent years with better understanding of the disease biology and its natural history and availability of new drugs, allowing for a more individualized approach,” said Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota.

“The revised guidelines reflect these changes and will be a valuable guide for patients in shared decision-making with their oncologists.”  

NCCN Guidelines for Patients are based on the same clinical practice guidelines used by healthcare professionals to determine the best way to treat a patient with cancer.

Each resource features expert guidance from US cancer centers designed to help people living with cancer talk to their physicians about the best treatment options for their disease.

The Guidelines for Patients and Quick Guide sheets are written in plain language and include patient-friendly elements, such as “questions to ask your doctor,” a glossary of terms, and medical illustrations of anatomy, tests, and treatment.

NCCN currently offers NCCN Guidelines for Patients covering the following topics: brain, breast, colon esophageal, kidney, non-small cell lung, ovarian, pancreatic, prostate, and stomach cancers; acute lymphoblastic leukemia; adolescents and young adults with cancer; chronic lymphocytic leukemia; chronic myelogenous leukemia; Hodgkin lymphoma; lung cancer screening; malignant pleural mesothelioma; melanoma; multiple myeloma; nausea and vomiting; non-Hodgkin lymphomas; soft tissue sarcoma; and WM/LPL.

Micrograph showing WM

The National Comprehensive Cancer Network® (NCCN) has published a set of

guidelines for patients with

Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL).

This resource describes what WM is and how it develops,

explains testing for WM, and provides information on the treatment of

primary, relapsed, and refractory WM.

NCCN Guidelines for Patients are adaptations of the

NCCN Clinical Practice Guidelines in Oncology.

The NCCN also publishes Quick Guide™ sheets, which are 1-page summaries of key points in the patient guidelines.

Both patient resources are available free of charge at NCCN.org/patients as well as on the NCCN Patient Guides for Cancer mobile app.

“The treatment approach to patients with Waldenström’s macroglobulinemia has significantly changed in the recent years with better understanding of the disease biology and its natural history and availability of new drugs, allowing for a more individualized approach,” said Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota.

“The revised guidelines reflect these changes and will be a valuable guide for patients in shared decision-making with their oncologists.”  

NCCN Guidelines for Patients are based on the same clinical practice guidelines used by healthcare professionals to determine the best way to treat a patient with cancer.

Each resource features expert guidance from US cancer centers designed to help people living with cancer talk to their physicians about the best treatment options for their disease.

The Guidelines for Patients and Quick Guide sheets are written in plain language and include patient-friendly elements, such as “questions to ask your doctor,” a glossary of terms, and medical illustrations of anatomy, tests, and treatment.

NCCN currently offers NCCN Guidelines for Patients covering the following topics: brain, breast, colon esophageal, kidney, non-small cell lung, ovarian, pancreatic, prostate, and stomach cancers; acute lymphoblastic leukemia; adolescents and young adults with cancer; chronic lymphocytic leukemia; chronic myelogenous leukemia; Hodgkin lymphoma; lung cancer screening; malignant pleural mesothelioma; melanoma; multiple myeloma; nausea and vomiting; non-Hodgkin lymphomas; soft tissue sarcoma; and WM/LPL.

Azathioprine tablets

Results of a large, retrospective study suggest that taking azathioprine, a drug commonly used to treat autoimmune disease, may increase a person’s risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Researchers analyzed data on more than 40,000 patients with 27 common autoimmune diseases and found that azathioprine use was significantly associated with an increased risk of MDS and AML.

“Similar associations were already documented in case reports and case series but have never been evaluated in a broad spectrum of autoimmune diseases in that many patients and in context of individual medications,” said study author Raoul Tibes, MD, PhD, of the Mayo Clinic in Phoenix, Arizona.

“Interestingly, there was no association with length of time on therapy and resulting myeloid neoplasm.”

Dr Tibes and his colleagues reported these findings in JAMA Oncology.

The researchers reviewed data on 40,011 patients with primary autoimmune disorders, such as lupus and rheumatoid arthritis, who were seen at 2 centers from January 1, 2004, to December 31, 2014.

There were 311 patients with MDS or AML, but only 86 met strict inclusion criteria. Fifty-five patients had MDS, 21 had de novo AML, and 10 had AML and a history of MDS.

The researchers collected detailed data on each patient’s drug exposures, treatment duration, and disease characteristics and compared this information to data from patients with autoimmune disorders who did not have MDS or AML.

This revealed that use of azathioprine sodium was more frequent in cases than controls, and azathioprine was significantly associated with an increased risk of MDS and AML. The odds ratio was 7.05 (P<0.001).

Other agents used showed a similar trend, but the results were not statistically significant. The odds ratios were 3.58 for cyclophosphamide and 2.73 for mitoxantrone hydrochloride.

The researchers said that, while these results are intriguing, they should not change or replace the clinical judgments, monitoring, and current standard treatments for patients with autoimmune diseases.

Despite its large size, this study had limitations, including its retrospective nature, the fact that many different autoimmune diseases were analyzed, and that the researchers only looked at cases of MDS and AML.

No definitive causal association was made between taking a particular drug and MDS or AML. The number of patients with autoimmune disease developing MDS or AML is still low overall, and no prediction for individual patients can be concluded from the study.

The researchers plan to perform molecular investigations into the genetic susceptibility for therapy-related myeloid neoplasms as the next phase of this research.

Azathioprine tablets

Results of a large, retrospective study suggest that taking azathioprine, a drug commonly used to treat autoimmune disease, may increase a person’s risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Researchers analyzed data on more than 40,000 patients with 27 common autoimmune diseases and found that azathioprine use was significantly associated with an increased risk of MDS and AML.

“Similar associations were already documented in case reports and case series but have never been evaluated in a broad spectrum of autoimmune diseases in that many patients and in context of individual medications,” said study author Raoul Tibes, MD, PhD, of the Mayo Clinic in Phoenix, Arizona.

“Interestingly, there was no association with length of time on therapy and resulting myeloid neoplasm.”

Dr Tibes and his colleagues reported these findings in JAMA Oncology.

The researchers reviewed data on 40,011 patients with primary autoimmune disorders, such as lupus and rheumatoid arthritis, who were seen at 2 centers from January 1, 2004, to December 31, 2014.

There were 311 patients with MDS or AML, but only 86 met strict inclusion criteria. Fifty-five patients had MDS, 21 had de novo AML, and 10 had AML and a history of MDS.

The researchers collected detailed data on each patient’s drug exposures, treatment duration, and disease characteristics and compared this information to data from patients with autoimmune disorders who did not have MDS or AML.

This revealed that use of azathioprine sodium was more frequent in cases than controls, and azathioprine was significantly associated with an increased risk of MDS and AML. The odds ratio was 7.05 (P<0.001).

Other agents used showed a similar trend, but the results were not statistically significant. The odds ratios were 3.58 for cyclophosphamide and 2.73 for mitoxantrone hydrochloride.

The researchers said that, while these results are intriguing, they should not change or replace the clinical judgments, monitoring, and current standard treatments for patients with autoimmune diseases.

Despite its large size, this study had limitations, including its retrospective nature, the fact that many different autoimmune diseases were analyzed, and that the researchers only looked at cases of MDS and AML.

No definitive causal association was made between taking a particular drug and MDS or AML. The number of patients with autoimmune disease developing MDS or AML is still low overall, and no prediction for individual patients can be concluded from the study.

The researchers plan to perform molecular investigations into the genetic susceptibility for therapy-related myeloid neoplasms as the next phase of this research.

Azathioprine tablets

Results of a large, retrospective study suggest that taking azathioprine, a drug commonly used to treat autoimmune disease, may increase a person’s risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Researchers analyzed data on more than 40,000 patients with 27 common autoimmune diseases and found that azathioprine use was significantly associated with an increased risk of MDS and AML.

“Similar associations were already documented in case reports and case series but have never been evaluated in a broad spectrum of autoimmune diseases in that many patients and in context of individual medications,” said study author Raoul Tibes, MD, PhD, of the Mayo Clinic in Phoenix, Arizona.

“Interestingly, there was no association with length of time on therapy and resulting myeloid neoplasm.”

Dr Tibes and his colleagues reported these findings in JAMA Oncology.

The researchers reviewed data on 40,011 patients with primary autoimmune disorders, such as lupus and rheumatoid arthritis, who were seen at 2 centers from January 1, 2004, to December 31, 2014.

There were 311 patients with MDS or AML, but only 86 met strict inclusion criteria. Fifty-five patients had MDS, 21 had de novo AML, and 10 had AML and a history of MDS.

The researchers collected detailed data on each patient’s drug exposures, treatment duration, and disease characteristics and compared this information to data from patients with autoimmune disorders who did not have MDS or AML.

This revealed that use of azathioprine sodium was more frequent in cases than controls, and azathioprine was significantly associated with an increased risk of MDS and AML. The odds ratio was 7.05 (P<0.001).

Other agents used showed a similar trend, but the results were not statistically significant. The odds ratios were 3.58 for cyclophosphamide and 2.73 for mitoxantrone hydrochloride.

The researchers said that, while these results are intriguing, they should not change or replace the clinical judgments, monitoring, and current standard treatments for patients with autoimmune diseases.

Despite its large size, this study had limitations, including its retrospective nature, the fact that many different autoimmune diseases were analyzed, and that the researchers only looked at cases of MDS and AML.

No definitive causal association was made between taking a particular drug and MDS or AML. The number of patients with autoimmune disease developing MDS or AML is still low overall, and no prediction for individual patients can be concluded from the study.

The researchers plan to perform molecular investigations into the genetic susceptibility for therapy-related myeloid neoplasms as the next phase of this research.

rFIXFc components

Photo courtesy of Biogen

A recombinant factor IX Fc fusion protein (rFIXFc) has produced favorable results in children with severe hemophilia B, researchers have reported.

The team said rFIXFc was generally well-tolerated in the phase 3 Kids B-LONG study, and none of the patients on this trial developed inhibitors.

In addition, the annualized bleeding rate was low, and most patients were able to maintain once-weekly dosing.

“To date, Kids B-LONG is the largest study to evaluate the safety and efficacy of extended half-life factor IX therapy in children with hemophilia B, and the study’s results align with those in studies of [rFIXFc] in adults and adolescents,” said Roshni Kulkarni, MD, of Michigan State University in East Lansing.

Dr Kulkarni and her colleagues reported results of Kids B-LONG in The Lancet Haematology. The research was funded by Biogen and Sobi, the companies marketing rFIXFc (also known as eftrenonacog alfa) as Alprolix.

The study included 30 males under the age of 12 with previously treated, severe hemophilia B.

All patients initially received rFIXFc prophylaxis (50-60 IU/kg) once per week. Doses were adjusted as needed (≤100 IU/kg per infusion, up to 2 times per week).

Twenty-seven patients (90%) completed the study. The median time spent on study was 49.4 weeks, and 24 patients received rFIXFc injections on at least 50 separate days.

None of the patients developed inhibitors to rFIXFc. There were no reports of anaphylaxis or serious hypersensitivity reactions, no vascular thrombotic events, and no deaths.

The most common adverse events were common cold (n=7, 23%) and fall (n=6, 20%). Four patients experienced serious adverse events while on study, all of which were considered unrelated to rFIXFc.

The median annualized bleeding rate was 2.0 overall, and there were no spontaneous joint bleeds.

Of all 30 patients treated, 10 (33%) experienced no bleeding episodes, and 19 (63%) reported no joint bleeding on-study.

Overall, 92% of bleeding episodes were controlled by 1 or 2 injections of rFIXFc.

Following a switch to rFIXFc, 80% of children who completed the study (22/27) extended their dosing interval compared to previous treatment.

One patient had his dosing interval reduced to 5 days, but all other patients remained on once-weekly prophylactic dosing throughout the study.

rFIXFc components

Photo courtesy of Biogen

A recombinant factor IX Fc fusion protein (rFIXFc) has produced favorable results in children with severe hemophilia B, researchers have reported.

The team said rFIXFc was generally well-tolerated in the phase 3 Kids B-LONG study, and none of the patients on this trial developed inhibitors.

In addition, the annualized bleeding rate was low, and most patients were able to maintain once-weekly dosing.

“To date, Kids B-LONG is the largest study to evaluate the safety and efficacy of extended half-life factor IX therapy in children with hemophilia B, and the study’s results align with those in studies of [rFIXFc] in adults and adolescents,” said Roshni Kulkarni, MD, of Michigan State University in East Lansing.

Dr Kulkarni and her colleagues reported results of Kids B-LONG in The Lancet Haematology. The research was funded by Biogen and Sobi, the companies marketing rFIXFc (also known as eftrenonacog alfa) as Alprolix.

The study included 30 males under the age of 12 with previously treated, severe hemophilia B.

All patients initially received rFIXFc prophylaxis (50-60 IU/kg) once per week. Doses were adjusted as needed (≤100 IU/kg per infusion, up to 2 times per week).

Twenty-seven patients (90%) completed the study. The median time spent on study was 49.4 weeks, and 24 patients received rFIXFc injections on at least 50 separate days.

None of the patients developed inhibitors to rFIXFc. There were no reports of anaphylaxis or serious hypersensitivity reactions, no vascular thrombotic events, and no deaths.

The most common adverse events were common cold (n=7, 23%) and fall (n=6, 20%). Four patients experienced serious adverse events while on study, all of which were considered unrelated to rFIXFc.

The median annualized bleeding rate was 2.0 overall, and there were no spontaneous joint bleeds.

Of all 30 patients treated, 10 (33%) experienced no bleeding episodes, and 19 (63%) reported no joint bleeding on-study.

Overall, 92% of bleeding episodes were controlled by 1 or 2 injections of rFIXFc.

Following a switch to rFIXFc, 80% of children who completed the study (22/27) extended their dosing interval compared to previous treatment.

One patient had his dosing interval reduced to 5 days, but all other patients remained on once-weekly prophylactic dosing throughout the study.

rFIXFc components

Photo courtesy of Biogen

A recombinant factor IX Fc fusion protein (rFIXFc) has produced favorable results in children with severe hemophilia B, researchers have reported.

The team said rFIXFc was generally well-tolerated in the phase 3 Kids B-LONG study, and none of the patients on this trial developed inhibitors.

In addition, the annualized bleeding rate was low, and most patients were able to maintain once-weekly dosing.

“To date, Kids B-LONG is the largest study to evaluate the safety and efficacy of extended half-life factor IX therapy in children with hemophilia B, and the study’s results align with those in studies of [rFIXFc] in adults and adolescents,” said Roshni Kulkarni, MD, of Michigan State University in East Lansing.

Dr Kulkarni and her colleagues reported results of Kids B-LONG in The Lancet Haematology. The research was funded by Biogen and Sobi, the companies marketing rFIXFc (also known as eftrenonacog alfa) as Alprolix.

The study included 30 males under the age of 12 with previously treated, severe hemophilia B.

All patients initially received rFIXFc prophylaxis (50-60 IU/kg) once per week. Doses were adjusted as needed (≤100 IU/kg per infusion, up to 2 times per week).

Twenty-seven patients (90%) completed the study. The median time spent on study was 49.4 weeks, and 24 patients received rFIXFc injections on at least 50 separate days.

None of the patients developed inhibitors to rFIXFc. There were no reports of anaphylaxis or serious hypersensitivity reactions, no vascular thrombotic events, and no deaths.

The most common adverse events were common cold (n=7, 23%) and fall (n=6, 20%). Four patients experienced serious adverse events while on study, all of which were considered unrelated to rFIXFc.

The median annualized bleeding rate was 2.0 overall, and there were no spontaneous joint bleeds.

Of all 30 patients treated, 10 (33%) experienced no bleeding episodes, and 19 (63%) reported no joint bleeding on-study.

Overall, 92% of bleeding episodes were controlled by 1 or 2 injections of rFIXFc.

Following a switch to rFIXFc, 80% of children who completed the study (22/27) extended their dosing interval compared to previous treatment.

One patient had his dosing interval reduced to 5 days, but all other patients remained on once-weekly prophylactic dosing throughout the study.

Dendritic cells in skin

Stemline Therapeutics, Inc. has announced another patient death in its ongoing phase 2 trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML).

The company became aware of this death, in a patient with BPDCN, on January 18.

The cause of death has not been determined, but the patient had developed capillary leak syndrome (CLS), a sometimes fatal and well-documented side effect of SL-401.

There have been 2 other deaths reported in patients with CLS in this trial. One of these deaths occurred in a patient with BPDCN and the other in a patient with AML.

Stemline said this study is ongoing, patient enrollment is ahead of schedule, and patients continue to receive SL-401 in the trial. Timelines for study completion and biologics licensing application submission remain on track.

The fact that CLS is an expected complication of SL-401 administration has been noted in filings with the Securities and Exchange Commission and US Food and Drug Administration (FDA), as well as in the study’s informed consent forms and other information provided to investigators.

Stemline said it has and will continue to report data to the FDA in accordance with the study protocol and applicable regulations. The company plans to provide a clinical and safety update on this cohort when the cohort and data are complete.

SL-410 in BPDCN

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies. SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

SL-401 is being tested in several clinical trials. Results from the phase 2 trial in BPDCN and AML patients were presented at the 2016 ASH Annual Meeting (abstract 342). However, the presentation only included data on the patients with BPDCN.

The trial consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

As of October 7, 2016, 32 BPDCN patients had been treated—9 in stage 1 and 23 in stage 2. Nineteen patients received SL-401 as first-line treatment, and 13 had relapsed/refractory disease. (Fourteen patients with relapsed/refractory AML were treated in stage 1.)

Efficacy

Of the 19 first-line BPDCN patients, 16 received the optimal dose (12 μg/kg). The overall response rate was 95% among all first-line patients (18/19) and 100% among those who received the optimal dose (16/16).

The complete response rates were 74% (14/19) and 81% (13/16), respectively. Six patients (all who received the optimal dose) proceeded to transplant (autologous and allogeneic).

All 13 relapsed/refractory BPDCN patients received the optimal dose. The overall response rate was 69% (9/13), and the complete response rate was 31% (4/13). One patient proceeded to allogeneic transplant.

Eleven first-line patients, including the 6 who went on to transplant, have ongoing responses. Six relapsed/refractory patients, including the patient who went on to transplant, have ongoing responses.

Among first-line patients treated at the optimal dose, the median progression-free and overall survival have not been reached. Among relapsed/refractory patients (all of whom were treated at the optimal dose), the median progression-free and overall survival are 8.5 months.

Safety

The most common treatment-related adverse events were transaminase elevation (52%), hypoalbuminemia (39%), chills (31%), pyrexia (27%), nausea (23%), fatigue (23%), peripheral edema (23%), thrombocytopenia (19%), hypotension (19%), weight increase (19%), anemia (19%), decreased appetite (19%), and CLS (19%).

In stage 1, two BPDCN patients had CLS—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS.

A second CLS-related death occurred in stage 1 in a patient with relapsed/refractory AML (16 μg/kg).

The other death in a BPDCN patient with CLS was reported after the ASH presentation. Stemline became aware of the death on January 18 and disclosed it to the public on February 2.

Dendritic cells in skin

Stemline Therapeutics, Inc. has announced another patient death in its ongoing phase 2 trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML).

The company became aware of this death, in a patient with BPDCN, on January 18.

The cause of death has not been determined, but the patient had developed capillary leak syndrome (CLS), a sometimes fatal and well-documented side effect of SL-401.

There have been 2 other deaths reported in patients with CLS in this trial. One of these deaths occurred in a patient with BPDCN and the other in a patient with AML.

Stemline said this study is ongoing, patient enrollment is ahead of schedule, and patients continue to receive SL-401 in the trial. Timelines for study completion and biologics licensing application submission remain on track.

The fact that CLS is an expected complication of SL-401 administration has been noted in filings with the Securities and Exchange Commission and US Food and Drug Administration (FDA), as well as in the study’s informed consent forms and other information provided to investigators.

Stemline said it has and will continue to report data to the FDA in accordance with the study protocol and applicable regulations. The company plans to provide a clinical and safety update on this cohort when the cohort and data are complete.

SL-410 in BPDCN

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies. SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

SL-401 is being tested in several clinical trials. Results from the phase 2 trial in BPDCN and AML patients were presented at the 2016 ASH Annual Meeting (abstract 342). However, the presentation only included data on the patients with BPDCN.

The trial consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

As of October 7, 2016, 32 BPDCN patients had been treated—9 in stage 1 and 23 in stage 2. Nineteen patients received SL-401 as first-line treatment, and 13 had relapsed/refractory disease. (Fourteen patients with relapsed/refractory AML were treated in stage 1.)

Efficacy

Of the 19 first-line BPDCN patients, 16 received the optimal dose (12 μg/kg). The overall response rate was 95% among all first-line patients (18/19) and 100% among those who received the optimal dose (16/16).

The complete response rates were 74% (14/19) and 81% (13/16), respectively. Six patients (all who received the optimal dose) proceeded to transplant (autologous and allogeneic).

All 13 relapsed/refractory BPDCN patients received the optimal dose. The overall response rate was 69% (9/13), and the complete response rate was 31% (4/13). One patient proceeded to allogeneic transplant.

Eleven first-line patients, including the 6 who went on to transplant, have ongoing responses. Six relapsed/refractory patients, including the patient who went on to transplant, have ongoing responses.

Among first-line patients treated at the optimal dose, the median progression-free and overall survival have not been reached. Among relapsed/refractory patients (all of whom were treated at the optimal dose), the median progression-free and overall survival are 8.5 months.

Safety

The most common treatment-related adverse events were transaminase elevation (52%), hypoalbuminemia (39%), chills (31%), pyrexia (27%), nausea (23%), fatigue (23%), peripheral edema (23%), thrombocytopenia (19%), hypotension (19%), weight increase (19%), anemia (19%), decreased appetite (19%), and CLS (19%).

In stage 1, two BPDCN patients had CLS—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS.

A second CLS-related death occurred in stage 1 in a patient with relapsed/refractory AML (16 μg/kg).

The other death in a BPDCN patient with CLS was reported after the ASH presentation. Stemline became aware of the death on January 18 and disclosed it to the public on February 2.

Dendritic cells in skin

Stemline Therapeutics, Inc. has announced another patient death in its ongoing phase 2 trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML).

The company became aware of this death, in a patient with BPDCN, on January 18.

The cause of death has not been determined, but the patient had developed capillary leak syndrome (CLS), a sometimes fatal and well-documented side effect of SL-401.

There have been 2 other deaths reported in patients with CLS in this trial. One of these deaths occurred in a patient with BPDCN and the other in a patient with AML.

Stemline said this study is ongoing, patient enrollment is ahead of schedule, and patients continue to receive SL-401 in the trial. Timelines for study completion and biologics licensing application submission remain on track.

The fact that CLS is an expected complication of SL-401 administration has been noted in filings with the Securities and Exchange Commission and US Food and Drug Administration (FDA), as well as in the study’s informed consent forms and other information provided to investigators.

Stemline said it has and will continue to report data to the FDA in accordance with the study protocol and applicable regulations. The company plans to provide a clinical and safety update on this cohort when the cohort and data are complete.

SL-410 in BPDCN

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies. SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

SL-401 is being tested in several clinical trials. Results from the phase 2 trial in BPDCN and AML patients were presented at the 2016 ASH Annual Meeting (abstract 342). However, the presentation only included data on the patients with BPDCN.

The trial consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

As of October 7, 2016, 32 BPDCN patients had been treated—9 in stage 1 and 23 in stage 2. Nineteen patients received SL-401 as first-line treatment, and 13 had relapsed/refractory disease. (Fourteen patients with relapsed/refractory AML were treated in stage 1.)

Efficacy

Of the 19 first-line BPDCN patients, 16 received the optimal dose (12 μg/kg). The overall response rate was 95% among all first-line patients (18/19) and 100% among those who received the optimal dose (16/16).

The complete response rates were 74% (14/19) and 81% (13/16), respectively. Six patients (all who received the optimal dose) proceeded to transplant (autologous and allogeneic).

All 13 relapsed/refractory BPDCN patients received the optimal dose. The overall response rate was 69% (9/13), and the complete response rate was 31% (4/13). One patient proceeded to allogeneic transplant.

Eleven first-line patients, including the 6 who went on to transplant, have ongoing responses. Six relapsed/refractory patients, including the patient who went on to transplant, have ongoing responses.

Among first-line patients treated at the optimal dose, the median progression-free and overall survival have not been reached. Among relapsed/refractory patients (all of whom were treated at the optimal dose), the median progression-free and overall survival are 8.5 months.

Safety

The most common treatment-related adverse events were transaminase elevation (52%), hypoalbuminemia (39%), chills (31%), pyrexia (27%), nausea (23%), fatigue (23%), peripheral edema (23%), thrombocytopenia (19%), hypotension (19%), weight increase (19%), anemia (19%), decreased appetite (19%), and CLS (19%).

In stage 1, two BPDCN patients had CLS—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS.

A second CLS-related death occurred in stage 1 in a patient with relapsed/refractory AML (16 μg/kg).

The other death in a BPDCN patient with CLS was reported after the ASH presentation. Stemline became aware of the death on January 18 and disclosed it to the public on February 2.

Frederick Lansigan, MD

Photo by Larry Young

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

Frederick Lansigan, MD

Photo by Larry Young

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

Frederick Lansigan, MD

Photo by Larry Young

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

Micrograph showing
mycosis fungoides

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted SGX301 (synthetic hypericin) Promising Innovative Medicine (PIM) designation for the treatment of cutaneous T-cell lymphoma (CTCL).

The PIM designation is the first step toward inclusion in the Early Access to Medicines Scheme (EAMS). 

EAMS provides early access to new medicines for patients with life-threatening and seriously debilitating conditions.

PIM status is awarded following an assessment of early nonclinical and clinical data by the MHRA.

PIM designation has been created as an early signal to companies that a product’s development plan is appropriate and indicates that a product could be a candidate for the second phase of the EAMS scheme once further development work has been conducted. 

In the second phase, the product is made available to UK patients before a marketing authorization is approved.

The requirements for PIM designation are:

1. The condition should be life-threatening or seriously debilitating with a high unmet medical need (ie, there is no method of treatment, diagnosis, or prevention available, or existing methods have serious limitations).
2. The medicinal product is likely to offer a major advantage over methods currently used in the UK.
3. The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit-risk balance. A positive benefit-risk balance should be based on preliminary scientific evidence, as justified by the applicant.

About SGX301

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. 

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is currently recruiting patients. SGX301 is under development by Soligenix, Inc.

Micrograph showing
mycosis fungoides

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted SGX301 (synthetic hypericin) Promising Innovative Medicine (PIM) designation for the treatment of cutaneous T-cell lymphoma (CTCL).

The PIM designation is the first step toward inclusion in the Early Access to Medicines Scheme (EAMS). 

EAMS provides early access to new medicines for patients with life-threatening and seriously debilitating conditions.

PIM status is awarded following an assessment of early nonclinical and clinical data by the MHRA.

PIM designation has been created as an early signal to companies that a product’s development plan is appropriate and indicates that a product could be a candidate for the second phase of the EAMS scheme once further development work has been conducted. 

In the second phase, the product is made available to UK patients before a marketing authorization is approved.

The requirements for PIM designation are:

1. The condition should be life-threatening or seriously debilitating with a high unmet medical need (ie, there is no method of treatment, diagnosis, or prevention available, or existing methods have serious limitations).
2. The medicinal product is likely to offer a major advantage over methods currently used in the UK.
3. The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit-risk balance. A positive benefit-risk balance should be based on preliminary scientific evidence, as justified by the applicant.

About SGX301

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. 

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is currently recruiting patients. SGX301 is under development by Soligenix, Inc.

Micrograph showing
mycosis fungoides

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted SGX301 (synthetic hypericin) Promising Innovative Medicine (PIM) designation for the treatment of cutaneous T-cell lymphoma (CTCL).

The PIM designation is the first step toward inclusion in the Early Access to Medicines Scheme (EAMS). 

EAMS provides early access to new medicines for patients with life-threatening and seriously debilitating conditions.

PIM status is awarded following an assessment of early nonclinical and clinical data by the MHRA.

PIM designation has been created as an early signal to companies that a product’s development plan is appropriate and indicates that a product could be a candidate for the second phase of the EAMS scheme once further development work has been conducted. 

In the second phase, the product is made available to UK patients before a marketing authorization is approved.

The requirements for PIM designation are:

1. The condition should be life-threatening or seriously debilitating with a high unmet medical need (ie, there is no method of treatment, diagnosis, or prevention available, or existing methods have serious limitations).
2. The medicinal product is likely to offer a major advantage over methods currently used in the UK.
3. The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit-risk balance. A positive benefit-risk balance should be based on preliminary scientific evidence, as justified by the applicant.

About SGX301

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. 

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is currently recruiting patients. SGX301 is under development by Soligenix, Inc.