Hodgkin Lymphoma

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.

For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.

The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.

Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.

As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.

By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.

Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).

The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).

Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.

[email protected]
On Twitter @maryjodales

CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.

For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.

The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.

Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.

As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.

By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.

Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).

The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).

Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.

[email protected]
On Twitter @maryjodales

CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.

For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.

The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.

Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.

As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.

By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.

Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).

The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).

Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.

[email protected]
On Twitter @maryjodales

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

Photo by Rhoda Baer

VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.

The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.

These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.

The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).

“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.

“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”

Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.

The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.

CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.

Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.

Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).

Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).

The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).

Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.

Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).

“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.

“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”

“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”

Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.

He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.

“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”

“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.” 

Photo by Rhoda Baer

VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.

The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.

These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.

The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).

“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.

“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”

Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.

The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.

CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.

Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.

Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).

Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).

The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).

Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.

Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).

“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.

“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”

“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”

Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.

He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.

“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”

“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.” 

Photo by Rhoda Baer

VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.

The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.

These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.

The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).

“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.

“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”

Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.

The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.

CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.

Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.

Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).

Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).

The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).

Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.

Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).

“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.

“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”

“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”

Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.

He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.

“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”

“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.” 

Photo by Rhoda Baer

BOSTON—A pair of preclinical studies suggest the FLT3/BTK inhibitor CG’806 is active in a range of hematologic malignancies.

In one of the studies, CG’806 proved particularly effective against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3, and the compound was able to eradicate AML in mice.

In another study, researchers found CG’806 exhibited “broad potency” against leukemias, lymphomas, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs).

Both studies were presented as posters at Hematologic Malignancies: Translating Discoveries to Novel Therapies (poster 25 and poster 44).

Both studies involved researchers from Aptose Biosciences, the company developing CG’806.

Poster 25

Weiguo Zhang, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented poster 25, “CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3.”

The researchers tested CG’806 and other FLT3 inhibitors in human or murine leukemia cell lines with wild-type (WT) FLT3, FLT3-ITD mutations, FLT3 TKD domain mutations, or ITD plus TKD mutations.

Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with ITD mutations, D835 mutations, ITD plus F691I/Y842D/D835 mutations, or in FLT3 WT cells.

With CG’086, the IC50s in human AML cell lines were 0.17 nM for MV4-11 (FLT3-ITD) and 0.82 nM for MOLM13 (FLT3-ITD).

The IC50s in the murine leukemia cell lines were 9.49 nM for Ba/F3 (FLT3-WT), 0.30 nM for Ba/F3 (FLT3-ITD), 8.26 nM for Ba/F3 (FLT3-D835Y), 9.72 nM for Ba/F3 (FLT3-ITD+D835Y), and 0.43 nM for Ba/F3 (FLT3-ITD+F691L).

The researchers also found that CG’806 “triggers marked apoptosis” in FLT3-ITD-mutated primary AML samples but minimal apoptosis in normal bone marrow cells.

Another finding was that once-daily oral dosing of CG’806 in a murine model of AML (MV4-11) resulted in sustained micromolar plasma concentration over a 24-hour period.

This was accompanied by complete elimination of AML FLT3-ITD tumors without toxicity, the researchers said.

Poster 44

Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented poster 44, “CG’806, a First-in-Class FLT3/BTK Inhibitor, Exhibits Potent Activity against AML Patient Samples with Mutant or Wild-Type FLT3, as well as Other Hematologic Malignancy Subtypes.”

The researchers tested CG’806 in samples from patients with AML (n=82), MDS/MPNs (n=15), acute lymphoblastic leukemia (ALL, n=17), chronic lymphocytic leukemia (CLL, n=58), and chronic myeloid leukemia (CML, n=4).

The team observed “broad sensitivity” to CG’806, with 59% (48/82) of AML, 53% (8/15) of MDS/MPN, 40% (23/58) of CLL, 29% (5/17) of ALL, and 25% (1/4) of CML cases exhibiting an IC50 of less than 100 nM.

Among the 38 tested AML samples with known FLT3 mutational status, the FLT3-ITD+ AML samples tended to have enhanced sensitivity to CG’806 (median IC50 = 20 nM, n=8) relative to the FLT3-WT samples (median IC50 = 120 nM, n=30).

The researchers also found that CG’806 exerted potent anti-proliferative activity against human AML, B-ALL, mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cell lines.

“The analyses of CG’806 against primary hematologic malignancy patient samples and cultured cell lines show evidence of potent and broad drug activity in AML and other disease subtypes and support further development of this agent for hematologic malignancies,” Dr Kurtz said. 

Photo by Rhoda Baer

BOSTON—A pair of preclinical studies suggest the FLT3/BTK inhibitor CG’806 is active in a range of hematologic malignancies.

In one of the studies, CG’806 proved particularly effective against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3, and the compound was able to eradicate AML in mice.

In another study, researchers found CG’806 exhibited “broad potency” against leukemias, lymphomas, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs).

Both studies were presented as posters at Hematologic Malignancies: Translating Discoveries to Novel Therapies (poster 25 and poster 44).

Both studies involved researchers from Aptose Biosciences, the company developing CG’806.

Poster 25

Weiguo Zhang, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented poster 25, “CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3.”

The researchers tested CG’806 and other FLT3 inhibitors in human or murine leukemia cell lines with wild-type (WT) FLT3, FLT3-ITD mutations, FLT3 TKD domain mutations, or ITD plus TKD mutations.

Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with ITD mutations, D835 mutations, ITD plus F691I/Y842D/D835 mutations, or in FLT3 WT cells.

With CG’086, the IC50s in human AML cell lines were 0.17 nM for MV4-11 (FLT3-ITD) and 0.82 nM for MOLM13 (FLT3-ITD).

The IC50s in the murine leukemia cell lines were 9.49 nM for Ba/F3 (FLT3-WT), 0.30 nM for Ba/F3 (FLT3-ITD), 8.26 nM for Ba/F3 (FLT3-D835Y), 9.72 nM for Ba/F3 (FLT3-ITD+D835Y), and 0.43 nM for Ba/F3 (FLT3-ITD+F691L).

The researchers also found that CG’806 “triggers marked apoptosis” in FLT3-ITD-mutated primary AML samples but minimal apoptosis in normal bone marrow cells.

Another finding was that once-daily oral dosing of CG’806 in a murine model of AML (MV4-11) resulted in sustained micromolar plasma concentration over a 24-hour period.

This was accompanied by complete elimination of AML FLT3-ITD tumors without toxicity, the researchers said.

Poster 44

Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented poster 44, “CG’806, a First-in-Class FLT3/BTK Inhibitor, Exhibits Potent Activity against AML Patient Samples with Mutant or Wild-Type FLT3, as well as Other Hematologic Malignancy Subtypes.”

The researchers tested CG’806 in samples from patients with AML (n=82), MDS/MPNs (n=15), acute lymphoblastic leukemia (ALL, n=17), chronic lymphocytic leukemia (CLL, n=58), and chronic myeloid leukemia (CML, n=4).

The team observed “broad sensitivity” to CG’806, with 59% (48/82) of AML, 53% (8/15) of MDS/MPN, 40% (23/58) of CLL, 29% (5/17) of ALL, and 25% (1/4) of CML cases exhibiting an IC50 of less than 100 nM.

Among the 38 tested AML samples with known FLT3 mutational status, the FLT3-ITD+ AML samples tended to have enhanced sensitivity to CG’806 (median IC50 = 20 nM, n=8) relative to the FLT3-WT samples (median IC50 = 120 nM, n=30).

The researchers also found that CG’806 exerted potent anti-proliferative activity against human AML, B-ALL, mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cell lines.

“The analyses of CG’806 against primary hematologic malignancy patient samples and cultured cell lines show evidence of potent and broad drug activity in AML and other disease subtypes and support further development of this agent for hematologic malignancies,” Dr Kurtz said. 

Photo by Rhoda Baer

BOSTON—A pair of preclinical studies suggest the FLT3/BTK inhibitor CG’806 is active in a range of hematologic malignancies.

In one of the studies, CG’806 proved particularly effective against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3, and the compound was able to eradicate AML in mice.

In another study, researchers found CG’806 exhibited “broad potency” against leukemias, lymphomas, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs).

Both studies were presented as posters at Hematologic Malignancies: Translating Discoveries to Novel Therapies (poster 25 and poster 44).

Both studies involved researchers from Aptose Biosciences, the company developing CG’806.

Poster 25

Weiguo Zhang, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented poster 25, “CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3.”

The researchers tested CG’806 and other FLT3 inhibitors in human or murine leukemia cell lines with wild-type (WT) FLT3, FLT3-ITD mutations, FLT3 TKD domain mutations, or ITD plus TKD mutations.

Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with ITD mutations, D835 mutations, ITD plus F691I/Y842D/D835 mutations, or in FLT3 WT cells.

With CG’086, the IC50s in human AML cell lines were 0.17 nM for MV4-11 (FLT3-ITD) and 0.82 nM for MOLM13 (FLT3-ITD).

The IC50s in the murine leukemia cell lines were 9.49 nM for Ba/F3 (FLT3-WT), 0.30 nM for Ba/F3 (FLT3-ITD), 8.26 nM for Ba/F3 (FLT3-D835Y), 9.72 nM for Ba/F3 (FLT3-ITD+D835Y), and 0.43 nM for Ba/F3 (FLT3-ITD+F691L).

The researchers also found that CG’806 “triggers marked apoptosis” in FLT3-ITD-mutated primary AML samples but minimal apoptosis in normal bone marrow cells.

Another finding was that once-daily oral dosing of CG’806 in a murine model of AML (MV4-11) resulted in sustained micromolar plasma concentration over a 24-hour period.

This was accompanied by complete elimination of AML FLT3-ITD tumors without toxicity, the researchers said.

Poster 44

Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented poster 44, “CG’806, a First-in-Class FLT3/BTK Inhibitor, Exhibits Potent Activity against AML Patient Samples with Mutant or Wild-Type FLT3, as well as Other Hematologic Malignancy Subtypes.”

The researchers tested CG’806 in samples from patients with AML (n=82), MDS/MPNs (n=15), acute lymphoblastic leukemia (ALL, n=17), chronic lymphocytic leukemia (CLL, n=58), and chronic myeloid leukemia (CML, n=4).

The team observed “broad sensitivity” to CG’806, with 59% (48/82) of AML, 53% (8/15) of MDS/MPN, 40% (23/58) of CLL, 29% (5/17) of ALL, and 25% (1/4) of CML cases exhibiting an IC50 of less than 100 nM.

Among the 38 tested AML samples with known FLT3 mutational status, the FLT3-ITD+ AML samples tended to have enhanced sensitivity to CG’806 (median IC50 = 20 nM, n=8) relative to the FLT3-WT samples (median IC50 = 120 nM, n=30).

The researchers also found that CG’806 exerted potent anti-proliferative activity against human AML, B-ALL, mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cell lines.

“The analyses of CG’806 against primary hematologic malignancy patient samples and cultured cell lines show evidence of potent and broad drug activity in AML and other disease subtypes and support further development of this agent for hematologic malignancies,” Dr Kurtz said. 

Photo courtesy of Merck

The European Commission (EC) has approved the anti-PD-1 therapy pembrolizumab (Keytruda) for use in patients with classical Hodgkin lymphoma (cHL).

The drug is now approved to treat adults with relapsed or refractory cHL who have failed autologous stem cell transplant (auto-SCT) and brentuximab vedotin (BV) or who are transplant-ineligible and have failed treatment with BV.

The approval allows marketing of pembrolizumab for this indication in the European Economic Area (EEA).

This is the first approval for pembrolizumab in a hematologic malignancy in the EEA. The drug was previously approved there as a treatment for melanoma and non-small-cell lung cancer.

The new approval for pembrolizumab was based on data from the KEYNOTE-087 and KEYNOTE-013 trials.

Results from KEYNOTE-013 were presented at the 2016 ASH Annual Meeting (abstract 1108), and results from KEYNOTE-087 were recently published in the Journal of Clinical Oncology.

KEYNOTE-087

In this phase 2 trial, researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%, and the CR rate was 21.7%.

In Cohort 2 (n=81), the ORR was 64.2%, and the CR rate was 24.7%.

In Cohort 3 (n=60), the ORR was 70.0%, and the CR rate was 20%.

For the entire study cohort, the median duration of response was not reached, and the median overall survival (OS) was not reached. At 9 months, the OS was 97.5%, and the progression-free survival (PFS) was 63.4%.

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%, and the CR rate was 19%. The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median PFS was 11.4 months (range, 4.9-27.8 months). The 6-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median OS was not reached. Six-month and 12-month OS rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths. 

Photo courtesy of Merck

The European Commission (EC) has approved the anti-PD-1 therapy pembrolizumab (Keytruda) for use in patients with classical Hodgkin lymphoma (cHL).

The drug is now approved to treat adults with relapsed or refractory cHL who have failed autologous stem cell transplant (auto-SCT) and brentuximab vedotin (BV) or who are transplant-ineligible and have failed treatment with BV.

The approval allows marketing of pembrolizumab for this indication in the European Economic Area (EEA).

This is the first approval for pembrolizumab in a hematologic malignancy in the EEA. The drug was previously approved there as a treatment for melanoma and non-small-cell lung cancer.

The new approval for pembrolizumab was based on data from the KEYNOTE-087 and KEYNOTE-013 trials.

Results from KEYNOTE-013 were presented at the 2016 ASH Annual Meeting (abstract 1108), and results from KEYNOTE-087 were recently published in the Journal of Clinical Oncology.

KEYNOTE-087

In this phase 2 trial, researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%, and the CR rate was 21.7%.

In Cohort 2 (n=81), the ORR was 64.2%, and the CR rate was 24.7%.

In Cohort 3 (n=60), the ORR was 70.0%, and the CR rate was 20%.

For the entire study cohort, the median duration of response was not reached, and the median overall survival (OS) was not reached. At 9 months, the OS was 97.5%, and the progression-free survival (PFS) was 63.4%.

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%, and the CR rate was 19%. The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median PFS was 11.4 months (range, 4.9-27.8 months). The 6-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median OS was not reached. Six-month and 12-month OS rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths. 

Photo courtesy of Merck

The European Commission (EC) has approved the anti-PD-1 therapy pembrolizumab (Keytruda) for use in patients with classical Hodgkin lymphoma (cHL).

The drug is now approved to treat adults with relapsed or refractory cHL who have failed autologous stem cell transplant (auto-SCT) and brentuximab vedotin (BV) or who are transplant-ineligible and have failed treatment with BV.

The approval allows marketing of pembrolizumab for this indication in the European Economic Area (EEA).

This is the first approval for pembrolizumab in a hematologic malignancy in the EEA. The drug was previously approved there as a treatment for melanoma and non-small-cell lung cancer.

The new approval for pembrolizumab was based on data from the KEYNOTE-087 and KEYNOTE-013 trials.

Results from KEYNOTE-013 were presented at the 2016 ASH Annual Meeting (abstract 1108), and results from KEYNOTE-087 were recently published in the Journal of Clinical Oncology.

KEYNOTE-087

In this phase 2 trial, researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

• Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
• Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
• Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%, and the CR rate was 21.7%.

In Cohort 2 (n=81), the ORR was 64.2%, and the CR rate was 24.7%.

In Cohort 3 (n=60), the ORR was 70.0%, and the CR rate was 20%.

For the entire study cohort, the median duration of response was not reached, and the median overall survival (OS) was not reached. At 9 months, the OS was 97.5%, and the progression-free survival (PFS) was 63.4%.

The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.

KEYNOTE-013

KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.

Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.

The ORR was 58%, and the CR rate was 19%. The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.

The median PFS was 11.4 months (range, 4.9-27.8 months). The 6-month PFS rate was 66%, and the 12-month PFS rate was 48%.

The median OS was not reached. Six-month and 12-month OS rates were 100% and 87%, respectively.

The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).

The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).

AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths. 

Lower-intensity radiation regimens for patients with early-stage Hodgkin lymphoma (HL) did not shorten progression-free survival (PFS), according to a long-term analysis. Further, for patients with unfavorable early-stage disease, a more intense chemotherapy or radiation regimen conferred no survival benefit.

The German Hodgkin Study Group included patients with early-stage HL who had both early-stage favorable HL and early-stage unfavorable HL. Stephanie Sasse, MD, and her study group colleagues published long-term follow-up findings from multiple trials, conducted from 1993 to 2003, that evaluated risk-adapted treatment strategies to reduce radiation field size and chemotherapy intensity, “aiming at achieving sufficient tumor control while potentially reducing treatment-associated toxicity,” wrote Dr. Sasse and her colleagues of the University Hospital of Cologne (Ger.) (J Clin Oncol. 2017 Apr 18. doi: JCO2016709410).

Trials in favorable HL

Of the 627 patients in the HD7 trial in patients with favorable HL, combined-modality therapy resulted in better rates of PFS (73%) over a 15-year period, compared with extended-field radiotherapy (RT) alone (52%) (hazard ratio, 0.5; 95% confidence interval, 0.3-0.6; P less than 0.001). Another study, called HD10, was in early-stage favorable HL patients. It compared a lower-intensity regimen of two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus 20 Gy involved-field RT with a four-cycle ABVD regimen combined with 30 Gy involved-field RT. The 1,190-patient study achieved a median follow-up of 98 months, finding that the less-intense regimen was not inferior with an identical 10-year PFS of 87% in both arms (HR 1.0; 95% CI 0.6-1.5). Overall survival (OS) was nearly identical as well, at 94% in each arm (HR 0.9; 95% CI, 0.5-1.6).

Both trials HD7 and HD10 tracked the incidence of secondary neoplasias and detected no significant differences between groups, though there was a nonsignificant trend toward more secondary neoplasias for the HD7 patients who received extended-field radiotherapy. These analyses “strongly support the current risk-adapted treatment strategy in early-stage favorable HL,” wrote Dr. Sasse and her coinvestigators.

Trials in unfavorable HL

The HD8 trial enrolled 1,064 patients and followed them for a median 153 months to compare the efficacy of involved-field RT with extended-field RT, finding involved-field RT noninferior for PFS (HR, 1.0; 95% CI, 0.8-1.2). However, the overall 15-year PFS rate of 74% and OS rate of 82% “leave room for improvement,” said the investigators.

Finally, trial HD11 compared two different chemotherapy regimens and two different radiation doses. Patients received four cycles of either ABVD or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone at baseline dosage (BEACOPP_baseline), followed by 20 or 30 Gy involved-field RT. The study, which followed 1,395 patients for a median of 106 months, had a 2x2 factorial design.

Following the HD11 cohort longitudinally showed that BEACOPP_baseline did not confer a PFS advantage over ABVD for patients receiving the 30 Gy RT regimen (HR 1.1; 95% CI, 0.7-1.5). Nor did patients who received 20 Gy RT have significantly longer PFS with the more intense BEACOPPbaseline chemotherapy regimen (HR 0.8; 95% CI, 0.6-1.1).

Overall survival and the incidence of secondary neoplasias did not differ between trial arms in HD11, said Dr. Sasse and her coinvestigators.

To further explore whether more intense chemotherapy might result in better PFS rates for patients with early-stage unfavorable HL, Dr. Sasse and her colleagues are following long-term results from more recent trial, HD14, that combined two cycles of BEACOPP_escalated and two cycles of ABVD. More short-term toxicity was seen, but patients in this trial arm have significantly better 5-year PFS rates than do those receiving four cycles of ABVD. “The improved tumor control is a relevant outcome parameter for patients,” wrote Dr. Sasse and her colleagues.

The investigators are reserving judgment about whether more radiation exposure and higher doses of alkylating agents and etoposide may eventually result in higher rates of secondary neoplasms. “Subsequent analyses with even longer follow-up will have to confirm that the reduction of RT field size or dose indeed translates into a reduced risk of [secondary neoplasms],” they wrote.

Several of the authors reported multiple relationships with pharmaceutical companies. The study was funded by a grant from the German Cancer Aid.

[email protected]

On Twitter @karioakes

Lower-intensity radiation regimens for patients with early-stage Hodgkin lymphoma (HL) did not shorten progression-free survival (PFS), according to a long-term analysis. Further, for patients with unfavorable early-stage disease, a more intense chemotherapy or radiation regimen conferred no survival benefit.

The German Hodgkin Study Group included patients with early-stage HL who had both early-stage favorable HL and early-stage unfavorable HL. Stephanie Sasse, MD, and her study group colleagues published long-term follow-up findings from multiple trials, conducted from 1993 to 2003, that evaluated risk-adapted treatment strategies to reduce radiation field size and chemotherapy intensity, “aiming at achieving sufficient tumor control while potentially reducing treatment-associated toxicity,” wrote Dr. Sasse and her colleagues of the University Hospital of Cologne (Ger.) (J Clin Oncol. 2017 Apr 18. doi: JCO2016709410).

Trials in favorable HL

Of the 627 patients in the HD7 trial in patients with favorable HL, combined-modality therapy resulted in better rates of PFS (73%) over a 15-year period, compared with extended-field radiotherapy (RT) alone (52%) (hazard ratio, 0.5; 95% confidence interval, 0.3-0.6; P less than 0.001). Another study, called HD10, was in early-stage favorable HL patients. It compared a lower-intensity regimen of two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus 20 Gy involved-field RT with a four-cycle ABVD regimen combined with 30 Gy involved-field RT. The 1,190-patient study achieved a median follow-up of 98 months, finding that the less-intense regimen was not inferior with an identical 10-year PFS of 87% in both arms (HR 1.0; 95% CI 0.6-1.5). Overall survival (OS) was nearly identical as well, at 94% in each arm (HR 0.9; 95% CI, 0.5-1.6).

Both trials HD7 and HD10 tracked the incidence of secondary neoplasias and detected no significant differences between groups, though there was a nonsignificant trend toward more secondary neoplasias for the HD7 patients who received extended-field radiotherapy. These analyses “strongly support the current risk-adapted treatment strategy in early-stage favorable HL,” wrote Dr. Sasse and her coinvestigators.

Trials in unfavorable HL

The HD8 trial enrolled 1,064 patients and followed them for a median 153 months to compare the efficacy of involved-field RT with extended-field RT, finding involved-field RT noninferior for PFS (HR, 1.0; 95% CI, 0.8-1.2). However, the overall 15-year PFS rate of 74% and OS rate of 82% “leave room for improvement,” said the investigators.

Finally, trial HD11 compared two different chemotherapy regimens and two different radiation doses. Patients received four cycles of either ABVD or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone at baseline dosage (BEACOPP_baseline), followed by 20 or 30 Gy involved-field RT. The study, which followed 1,395 patients for a median of 106 months, had a 2x2 factorial design.

Following the HD11 cohort longitudinally showed that BEACOPP_baseline did not confer a PFS advantage over ABVD for patients receiving the 30 Gy RT regimen (HR 1.1; 95% CI, 0.7-1.5). Nor did patients who received 20 Gy RT have significantly longer PFS with the more intense BEACOPPbaseline chemotherapy regimen (HR 0.8; 95% CI, 0.6-1.1).

Overall survival and the incidence of secondary neoplasias did not differ between trial arms in HD11, said Dr. Sasse and her coinvestigators.

To further explore whether more intense chemotherapy might result in better PFS rates for patients with early-stage unfavorable HL, Dr. Sasse and her colleagues are following long-term results from more recent trial, HD14, that combined two cycles of BEACOPP_escalated and two cycles of ABVD. More short-term toxicity was seen, but patients in this trial arm have significantly better 5-year PFS rates than do those receiving four cycles of ABVD. “The improved tumor control is a relevant outcome parameter for patients,” wrote Dr. Sasse and her colleagues.

The investigators are reserving judgment about whether more radiation exposure and higher doses of alkylating agents and etoposide may eventually result in higher rates of secondary neoplasms. “Subsequent analyses with even longer follow-up will have to confirm that the reduction of RT field size or dose indeed translates into a reduced risk of [secondary neoplasms],” they wrote.

Several of the authors reported multiple relationships with pharmaceutical companies. The study was funded by a grant from the German Cancer Aid.

[email protected]

On Twitter @karioakes

Lower-intensity radiation regimens for patients with early-stage Hodgkin lymphoma (HL) did not shorten progression-free survival (PFS), according to a long-term analysis. Further, for patients with unfavorable early-stage disease, a more intense chemotherapy or radiation regimen conferred no survival benefit.

The German Hodgkin Study Group included patients with early-stage HL who had both early-stage favorable HL and early-stage unfavorable HL. Stephanie Sasse, MD, and her study group colleagues published long-term follow-up findings from multiple trials, conducted from 1993 to 2003, that evaluated risk-adapted treatment strategies to reduce radiation field size and chemotherapy intensity, “aiming at achieving sufficient tumor control while potentially reducing treatment-associated toxicity,” wrote Dr. Sasse and her colleagues of the University Hospital of Cologne (Ger.) (J Clin Oncol. 2017 Apr 18. doi: JCO2016709410).

Trials in favorable HL

Of the 627 patients in the HD7 trial in patients with favorable HL, combined-modality therapy resulted in better rates of PFS (73%) over a 15-year period, compared with extended-field radiotherapy (RT) alone (52%) (hazard ratio, 0.5; 95% confidence interval, 0.3-0.6; P less than 0.001). Another study, called HD10, was in early-stage favorable HL patients. It compared a lower-intensity regimen of two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus 20 Gy involved-field RT with a four-cycle ABVD regimen combined with 30 Gy involved-field RT. The 1,190-patient study achieved a median follow-up of 98 months, finding that the less-intense regimen was not inferior with an identical 10-year PFS of 87% in both arms (HR 1.0; 95% CI 0.6-1.5). Overall survival (OS) was nearly identical as well, at 94% in each arm (HR 0.9; 95% CI, 0.5-1.6).

Both trials HD7 and HD10 tracked the incidence of secondary neoplasias and detected no significant differences between groups, though there was a nonsignificant trend toward more secondary neoplasias for the HD7 patients who received extended-field radiotherapy. These analyses “strongly support the current risk-adapted treatment strategy in early-stage favorable HL,” wrote Dr. Sasse and her coinvestigators.

Trials in unfavorable HL

The HD8 trial enrolled 1,064 patients and followed them for a median 153 months to compare the efficacy of involved-field RT with extended-field RT, finding involved-field RT noninferior for PFS (HR, 1.0; 95% CI, 0.8-1.2). However, the overall 15-year PFS rate of 74% and OS rate of 82% “leave room for improvement,” said the investigators.

Finally, trial HD11 compared two different chemotherapy regimens and two different radiation doses. Patients received four cycles of either ABVD or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone at baseline dosage (BEACOPP_baseline), followed by 20 or 30 Gy involved-field RT. The study, which followed 1,395 patients for a median of 106 months, had a 2x2 factorial design.

Following the HD11 cohort longitudinally showed that BEACOPP_baseline did not confer a PFS advantage over ABVD for patients receiving the 30 Gy RT regimen (HR 1.1; 95% CI, 0.7-1.5). Nor did patients who received 20 Gy RT have significantly longer PFS with the more intense BEACOPPbaseline chemotherapy regimen (HR 0.8; 95% CI, 0.6-1.1).

Overall survival and the incidence of secondary neoplasias did not differ between trial arms in HD11, said Dr. Sasse and her coinvestigators.

To further explore whether more intense chemotherapy might result in better PFS rates for patients with early-stage unfavorable HL, Dr. Sasse and her colleagues are following long-term results from more recent trial, HD14, that combined two cycles of BEACOPP_escalated and two cycles of ABVD. More short-term toxicity was seen, but patients in this trial arm have significantly better 5-year PFS rates than do those receiving four cycles of ABVD. “The improved tumor control is a relevant outcome parameter for patients,” wrote Dr. Sasse and her colleagues.

The investigators are reserving judgment about whether more radiation exposure and higher doses of alkylating agents and etoposide may eventually result in higher rates of secondary neoplasms. “Subsequent analyses with even longer follow-up will have to confirm that the reduction of RT field size or dose indeed translates into a reduced risk of [secondary neoplasms],” they wrote.

Several of the authors reported multiple relationships with pharmaceutical companies. The study was funded by a grant from the German Cancer Aid.

[email protected]

On Twitter @karioakes

The immune checkpoint inhibitor pembrolizumab has good antitumor activity and a favorable safety profile when used to treat relapsed or refractory classic Hodgkin lymphoma, according to findings from the KEYNOTE-087 trial.

Pembrolizumab has garnered interest for this population because Hodgkin Reed-Sternberg cells have a chromosomal alteration leading to overexpression of both programmed death ligand 1 and programmed death ligand 2.

Neil Osterweil

The immune checkpoint inhibitor pembrolizumab has good antitumor activity and a favorable safety profile when used to treat relapsed or refractory classic Hodgkin lymphoma, according to findings from the KEYNOTE-087 trial.

Pembrolizumab has garnered interest for this population because Hodgkin Reed-Sternberg cells have a chromosomal alteration leading to overexpression of both programmed death ligand 1 and programmed death ligand 2.

Neil Osterweil

The immune checkpoint inhibitor pembrolizumab has good antitumor activity and a favorable safety profile when used to treat relapsed or refractory classic Hodgkin lymphoma, according to findings from the KEYNOTE-087 trial.

Pembrolizumab has garnered interest for this population because Hodgkin Reed-Sternberg cells have a chromosomal alteration leading to overexpression of both programmed death ligand 1 and programmed death ligand 2.

Neil Osterweil

Micrograph showing HL

The anti-PD-1 therapy pembrolizumab could change the treatment paradigm of relapsed or refractory classic Hodgkin lymphoma (cHL), according to researchers.

In a phase 2 trial, pembrolizumab produced an overall response rate (ORR) of 69% and a complete response (CR) rate of 22% in adults with cHL who had failed treatment with brentuximab vedotin (BV), autologous hematopoietic stem cell transplant (auto-HSCT), or both.

The researchers said the safety profile of pembrolizumab was “acceptable” and largely consistent with safety in previous studies of the drug.

Twelve percent of patients temporarily stopped taking pembrolizumab due to treatment-related adverse events (AEs), and 4% stopped taking the drug entirely as a result of AEs.

Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues reported these results, from the KEYNOTE-087 trial, in the Journal of Clinical Oncology.

The trial was sponsored by Merck, the company that markets pembrolizumab as Keytruda.

In KEYNOTE-087, the researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV

Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV

Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Efficacy

Across all 210 enrolled patients, the ORR was 69.0%, and the CR rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

For the entire study cohort, the median duration of response was not reached, and the median overall survival was not reached. At 9 months, the overall survival rate was 97.5%, and the progression-free survival rate was 63.4%.

Safety

The most common AEs related to pembrolizumab were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

Nine patients (4.3%) stopped taking pembrolizumab due to treatment-related AEs, including myocarditis, myelitis, myositis, pneumonitis, infusion-related reactions, and cytokine release syndrome.

Twenty-six patients (12.4%) had treatment interruptions due to pembrolizumab-related AEs.

Two patients died during follow-up, but neither death was considered related to pembrolizumab. One patient died of septic shock and the other of acute graft-versus-host disease.

Micrograph showing HL

The anti-PD-1 therapy pembrolizumab could change the treatment paradigm of relapsed or refractory classic Hodgkin lymphoma (cHL), according to researchers.

In a phase 2 trial, pembrolizumab produced an overall response rate (ORR) of 69% and a complete response (CR) rate of 22% in adults with cHL who had failed treatment with brentuximab vedotin (BV), autologous hematopoietic stem cell transplant (auto-HSCT), or both.

The researchers said the safety profile of pembrolizumab was “acceptable” and largely consistent with safety in previous studies of the drug.

Twelve percent of patients temporarily stopped taking pembrolizumab due to treatment-related adverse events (AEs), and 4% stopped taking the drug entirely as a result of AEs.

Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues reported these results, from the KEYNOTE-087 trial, in the Journal of Clinical Oncology.

The trial was sponsored by Merck, the company that markets pembrolizumab as Keytruda.

In KEYNOTE-087, the researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV

Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV

Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Efficacy

Across all 210 enrolled patients, the ORR was 69.0%, and the CR rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

For the entire study cohort, the median duration of response was not reached, and the median overall survival was not reached. At 9 months, the overall survival rate was 97.5%, and the progression-free survival rate was 63.4%.

Safety

The most common AEs related to pembrolizumab were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

Nine patients (4.3%) stopped taking pembrolizumab due to treatment-related AEs, including myocarditis, myelitis, myositis, pneumonitis, infusion-related reactions, and cytokine release syndrome.

Twenty-six patients (12.4%) had treatment interruptions due to pembrolizumab-related AEs.

Two patients died during follow-up, but neither death was considered related to pembrolizumab. One patient died of septic shock and the other of acute graft-versus-host disease.

Micrograph showing HL

The anti-PD-1 therapy pembrolizumab could change the treatment paradigm of relapsed or refractory classic Hodgkin lymphoma (cHL), according to researchers.

In a phase 2 trial, pembrolizumab produced an overall response rate (ORR) of 69% and a complete response (CR) rate of 22% in adults with cHL who had failed treatment with brentuximab vedotin (BV), autologous hematopoietic stem cell transplant (auto-HSCT), or both.

The researchers said the safety profile of pembrolizumab was “acceptable” and largely consistent with safety in previous studies of the drug.

Twelve percent of patients temporarily stopped taking pembrolizumab due to treatment-related adverse events (AEs), and 4% stopped taking the drug entirely as a result of AEs.

Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues reported these results, from the KEYNOTE-087 trial, in the Journal of Clinical Oncology.

The trial was sponsored by Merck, the company that markets pembrolizumab as Keytruda.

In KEYNOTE-087, the researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:

Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV

Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV

Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.

Efficacy

Across all 210 enrolled patients, the ORR was 69.0%, and the CR rate was 22.4%.

In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.

In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.

In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.

Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.

An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).

For the entire study cohort, the median duration of response was not reached, and the median overall survival was not reached. At 9 months, the overall survival rate was 97.5%, and the progression-free survival rate was 63.4%.

Safety

The most common AEs related to pembrolizumab were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).

The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).

Nine patients (4.3%) stopped taking pembrolizumab due to treatment-related AEs, including myocarditis, myelitis, myositis, pneumonitis, infusion-related reactions, and cytokine release syndrome.

Twenty-six patients (12.4%) had treatment interruptions due to pembrolizumab-related AEs.

Two patients died during follow-up, but neither death was considered related to pembrolizumab. One patient died of septic shock and the other of acute graft-versus-host disease.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has added 9 disease sites to its NCCN Radiation Therapy Compendium™, a resource that provides a single access point for NCCN recommendations pertaining to radiation therapy (RT).

The compendium provides guidance on all RT modalities recommended within NCCN guidelines, including intensity modulated RT, intra-operative RT, stereotactic radiosurgery/stereotactic body RT/stereotactic ablative RT, image-guided RT, low dose-rate brachytherapy/high dose-rate brachytherapy, radioisotope, and particle therapy.

The NCCN Radiation Therapy Compendium was launched with recommendations pertaining to 24 cancer types.

Now, NCCN has added RT recommendations from an additional 9 NCCN Clinical Practice Guidelines in Oncology:

Acute lymphoblastic leukemia (ALL), Version 2.2016

Basal cell skin cancer, Version 1.2017

Dermatofibrosarcoma protuberans, Version 1.2017

Gastric cancer, Version 1.2017

Hodgkin lymphoma (HL), Version 1.2017

Merkel cell carcinoma, Version 1.2017

Ovarian cancer, Version 1.2017

Squamous cell skin cancer, Version 1.2017

Thymomas and thymic carcinomas, Version 1.2017

The first 24 disease sites included in the NCCN Radiation Therapy Compendium were:

Acute myeloid leukemia

Anal cancer

B-cell lymphomas

Bladder cancer

Breast cancer

Chronic lymphocytic leukemia/small lymphoblastic lymphoma

Colon cancer

Hepatobiliary cancers

Kidney cancer

Malignant pleural mesothelioma

Melanoma

Multiple myeloma

Neuroendocrine tumors

Non-small cell lung cancer

Occult primary cancer

Pancreatic adenocarcinoma

Penile cancer

Primary cutaneous B-cell lymphomas

Prostate cancer

Rectal cancer

Small cell lung cancer

Soft tissue sarcoma

T-cell lymphomas

Testicular cancer

The NCCN said additional cancer types will be added to the NCCN Radiation Therapy Compendium on a rolling basis over the coming months.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has added 9 disease sites to its NCCN Radiation Therapy Compendium™, a resource that provides a single access point for NCCN recommendations pertaining to radiation therapy (RT).

The compendium provides guidance on all RT modalities recommended within NCCN guidelines, including intensity modulated RT, intra-operative RT, stereotactic radiosurgery/stereotactic body RT/stereotactic ablative RT, image-guided RT, low dose-rate brachytherapy/high dose-rate brachytherapy, radioisotope, and particle therapy.

The NCCN Radiation Therapy Compendium was launched with recommendations pertaining to 24 cancer types.

Now, NCCN has added RT recommendations from an additional 9 NCCN Clinical Practice Guidelines in Oncology:

Acute lymphoblastic leukemia (ALL), Version 2.2016

Basal cell skin cancer, Version 1.2017

Dermatofibrosarcoma protuberans, Version 1.2017

Gastric cancer, Version 1.2017

Hodgkin lymphoma (HL), Version 1.2017

Merkel cell carcinoma, Version 1.2017

Ovarian cancer, Version 1.2017

Squamous cell skin cancer, Version 1.2017

Thymomas and thymic carcinomas, Version 1.2017

The first 24 disease sites included in the NCCN Radiation Therapy Compendium were:

Acute myeloid leukemia

Anal cancer

B-cell lymphomas

Bladder cancer

Breast cancer

Chronic lymphocytic leukemia/small lymphoblastic lymphoma

Colon cancer

Hepatobiliary cancers

Kidney cancer

Malignant pleural mesothelioma

Melanoma

Multiple myeloma

Neuroendocrine tumors

Non-small cell lung cancer

Occult primary cancer

Pancreatic adenocarcinoma

Penile cancer

Primary cutaneous B-cell lymphomas

Prostate cancer

Rectal cancer

Small cell lung cancer

Soft tissue sarcoma

T-cell lymphomas

Testicular cancer

The NCCN said additional cancer types will be added to the NCCN Radiation Therapy Compendium on a rolling basis over the coming months.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has added 9 disease sites to its NCCN Radiation Therapy Compendium™, a resource that provides a single access point for NCCN recommendations pertaining to radiation therapy (RT).

The compendium provides guidance on all RT modalities recommended within NCCN guidelines, including intensity modulated RT, intra-operative RT, stereotactic radiosurgery/stereotactic body RT/stereotactic ablative RT, image-guided RT, low dose-rate brachytherapy/high dose-rate brachytherapy, radioisotope, and particle therapy.

The NCCN Radiation Therapy Compendium was launched with recommendations pertaining to 24 cancer types.

Now, NCCN has added RT recommendations from an additional 9 NCCN Clinical Practice Guidelines in Oncology:

Acute lymphoblastic leukemia (ALL), Version 2.2016

Basal cell skin cancer, Version 1.2017

Dermatofibrosarcoma protuberans, Version 1.2017

Gastric cancer, Version 1.2017

Hodgkin lymphoma (HL), Version 1.2017

Merkel cell carcinoma, Version 1.2017

Ovarian cancer, Version 1.2017

Squamous cell skin cancer, Version 1.2017

Thymomas and thymic carcinomas, Version 1.2017

The first 24 disease sites included in the NCCN Radiation Therapy Compendium were:

Acute myeloid leukemia

Anal cancer

B-cell lymphomas

Bladder cancer

Breast cancer

Chronic lymphocytic leukemia/small lymphoblastic lymphoma

Colon cancer

Hepatobiliary cancers

Kidney cancer

Malignant pleural mesothelioma

Melanoma

Multiple myeloma

Neuroendocrine tumors

Non-small cell lung cancer

Occult primary cancer

Pancreatic adenocarcinoma

Penile cancer

Primary cutaneous B-cell lymphomas

Prostate cancer

Rectal cancer

Small cell lung cancer

Soft tissue sarcoma

T-cell lymphomas

Testicular cancer

The NCCN said additional cancer types will be added to the NCCN Radiation Therapy Compendium on a rolling basis over the coming months.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium.