Leukemia, Myelodysplasia, Transplantation

T cells

Credit: NIAID

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE^®) antibody construct designed to direct the body’s T cells against target cells expressing CD19, a protein found on the surface of B cells.

Blinatumomab is the first anti-CD19 drug to receive FDA approval. It will be available as a 35 mcg single-use vial.

“Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent.”

Approval details

The FDA granted blinatumomab accelerated approval based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Before granting the drug full approval, the FDA is requiring that blinatumomab’s manufacturer, Amgen, conduct a study to verify that the drug improves survival in patients with relapsed or refractory Philadelphia-negative precursor B-cell ALL.

Blinatumomab was approved with a boxed warning detailing the risk of cytokine release syndrome and neurological toxicities. The FDA also approved the drug with a Risk Evaluation and Mitigation Strategy, which consists of a communication plan to inform healthcare providers about the serious risks and the potential for preparation and administration errors.

Blinatumomab was approved more than 5 months ahead of the date the FDA was scheduled to complete review of the drug’s application (May 19, 2015).

The agency had granted blinatumomab breakthrough therapy designation, priority review, and orphan product designation because Amgen demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies.

That evidence came in the form of a phase 2 study, the results of which were presented at the 19th Congress of the European Hematology Association (EHA) in June.

Trial results

Researchers evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-cell ALL and a median age of 39 (range, 18-79). The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Thirty-three percent of patients achieved a complete remission, and 9% achieved a complete remission with partial hematologic recovery. Seventy-one percent of these patients were negative for minimal residual disease.

The median relapse-free survival was 5.9 months.

Major toxicities were related to cytokine release syndrome, but cytopenias and central nervous system events were also common. The most frequent adverse events were pyrexia (59%), headache (35%), and febrile neutropenia (29%).

The most frequent grade 3 or higher adverse events were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system events were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 events considered treatment-related—2 with sepsis and 1 with Candida infection.

T cells

Credit: NIAID

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE^®) antibody construct designed to direct the body’s T cells against target cells expressing CD19, a protein found on the surface of B cells.

Blinatumomab is the first anti-CD19 drug to receive FDA approval. It will be available as a 35 mcg single-use vial.

“Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent.”

Approval details

The FDA granted blinatumomab accelerated approval based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Before granting the drug full approval, the FDA is requiring that blinatumomab’s manufacturer, Amgen, conduct a study to verify that the drug improves survival in patients with relapsed or refractory Philadelphia-negative precursor B-cell ALL.

Blinatumomab was approved with a boxed warning detailing the risk of cytokine release syndrome and neurological toxicities. The FDA also approved the drug with a Risk Evaluation and Mitigation Strategy, which consists of a communication plan to inform healthcare providers about the serious risks and the potential for preparation and administration errors.

Blinatumomab was approved more than 5 months ahead of the date the FDA was scheduled to complete review of the drug’s application (May 19, 2015).

The agency had granted blinatumomab breakthrough therapy designation, priority review, and orphan product designation because Amgen demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies.

That evidence came in the form of a phase 2 study, the results of which were presented at the 19th Congress of the European Hematology Association (EHA) in June.

Trial results

Researchers evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-cell ALL and a median age of 39 (range, 18-79). The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Thirty-three percent of patients achieved a complete remission, and 9% achieved a complete remission with partial hematologic recovery. Seventy-one percent of these patients were negative for minimal residual disease.

The median relapse-free survival was 5.9 months.

Major toxicities were related to cytokine release syndrome, but cytopenias and central nervous system events were also common. The most frequent adverse events were pyrexia (59%), headache (35%), and febrile neutropenia (29%).

The most frequent grade 3 or higher adverse events were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system events were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 events considered treatment-related—2 with sepsis and 1 with Candida infection.

T cells

Credit: NIAID

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (ALL).

Blinatumomab is a bispecific T-cell engager (BiTE^®) antibody construct designed to direct the body’s T cells against target cells expressing CD19, a protein found on the surface of B cells.

Blinatumomab is the first anti-CD19 drug to receive FDA approval. It will be available as a 35 mcg single-use vial.

“Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

“Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent.”

Approval details

The FDA granted blinatumomab accelerated approval based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.

Before granting the drug full approval, the FDA is requiring that blinatumomab’s manufacturer, Amgen, conduct a study to verify that the drug improves survival in patients with relapsed or refractory Philadelphia-negative precursor B-cell ALL.

Blinatumomab was approved with a boxed warning detailing the risk of cytokine release syndrome and neurological toxicities. The FDA also approved the drug with a Risk Evaluation and Mitigation Strategy, which consists of a communication plan to inform healthcare providers about the serious risks and the potential for preparation and administration errors.

Blinatumomab was approved more than 5 months ahead of the date the FDA was scheduled to complete review of the drug’s application (May 19, 2015).

The agency had granted blinatumomab breakthrough therapy designation, priority review, and orphan product designation because Amgen demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies.

That evidence came in the form of a phase 2 study, the results of which were presented at the 19th Congress of the European Hematology Association (EHA) in June.

Trial results

Researchers evaluated blinatumomab monotherapy in 189 patients with relapsed or refractory B-cell ALL and a median age of 39 (range, 18-79). The patients received blinatumomab by continuous intravenous infusion—4 weeks on and 2 weeks off—for up to 5 cycles.

Thirty-three percent of patients achieved a complete remission, and 9% achieved a complete remission with partial hematologic recovery. Seventy-one percent of these patients were negative for minimal residual disease.

The median relapse-free survival was 5.9 months.

Major toxicities were related to cytokine release syndrome, but cytopenias and central nervous system events were also common. The most frequent adverse events were pyrexia (59%), headache (35%), and febrile neutropenia (29%).

The most frequent grade 3 or higher adverse events were febrile neutropenia (26%), anemia (15%), and neutropenia (15%). Two percent of patients had grade 3 or higher cytokine release syndrome.

The most common grade 3 or higher nervous system events were headache (4%), encephalopathy (3%), and ataxia (2%). Three patients (2%) had grade 5 events considered treatment-related—2 with sepsis and 1 with Candida infection.

Patient receiving chemotherapy

Credit: Rhoda Baer

A new study suggests that half of all people recently diagnosed with cancer in England and Wales should survive their disease for at least 10 years, whereas, 40 years ago, only about a quarter of cancer patients could expect the same.

The research, published in The Lancet, showed significant improvements in long-term cancer survival rates from 1971 to 2011, particularly among patients with hematologic malignancies.

Unfortunately, the outlook for some malignancies remained extremely poor over the period studied.

“Although survival for some cancers has improved dramatically over the past 40 years, others are lagging far behind,” said Manuela Quaresma, of the London School of Hygiene & Tropical Medicine in the UK.

“More investment is urgently needed to improve early diagnosis and provide the best treatment, including more specialist surgeons for poor-prognosis cancers like lung cancer, which have shown little or no evidence of improvement in long-term survival (5 and 10 years after diagnosis) over the past 40 years.”

Quaresma and her colleagues analyzed survival trends for more than 7 million adults (aged 15 to 99 years) diagnosed with one of 21 common cancers in England and Wales between 1971 and 2011, and followed up to the end of 2012.

The researchers observed an increase in 10-year survival for all cancers combined. Twenty-four percent of patients diagnosed in 1971-1972 survived at least 10 years. And 49.8% of patients diagnosed in 2010-2011 are expected to survive at least 10 years.

The data revealed substantial improvements for patients with hematologic malignancies as well. For Hodgkin lymphoma, the 10-year survival rate rose from 47.7% for patients diagnosed in 1971-1972 to 80% for those diagnosed in 2010-2011.

For non-Hodgkin lymphoma, the 10-year survival rate increased from 22% to 63.1%. For multiple myeloma, it rose from 6.2% to 32.6%. And for leukemia, it rose from 6.9% to 46.1%.

The researchers noted that the most recent 10-year survival estimates are above 70% for cancers of the breast, prostate, testis, and uterus, as well as for melanoma and Hodgkin lymphoma. Furthermore, improvements in survival are greatest for these cancers.

Unfortunately, several other malignancies continue to have poor long-term survival. For cancers of the brain, stomach, lung, esophagus, and pancreas, 10-year survival after diagnosis is still below 15% for patients diagnosed in 2010-2011.

“These 5 cancers impose a huge public health burden, both because they are common and because they are often diagnosed at a late stage, when they are much harder to treat,” said study author Bernard Rachet, MD, PhD, of the London School of Hygiene & Tropical Medicine.

Dr Rachet also noted that this research confirms a persistent “age gap” in survival between younger and older patients for all cancers.

“Even after we have adjusted for the fact that older people have much higher death rates from other diseases than younger people, elderly cancer patients are doing worse for all cancers,” he said.

“This problem is particularly marked in the UK. In other countries, the age gap in cancer survival has become much narrower over the last 15 to 20 years than in England and Wales.”

Patient receiving chemotherapy

Credit: Rhoda Baer

A new study suggests that half of all people recently diagnosed with cancer in England and Wales should survive their disease for at least 10 years, whereas, 40 years ago, only about a quarter of cancer patients could expect the same.

The research, published in The Lancet, showed significant improvements in long-term cancer survival rates from 1971 to 2011, particularly among patients with hematologic malignancies.

Unfortunately, the outlook for some malignancies remained extremely poor over the period studied.

“Although survival for some cancers has improved dramatically over the past 40 years, others are lagging far behind,” said Manuela Quaresma, of the London School of Hygiene & Tropical Medicine in the UK.

“More investment is urgently needed to improve early diagnosis and provide the best treatment, including more specialist surgeons for poor-prognosis cancers like lung cancer, which have shown little or no evidence of improvement in long-term survival (5 and 10 years after diagnosis) over the past 40 years.”

Quaresma and her colleagues analyzed survival trends for more than 7 million adults (aged 15 to 99 years) diagnosed with one of 21 common cancers in England and Wales between 1971 and 2011, and followed up to the end of 2012.

The researchers observed an increase in 10-year survival for all cancers combined. Twenty-four percent of patients diagnosed in 1971-1972 survived at least 10 years. And 49.8% of patients diagnosed in 2010-2011 are expected to survive at least 10 years.

The data revealed substantial improvements for patients with hematologic malignancies as well. For Hodgkin lymphoma, the 10-year survival rate rose from 47.7% for patients diagnosed in 1971-1972 to 80% for those diagnosed in 2010-2011.

For non-Hodgkin lymphoma, the 10-year survival rate increased from 22% to 63.1%. For multiple myeloma, it rose from 6.2% to 32.6%. And for leukemia, it rose from 6.9% to 46.1%.

The researchers noted that the most recent 10-year survival estimates are above 70% for cancers of the breast, prostate, testis, and uterus, as well as for melanoma and Hodgkin lymphoma. Furthermore, improvements in survival are greatest for these cancers.

Unfortunately, several other malignancies continue to have poor long-term survival. For cancers of the brain, stomach, lung, esophagus, and pancreas, 10-year survival after diagnosis is still below 15% for patients diagnosed in 2010-2011.

“These 5 cancers impose a huge public health burden, both because they are common and because they are often diagnosed at a late stage, when they are much harder to treat,” said study author Bernard Rachet, MD, PhD, of the London School of Hygiene & Tropical Medicine.

Dr Rachet also noted that this research confirms a persistent “age gap” in survival between younger and older patients for all cancers.

“Even after we have adjusted for the fact that older people have much higher death rates from other diseases than younger people, elderly cancer patients are doing worse for all cancers,” he said.

“This problem is particularly marked in the UK. In other countries, the age gap in cancer survival has become much narrower over the last 15 to 20 years than in England and Wales.”

Patient receiving chemotherapy

Credit: Rhoda Baer

A new study suggests that half of all people recently diagnosed with cancer in England and Wales should survive their disease for at least 10 years, whereas, 40 years ago, only about a quarter of cancer patients could expect the same.

The research, published in The Lancet, showed significant improvements in long-term cancer survival rates from 1971 to 2011, particularly among patients with hematologic malignancies.

Unfortunately, the outlook for some malignancies remained extremely poor over the period studied.

“Although survival for some cancers has improved dramatically over the past 40 years, others are lagging far behind,” said Manuela Quaresma, of the London School of Hygiene & Tropical Medicine in the UK.

“More investment is urgently needed to improve early diagnosis and provide the best treatment, including more specialist surgeons for poor-prognosis cancers like lung cancer, which have shown little or no evidence of improvement in long-term survival (5 and 10 years after diagnosis) over the past 40 years.”

Quaresma and her colleagues analyzed survival trends for more than 7 million adults (aged 15 to 99 years) diagnosed with one of 21 common cancers in England and Wales between 1971 and 2011, and followed up to the end of 2012.

The researchers observed an increase in 10-year survival for all cancers combined. Twenty-four percent of patients diagnosed in 1971-1972 survived at least 10 years. And 49.8% of patients diagnosed in 2010-2011 are expected to survive at least 10 years.

The data revealed substantial improvements for patients with hematologic malignancies as well. For Hodgkin lymphoma, the 10-year survival rate rose from 47.7% for patients diagnosed in 1971-1972 to 80% for those diagnosed in 2010-2011.

For non-Hodgkin lymphoma, the 10-year survival rate increased from 22% to 63.1%. For multiple myeloma, it rose from 6.2% to 32.6%. And for leukemia, it rose from 6.9% to 46.1%.

The researchers noted that the most recent 10-year survival estimates are above 70% for cancers of the breast, prostate, testis, and uterus, as well as for melanoma and Hodgkin lymphoma. Furthermore, improvements in survival are greatest for these cancers.

Unfortunately, several other malignancies continue to have poor long-term survival. For cancers of the brain, stomach, lung, esophagus, and pancreas, 10-year survival after diagnosis is still below 15% for patients diagnosed in 2010-2011.

“These 5 cancers impose a huge public health burden, both because they are common and because they are often diagnosed at a late stage, when they are much harder to treat,” said study author Bernard Rachet, MD, PhD, of the London School of Hygiene & Tropical Medicine.

Dr Rachet also noted that this research confirms a persistent “age gap” in survival between younger and older patients for all cancers.

“Even after we have adjusted for the fact that older people have much higher death rates from other diseases than younger people, elderly cancer patients are doing worse for all cancers,” he said.

“This problem is particularly marked in the UK. In other countries, the age gap in cancer survival has become much narrower over the last 15 to 20 years than in England and Wales.”

The US Food and Drug Administration (FDA) has granted orphan drug designation for Actimab-A, an alpha radiolabeled antibody, to treat patients over the age of 60 who are newly diagnosed with acute myeloid leukemia (AML).

Actimab-A consists of the CD33 antibody lintuzumab linked to the actinium-225 payload. The product is currently under investigation in a multicenter, phase 1/2 trial of elderly AML patients.

The company developing Actimab-A, Actinium Pharmaceuticals, Inc., recently announced positive interim data from this trial.

Nine patients were evaluable. They had a median age of 76 (range, 73-81) and intermediate- or poor-risk cytogenetics.

The median overall survival was 5.4 months (range, 2.2-24 months), but survival was better for the 7 patients who had secondary AML. These patients had a median overall survival of 9.1 months from study entry (range, 2.3-24 months).

Two secondary AML patients lived longer than 12 months, and the longest surviving patient lived more than 24 months.

Two dosing levels of Actimab-A have been evaluated to date (0.5 or 1.0 μCi/kg/fraction), and the study is ongoing at higher doses until the maximum tolerated dose is reached.

Actinium expects additional data from this trial to be available in 2015.

“The FDA’s decision to grant orphan drug status for Actimab-A is a significant milestone for the company and recognizes the need for innovative new approaches to treat AML,” said Kaushik J. Dave, PhD, President and CEO of Actinium.

“The designation will provide Actinium access to various development benefits and financial incentives from the agency, including an exemption from prescription drug user fees for Actimab-A for this indication and, if the drug receives marketing approval, it will enjoy 7 years of market exclusivity in the United States.”

The US Food and Drug Administration (FDA) has granted orphan drug designation for Actimab-A, an alpha radiolabeled antibody, to treat patients over the age of 60 who are newly diagnosed with acute myeloid leukemia (AML).

Actimab-A consists of the CD33 antibody lintuzumab linked to the actinium-225 payload. The product is currently under investigation in a multicenter, phase 1/2 trial of elderly AML patients.

The company developing Actimab-A, Actinium Pharmaceuticals, Inc., recently announced positive interim data from this trial.

Nine patients were evaluable. They had a median age of 76 (range, 73-81) and intermediate- or poor-risk cytogenetics.

The median overall survival was 5.4 months (range, 2.2-24 months), but survival was better for the 7 patients who had secondary AML. These patients had a median overall survival of 9.1 months from study entry (range, 2.3-24 months).

Two secondary AML patients lived longer than 12 months, and the longest surviving patient lived more than 24 months.

Two dosing levels of Actimab-A have been evaluated to date (0.5 or 1.0 μCi/kg/fraction), and the study is ongoing at higher doses until the maximum tolerated dose is reached.

Actinium expects additional data from this trial to be available in 2015.

“The FDA’s decision to grant orphan drug status for Actimab-A is a significant milestone for the company and recognizes the need for innovative new approaches to treat AML,” said Kaushik J. Dave, PhD, President and CEO of Actinium.

“The designation will provide Actinium access to various development benefits and financial incentives from the agency, including an exemption from prescription drug user fees for Actimab-A for this indication and, if the drug receives marketing approval, it will enjoy 7 years of market exclusivity in the United States.”

The US Food and Drug Administration (FDA) has granted orphan drug designation for Actimab-A, an alpha radiolabeled antibody, to treat patients over the age of 60 who are newly diagnosed with acute myeloid leukemia (AML).

Actimab-A consists of the CD33 antibody lintuzumab linked to the actinium-225 payload. The product is currently under investigation in a multicenter, phase 1/2 trial of elderly AML patients.

The company developing Actimab-A, Actinium Pharmaceuticals, Inc., recently announced positive interim data from this trial.

Nine patients were evaluable. They had a median age of 76 (range, 73-81) and intermediate- or poor-risk cytogenetics.

The median overall survival was 5.4 months (range, 2.2-24 months), but survival was better for the 7 patients who had secondary AML. These patients had a median overall survival of 9.1 months from study entry (range, 2.3-24 months).

Two secondary AML patients lived longer than 12 months, and the longest surviving patient lived more than 24 months.

Two dosing levels of Actimab-A have been evaluated to date (0.5 or 1.0 μCi/kg/fraction), and the study is ongoing at higher doses until the maximum tolerated dose is reached.

Actinium expects additional data from this trial to be available in 2015.

“The FDA’s decision to grant orphan drug status for Actimab-A is a significant milestone for the company and recognizes the need for innovative new approaches to treat AML,” said Kaushik J. Dave, PhD, President and CEO of Actinium.

“The designation will provide Actinium access to various development benefits and financial incentives from the agency, including an exemption from prescription drug user fees for Actimab-A for this indication and, if the drug receives marketing approval, it will enjoy 7 years of market exclusivity in the United States.”

AML cells in the bone marrow

Inhibiting the enzyme 5-lipoxygenase (5-LO) can eradicate cancer stem cell-like cells (CSCs) in acute myeloid leukemia (AML), according to a preclinical study

published in Cancer Research.

Previous research suggested the enzyme is needed to maintain CSCs in chronic myeloid leukemia.

So investigators theorized that 5-LO could be a therapeutic target for AML, as CSCs are thought to cause the spread and relapse of this disease.

To test that theory, the team evaluated the effects of 5-LO inhibition in a PML/RARα-positive model of AML. As a model of CSCs, they used Sca-1⁺/lin⁻ murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The researchers targeted 5-LO genetically and pharmacologically. And they found that 5-LO inhibition interfered with the aberrant stem cell capacity of PML/RARα-expressing HSPCs.

Inhibiting 5-LO also inhibited Wnt signaling, which has been shown to be critical for CSC maintenance.

Additional investigation revealed that inhibition of Wnt signaling and CSCs was due to the generation of a catalytically inactive form of 5-LO, which hindered nuclear translocation of β-catenin.

Considering these results together, as well as evidence that CSCs mediate AML relapse, the investigators concluded that eradicating CSCs via 5-LO inhibition may offer a new treatment approach for AML.

“These results form the basis for a possible use of the 5-lipoxygenase inhibitors as stem cell therapy for a sustainable cure for acute myeloid leukemia,” said Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany. “But this must firstly be studied further in preclinical and clinical studies in humans.”

“We are now in the process of examining the molecular mechanism in more detail in order to find out how the inhibitors precisely work on the leukemia stem cells,” added Thorsten Jürgen Maier, MD, PhD, of Goethe University and Aarhus University in Denmark. “We very much hope that our results will be of benefit for leukemia patients.”

AML cells in the bone marrow

Inhibiting the enzyme 5-lipoxygenase (5-LO) can eradicate cancer stem cell-like cells (CSCs) in acute myeloid leukemia (AML), according to a preclinical study

published in Cancer Research.

Previous research suggested the enzyme is needed to maintain CSCs in chronic myeloid leukemia.

So investigators theorized that 5-LO could be a therapeutic target for AML, as CSCs are thought to cause the spread and relapse of this disease.

To test that theory, the team evaluated the effects of 5-LO inhibition in a PML/RARα-positive model of AML. As a model of CSCs, they used Sca-1⁺/lin⁻ murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The researchers targeted 5-LO genetically and pharmacologically. And they found that 5-LO inhibition interfered with the aberrant stem cell capacity of PML/RARα-expressing HSPCs.

Inhibiting 5-LO also inhibited Wnt signaling, which has been shown to be critical for CSC maintenance.

Additional investigation revealed that inhibition of Wnt signaling and CSCs was due to the generation of a catalytically inactive form of 5-LO, which hindered nuclear translocation of β-catenin.

Considering these results together, as well as evidence that CSCs mediate AML relapse, the investigators concluded that eradicating CSCs via 5-LO inhibition may offer a new treatment approach for AML.

“These results form the basis for a possible use of the 5-lipoxygenase inhibitors as stem cell therapy for a sustainable cure for acute myeloid leukemia,” said Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany. “But this must firstly be studied further in preclinical and clinical studies in humans.”

“We are now in the process of examining the molecular mechanism in more detail in order to find out how the inhibitors precisely work on the leukemia stem cells,” added Thorsten Jürgen Maier, MD, PhD, of Goethe University and Aarhus University in Denmark. “We very much hope that our results will be of benefit for leukemia patients.”

AML cells in the bone marrow

Inhibiting the enzyme 5-lipoxygenase (5-LO) can eradicate cancer stem cell-like cells (CSCs) in acute myeloid leukemia (AML), according to a preclinical study

published in Cancer Research.

Previous research suggested the enzyme is needed to maintain CSCs in chronic myeloid leukemia.

So investigators theorized that 5-LO could be a therapeutic target for AML, as CSCs are thought to cause the spread and relapse of this disease.

To test that theory, the team evaluated the effects of 5-LO inhibition in a PML/RARα-positive model of AML. As a model of CSCs, they used Sca-1⁺/lin⁻ murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The researchers targeted 5-LO genetically and pharmacologically. And they found that 5-LO inhibition interfered with the aberrant stem cell capacity of PML/RARα-expressing HSPCs.

Inhibiting 5-LO also inhibited Wnt signaling, which has been shown to be critical for CSC maintenance.

Additional investigation revealed that inhibition of Wnt signaling and CSCs was due to the generation of a catalytically inactive form of 5-LO, which hindered nuclear translocation of β-catenin.

Considering these results together, as well as evidence that CSCs mediate AML relapse, the investigators concluded that eradicating CSCs via 5-LO inhibition may offer a new treatment approach for AML.

“These results form the basis for a possible use of the 5-lipoxygenase inhibitors as stem cell therapy for a sustainable cure for acute myeloid leukemia,” said Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany. “But this must firstly be studied further in preclinical and clinical studies in humans.”

“We are now in the process of examining the molecular mechanism in more detail in order to find out how the inhibitors precisely work on the leukemia stem cells,” added Thorsten Jürgen Maier, MD, PhD, of Goethe University and Aarhus University in Denmark. “We very much hope that our results will be of benefit for leukemia patients.”

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

The UK’s National Institute for Health and Care Excellence (NICE) has updated its guidance to expand the use of erythropoiesis-stimulating agents (ESAs) in cancer patients.

In 2008, NICE issued a guidance recommending ESAs as a possible treatment for certain patients with anemia caused by cancer treatment.

Now, NICE has updated the recommendations to expand the use of ESAs—epoetin alfa, beta, theta, and zeta, as well as darbepoetin alfa—to all other indications within their UK marketing authorizations.

“A lot of people with cancer having chemotherapy will become anemic,” noted Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“Managing anemia often requires extra trips to the hospital and can significantly affect a person’s quality of life. This updated final guidance recommends more options, epoetin and darbepoetin, that are both clinically and cost-effective and which also significantly improve quality of life for people who develop anemia whilst having cancer therapy.”

The 2008 NICE guidance recommended erythropoietin analogues with iron injections as a possible treatment for anemia caused by cancer treatment only in:

• Women receiving platinum-based chemotherapy for cancer of the ovaries who have a blood hemoglobin level of 8 g/100 mL or lower
• Patients who have very severe anemia and cannot receive blood transfusions.

NICE’s updated final guidance recommends using darbepoetin alfa and epoetin alfa, beta, theta, and zeta within their marketing authorizations as an option for treating anemia in cancer patients undergoing chemotherapy.

Epoetin alfa (Eprex, Janssen-Cilag, and Binocrit, Sandoz), and epoetin zeta (Retacrit, Hospira UK) have UK marketing authorization to treat anemia and to reduce transfusion requirements in adult patients receiving chemotherapy for solid tumors, malignant lymphoma, or multiple myeloma, who are at risk of transfusion as assessed by the patients’ general status (eg, cardiovascular status, pre-existing anemia at the start of chemotherapy).

Binocrit and Retacrit are both biosimilar medicines referenced to Eprex. Eprex, Binocrit, and Retacrit are available in pre-filled syringes at net prices of £5.53, £4.33, and £5.66 per 1000 units, respectively.

Epoetin beta (NeoRecormon, Roche Products) and epoetin theta (Eporatio, Teva UK) have UK marketing authorization to treat symptomatic anemia in adult patients with non-myeloid malignancies who are receiving chemotherapy.

NeoRecormon is available in a pre-filled syringe at a net price of £3.51 per 500 units, and Eporatio is available in a pre-filled syringe at a net price of £5.99 per 1000 units.

Darbepoetin alfa (Aranesp, Amgen) has UK marketing authorization to treat symptomatic anemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy. Aranesp is available in a pre-filled syringe at a net price of £14.68 per 10 micrograms.

Costs (excluding value-added tax) may vary in different settings because of negotiated procurement discounts.

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

The UK’s National Institute for Health and Care Excellence (NICE) has updated its guidance to expand the use of erythropoiesis-stimulating agents (ESAs) in cancer patients.

In 2008, NICE issued a guidance recommending ESAs as a possible treatment for certain patients with anemia caused by cancer treatment.

Now, NICE has updated the recommendations to expand the use of ESAs—epoetin alfa, beta, theta, and zeta, as well as darbepoetin alfa—to all other indications within their UK marketing authorizations.

“A lot of people with cancer having chemotherapy will become anemic,” noted Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“Managing anemia often requires extra trips to the hospital and can significantly affect a person’s quality of life. This updated final guidance recommends more options, epoetin and darbepoetin, that are both clinically and cost-effective and which also significantly improve quality of life for people who develop anemia whilst having cancer therapy.”

The 2008 NICE guidance recommended erythropoietin analogues with iron injections as a possible treatment for anemia caused by cancer treatment only in:

• Women receiving platinum-based chemotherapy for cancer of the ovaries who have a blood hemoglobin level of 8 g/100 mL or lower
• Patients who have very severe anemia and cannot receive blood transfusions.

NICE’s updated final guidance recommends using darbepoetin alfa and epoetin alfa, beta, theta, and zeta within their marketing authorizations as an option for treating anemia in cancer patients undergoing chemotherapy.

Epoetin alfa (Eprex, Janssen-Cilag, and Binocrit, Sandoz), and epoetin zeta (Retacrit, Hospira UK) have UK marketing authorization to treat anemia and to reduce transfusion requirements in adult patients receiving chemotherapy for solid tumors, malignant lymphoma, or multiple myeloma, who are at risk of transfusion as assessed by the patients’ general status (eg, cardiovascular status, pre-existing anemia at the start of chemotherapy).

Binocrit and Retacrit are both biosimilar medicines referenced to Eprex. Eprex, Binocrit, and Retacrit are available in pre-filled syringes at net prices of £5.53, £4.33, and £5.66 per 1000 units, respectively.

Epoetin beta (NeoRecormon, Roche Products) and epoetin theta (Eporatio, Teva UK) have UK marketing authorization to treat symptomatic anemia in adult patients with non-myeloid malignancies who are receiving chemotherapy.

NeoRecormon is available in a pre-filled syringe at a net price of £3.51 per 500 units, and Eporatio is available in a pre-filled syringe at a net price of £5.99 per 1000 units.

Darbepoetin alfa (Aranesp, Amgen) has UK marketing authorization to treat symptomatic anemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy. Aranesp is available in a pre-filled syringe at a net price of £14.68 per 10 micrograms.

Costs (excluding value-added tax) may vary in different settings because of negotiated procurement discounts.

Cancer patient receiving

chemotherapy

Credit: Rhoda Baer

The UK’s National Institute for Health and Care Excellence (NICE) has updated its guidance to expand the use of erythropoiesis-stimulating agents (ESAs) in cancer patients.

In 2008, NICE issued a guidance recommending ESAs as a possible treatment for certain patients with anemia caused by cancer treatment.

Now, NICE has updated the recommendations to expand the use of ESAs—epoetin alfa, beta, theta, and zeta, as well as darbepoetin alfa—to all other indications within their UK marketing authorizations.

“A lot of people with cancer having chemotherapy will become anemic,” noted Carole Longson, director of the Centre for Health Technology Evaluation at NICE.

“Managing anemia often requires extra trips to the hospital and can significantly affect a person’s quality of life. This updated final guidance recommends more options, epoetin and darbepoetin, that are both clinically and cost-effective and which also significantly improve quality of life for people who develop anemia whilst having cancer therapy.”

The 2008 NICE guidance recommended erythropoietin analogues with iron injections as a possible treatment for anemia caused by cancer treatment only in:

• Women receiving platinum-based chemotherapy for cancer of the ovaries who have a blood hemoglobin level of 8 g/100 mL or lower
• Patients who have very severe anemia and cannot receive blood transfusions.

NICE’s updated final guidance recommends using darbepoetin alfa and epoetin alfa, beta, theta, and zeta within their marketing authorizations as an option for treating anemia in cancer patients undergoing chemotherapy.

Epoetin alfa (Eprex, Janssen-Cilag, and Binocrit, Sandoz), and epoetin zeta (Retacrit, Hospira UK) have UK marketing authorization to treat anemia and to reduce transfusion requirements in adult patients receiving chemotherapy for solid tumors, malignant lymphoma, or multiple myeloma, who are at risk of transfusion as assessed by the patients’ general status (eg, cardiovascular status, pre-existing anemia at the start of chemotherapy).

Binocrit and Retacrit are both biosimilar medicines referenced to Eprex. Eprex, Binocrit, and Retacrit are available in pre-filled syringes at net prices of £5.53, £4.33, and £5.66 per 1000 units, respectively.

Epoetin beta (NeoRecormon, Roche Products) and epoetin theta (Eporatio, Teva UK) have UK marketing authorization to treat symptomatic anemia in adult patients with non-myeloid malignancies who are receiving chemotherapy.

NeoRecormon is available in a pre-filled syringe at a net price of £3.51 per 500 units, and Eporatio is available in a pre-filled syringe at a net price of £5.99 per 1000 units.

Darbepoetin alfa (Aranesp, Amgen) has UK marketing authorization to treat symptomatic anemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy. Aranesp is available in a pre-filled syringe at a net price of £14.68 per 10 micrograms.

Costs (excluding value-added tax) may vary in different settings because of negotiated procurement discounts.

Blood samples

Credit: Graham Colm

Two teams of researchers have identified somatic mutations that increase the likelihood a person will develop a hematologic malignancy.

This “pre-malignant” stage was detected simply by sequencing DNA from blood samples.

The researchers found that subjects carrying certain mutations had more than 10 times the risk of developing a hematologic malignancy than individuals without the mutations. And the risk increased with age.

Steven McCarroll, PhD, of Harvard Medical School in Boston, Massachusetts, and Benjamin Ebert, MD, PhD, also of Harvard Medical School, reported these findings in NEJM.

Both research teams looked at somatic mutations in DNA samples collected from the blood of subjects who had not been diagnosed with cancer or blood disorders.

Taking two very different approaches, the teams found that a surprising percentage of individuals had acquired a subset of the somatic mutations present in hematologic malignancies. And subjects with the mutations were more likely to develop these cancers.

This pre-malignant state was rare in individuals under the age of 40. But it appeared with increasing frequency with each decade of life, ultimately appearing in more than 10% of individuals over the age of 70.

The researchers believe these early mutations lie in wait for follow-on, cooperating mutations that, when they occur in the same cells as the earlier mutations, drive the cells toward cancer. The majority of mutations occurred in just 3 genes: DNMT3A, TET2, and ASXL1.

Dr Ebert’s group

Dr Ebert and his colleagues had hypothesized that, since hematologic malignancies increase with age, it might be possible to detect early somatic mutations that could be initiating the disease process, and these mutations might increase with age.

The researchers looked specifically at 160 genes known to be recurrently mutated in hematologic malignancies, using genetic data derived from approximately 17,000 blood samples originally obtained for studies on the genetics of type 2 diabetes.

The team found a roughly 11-fold increase in the risk of hematologic malignancy among subjects with the subset of somatic mutations linked to blood cancers. And there was a clear association between age and the frequency of these mutations.

Men were slightly more likely to have the mutations than women, and Hispanics were slightly less likely to have the mutations than other racial/ethnic groups.

The researchers also found an association between the presence of this pre-malignant state and the risk of overall mortality independent of malignancy. Individuals with the mutations had a higher risk of type 2 diabetes, coronary heart disease, and ischemic stroke as well.

However, additional research will be needed to determine the nature of these associations.

Dr McCarroll’s group

Dr McCarroll and his colleagues discovered the same phenomenon while trying to determine whether somatic mutations contribute to the risk of developing schizophrenia.

The team studied roughly 12,000 DNA samples from patients with schizophrenia and bipolar disorder, as well as healthy controls, searching across the whole genome at all of the protein-coding genes for patterns in somatic mutations.

The somatic mutations were concentrated in a handful of genes that turned out to be cancer genes.

So the researchers used electronic medical records to follow the patients’ medical histories, finding that subjects with these acquired mutations had a nearly 13-fold higher risk of developing a hematologic malignancy than subjects without the mutations.

The team conducted follow-up analyses on tumor samples from 2 patients who had progressed from this pre-malignant state to cancer. In both cases, the cancer developed from the same cells that had harbored the initiating mutations years earlier.

“The fact that both teams converged on strikingly similar findings, using very different approaches and looking at DNA from very different sets of patients, has given us great confidence in the results,” said study author Giulio Genovese, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.

Next steps

The researchers emphasized that there is no clinical benefit today for testing for this pre-malignant state, as there are no treatments currently available that would address this condition in otherwise healthy people.

However, they said the results open the door to entirely new directions for research, toward early detection and even prevention of hematologic malignancies.

“The results demonstrate a way to identify high-risk cohorts—people who are at much higher than average risk of progressing to cancer—which could be a population for clinical trials of future prevention strategies,” Dr McCarroll said. “The abundance of these mutated cells could also serve as a biomarker—like LDL cholesterol is for cardiovascular disease—to test the effects of potential prevention therapies in clinical trials.”

Dr Ebert added, “A new focus of investigation will now be to develop interventions that might decrease the likelihood that individuals with these mutations will go on to develop overt malignancies, or therapeutic strategies to decrease mortality from other conditions that may be instigated by these mutations.”

This research is set to be presented on December 9 at the 56th ASH Annual Meeting in San Francisco.

Blood samples

Credit: Graham Colm

Two teams of researchers have identified somatic mutations that increase the likelihood a person will develop a hematologic malignancy.

This “pre-malignant” stage was detected simply by sequencing DNA from blood samples.

The researchers found that subjects carrying certain mutations had more than 10 times the risk of developing a hematologic malignancy than individuals without the mutations. And the risk increased with age.

Steven McCarroll, PhD, of Harvard Medical School in Boston, Massachusetts, and Benjamin Ebert, MD, PhD, also of Harvard Medical School, reported these findings in NEJM.

Both research teams looked at somatic mutations in DNA samples collected from the blood of subjects who had not been diagnosed with cancer or blood disorders.

Taking two very different approaches, the teams found that a surprising percentage of individuals had acquired a subset of the somatic mutations present in hematologic malignancies. And subjects with the mutations were more likely to develop these cancers.

This pre-malignant state was rare in individuals under the age of 40. But it appeared with increasing frequency with each decade of life, ultimately appearing in more than 10% of individuals over the age of 70.

The researchers believe these early mutations lie in wait for follow-on, cooperating mutations that, when they occur in the same cells as the earlier mutations, drive the cells toward cancer. The majority of mutations occurred in just 3 genes: DNMT3A, TET2, and ASXL1.

Dr Ebert’s group

Dr Ebert and his colleagues had hypothesized that, since hematologic malignancies increase with age, it might be possible to detect early somatic mutations that could be initiating the disease process, and these mutations might increase with age.

The researchers looked specifically at 160 genes known to be recurrently mutated in hematologic malignancies, using genetic data derived from approximately 17,000 blood samples originally obtained for studies on the genetics of type 2 diabetes.

The team found a roughly 11-fold increase in the risk of hematologic malignancy among subjects with the subset of somatic mutations linked to blood cancers. And there was a clear association between age and the frequency of these mutations.

Men were slightly more likely to have the mutations than women, and Hispanics were slightly less likely to have the mutations than other racial/ethnic groups.

The researchers also found an association between the presence of this pre-malignant state and the risk of overall mortality independent of malignancy. Individuals with the mutations had a higher risk of type 2 diabetes, coronary heart disease, and ischemic stroke as well.

However, additional research will be needed to determine the nature of these associations.

Dr McCarroll’s group

Dr McCarroll and his colleagues discovered the same phenomenon while trying to determine whether somatic mutations contribute to the risk of developing schizophrenia.

The team studied roughly 12,000 DNA samples from patients with schizophrenia and bipolar disorder, as well as healthy controls, searching across the whole genome at all of the protein-coding genes for patterns in somatic mutations.

The somatic mutations were concentrated in a handful of genes that turned out to be cancer genes.

So the researchers used electronic medical records to follow the patients’ medical histories, finding that subjects with these acquired mutations had a nearly 13-fold higher risk of developing a hematologic malignancy than subjects without the mutations.

The team conducted follow-up analyses on tumor samples from 2 patients who had progressed from this pre-malignant state to cancer. In both cases, the cancer developed from the same cells that had harbored the initiating mutations years earlier.

“The fact that both teams converged on strikingly similar findings, using very different approaches and looking at DNA from very different sets of patients, has given us great confidence in the results,” said study author Giulio Genovese, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.

Next steps

The researchers emphasized that there is no clinical benefit today for testing for this pre-malignant state, as there are no treatments currently available that would address this condition in otherwise healthy people.

However, they said the results open the door to entirely new directions for research, toward early detection and even prevention of hematologic malignancies.

“The results demonstrate a way to identify high-risk cohorts—people who are at much higher than average risk of progressing to cancer—which could be a population for clinical trials of future prevention strategies,” Dr McCarroll said. “The abundance of these mutated cells could also serve as a biomarker—like LDL cholesterol is for cardiovascular disease—to test the effects of potential prevention therapies in clinical trials.”

Dr Ebert added, “A new focus of investigation will now be to develop interventions that might decrease the likelihood that individuals with these mutations will go on to develop overt malignancies, or therapeutic strategies to decrease mortality from other conditions that may be instigated by these mutations.”

This research is set to be presented on December 9 at the 56th ASH Annual Meeting in San Francisco.

Blood samples

Credit: Graham Colm

Two teams of researchers have identified somatic mutations that increase the likelihood a person will develop a hematologic malignancy.

This “pre-malignant” stage was detected simply by sequencing DNA from blood samples.

The researchers found that subjects carrying certain mutations had more than 10 times the risk of developing a hematologic malignancy than individuals without the mutations. And the risk increased with age.

Steven McCarroll, PhD, of Harvard Medical School in Boston, Massachusetts, and Benjamin Ebert, MD, PhD, also of Harvard Medical School, reported these findings in NEJM.

Both research teams looked at somatic mutations in DNA samples collected from the blood of subjects who had not been diagnosed with cancer or blood disorders.

Taking two very different approaches, the teams found that a surprising percentage of individuals had acquired a subset of the somatic mutations present in hematologic malignancies. And subjects with the mutations were more likely to develop these cancers.

This pre-malignant state was rare in individuals under the age of 40. But it appeared with increasing frequency with each decade of life, ultimately appearing in more than 10% of individuals over the age of 70.

The researchers believe these early mutations lie in wait for follow-on, cooperating mutations that, when they occur in the same cells as the earlier mutations, drive the cells toward cancer. The majority of mutations occurred in just 3 genes: DNMT3A, TET2, and ASXL1.

Dr Ebert’s group

Dr Ebert and his colleagues had hypothesized that, since hematologic malignancies increase with age, it might be possible to detect early somatic mutations that could be initiating the disease process, and these mutations might increase with age.

The researchers looked specifically at 160 genes known to be recurrently mutated in hematologic malignancies, using genetic data derived from approximately 17,000 blood samples originally obtained for studies on the genetics of type 2 diabetes.

The team found a roughly 11-fold increase in the risk of hematologic malignancy among subjects with the subset of somatic mutations linked to blood cancers. And there was a clear association between age and the frequency of these mutations.

Men were slightly more likely to have the mutations than women, and Hispanics were slightly less likely to have the mutations than other racial/ethnic groups.

The researchers also found an association between the presence of this pre-malignant state and the risk of overall mortality independent of malignancy. Individuals with the mutations had a higher risk of type 2 diabetes, coronary heart disease, and ischemic stroke as well.

However, additional research will be needed to determine the nature of these associations.

Dr McCarroll’s group

Dr McCarroll and his colleagues discovered the same phenomenon while trying to determine whether somatic mutations contribute to the risk of developing schizophrenia.

The team studied roughly 12,000 DNA samples from patients with schizophrenia and bipolar disorder, as well as healthy controls, searching across the whole genome at all of the protein-coding genes for patterns in somatic mutations.

The somatic mutations were concentrated in a handful of genes that turned out to be cancer genes.

So the researchers used electronic medical records to follow the patients’ medical histories, finding that subjects with these acquired mutations had a nearly 13-fold higher risk of developing a hematologic malignancy than subjects without the mutations.

The team conducted follow-up analyses on tumor samples from 2 patients who had progressed from this pre-malignant state to cancer. In both cases, the cancer developed from the same cells that had harbored the initiating mutations years earlier.

“The fact that both teams converged on strikingly similar findings, using very different approaches and looking at DNA from very different sets of patients, has given us great confidence in the results,” said study author Giulio Genovese, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.

Next steps

The researchers emphasized that there is no clinical benefit today for testing for this pre-malignant state, as there are no treatments currently available that would address this condition in otherwise healthy people.

However, they said the results open the door to entirely new directions for research, toward early detection and even prevention of hematologic malignancies.

“The results demonstrate a way to identify high-risk cohorts—people who are at much higher than average risk of progressing to cancer—which could be a population for clinical trials of future prevention strategies,” Dr McCarroll said. “The abundance of these mutated cells could also serve as a biomarker—like LDL cholesterol is for cardiovascular disease—to test the effects of potential prevention therapies in clinical trials.”

Dr Ebert added, “A new focus of investigation will now be to develop interventions that might decrease the likelihood that individuals with these mutations will go on to develop overt malignancies, or therapeutic strategies to decrease mortality from other conditions that may be instigated by these mutations.”

This research is set to be presented on December 9 at the 56th ASH Annual Meeting in San Francisco.

ALL patient

Credit: Bill Branson

A large, international study has revealed sizable differences in cancer survival rates between countries.

In particular, investigators observed a wide gap in survival for children with acute lymphoblastic leukemia (ALL).

The most recent 5-year survival rate was less than 60% in several countries—and as low as 16% in one nation—but more than 90% in other countries.

This indicates major deficiencies in managing this largely curable disease, according to researchers.

Results from this study, known as CONCORD-2, appear in The Lancet alongside a linked comment article.

Claudia Allemani, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues analyzed individual patient data from 279 cancer registries in 67 countries.

The team reported 5-year survival estimates for 25.7 million cancer patients diagnosed with 1 of 10 common cancers—stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, prostate, and leukemia (n=873,588)—from 1995 through 2009.

The investigators also reported survival estimates for 74,343 children diagnosed with ALL during that period.

Even after they adjusted for differences between countries and regions in the risk of death from other causes by age, sex, and race, and over time, the researchers found very large variations between countries in survival for specific cancers.

Adult leukemia

For adults diagnosed with leukemia from 2005 through 2009, the 5-year net survival was 50% to 60% in 21 countries in North America, west Asia, Europe, and Oceania. Survival rates were generally much lower in the 15 participating Asian countries than in other parts of the world.

Survival rates tended to be low in east Asia—ranging from 19% in Japan to 23% in South Korea and Taiwan—but higher in west Asia—ranging from 33% in Turkey to 53% in Qatar. And results were mixed in other Asian countries—ranging from 7% in Jordan to 40% in Indonesia.

ALL in children

For children diagnosed with ALL from 2005 through 2009, 5-year survival was 90% or higher in Austria, Belgium, Canada, Germany, and Norway. It was 80% to 89% in 21 countries on various continents.

However, 5-year survival was lower than 60% in several countries and the lowest—16%—in Jordan.

The range of survival estimates for childhood ALL in Central/South America and Asia was much lower than the range in North America, Europe, and Oceania.

Solid tumor malignancies

The study also showed that liver and lung cancer have the worst prognosis among the 10 cancers examined, with 5-year survival of less than 20% in both developed and developing countries. The researchers said this suggests most patients still visit their doctors too late for treatment to be effective.

Five-year survival from breast and colorectal cancers increased in most developed countries and in South America (Brazil, Colombia, and Ecuador) from the beginning of the study period to the end. These trends likely reflect earlier diagnosis and the availability of better treatment options, according to the investigators.

Stomach cancer survival was higher in Southeast Asia than in other regions. This is likely a result of intensive diagnostic activity, early stage at diagnosis, and radical surgery, the researchers said. And this suggests important lessons could be learned from these countries about diagnosis and treatment.

Cervical and ovarian cancers showed particularly wide differences in survival, and overall improvements during the study period were slight.

“Our findings show that, in some countries, cancer is far more lethal than in others,” Dr Allemani said. “In the 21st century, there should not be such a dramatic gulf in survival. The majority of the variability in survival is probably due to factors that can be changed, such as the availability and quality of diagnostic and treatment services.”

“The findings can be used to evaluate the extent to which investment in healthcare systems is improving their effectiveness. We expect them to act as a stimulus for politicians to improve health policy and invest in healthcare.”

ALL patient

Credit: Bill Branson

A large, international study has revealed sizable differences in cancer survival rates between countries.

In particular, investigators observed a wide gap in survival for children with acute lymphoblastic leukemia (ALL).

The most recent 5-year survival rate was less than 60% in several countries—and as low as 16% in one nation—but more than 90% in other countries.

This indicates major deficiencies in managing this largely curable disease, according to researchers.

Results from this study, known as CONCORD-2, appear in The Lancet alongside a linked comment article.

Claudia Allemani, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues analyzed individual patient data from 279 cancer registries in 67 countries.

The team reported 5-year survival estimates for 25.7 million cancer patients diagnosed with 1 of 10 common cancers—stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, prostate, and leukemia (n=873,588)—from 1995 through 2009.

The investigators also reported survival estimates for 74,343 children diagnosed with ALL during that period.

Even after they adjusted for differences between countries and regions in the risk of death from other causes by age, sex, and race, and over time, the researchers found very large variations between countries in survival for specific cancers.

Adult leukemia

For adults diagnosed with leukemia from 2005 through 2009, the 5-year net survival was 50% to 60% in 21 countries in North America, west Asia, Europe, and Oceania. Survival rates were generally much lower in the 15 participating Asian countries than in other parts of the world.

Survival rates tended to be low in east Asia—ranging from 19% in Japan to 23% in South Korea and Taiwan—but higher in west Asia—ranging from 33% in Turkey to 53% in Qatar. And results were mixed in other Asian countries—ranging from 7% in Jordan to 40% in Indonesia.

ALL in children

For children diagnosed with ALL from 2005 through 2009, 5-year survival was 90% or higher in Austria, Belgium, Canada, Germany, and Norway. It was 80% to 89% in 21 countries on various continents.

However, 5-year survival was lower than 60% in several countries and the lowest—16%—in Jordan.

The range of survival estimates for childhood ALL in Central/South America and Asia was much lower than the range in North America, Europe, and Oceania.

Solid tumor malignancies

The study also showed that liver and lung cancer have the worst prognosis among the 10 cancers examined, with 5-year survival of less than 20% in both developed and developing countries. The researchers said this suggests most patients still visit their doctors too late for treatment to be effective.

Five-year survival from breast and colorectal cancers increased in most developed countries and in South America (Brazil, Colombia, and Ecuador) from the beginning of the study period to the end. These trends likely reflect earlier diagnosis and the availability of better treatment options, according to the investigators.

Stomach cancer survival was higher in Southeast Asia than in other regions. This is likely a result of intensive diagnostic activity, early stage at diagnosis, and radical surgery, the researchers said. And this suggests important lessons could be learned from these countries about diagnosis and treatment.

Cervical and ovarian cancers showed particularly wide differences in survival, and overall improvements during the study period were slight.

“Our findings show that, in some countries, cancer is far more lethal than in others,” Dr Allemani said. “In the 21st century, there should not be such a dramatic gulf in survival. The majority of the variability in survival is probably due to factors that can be changed, such as the availability and quality of diagnostic and treatment services.”

“The findings can be used to evaluate the extent to which investment in healthcare systems is improving their effectiveness. We expect them to act as a stimulus for politicians to improve health policy and invest in healthcare.”

ALL patient

Credit: Bill Branson

A large, international study has revealed sizable differences in cancer survival rates between countries.

In particular, investigators observed a wide gap in survival for children with acute lymphoblastic leukemia (ALL).

The most recent 5-year survival rate was less than 60% in several countries—and as low as 16% in one nation—but more than 90% in other countries.

This indicates major deficiencies in managing this largely curable disease, according to researchers.

Results from this study, known as CONCORD-2, appear in The Lancet alongside a linked comment article.

Claudia Allemani, PhD, of the London School of Hygiene & Tropical Medicine in the UK, and her colleagues analyzed individual patient data from 279 cancer registries in 67 countries.

The team reported 5-year survival estimates for 25.7 million cancer patients diagnosed with 1 of 10 common cancers—stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, prostate, and leukemia (n=873,588)—from 1995 through 2009.

The investigators also reported survival estimates for 74,343 children diagnosed with ALL during that period.

Even after they adjusted for differences between countries and regions in the risk of death from other causes by age, sex, and race, and over time, the researchers found very large variations between countries in survival for specific cancers.

Adult leukemia

For adults diagnosed with leukemia from 2005 through 2009, the 5-year net survival was 50% to 60% in 21 countries in North America, west Asia, Europe, and Oceania. Survival rates were generally much lower in the 15 participating Asian countries than in other parts of the world.

Survival rates tended to be low in east Asia—ranging from 19% in Japan to 23% in South Korea and Taiwan—but higher in west Asia—ranging from 33% in Turkey to 53% in Qatar. And results were mixed in other Asian countries—ranging from 7% in Jordan to 40% in Indonesia.

ALL in children

For children diagnosed with ALL from 2005 through 2009, 5-year survival was 90% or higher in Austria, Belgium, Canada, Germany, and Norway. It was 80% to 89% in 21 countries on various continents.

However, 5-year survival was lower than 60% in several countries and the lowest—16%—in Jordan.

The range of survival estimates for childhood ALL in Central/South America and Asia was much lower than the range in North America, Europe, and Oceania.

Solid tumor malignancies

The study also showed that liver and lung cancer have the worst prognosis among the 10 cancers examined, with 5-year survival of less than 20% in both developed and developing countries. The researchers said this suggests most patients still visit their doctors too late for treatment to be effective.

Five-year survival from breast and colorectal cancers increased in most developed countries and in South America (Brazil, Colombia, and Ecuador) from the beginning of the study period to the end. These trends likely reflect earlier diagnosis and the availability of better treatment options, according to the investigators.

Stomach cancer survival was higher in Southeast Asia than in other regions. This is likely a result of intensive diagnostic activity, early stage at diagnosis, and radical surgery, the researchers said. And this suggests important lessons could be learned from these countries about diagnosis and treatment.

Cervical and ovarian cancers showed particularly wide differences in survival, and overall improvements during the study period were slight.

“Our findings show that, in some countries, cancer is far more lethal than in others,” Dr Allemani said. “In the 21st century, there should not be such a dramatic gulf in survival. The majority of the variability in survival is probably due to factors that can be changed, such as the availability and quality of diagnostic and treatment services.”

“The findings can be used to evaluate the extent to which investment in healthcare systems is improving their effectiveness. We expect them to act as a stimulus for politicians to improve health policy and invest in healthcare.”

Prescription pills

The Therapeutic Goods Administration (TGA) has approved marketing of ponatinib (Iclusig) in Australia.

The drug is now approved to treat adults with chronic myeloid leukemia (CML) who could not tolerate or were resistant to at least 2 prior tyrosine kinase inhibitors (TKIs), or those patients with a T315I mutation.

Ponatinib is also approved to treat certain adults with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

These patients must be resistant to or intolerant of dasatinib and ineligible for treatment with imatinib, or they must have a T315I mutation.

Ponatinib is the only TKI approved in Australia for an indication that includes CML and Ph+ ALL patients with the T315I mutation.

The drug’s developers, Ariad Pharmaceuticals, Inc., and Specialized Therapeutics Australia Pty. Ltd., expect to launch ponatinib in early 2015.

The PACE trial

The TGA’s decision to approve ponatinib was based on results from the phase 2 PACE trial, which included patients with CML or Ph+ ALL who were resistant to or intolerant of prior TKI therapy, or who had the T315I mutation.

The median follow-up times were 15.3 months in chronic-phase CML patients, 15.8 months in accelerated-phase CML patients, and 6.2 months in patients with blast-phase CML or Ph+ ALL.

In chronic-phase CML, the primary endpoint was major cytogenetic response, and it occurred in 56% of patients. Among chronic-phase patients with the T315I mutation, 70% achieved a major cytogenetic response. Among patients who had failed treatment with dasatinib or nilotinib, 51% achieved a major cytogenetic response.

In accelerated-phase CML, the primary endpoint was major hematologic response. This occurred in 57% of all patients in this group, 50% of patients with the T315I mutation, and 58% of patients who had failed treatment with dasatinib or nilotinib.

The primary endpoint was major hematologic response in blast-phase CML/Ph+ ALL as well. Thirty-four percent of all patients in this group met this endpoint, as did 33% of patients with the T315I mutation and 35% of patients who had failed treatment with dasatinib or nilotinib.

Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).

Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). And serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.

Safety concerns

Ponatinib is also approved to treat CML and Ph+ ALL in the European Union and the US. However, the drug was pulled from the US market for a little over 2 months, and ponatinib trials were placed on partial hold, after extended follow-up from the PACE trial showed an increase in thrombotic events.

The drug went back on the market last January, with new safety measures in place.

Ponatinib was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of the drug. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.

Prescription pills

The Therapeutic Goods Administration (TGA) has approved marketing of ponatinib (Iclusig) in Australia.

The drug is now approved to treat adults with chronic myeloid leukemia (CML) who could not tolerate or were resistant to at least 2 prior tyrosine kinase inhibitors (TKIs), or those patients with a T315I mutation.

Ponatinib is also approved to treat certain adults with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

These patients must be resistant to or intolerant of dasatinib and ineligible for treatment with imatinib, or they must have a T315I mutation.

Ponatinib is the only TKI approved in Australia for an indication that includes CML and Ph+ ALL patients with the T315I mutation.

The drug’s developers, Ariad Pharmaceuticals, Inc., and Specialized Therapeutics Australia Pty. Ltd., expect to launch ponatinib in early 2015.

The PACE trial

The TGA’s decision to approve ponatinib was based on results from the phase 2 PACE trial, which included patients with CML or Ph+ ALL who were resistant to or intolerant of prior TKI therapy, or who had the T315I mutation.

The median follow-up times were 15.3 months in chronic-phase CML patients, 15.8 months in accelerated-phase CML patients, and 6.2 months in patients with blast-phase CML or Ph+ ALL.

In chronic-phase CML, the primary endpoint was major cytogenetic response, and it occurred in 56% of patients. Among chronic-phase patients with the T315I mutation, 70% achieved a major cytogenetic response. Among patients who had failed treatment with dasatinib or nilotinib, 51% achieved a major cytogenetic response.

In accelerated-phase CML, the primary endpoint was major hematologic response. This occurred in 57% of all patients in this group, 50% of patients with the T315I mutation, and 58% of patients who had failed treatment with dasatinib or nilotinib.

The primary endpoint was major hematologic response in blast-phase CML/Ph+ ALL as well. Thirty-four percent of all patients in this group met this endpoint, as did 33% of patients with the T315I mutation and 35% of patients who had failed treatment with dasatinib or nilotinib.

Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).

Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). And serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.

Safety concerns

Ponatinib is also approved to treat CML and Ph+ ALL in the European Union and the US. However, the drug was pulled from the US market for a little over 2 months, and ponatinib trials were placed on partial hold, after extended follow-up from the PACE trial showed an increase in thrombotic events.

The drug went back on the market last January, with new safety measures in place.

Ponatinib was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of the drug. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.

Prescription pills

The Therapeutic Goods Administration (TGA) has approved marketing of ponatinib (Iclusig) in Australia.

The drug is now approved to treat adults with chronic myeloid leukemia (CML) who could not tolerate or were resistant to at least 2 prior tyrosine kinase inhibitors (TKIs), or those patients with a T315I mutation.

Ponatinib is also approved to treat certain adults with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

These patients must be resistant to or intolerant of dasatinib and ineligible for treatment with imatinib, or they must have a T315I mutation.

Ponatinib is the only TKI approved in Australia for an indication that includes CML and Ph+ ALL patients with the T315I mutation.

The drug’s developers, Ariad Pharmaceuticals, Inc., and Specialized Therapeutics Australia Pty. Ltd., expect to launch ponatinib in early 2015.

The PACE trial

The TGA’s decision to approve ponatinib was based on results from the phase 2 PACE trial, which included patients with CML or Ph+ ALL who were resistant to or intolerant of prior TKI therapy, or who had the T315I mutation.

The median follow-up times were 15.3 months in chronic-phase CML patients, 15.8 months in accelerated-phase CML patients, and 6.2 months in patients with blast-phase CML or Ph+ ALL.

In chronic-phase CML, the primary endpoint was major cytogenetic response, and it occurred in 56% of patients. Among chronic-phase patients with the T315I mutation, 70% achieved a major cytogenetic response. Among patients who had failed treatment with dasatinib or nilotinib, 51% achieved a major cytogenetic response.

In accelerated-phase CML, the primary endpoint was major hematologic response. This occurred in 57% of all patients in this group, 50% of patients with the T315I mutation, and 58% of patients who had failed treatment with dasatinib or nilotinib.

The primary endpoint was major hematologic response in blast-phase CML/Ph+ ALL as well. Thirty-four percent of all patients in this group met this endpoint, as did 33% of patients with the T315I mutation and 35% of patients who had failed treatment with dasatinib or nilotinib.

Common non-hematologic adverse events included rash (38%), abdominal pain (38%), headache (35%), dry skin (35%), constipation (34%), fatigue (27%), pyrexia (27%), nausea (26%), arthralgia (25%), hypertension (21%), increased lipase (19%), and increased amylase (7%).

Hematologic events of any grade included thrombocytopenia (42%), neutropenia (24%), and anemia (20%). And serious adverse events of arterial thromboembolism, including arterial stenosis, occurred in patients with cardiovascular risk factors.

Safety concerns

Ponatinib is also approved to treat CML and Ph+ ALL in the European Union and the US. However, the drug was pulled from the US market for a little over 2 months, and ponatinib trials were placed on partial hold, after extended follow-up from the PACE trial showed an increase in thrombotic events.

The drug went back on the market last January, with new safety measures in place.

Ponatinib was not pulled from the market in the European Union, but the European Medicine’s Agency released recommendations for safer use of the drug. The Committee for Medicinal Products for Human Use reviewed data on ponatinib and decided the drug’s benefits outweigh its risks.