Hematology Times

Red blood cells

Researchers say they’ve developed a technique that uses light to activate a drug stored in circulating red blood cells (RBCs) so the drug is released exactly when and where it’s needed.

The group believes the work could have profound implications for the field of drug delivery.

They say the technique could drastically reduce the amount of drug needed to treat diseases and therefore decrease the risk of side effects.

“Using light to treat a disease site has a lot of benefits beyond the ‘isn’t-that-cool’ factor,” said study author David Lawrence, PhD, of the University of North Carolina at Chapel Hill.

“Those benefits could include avoiding surgery and the risk of infection, making anesthesia unnecessary, and allowing people to treat themselves by shining a light on a problem area, such as an arthritic knee.”

Dr Lawrence and his colleagues described their technique in Angewandte Chemie.

The researchers attached various drug molecules (methotrexate, colchicine, and paclitaxel) to vitamin B12 and loaded the compounds into RBCs, which can circulate for up to 4 months, potentially providing a lasting reservoir of treatment that could be tapped as needed.

The team then demonstrated their ability to overcome a long-time technical hurdle: using long-wavelength light to penetrate deep enough into the body to break molecular bonds; in this case, the drug linked to vitamin B12.

Long-wavelength light can penetrate much more deeply into the body, but it doesn’t carry as much energy as short-wavelength light and cannot typically break molecular bonds.

To activate the drugs with long-wavelength light, the researchers had to determine how to do it in a way that required less energy.

“That’s the trick, and that’s where we’ve been successful,” Dr Lawrence said.

The team solved the energy problem by introducing a weak energy bond between vitamin B12 and the drug and then attaching a fluorescent molecule to the bond.

The fluorescent molecule acts as an antenna, capturing long-wavelength light and using it to cut the bond between the drug and the vitamin carrier.

Dr Lawrence noted that this technique could prove useful in treating cancers for which patients may need to receive a wide array of anticancer agents.

“The problem is, when you start using 4 or 5 very toxic drugs, you’re going to have intolerable side effects,” he said. “However, by focusing powerful drugs at a specific site, it may be possible to significantly reduce or eliminate the side effects that commonly accompany cancer chemotherapy.”

Dr Lawrence has created a company in partnership with the University of North Carolina, Iris BioMed, to further develop the technology to be used in humans.

Red blood cells

Researchers say they’ve developed a technique that uses light to activate a drug stored in circulating red blood cells (RBCs) so the drug is released exactly when and where it’s needed.

The group believes the work could have profound implications for the field of drug delivery.

They say the technique could drastically reduce the amount of drug needed to treat diseases and therefore decrease the risk of side effects.

“Using light to treat a disease site has a lot of benefits beyond the ‘isn’t-that-cool’ factor,” said study author David Lawrence, PhD, of the University of North Carolina at Chapel Hill.

“Those benefits could include avoiding surgery and the risk of infection, making anesthesia unnecessary, and allowing people to treat themselves by shining a light on a problem area, such as an arthritic knee.”

Dr Lawrence and his colleagues described their technique in Angewandte Chemie.

The researchers attached various drug molecules (methotrexate, colchicine, and paclitaxel) to vitamin B12 and loaded the compounds into RBCs, which can circulate for up to 4 months, potentially providing a lasting reservoir of treatment that could be tapped as needed.

The team then demonstrated their ability to overcome a long-time technical hurdle: using long-wavelength light to penetrate deep enough into the body to break molecular bonds; in this case, the drug linked to vitamin B12.

Long-wavelength light can penetrate much more deeply into the body, but it doesn’t carry as much energy as short-wavelength light and cannot typically break molecular bonds.

To activate the drugs with long-wavelength light, the researchers had to determine how to do it in a way that required less energy.

“That’s the trick, and that’s where we’ve been successful,” Dr Lawrence said.

The team solved the energy problem by introducing a weak energy bond between vitamin B12 and the drug and then attaching a fluorescent molecule to the bond.

The fluorescent molecule acts as an antenna, capturing long-wavelength light and using it to cut the bond between the drug and the vitamin carrier.

Dr Lawrence noted that this technique could prove useful in treating cancers for which patients may need to receive a wide array of anticancer agents.

“The problem is, when you start using 4 or 5 very toxic drugs, you’re going to have intolerable side effects,” he said. “However, by focusing powerful drugs at a specific site, it may be possible to significantly reduce or eliminate the side effects that commonly accompany cancer chemotherapy.”

Dr Lawrence has created a company in partnership with the University of North Carolina, Iris BioMed, to further develop the technology to be used in humans.

Red blood cells

Researchers say they’ve developed a technique that uses light to activate a drug stored in circulating red blood cells (RBCs) so the drug is released exactly when and where it’s needed.

The group believes the work could have profound implications for the field of drug delivery.

They say the technique could drastically reduce the amount of drug needed to treat diseases and therefore decrease the risk of side effects.

“Using light to treat a disease site has a lot of benefits beyond the ‘isn’t-that-cool’ factor,” said study author David Lawrence, PhD, of the University of North Carolina at Chapel Hill.

“Those benefits could include avoiding surgery and the risk of infection, making anesthesia unnecessary, and allowing people to treat themselves by shining a light on a problem area, such as an arthritic knee.”

Dr Lawrence and his colleagues described their technique in Angewandte Chemie.

The researchers attached various drug molecules (methotrexate, colchicine, and paclitaxel) to vitamin B12 and loaded the compounds into RBCs, which can circulate for up to 4 months, potentially providing a lasting reservoir of treatment that could be tapped as needed.

The team then demonstrated their ability to overcome a long-time technical hurdle: using long-wavelength light to penetrate deep enough into the body to break molecular bonds; in this case, the drug linked to vitamin B12.

Long-wavelength light can penetrate much more deeply into the body, but it doesn’t carry as much energy as short-wavelength light and cannot typically break molecular bonds.

To activate the drugs with long-wavelength light, the researchers had to determine how to do it in a way that required less energy.

“That’s the trick, and that’s where we’ve been successful,” Dr Lawrence said.

The team solved the energy problem by introducing a weak energy bond between vitamin B12 and the drug and then attaching a fluorescent molecule to the bond.

The fluorescent molecule acts as an antenna, capturing long-wavelength light and using it to cut the bond between the drug and the vitamin carrier.

Dr Lawrence noted that this technique could prove useful in treating cancers for which patients may need to receive a wide array of anticancer agents.

“The problem is, when you start using 4 or 5 very toxic drugs, you’re going to have intolerable side effects,” he said. “However, by focusing powerful drugs at a specific site, it may be possible to significantly reduce or eliminate the side effects that commonly accompany cancer chemotherapy.”

Dr Lawrence has created a company in partnership with the University of North Carolina, Iris BioMed, to further develop the technology to be used in humans.

Transfusions of blood that has been stored for 6 weeks can release large and potentially harmful amounts of iron into patients’ bloodstreams, a new study suggests.

Based on these findings, researchers are recommending the US Food and Drug Administration (FDA) reduce the maximum storage limit of red blood cells (RBCs) from 6 weeks to 5 weeks, as long as there is a sufficient supply of blood.

“Our recommendation will be controversial, but we think we have real data to support it,” said study author Steven Spitalnik, MD, of Columbia University College of Physicians and Surgeons — New York Presbyterian Hospital in New York, New York.

“Recent studies have concluded that transfusing old blood has no impact on patient outcomes, but those studies didn’t exclusively examine the oldest blood available for transfusions. Our new study found a real problem when transfusing blood that’s older than 5 weeks.”

Dr Spitalnik and his colleagues described their study in The Journal of Clinical Investigation.

The researchers randomly assigned a group of 60 healthy volunteers to receive a unit of RBCs that had been stored for 1, 2, 3, 4, 5, or 6 weeks. The volunteers were then monitored for 20 hours after transfusion.

The researchers found that a longer duration of RBC storage was associated with a progressive increase in extravascular hemolysis, decreasing post-transfusion RBC recovery, decreasing elevations in hematocrit, and increasing serum ferritin.

None of the volunteers were harmed by the transfusions, but subjects who received 6-week-old blood had outcomes associated with an increased risk of harm.

In 7 of the 9 subjects who received the 6-week-old blood (78%), the amount of iron entering the circulation exceeded the iron-uptake capacity of transferrin, producing circulating nontransferrin-bound iron. The same effect occurred in 1 of the 10 subjects who received 5-week-old blood (10%, P=0.003).

The area under the curve of the change in nontransferrin-bound iron was significantly higher for subjects who received the 6-week-old blood than for all other subjects (P<0.001). The same was true for serum iron (P<0.01) and transferrin saturation (P<0.001).

“Based on the amount of iron circulating in the blood of the volunteers who received 6-week-old blood, we’d predict that certain existing infections could be exacerbated,” said study author Eldad Hod, MD, also of Columbia University College of Physicians and Surgeons — New York Presbyterian Hospital.

“Thus, for ill, hospitalized patients, this excess iron could lead to serious complications,” Dr Spitalnik added.

The researchers said the true impact of 6-week-old blood on the rate of complications is likely to be small. However, since millions of Americans receive transfusions each year, even a 1% difference in complications could affect a large number of patients.

“It’s estimated that up to 10% to 20% of blood units used for transfusions have been stored for more than 5 weeks, so the number of patients who are likely to receive a unit of very old blood is substantial,” Dr Hod noted.

“Based on our findings of potential harm, we think the prudent thing to do, at this time, is for the FDA to reduce the maximum storage period,” Dr Spitalnik added.

“The UK, Ireland, the Netherlands, and the National Institutes of Health have limited storage to 35 days, and we think that can be achieved throughout the US without seriously affecting the blood supply.”

This study was supported by grants from the National Institutes of Health (HL115557 and UL1TR000040).

Transfusions of blood that has been stored for 6 weeks can release large and potentially harmful amounts of iron into patients’ bloodstreams, a new study suggests.

Based on these findings, researchers are recommending the US Food and Drug Administration (FDA) reduce the maximum storage limit of red blood cells (RBCs) from 6 weeks to 5 weeks, as long as there is a sufficient supply of blood.

“Our recommendation will be controversial, but we think we have real data to support it,” said study author Steven Spitalnik, MD, of Columbia University College of Physicians and Surgeons — New York Presbyterian Hospital in New York, New York.

“Recent studies have concluded that transfusing old blood has no impact on patient outcomes, but those studies didn’t exclusively examine the oldest blood available for transfusions. Our new study found a real problem when transfusing blood that’s older than 5 weeks.”

Dr Spitalnik and his colleagues described their study in The Journal of Clinical Investigation.

The researchers randomly assigned a group of 60 healthy volunteers to receive a unit of RBCs that had been stored for 1, 2, 3, 4, 5, or 6 weeks. The volunteers were then monitored for 20 hours after transfusion.

The researchers found that a longer duration of RBC storage was associated with a progressive increase in extravascular hemolysis, decreasing post-transfusion RBC recovery, decreasing elevations in hematocrit, and increasing serum ferritin.

None of the volunteers were harmed by the transfusions, but subjects who received 6-week-old blood had outcomes associated with an increased risk of harm.

In 7 of the 9 subjects who received the 6-week-old blood (78%), the amount of iron entering the circulation exceeded the iron-uptake capacity of transferrin, producing circulating nontransferrin-bound iron. The same effect occurred in 1 of the 10 subjects who received 5-week-old blood (10%, P=0.003).

The area under the curve of the change in nontransferrin-bound iron was significantly higher for subjects who received the 6-week-old blood than for all other subjects (P<0.001). The same was true for serum iron (P<0.01) and transferrin saturation (P<0.001).

“Based on the amount of iron circulating in the blood of the volunteers who received 6-week-old blood, we’d predict that certain existing infections could be exacerbated,” said study author Eldad Hod, MD, also of Columbia University College of Physicians and Surgeons — New York Presbyterian Hospital.

“Thus, for ill, hospitalized patients, this excess iron could lead to serious complications,” Dr Spitalnik added.

The researchers said the true impact of 6-week-old blood on the rate of complications is likely to be small. However, since millions of Americans receive transfusions each year, even a 1% difference in complications could affect a large number of patients.

“It’s estimated that up to 10% to 20% of blood units used for transfusions have been stored for more than 5 weeks, so the number of patients who are likely to receive a unit of very old blood is substantial,” Dr Hod noted.

“Based on our findings of potential harm, we think the prudent thing to do, at this time, is for the FDA to reduce the maximum storage period,” Dr Spitalnik added.

“The UK, Ireland, the Netherlands, and the National Institutes of Health have limited storage to 35 days, and we think that can be achieved throughout the US without seriously affecting the blood supply.”

This study was supported by grants from the National Institutes of Health (HL115557 and UL1TR000040).

Transfusions of blood that has been stored for 6 weeks can release large and potentially harmful amounts of iron into patients’ bloodstreams, a new study suggests.

Based on these findings, researchers are recommending the US Food and Drug Administration (FDA) reduce the maximum storage limit of red blood cells (RBCs) from 6 weeks to 5 weeks, as long as there is a sufficient supply of blood.

“Our recommendation will be controversial, but we think we have real data to support it,” said study author Steven Spitalnik, MD, of Columbia University College of Physicians and Surgeons — New York Presbyterian Hospital in New York, New York.

“Recent studies have concluded that transfusing old blood has no impact on patient outcomes, but those studies didn’t exclusively examine the oldest blood available for transfusions. Our new study found a real problem when transfusing blood that’s older than 5 weeks.”

Dr Spitalnik and his colleagues described their study in The Journal of Clinical Investigation.

The researchers randomly assigned a group of 60 healthy volunteers to receive a unit of RBCs that had been stored for 1, 2, 3, 4, 5, or 6 weeks. The volunteers were then monitored for 20 hours after transfusion.

The researchers found that a longer duration of RBC storage was associated with a progressive increase in extravascular hemolysis, decreasing post-transfusion RBC recovery, decreasing elevations in hematocrit, and increasing serum ferritin.

None of the volunteers were harmed by the transfusions, but subjects who received 6-week-old blood had outcomes associated with an increased risk of harm.

In 7 of the 9 subjects who received the 6-week-old blood (78%), the amount of iron entering the circulation exceeded the iron-uptake capacity of transferrin, producing circulating nontransferrin-bound iron. The same effect occurred in 1 of the 10 subjects who received 5-week-old blood (10%, P=0.003).

The area under the curve of the change in nontransferrin-bound iron was significantly higher for subjects who received the 6-week-old blood than for all other subjects (P<0.001). The same was true for serum iron (P<0.01) and transferrin saturation (P<0.001).

“Based on the amount of iron circulating in the blood of the volunteers who received 6-week-old blood, we’d predict that certain existing infections could be exacerbated,” said study author Eldad Hod, MD, also of Columbia University College of Physicians and Surgeons — New York Presbyterian Hospital.

“Thus, for ill, hospitalized patients, this excess iron could lead to serious complications,” Dr Spitalnik added.

The researchers said the true impact of 6-week-old blood on the rate of complications is likely to be small. However, since millions of Americans receive transfusions each year, even a 1% difference in complications could affect a large number of patients.

“It’s estimated that up to 10% to 20% of blood units used for transfusions have been stored for more than 5 weeks, so the number of patients who are likely to receive a unit of very old blood is substantial,” Dr Hod noted.

“Based on our findings of potential harm, we think the prudent thing to do, at this time, is for the FDA to reduce the maximum storage period,” Dr Spitalnik added.

“The UK, Ireland, the Netherlands, and the National Institutes of Health have limited storage to 35 days, and we think that can be achieved throughout the US without seriously affecting the blood supply.”

This study was supported by grants from the National Institutes of Health (HL115557 and UL1TR000040).

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Micrograph showing TTP
Image by Erhabor Osaro

SAN DIEGO—The US Thrombotic Microangiopathies (USTMA) Consortium is planning a longitudinal study to identify biomarkers of relapse and neurocognitive dysfunction in acquired thrombotic thrombocytopenic purpura (TTP).

Earlier studies suggested that ADAMTS13 activity during remission has

limited utility in estimating relapse risk, and cognitive dysfunction

observed in TTP appears to be progressive and independent of relapses.

However, these studies were small with minimal longitudinal data.

Now, the USTMA Consortium, with 13 large referral centers for thrombotic microangiopathies (TMAs) in the US, is providing “the infrastructure for larger US studies in TTP with the goal of improving outcomes in TMAs,” said Marshall A. Mazepa, MD, of the University of Minnesota in Minneapolis.

He described the efforts of the consortium and its plans to conduct a long-term study at the first TTP-TMA Workshop, which took place immediately before the 2016 ASH Annual Meeting.

Dr Mazepa said the objective of the study is to identify biomarkers that

predict the danger period for neurocognitive dysfunction and relapse.

“Hematologists usually do not realize the

neurocognitive dysfunction among patients with TTP, and it is important

that they [hematologists] talk to neurologists,” said Spero Cataland, MD, an organizer of the TTP-TMA Workshop from The Ohio State University in

Columbus.

“This study will be crucial in

improving our understanding of this issue.”

The consortium plans to study 100 TTP patients in remission for 3 years.

Every

3 months, patients will complete neuropsychologic testing, and

investigators will evaluate patients’ end-organ ischemic biomarkers,

ADAMTS13 activity, ultra-large von Willebrand factor levels, and

complement activation biomarkers.

In addition to this study, the USTMA Consortium is participating in the phase 3 HERCULES study of caplacizumab for acquired TTP.

Caplacizumab, which is being developed by Ablynx, was previously evaluated for acquired TTP in the phase 2 TITAN study.

The phase 3 study is a double-blind, placebo-controlled trial designed to determine whether neurocognitive function can be preserved with caplacizumab intervention.

Investigators intend to enroll 92 patients at clinical sites in 17 countries. Recruitment is expected to be complete by the end of 2017.

In closing, Dr Mazepa invited interested clinicians to join the USTMA Consortium by contacting him (mmazepa@umn.edu) or Dr Cataland (spero.cataland@osumc.edu).

Micrograph showing TTP
Image by Erhabor Osaro

SAN DIEGO—The US Thrombotic Microangiopathies (USTMA) Consortium is planning a longitudinal study to identify biomarkers of relapse and neurocognitive dysfunction in acquired thrombotic thrombocytopenic purpura (TTP).

Earlier studies suggested that ADAMTS13 activity during remission has

limited utility in estimating relapse risk, and cognitive dysfunction

observed in TTP appears to be progressive and independent of relapses.

However, these studies were small with minimal longitudinal data.

Now, the USTMA Consortium, with 13 large referral centers for thrombotic microangiopathies (TMAs) in the US, is providing “the infrastructure for larger US studies in TTP with the goal of improving outcomes in TMAs,” said Marshall A. Mazepa, MD, of the University of Minnesota in Minneapolis.

He described the efforts of the consortium and its plans to conduct a long-term study at the first TTP-TMA Workshop, which took place immediately before the 2016 ASH Annual Meeting.

Dr Mazepa said the objective of the study is to identify biomarkers that

predict the danger period for neurocognitive dysfunction and relapse.

“Hematologists usually do not realize the

neurocognitive dysfunction among patients with TTP, and it is important

that they [hematologists] talk to neurologists,” said Spero Cataland, MD, an organizer of the TTP-TMA Workshop from The Ohio State University in

Columbus.

“This study will be crucial in

improving our understanding of this issue.”

The consortium plans to study 100 TTP patients in remission for 3 years.

Every

3 months, patients will complete neuropsychologic testing, and

investigators will evaluate patients’ end-organ ischemic biomarkers,

ADAMTS13 activity, ultra-large von Willebrand factor levels, and

complement activation biomarkers.

In addition to this study, the USTMA Consortium is participating in the phase 3 HERCULES study of caplacizumab for acquired TTP.

Caplacizumab, which is being developed by Ablynx, was previously evaluated for acquired TTP in the phase 2 TITAN study.

The phase 3 study is a double-blind, placebo-controlled trial designed to determine whether neurocognitive function can be preserved with caplacizumab intervention.

Investigators intend to enroll 92 patients at clinical sites in 17 countries. Recruitment is expected to be complete by the end of 2017.

In closing, Dr Mazepa invited interested clinicians to join the USTMA Consortium by contacting him (mmazepa@umn.edu) or Dr Cataland (spero.cataland@osumc.edu).

Micrograph showing TTP
Image by Erhabor Osaro

SAN DIEGO—The US Thrombotic Microangiopathies (USTMA) Consortium is planning a longitudinal study to identify biomarkers of relapse and neurocognitive dysfunction in acquired thrombotic thrombocytopenic purpura (TTP).

Earlier studies suggested that ADAMTS13 activity during remission has

limited utility in estimating relapse risk, and cognitive dysfunction

observed in TTP appears to be progressive and independent of relapses.

However, these studies were small with minimal longitudinal data.

Now, the USTMA Consortium, with 13 large referral centers for thrombotic microangiopathies (TMAs) in the US, is providing “the infrastructure for larger US studies in TTP with the goal of improving outcomes in TMAs,” said Marshall A. Mazepa, MD, of the University of Minnesota in Minneapolis.

He described the efforts of the consortium and its plans to conduct a long-term study at the first TTP-TMA Workshop, which took place immediately before the 2016 ASH Annual Meeting.

Dr Mazepa said the objective of the study is to identify biomarkers that

predict the danger period for neurocognitive dysfunction and relapse.

“Hematologists usually do not realize the

neurocognitive dysfunction among patients with TTP, and it is important

that they [hematologists] talk to neurologists,” said Spero Cataland, MD, an organizer of the TTP-TMA Workshop from The Ohio State University in

Columbus.

“This study will be crucial in

improving our understanding of this issue.”

The consortium plans to study 100 TTP patients in remission for 3 years.

Every

3 months, patients will complete neuropsychologic testing, and

investigators will evaluate patients’ end-organ ischemic biomarkers,

ADAMTS13 activity, ultra-large von Willebrand factor levels, and

complement activation biomarkers.

In addition to this study, the USTMA Consortium is participating in the phase 3 HERCULES study of caplacizumab for acquired TTP.

Caplacizumab, which is being developed by Ablynx, was previously evaluated for acquired TTP in the phase 2 TITAN study.

The phase 3 study is a double-blind, placebo-controlled trial designed to determine whether neurocognitive function can be preserved with caplacizumab intervention.

Investigators intend to enroll 92 patients at clinical sites in 17 countries. Recruitment is expected to be complete by the end of 2017.

In closing, Dr Mazepa invited interested clinicians to join the USTMA Consortium by contacting him (mmazepa@umn.edu) or Dr Cataland (spero.cataland@osumc.edu).

Children in The Gambia
Photo by Aurimas Rimsa

New research suggests that, for young children, iron deficiency anemia offers a

greater protective effect against malaria than sickle cell trait.

The

study indicates that iron deficiency anemia can protect children age 2 and

younger from the blood stage of Plasmodium falciparum malaria, and

treating the anemia with iron supplementation removes this protective

effect.

The researchers reported these findings in EBioMedicine.

“This study is elegant in its simplicity yet remains one of the most

substantial and systematic attempts to unveil the cellular-level

relationship between anemia, iron supplementation, and malaria risk,”

said study author Carla Cerami, MD, PhD, of the Medical Research Council

Unit The Gambia in Banjul, Gambia.

For this study, she and her colleagues analyzed the red blood cells of 135 anemic children who were participating in an iron supplementation trial.

The children ranged in age from 6 months to 24 months and lived in a malaria-endemic region of The Gambia where sickle cell trait was also common.

The children received iron (12 mg/day) through micronutrient powder for 84 days, and the researchers analyzed the children’s red blood cells at baseline, day 49, and day 84.

The team conducted in vitro growth and invasion assays with P falciparum laboratory and field strains. The study’s primary endpoint was in vitro parasite growth in the children’s RBCs.

The researchers found that “anemia substantially reduced the invasion and growth of both laboratory and field strains of P falciparum.” The team noted a roughly 10% growth reduction per standard deviation shift in hemoglobin.

On a population-wide basis, anemia reduced the blood stage of malaria by 15.9%, while the sickle cell trait reduced it by 3.5%.

“Our finding that anemia offers greater natural protection against blood-stage malaria infection than sickle cell trait has led us to formulate the interesting hypothesis that the widespread prevalence of anemia in people of African descent is a genetic signature of malaria,” said study author Morgan Goheen, PhD, of University of North Carolina in Chapel Hill.

The researchers also found that deficits in invasion and growth for blood-stage P falciparum were reversed when anemic children had received 7 weeks of iron supplementation. Parasite growth was 2.4-fold higher after supplementation than it was at baseline (P<0.001).

Prior work by the same research group suggested the increased invasion and growth rates following iron supplementation are caused by the parasites’ strong preference for young red blood cells.

The researchers said these new field results consolidate the evidence that iron supplementation increases the risk of P falciparum malaria and provide support for the use of malaria prophylaxis in

conjunction with iron supplementation, especially during the early

phases of erythroid recovery.

Children in The Gambia
Photo by Aurimas Rimsa

New research suggests that, for young children, iron deficiency anemia offers a

greater protective effect against malaria than sickle cell trait.

The

study indicates that iron deficiency anemia can protect children age 2 and

younger from the blood stage of Plasmodium falciparum malaria, and

treating the anemia with iron supplementation removes this protective

effect.

The researchers reported these findings in EBioMedicine.

“This study is elegant in its simplicity yet remains one of the most

substantial and systematic attempts to unveil the cellular-level

relationship between anemia, iron supplementation, and malaria risk,”

said study author Carla Cerami, MD, PhD, of the Medical Research Council

Unit The Gambia in Banjul, Gambia.

For this study, she and her colleagues analyzed the red blood cells of 135 anemic children who were participating in an iron supplementation trial.

The children ranged in age from 6 months to 24 months and lived in a malaria-endemic region of The Gambia where sickle cell trait was also common.

The children received iron (12 mg/day) through micronutrient powder for 84 days, and the researchers analyzed the children’s red blood cells at baseline, day 49, and day 84.

The team conducted in vitro growth and invasion assays with P falciparum laboratory and field strains. The study’s primary endpoint was in vitro parasite growth in the children’s RBCs.

The researchers found that “anemia substantially reduced the invasion and growth of both laboratory and field strains of P falciparum.” The team noted a roughly 10% growth reduction per standard deviation shift in hemoglobin.

On a population-wide basis, anemia reduced the blood stage of malaria by 15.9%, while the sickle cell trait reduced it by 3.5%.

“Our finding that anemia offers greater natural protection against blood-stage malaria infection than sickle cell trait has led us to formulate the interesting hypothesis that the widespread prevalence of anemia in people of African descent is a genetic signature of malaria,” said study author Morgan Goheen, PhD, of University of North Carolina in Chapel Hill.

The researchers also found that deficits in invasion and growth for blood-stage P falciparum were reversed when anemic children had received 7 weeks of iron supplementation. Parasite growth was 2.4-fold higher after supplementation than it was at baseline (P<0.001).

Prior work by the same research group suggested the increased invasion and growth rates following iron supplementation are caused by the parasites’ strong preference for young red blood cells.

The researchers said these new field results consolidate the evidence that iron supplementation increases the risk of P falciparum malaria and provide support for the use of malaria prophylaxis in

conjunction with iron supplementation, especially during the early

phases of erythroid recovery.

Children in The Gambia
Photo by Aurimas Rimsa

New research suggests that, for young children, iron deficiency anemia offers a

greater protective effect against malaria than sickle cell trait.

The

study indicates that iron deficiency anemia can protect children age 2 and

younger from the blood stage of Plasmodium falciparum malaria, and

treating the anemia with iron supplementation removes this protective

effect.

The researchers reported these findings in EBioMedicine.

“This study is elegant in its simplicity yet remains one of the most

substantial and systematic attempts to unveil the cellular-level

relationship between anemia, iron supplementation, and malaria risk,”

said study author Carla Cerami, MD, PhD, of the Medical Research Council

Unit The Gambia in Banjul, Gambia.

For this study, she and her colleagues analyzed the red blood cells of 135 anemic children who were participating in an iron supplementation trial.

The children ranged in age from 6 months to 24 months and lived in a malaria-endemic region of The Gambia where sickle cell trait was also common.

The children received iron (12 mg/day) through micronutrient powder for 84 days, and the researchers analyzed the children’s red blood cells at baseline, day 49, and day 84.

The team conducted in vitro growth and invasion assays with P falciparum laboratory and field strains. The study’s primary endpoint was in vitro parasite growth in the children’s RBCs.

The researchers found that “anemia substantially reduced the invasion and growth of both laboratory and field strains of P falciparum.” The team noted a roughly 10% growth reduction per standard deviation shift in hemoglobin.

On a population-wide basis, anemia reduced the blood stage of malaria by 15.9%, while the sickle cell trait reduced it by 3.5%.

“Our finding that anemia offers greater natural protection against blood-stage malaria infection than sickle cell trait has led us to formulate the interesting hypothesis that the widespread prevalence of anemia in people of African descent is a genetic signature of malaria,” said study author Morgan Goheen, PhD, of University of North Carolina in Chapel Hill.

The researchers also found that deficits in invasion and growth for blood-stage P falciparum were reversed when anemic children had received 7 weeks of iron supplementation. Parasite growth was 2.4-fold higher after supplementation than it was at baseline (P<0.001).

Prior work by the same research group suggested the increased invasion and growth rates following iron supplementation are caused by the parasites’ strong preference for young red blood cells.

The researchers said these new field results consolidate the evidence that iron supplementation increases the risk of P falciparum malaria and provide support for the use of malaria prophylaxis in

conjunction with iron supplementation, especially during the early

phases of erythroid recovery.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Child with cancer
Photo by Bill Branson

A yoga program for children with cancer can be carried out during cancer treatment and has quality of life (QOL) benefits for the children as well as their caregivers, according to research published in Rehabilitation Oncology.

However, the program was not feasible for all patients. More than half of those initially enrolled could not complete the study due to treatment toxicity or scheduling conflicts.

Andrea Orsey, MD, of Connecticut Children’s Medical Center in Hartford, and her colleagues conducted this research to evaluate the feasibility and effectiveness of a yoga intervention for children with cancer and their families.

The team began by conducting a survey of 20 children and adolescents with cancer and their parents/guardians.

Survey respondents expressed interest in a yoga program. But they also perceived several barriers to such a program, including concerns about side effects, pain/discomfort, and physical limitations.

With these barriers in mind, Dr Orsey and her colleagues developed a yoga intervention for pediatric cancer patients, delivered by certified yoga instructors.

The program was designed to be performed in a variety of settings and tailored to the children’s physical condition or mobility issues.

A pilot evaluation included 10 children with cancer and their caregivers. Twenty-two patient/caregiver pairs were actually enrolled, but 6 pairs withdrew because of treatment toxicity, and 6 had the study window lapse due to scheduling conflicts.

Although limited by its small size, the study suggested that yoga improved health-related QOL for both caregivers and children.

The children had significant improvements in both social and emotional QOL. They had an overall improvement in fatigue, but this was not statistically significant.

Caregivers had a significant improvement in mental health but not physical health or caregiver burden.

Both caregivers and children said they were satisfied with the yoga program and would recommend it to others.

Dr Orsey and her colleagues hope this pilot study will help guide future efforts to provide yoga to children with cancer and their families.

The researchers noted that a key issue will be coordinating yoga sessions with the medical demands of chemotherapy.

Child with cancer
Photo by Bill Branson

A yoga program for children with cancer can be carried out during cancer treatment and has quality of life (QOL) benefits for the children as well as their caregivers, according to research published in Rehabilitation Oncology.

However, the program was not feasible for all patients. More than half of those initially enrolled could not complete the study due to treatment toxicity or scheduling conflicts.

Andrea Orsey, MD, of Connecticut Children’s Medical Center in Hartford, and her colleagues conducted this research to evaluate the feasibility and effectiveness of a yoga intervention for children with cancer and their families.

The team began by conducting a survey of 20 children and adolescents with cancer and their parents/guardians.

Survey respondents expressed interest in a yoga program. But they also perceived several barriers to such a program, including concerns about side effects, pain/discomfort, and physical limitations.

With these barriers in mind, Dr Orsey and her colleagues developed a yoga intervention for pediatric cancer patients, delivered by certified yoga instructors.

The program was designed to be performed in a variety of settings and tailored to the children’s physical condition or mobility issues.

A pilot evaluation included 10 children with cancer and their caregivers. Twenty-two patient/caregiver pairs were actually enrolled, but 6 pairs withdrew because of treatment toxicity, and 6 had the study window lapse due to scheduling conflicts.

Although limited by its small size, the study suggested that yoga improved health-related QOL for both caregivers and children.

The children had significant improvements in both social and emotional QOL. They had an overall improvement in fatigue, but this was not statistically significant.

Caregivers had a significant improvement in mental health but not physical health or caregiver burden.

Both caregivers and children said they were satisfied with the yoga program and would recommend it to others.

Dr Orsey and her colleagues hope this pilot study will help guide future efforts to provide yoga to children with cancer and their families.

The researchers noted that a key issue will be coordinating yoga sessions with the medical demands of chemotherapy.

Child with cancer
Photo by Bill Branson

A yoga program for children with cancer can be carried out during cancer treatment and has quality of life (QOL) benefits for the children as well as their caregivers, according to research published in Rehabilitation Oncology.

However, the program was not feasible for all patients. More than half of those initially enrolled could not complete the study due to treatment toxicity or scheduling conflicts.

Andrea Orsey, MD, of Connecticut Children’s Medical Center in Hartford, and her colleagues conducted this research to evaluate the feasibility and effectiveness of a yoga intervention for children with cancer and their families.

The team began by conducting a survey of 20 children and adolescents with cancer and their parents/guardians.

Survey respondents expressed interest in a yoga program. But they also perceived several barriers to such a program, including concerns about side effects, pain/discomfort, and physical limitations.

With these barriers in mind, Dr Orsey and her colleagues developed a yoga intervention for pediatric cancer patients, delivered by certified yoga instructors.

The program was designed to be performed in a variety of settings and tailored to the children’s physical condition or mobility issues.

A pilot evaluation included 10 children with cancer and their caregivers. Twenty-two patient/caregiver pairs were actually enrolled, but 6 pairs withdrew because of treatment toxicity, and 6 had the study window lapse due to scheduling conflicts.

Although limited by its small size, the study suggested that yoga improved health-related QOL for both caregivers and children.

The children had significant improvements in both social and emotional QOL. They had an overall improvement in fatigue, but this was not statistically significant.

Caregivers had a significant improvement in mental health but not physical health or caregiver burden.

Both caregivers and children said they were satisfied with the yoga program and would recommend it to others.

Dr Orsey and her colleagues hope this pilot study will help guide future efforts to provide yoga to children with cancer and their families.

The researchers noted that a key issue will be coordinating yoga sessions with the medical demands of chemotherapy.

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

The US may see nearly 1.7 million new cancer cases in 2017 and more than 600,000 cancer-related deaths, according to a report from the American Cancer Society (ACS).

In addition to estimates for 2017, the report, “Cancer Statistics 2017,” includes the most recent data on cancer incidence, mortality, and survival in the US.

The report was published in CA: A Cancer Journal for Clinicians.

The report projects there will be 1,688,780 new cancer cases and 600,920 cancer deaths in the US this year.

This includes:

• 80,500 new cases of lymphoma and 21,210 lymphoma deaths
• 62,130 new cases of leukemia and 24,500 leukemia deaths
• 30,280 new cases of myeloma and 12,590 myeloma deaths.

The report also shows that, from 2004 to 2013, the overall cancer incidence rate was stable in women and declined by about 2% per year in men. From 2005 to 2014, the cancer death rate declined by about 1.5% annually in both men and women.

Overall, the cancer death rate dropped 25% from its peak of 215.1 (per 100,000 population) in 1991 to 161.2 (per 100,000 population) in 2014, the latest year for which data was available. This translates to about 2,143,200 fewer cancer deaths.

“The continuing drops in the cancer death rate are a powerful sign of the potential we have to reduce cancer’s deadly toll,” said Otis W. Brawley, MD, chief medical officer of the ACS.

He said the decrease in cancer death rates is the result of steady reductions in smoking and advances in early detection and treatment. The decrease is driven by decreasing death rates for the 4 major cancer sites—lung, breast, colorectal, and prostate.

The report also shows that racial disparities in cancer death rates continue to decline. The excess risk of cancer death in black men has dropped from 47% in 1990 to 21% in 2014. The black/white disparity declined similarly in women, from a peak of 20% in 1998 to 13% in 2014.

On the other hand, significant gender disparities persist for both cancer incidence and death in the US. For all cancer sites combined, the incidence rate is 20% higher in men than in women, and the cancer death rate is 40% higher in men.

Dr Brawley said the gender gap in cancer mortality largely reflects variation in the distribution of cancers that occur in men and women, much of which is due to differences in the prevalence of cancer risk factors.

The yearly “Cancer Statistics” reports have been published by ACS researchers since 1967 to inform and guide clinicians, investigators, and others in public health in prioritizing efforts to reduce the burden of cancer.

Cancer incidence data for the current report were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics.

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

The US may see nearly 1.7 million new cancer cases in 2017 and more than 600,000 cancer-related deaths, according to a report from the American Cancer Society (ACS).

In addition to estimates for 2017, the report, “Cancer Statistics 2017,” includes the most recent data on cancer incidence, mortality, and survival in the US.

The report was published in CA: A Cancer Journal for Clinicians.

The report projects there will be 1,688,780 new cancer cases and 600,920 cancer deaths in the US this year.

This includes:

• 80,500 new cases of lymphoma and 21,210 lymphoma deaths
• 62,130 new cases of leukemia and 24,500 leukemia deaths
• 30,280 new cases of myeloma and 12,590 myeloma deaths.

The report also shows that, from 2004 to 2013, the overall cancer incidence rate was stable in women and declined by about 2% per year in men. From 2005 to 2014, the cancer death rate declined by about 1.5% annually in both men and women.

Overall, the cancer death rate dropped 25% from its peak of 215.1 (per 100,000 population) in 1991 to 161.2 (per 100,000 population) in 2014, the latest year for which data was available. This translates to about 2,143,200 fewer cancer deaths.

“The continuing drops in the cancer death rate are a powerful sign of the potential we have to reduce cancer’s deadly toll,” said Otis W. Brawley, MD, chief medical officer of the ACS.

He said the decrease in cancer death rates is the result of steady reductions in smoking and advances in early detection and treatment. The decrease is driven by decreasing death rates for the 4 major cancer sites—lung, breast, colorectal, and prostate.

The report also shows that racial disparities in cancer death rates continue to decline. The excess risk of cancer death in black men has dropped from 47% in 1990 to 21% in 2014. The black/white disparity declined similarly in women, from a peak of 20% in 1998 to 13% in 2014.

On the other hand, significant gender disparities persist for both cancer incidence and death in the US. For all cancer sites combined, the incidence rate is 20% higher in men than in women, and the cancer death rate is 40% higher in men.

Dr Brawley said the gender gap in cancer mortality largely reflects variation in the distribution of cancers that occur in men and women, much of which is due to differences in the prevalence of cancer risk factors.

The yearly “Cancer Statistics” reports have been published by ACS researchers since 1967 to inform and guide clinicians, investigators, and others in public health in prioritizing efforts to reduce the burden of cancer.

Cancer incidence data for the current report were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics.

Doctor consults with cancer
patient and her father
Photo by Rhoda Baer

The US may see nearly 1.7 million new cancer cases in 2017 and more than 600,000 cancer-related deaths, according to a report from the American Cancer Society (ACS).

In addition to estimates for 2017, the report, “Cancer Statistics 2017,” includes the most recent data on cancer incidence, mortality, and survival in the US.

The report was published in CA: A Cancer Journal for Clinicians.

The report projects there will be 1,688,780 new cancer cases and 600,920 cancer deaths in the US this year.

This includes:

• 80,500 new cases of lymphoma and 21,210 lymphoma deaths
• 62,130 new cases of leukemia and 24,500 leukemia deaths
• 30,280 new cases of myeloma and 12,590 myeloma deaths.

The report also shows that, from 2004 to 2013, the overall cancer incidence rate was stable in women and declined by about 2% per year in men. From 2005 to 2014, the cancer death rate declined by about 1.5% annually in both men and women.

Overall, the cancer death rate dropped 25% from its peak of 215.1 (per 100,000 population) in 1991 to 161.2 (per 100,000 population) in 2014, the latest year for which data was available. This translates to about 2,143,200 fewer cancer deaths.

“The continuing drops in the cancer death rate are a powerful sign of the potential we have to reduce cancer’s deadly toll,” said Otis W. Brawley, MD, chief medical officer of the ACS.

He said the decrease in cancer death rates is the result of steady reductions in smoking and advances in early detection and treatment. The decrease is driven by decreasing death rates for the 4 major cancer sites—lung, breast, colorectal, and prostate.

The report also shows that racial disparities in cancer death rates continue to decline. The excess risk of cancer death in black men has dropped from 47% in 1990 to 21% in 2014. The black/white disparity declined similarly in women, from a peak of 20% in 1998 to 13% in 2014.

On the other hand, significant gender disparities persist for both cancer incidence and death in the US. For all cancer sites combined, the incidence rate is 20% higher in men than in women, and the cancer death rate is 40% higher in men.

Dr Brawley said the gender gap in cancer mortality largely reflects variation in the distribution of cancers that occur in men and women, much of which is due to differences in the prevalence of cancer risk factors.

The yearly “Cancer Statistics” reports have been published by ACS researchers since 1967 to inform and guide clinicians, investigators, and others in public health in prioritizing efforts to reduce the burden of cancer.

Cancer incidence data for the current report were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics.

Genome testing
Photo courtesy of the
National Institute of
General Medical Sciences

The American Association for Cancer Research (AACR) has announced the first public release of cancer genomic data aggregated through the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The data set includes nearly 19,000 de-identified genomic records collected from patients who were treated at 8 international institutions, making it one of the largest public cancer genomic data sets released to date.

The release includes data for 59 major cancer types, including leukemias, lymphomas, and multiple myeloma.

The genomic data and a limited amount of linked clinical data for each patient can be accessed via the AACR Project GENIE cBioPortal or from Sage Bionetworks. (Users must create an account for either site to access the data.)

“We are excited to make publicly available this very large set of clinical-grade, next-generation sequencing data obtained during routine patient care,” said Charles L. Sawyers, MD, AACR Project GENIE Steering Committee chairperson.

“These data were generated as part of routine patient care and, without AACR Project GENIE, they would likely never have been shared with the global cancer research community.”

AACR Project GENIE is a multi-phase, international data-sharing project aimed at catalyzing precision oncology through the development of a registry that aggregates and links clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at multiple institutions.

The newly released data are fully de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

The data are derived from patients whose tumors were genetically sequenced as part of their care at any of the 8 institutions that participated in the first phase of AACR Project GENIE.

The goal of releasing these data to the cancer research community is to aid new research that will accelerate the pace of progress against cancer.

According to AACR, the data can be used to validate gene signatures of drug response or prognosis, identify new patient populations for drugs that are currently available, and uncover new drug targets and biomarkers.

“I am extremely proud that the American Association for Cancer Research, as the coordinating center for AACR Project GENIE, is delivering on its promise to make these important data publicly available just over a year after unveiling the initiative,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

To expand the AACR Project GENIE registry, the consortium is accepting applications for new participating centers. Any nonprofit institution that meets certain criteria can submit an application to become a project participant.

For more information on AACR Project GENIE, visit the project website or send an email to info@aacrgenie.org.

Genome testing
Photo courtesy of the
National Institute of
General Medical Sciences

The American Association for Cancer Research (AACR) has announced the first public release of cancer genomic data aggregated through the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The data set includes nearly 19,000 de-identified genomic records collected from patients who were treated at 8 international institutions, making it one of the largest public cancer genomic data sets released to date.

The release includes data for 59 major cancer types, including leukemias, lymphomas, and multiple myeloma.

The genomic data and a limited amount of linked clinical data for each patient can be accessed via the AACR Project GENIE cBioPortal or from Sage Bionetworks. (Users must create an account for either site to access the data.)

“We are excited to make publicly available this very large set of clinical-grade, next-generation sequencing data obtained during routine patient care,” said Charles L. Sawyers, MD, AACR Project GENIE Steering Committee chairperson.

“These data were generated as part of routine patient care and, without AACR Project GENIE, they would likely never have been shared with the global cancer research community.”

AACR Project GENIE is a multi-phase, international data-sharing project aimed at catalyzing precision oncology through the development of a registry that aggregates and links clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at multiple institutions.

The newly released data are fully de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

The data are derived from patients whose tumors were genetically sequenced as part of their care at any of the 8 institutions that participated in the first phase of AACR Project GENIE.

The goal of releasing these data to the cancer research community is to aid new research that will accelerate the pace of progress against cancer.

According to AACR, the data can be used to validate gene signatures of drug response or prognosis, identify new patient populations for drugs that are currently available, and uncover new drug targets and biomarkers.

“I am extremely proud that the American Association for Cancer Research, as the coordinating center for AACR Project GENIE, is delivering on its promise to make these important data publicly available just over a year after unveiling the initiative,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

To expand the AACR Project GENIE registry, the consortium is accepting applications for new participating centers. Any nonprofit institution that meets certain criteria can submit an application to become a project participant.

For more information on AACR Project GENIE, visit the project website or send an email to info@aacrgenie.org.

Genome testing
Photo courtesy of the
National Institute of
General Medical Sciences

The American Association for Cancer Research (AACR) has announced the first public release of cancer genomic data aggregated through the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE).

The data set includes nearly 19,000 de-identified genomic records collected from patients who were treated at 8 international institutions, making it one of the largest public cancer genomic data sets released to date.

The release includes data for 59 major cancer types, including leukemias, lymphomas, and multiple myeloma.

The genomic data and a limited amount of linked clinical data for each patient can be accessed via the AACR Project GENIE cBioPortal or from Sage Bionetworks. (Users must create an account for either site to access the data.)

“We are excited to make publicly available this very large set of clinical-grade, next-generation sequencing data obtained during routine patient care,” said Charles L. Sawyers, MD, AACR Project GENIE Steering Committee chairperson.

“These data were generated as part of routine patient care and, without AACR Project GENIE, they would likely never have been shared with the global cancer research community.”

AACR Project GENIE is a multi-phase, international data-sharing project aimed at catalyzing precision oncology through the development of a registry that aggregates and links clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at multiple institutions.

The newly released data are fully de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

The data are derived from patients whose tumors were genetically sequenced as part of their care at any of the 8 institutions that participated in the first phase of AACR Project GENIE.

The goal of releasing these data to the cancer research community is to aid new research that will accelerate the pace of progress against cancer.

According to AACR, the data can be used to validate gene signatures of drug response or prognosis, identify new patient populations for drugs that are currently available, and uncover new drug targets and biomarkers.

“I am extremely proud that the American Association for Cancer Research, as the coordinating center for AACR Project GENIE, is delivering on its promise to make these important data publicly available just over a year after unveiling the initiative,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

To expand the AACR Project GENIE registry, the consortium is accepting applications for new participating centers. Any nonprofit institution that meets certain criteria can submit an application to become a project participant.

For more information on AACR Project GENIE, visit the project website or send an email to info@aacrgenie.org.

Micrograph showing MF

The US Food and Drug Administration (FDA) has lifted the full clinical hold placed on all clinical trials conducted under the investigational new drug application for pacritinib, an oral kinase inhibitor being developed as a treatment for myelofibrosis (MF).

The FDA placed the hold on pacritinib trials in February 2016 after results from 2 phase 3 trials, PERSIST-1 and PERSIST-2, showed excess mortality in patients who received pacritinib.

Both trials suggested pacritinib can be more effective than the best available therapy for MF.

However, interim overall survival results from PERSIST-2 indicated that pacritinib had a detrimental effect on survival, which was consistent with the results from PERSIST-1.

Due to the full clinical hold, CTI BioPharma withdrew the new drug application for pacritinib while reviewing data from PERSIST-2.

When the FDA enacted the hold, the agency recommended that CTI BioPharma conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, make certain modifications to protocols and study-related documents, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma followed the FDA’s recommendations and submitted a response to the hold that included final clinical study reports for PERSIST-1 and PERSIST-2 and a protocol for a dose-exploration trial. 

The trial, PAC203, should enroll up to approximately 105 patients with primary MF who have failed prior ruxolitinib therapy. The goal is to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of pacritinib at 3 doses: 100 mg once daily, 100 mg twice daily (BID), and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2.

CTI BioPharma said it expects to start the trial in the second quarter of 2017.

“We are pleased to resolve the full clinical hold through working diligently with the FDA to provide a comprehensive response to their requests,” said Richard Love, interim president and chief executive officer of CTI BioPharma.

“We look forward to discussing with the FDA the future development of pacritinib. We believe pacritinib can ultimately address the unmet need of patients with myelofibrosis who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited treatment options.”

Micrograph showing MF

The US Food and Drug Administration (FDA) has lifted the full clinical hold placed on all clinical trials conducted under the investigational new drug application for pacritinib, an oral kinase inhibitor being developed as a treatment for myelofibrosis (MF).

The FDA placed the hold on pacritinib trials in February 2016 after results from 2 phase 3 trials, PERSIST-1 and PERSIST-2, showed excess mortality in patients who received pacritinib.

Both trials suggested pacritinib can be more effective than the best available therapy for MF.

However, interim overall survival results from PERSIST-2 indicated that pacritinib had a detrimental effect on survival, which was consistent with the results from PERSIST-1.

Due to the full clinical hold, CTI BioPharma withdrew the new drug application for pacritinib while reviewing data from PERSIST-2.

When the FDA enacted the hold, the agency recommended that CTI BioPharma conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, make certain modifications to protocols and study-related documents, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma followed the FDA’s recommendations and submitted a response to the hold that included final clinical study reports for PERSIST-1 and PERSIST-2 and a protocol for a dose-exploration trial. 

The trial, PAC203, should enroll up to approximately 105 patients with primary MF who have failed prior ruxolitinib therapy. The goal is to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of pacritinib at 3 doses: 100 mg once daily, 100 mg twice daily (BID), and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2.

CTI BioPharma said it expects to start the trial in the second quarter of 2017.

“We are pleased to resolve the full clinical hold through working diligently with the FDA to provide a comprehensive response to their requests,” said Richard Love, interim president and chief executive officer of CTI BioPharma.

“We look forward to discussing with the FDA the future development of pacritinib. We believe pacritinib can ultimately address the unmet need of patients with myelofibrosis who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited treatment options.”

Micrograph showing MF

The US Food and Drug Administration (FDA) has lifted the full clinical hold placed on all clinical trials conducted under the investigational new drug application for pacritinib, an oral kinase inhibitor being developed as a treatment for myelofibrosis (MF).

The FDA placed the hold on pacritinib trials in February 2016 after results from 2 phase 3 trials, PERSIST-1 and PERSIST-2, showed excess mortality in patients who received pacritinib.

Both trials suggested pacritinib can be more effective than the best available therapy for MF.

However, interim overall survival results from PERSIST-2 indicated that pacritinib had a detrimental effect on survival, which was consistent with the results from PERSIST-1.

Due to the full clinical hold, CTI BioPharma withdrew the new drug application for pacritinib while reviewing data from PERSIST-2.

When the FDA enacted the hold, the agency recommended that CTI BioPharma conduct dose-exploration studies for pacritinib, submit final study reports and data sets for PERSIST-1 and PERSIST-2, make certain modifications to protocols and study-related documents, and request a meeting with the FDA prior to submitting a response to the full clinical hold.

CTI BioPharma followed the FDA’s recommendations and submitted a response to the hold that included final clinical study reports for PERSIST-1 and PERSIST-2 and a protocol for a dose-exploration trial. 

The trial, PAC203, should enroll up to approximately 105 patients with primary MF who have failed prior ruxolitinib therapy. The goal is to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of pacritinib at 3 doses: 100 mg once daily, 100 mg twice daily (BID), and 200 mg BID. The 200 mg BID dose regimen was used in PERSIST-2.

CTI BioPharma said it expects to start the trial in the second quarter of 2017.

“We are pleased to resolve the full clinical hold through working diligently with the FDA to provide a comprehensive response to their requests,” said Richard Love, interim president and chief executive officer of CTI BioPharma.

“We look forward to discussing with the FDA the future development of pacritinib. We believe pacritinib can ultimately address the unmet need of patients with myelofibrosis who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib, as these patients have limited treatment options.”