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Team develops hospital-based Zika test
Photo by Juan D. Alfonso
Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.
Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.
The test can be performed on blood, amniotic fluid, urine, or spinal fluid.
The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.
Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.
Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.
The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.
“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.
“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”
The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area. 
Photo by Juan D. Alfonso
Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.
Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.
The test can be performed on blood, amniotic fluid, urine, or spinal fluid.
The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.
Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.
Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.
The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.
“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.
“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”
The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.
Photo by Juan D. Alfonso
Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.
Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.
The test can be performed on blood, amniotic fluid, urine, or spinal fluid.
The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.
Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.
Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.
The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.
“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.
“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”
The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.
Histone levels may predict thrombocytopenia
Image by Eric Smith
Measuring circulating histones may help physicians predict the onset of thrombocytopenia or allow them to monitor the condition in patients who are critically ill, according to researchers.
They noted that histones induce profound thrombocytopenia in mice and are associated with organ injury when released after extensive cell damage in patients who are critically ill.
So the team decided to examine the association between circulating histones and thrombocytopenia in patients in the intensive care unit (ICU).
Cheng-Hock Toh, MD, of the University of Liverpool in the UK, and his colleagues conducted this research and reported the results in a letter to JAMA.
The researchers analyzed 56 patients with thrombocytopenia and 56 controls with normal platelet counts who were admitted to the ICU at Royal Liverpool University Hospital between June 2013 and January 2014.
Thrombocytopenia was defined as a platelet count less than 150 × 103/µL, a 25% or greater decrease in platelet count, or both within the first 96 hours of ICU admission.
The researchers noted that, at approximately 30 µg/mL, histones bind platelets and cause platelet aggregation, which results in profound thrombocytopenia in mice.
So the team used this as a cutoff to stratify thrombocytopenic patients. A “high” level of histones was 30 µg/mL or greater, and a “low” level was below 30 µg/mL.
The researchers detected circulating histones in 51 of the thrombocytopenic patients and 31 controls—91% and 55%, respectively (P<0.001). Histone levels were 2.5- to 5.5-fold higher in thrombocytopenic patients than in controls.
Thrombocytopenic patients with high histone levels at ICU admission had significantly lower platelet counts and a significantly higher percentage of decrease in platelet counts at 24 hours (P=0.02 and P=0.04, respectively) and 48 hours (P=0.003 and P=0.005, respectively) after admission.
High admission histone levels were associated with moderate to severe thrombocytopenia and the development of clinically important thrombocytopenia (P<0.001).
A 30 µg/mL histone concentration was able to predict thrombocytopenia with 76% sensitivity and 91% specificity. The positive predictive value was 79.4%, and the negative predictive value was 89.2%.
Image by Eric Smith
Measuring circulating histones may help physicians predict the onset of thrombocytopenia or allow them to monitor the condition in patients who are critically ill, according to researchers.
They noted that histones induce profound thrombocytopenia in mice and are associated with organ injury when released after extensive cell damage in patients who are critically ill.
So the team decided to examine the association between circulating histones and thrombocytopenia in patients in the intensive care unit (ICU).
Cheng-Hock Toh, MD, of the University of Liverpool in the UK, and his colleagues conducted this research and reported the results in a letter to JAMA.
The researchers analyzed 56 patients with thrombocytopenia and 56 controls with normal platelet counts who were admitted to the ICU at Royal Liverpool University Hospital between June 2013 and January 2014.
Thrombocytopenia was defined as a platelet count less than 150 × 103/µL, a 25% or greater decrease in platelet count, or both within the first 96 hours of ICU admission.
The researchers noted that, at approximately 30 µg/mL, histones bind platelets and cause platelet aggregation, which results in profound thrombocytopenia in mice.
So the team used this as a cutoff to stratify thrombocytopenic patients. A “high” level of histones was 30 µg/mL or greater, and a “low” level was below 30 µg/mL.
The researchers detected circulating histones in 51 of the thrombocytopenic patients and 31 controls—91% and 55%, respectively (P<0.001). Histone levels were 2.5- to 5.5-fold higher in thrombocytopenic patients than in controls.
Thrombocytopenic patients with high histone levels at ICU admission had significantly lower platelet counts and a significantly higher percentage of decrease in platelet counts at 24 hours (P=0.02 and P=0.04, respectively) and 48 hours (P=0.003 and P=0.005, respectively) after admission.
High admission histone levels were associated with moderate to severe thrombocytopenia and the development of clinically important thrombocytopenia (P<0.001).
A 30 µg/mL histone concentration was able to predict thrombocytopenia with 76% sensitivity and 91% specificity. The positive predictive value was 79.4%, and the negative predictive value was 89.2%.
Image by Eric Smith
Measuring circulating histones may help physicians predict the onset of thrombocytopenia or allow them to monitor the condition in patients who are critically ill, according to researchers.
They noted that histones induce profound thrombocytopenia in mice and are associated with organ injury when released after extensive cell damage in patients who are critically ill.
So the team decided to examine the association between circulating histones and thrombocytopenia in patients in the intensive care unit (ICU).
Cheng-Hock Toh, MD, of the University of Liverpool in the UK, and his colleagues conducted this research and reported the results in a letter to JAMA.
The researchers analyzed 56 patients with thrombocytopenia and 56 controls with normal platelet counts who were admitted to the ICU at Royal Liverpool University Hospital between June 2013 and January 2014.
Thrombocytopenia was defined as a platelet count less than 150 × 103/µL, a 25% or greater decrease in platelet count, or both within the first 96 hours of ICU admission.
The researchers noted that, at approximately 30 µg/mL, histones bind platelets and cause platelet aggregation, which results in profound thrombocytopenia in mice.
So the team used this as a cutoff to stratify thrombocytopenic patients. A “high” level of histones was 30 µg/mL or greater, and a “low” level was below 30 µg/mL.
The researchers detected circulating histones in 51 of the thrombocytopenic patients and 31 controls—91% and 55%, respectively (P<0.001). Histone levels were 2.5- to 5.5-fold higher in thrombocytopenic patients than in controls.
Thrombocytopenic patients with high histone levels at ICU admission had significantly lower platelet counts and a significantly higher percentage of decrease in platelet counts at 24 hours (P=0.02 and P=0.04, respectively) and 48 hours (P=0.003 and P=0.005, respectively) after admission.
High admission histone levels were associated with moderate to severe thrombocytopenia and the development of clinically important thrombocytopenia (P<0.001).
A 30 µg/mL histone concentration was able to predict thrombocytopenia with 76% sensitivity and 91% specificity. The positive predictive value was 79.4%, and the negative predictive value was 89.2%.
Adjunct T-cell therapy granted orphan designation
The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.
The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.
The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.
This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.
Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.
The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.
BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.
About orphan designation
The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.
Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.
The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.
The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.
The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.
This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.
Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.
The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.
BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.
About orphan designation
The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.
Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.
The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.
The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.
The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.
This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.
Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.
The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.
BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.
About orphan designation
The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.
Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.
MSC product may treat refractory aGVHD
HONOLULU—A mesenchymal stem cell (MSC) product has shown promise for treating children with steroid-refractory acute graft-versus-host disease (aGVHD), according to researchers.
The product, remestemcel-L (MSC-100-IV, formerly Prochymal), produced an overall response rate of 65% by 28 days after treatment.
And patients who responded to remestemcel-L had significantly better survival at day 100 than patients who did not respond.
Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina, presented these data at the 2016 BMT Tandem Meetings (abstract 54). The study was sponsored by Mesoblast, the company developing remestemcel-L.
“There is a critical and urgent need for an effective and well-tolerated treatment for the very ill children who develop [GVHD] after a bone marrow transplant,” Dr Kurtzberg said. “While, historically, there is a high mortality rate associated with this complication, we are now seeing the majority of children who receive Mesoblast’s cell therapy respond and survive.”
For this study, Dr Kurtzberg and her colleagues assessed 241 children treated in Mesoblast’s Expanded Access Program, which was conducted at 50 sites in North American and Europe from 2007 to 2014.
Forty-five percent of the children received a bone marrow transplant, 31% received cord blood, and 45% had a mismatched transplant. Their median age was 9.6 (range, 2 months-18 years), 61% were male, and 60% were Caucasian.
All of the patients had steroid-refractory aGVHD. Thirty percent had grade C GVHD, 50% had grade D, 50% had multi-organ disease, and 79% were classified as “high-risk” disease.
Treatment
All 241 children received remestemcel-L, which consists of bone-marrow derived and culture-expanded human MSCs. The initial treatment was 2 million MSCs/kg twice a week for 4 weeks, at least 3 days apart.
Continued treatment consisted of 2 million MSCs/kg once a week for 4 weeks if patients achieved a partial or mixed response (improvement in one organ with deterioration in another organ) at the day-28 assessment.
The patients received a total of 2434 infusions. The median number of infusions was 11 (range, 1-24), and the median duration of treatment was 46 days (range, 1-186). Eighty-one percent (123/152) of eligible patients with a partial or mixed response at day 28 received continued therapy of 1 infusion a week for 4 weeks.
Results
Fifty-seven percent of patients (n=138) had at least 1 serious adverse event. About 5% (n=11) were considered treatment-related, and 1.7% (n=4) led to study discontinuation. There was 1 infusion reaction.
Thirty-four percent of patients (n=81) died through day 100, and 2.5% (n=6) experienced a relapse of their underlying disease.
At day 28 after treatment, the overall response rate was 65%, with a complete response rate of 14% and partial response rate of 51%. Responses were observed for all aGVHD grades and did not differ by baseline organ involvement.
When remestemcel-L was used as front-line therapy following steroid failure, the response rate was 81%. In patients with gastrointestinal and liver disease, the overall response rates were 65% and 62%, respectively.
Children who achieved a response at day 28 had significantly improved survival, compared to those who did not—82% and 39%, respectively (P<0.0001).
Extending therapy beyond day 28 in children who had a mixed response at day 28 resulted in significantly improved survival as well. Survival was 72% for these patients, compared to 18% for patients with a mixed response who did not receive additional therapy (P=0.003).
Mesoblast is now conducting a 60-patient, open label, phase 3 trial using remestemcel-L as front-line therapy in children with steroid-refractory aGVHD.
HONOLULU—A mesenchymal stem cell (MSC) product has shown promise for treating children with steroid-refractory acute graft-versus-host disease (aGVHD), according to researchers.
The product, remestemcel-L (MSC-100-IV, formerly Prochymal), produced an overall response rate of 65% by 28 days after treatment.
And patients who responded to remestemcel-L had significantly better survival at day 100 than patients who did not respond.
Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina, presented these data at the 2016 BMT Tandem Meetings (abstract 54). The study was sponsored by Mesoblast, the company developing remestemcel-L.
“There is a critical and urgent need for an effective and well-tolerated treatment for the very ill children who develop [GVHD] after a bone marrow transplant,” Dr Kurtzberg said. “While, historically, there is a high mortality rate associated with this complication, we are now seeing the majority of children who receive Mesoblast’s cell therapy respond and survive.”
For this study, Dr Kurtzberg and her colleagues assessed 241 children treated in Mesoblast’s Expanded Access Program, which was conducted at 50 sites in North American and Europe from 2007 to 2014.
Forty-five percent of the children received a bone marrow transplant, 31% received cord blood, and 45% had a mismatched transplant. Their median age was 9.6 (range, 2 months-18 years), 61% were male, and 60% were Caucasian.
All of the patients had steroid-refractory aGVHD. Thirty percent had grade C GVHD, 50% had grade D, 50% had multi-organ disease, and 79% were classified as “high-risk” disease.
Treatment
All 241 children received remestemcel-L, which consists of bone-marrow derived and culture-expanded human MSCs. The initial treatment was 2 million MSCs/kg twice a week for 4 weeks, at least 3 days apart.
Continued treatment consisted of 2 million MSCs/kg once a week for 4 weeks if patients achieved a partial or mixed response (improvement in one organ with deterioration in another organ) at the day-28 assessment.
The patients received a total of 2434 infusions. The median number of infusions was 11 (range, 1-24), and the median duration of treatment was 46 days (range, 1-186). Eighty-one percent (123/152) of eligible patients with a partial or mixed response at day 28 received continued therapy of 1 infusion a week for 4 weeks.
Results
Fifty-seven percent of patients (n=138) had at least 1 serious adverse event. About 5% (n=11) were considered treatment-related, and 1.7% (n=4) led to study discontinuation. There was 1 infusion reaction.
Thirty-four percent of patients (n=81) died through day 100, and 2.5% (n=6) experienced a relapse of their underlying disease.
At day 28 after treatment, the overall response rate was 65%, with a complete response rate of 14% and partial response rate of 51%. Responses were observed for all aGVHD grades and did not differ by baseline organ involvement.
When remestemcel-L was used as front-line therapy following steroid failure, the response rate was 81%. In patients with gastrointestinal and liver disease, the overall response rates were 65% and 62%, respectively.
Children who achieved a response at day 28 had significantly improved survival, compared to those who did not—82% and 39%, respectively (P<0.0001).
Extending therapy beyond day 28 in children who had a mixed response at day 28 resulted in significantly improved survival as well. Survival was 72% for these patients, compared to 18% for patients with a mixed response who did not receive additional therapy (P=0.003).
Mesoblast is now conducting a 60-patient, open label, phase 3 trial using remestemcel-L as front-line therapy in children with steroid-refractory aGVHD.
HONOLULU—A mesenchymal stem cell (MSC) product has shown promise for treating children with steroid-refractory acute graft-versus-host disease (aGVHD), according to researchers.
The product, remestemcel-L (MSC-100-IV, formerly Prochymal), produced an overall response rate of 65% by 28 days after treatment.
And patients who responded to remestemcel-L had significantly better survival at day 100 than patients who did not respond.
Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina, presented these data at the 2016 BMT Tandem Meetings (abstract 54). The study was sponsored by Mesoblast, the company developing remestemcel-L.
“There is a critical and urgent need for an effective and well-tolerated treatment for the very ill children who develop [GVHD] after a bone marrow transplant,” Dr Kurtzberg said. “While, historically, there is a high mortality rate associated with this complication, we are now seeing the majority of children who receive Mesoblast’s cell therapy respond and survive.”
For this study, Dr Kurtzberg and her colleagues assessed 241 children treated in Mesoblast’s Expanded Access Program, which was conducted at 50 sites in North American and Europe from 2007 to 2014.
Forty-five percent of the children received a bone marrow transplant, 31% received cord blood, and 45% had a mismatched transplant. Their median age was 9.6 (range, 2 months-18 years), 61% were male, and 60% were Caucasian.
All of the patients had steroid-refractory aGVHD. Thirty percent had grade C GVHD, 50% had grade D, 50% had multi-organ disease, and 79% were classified as “high-risk” disease.
Treatment
All 241 children received remestemcel-L, which consists of bone-marrow derived and culture-expanded human MSCs. The initial treatment was 2 million MSCs/kg twice a week for 4 weeks, at least 3 days apart.
Continued treatment consisted of 2 million MSCs/kg once a week for 4 weeks if patients achieved a partial or mixed response (improvement in one organ with deterioration in another organ) at the day-28 assessment.
The patients received a total of 2434 infusions. The median number of infusions was 11 (range, 1-24), and the median duration of treatment was 46 days (range, 1-186). Eighty-one percent (123/152) of eligible patients with a partial or mixed response at day 28 received continued therapy of 1 infusion a week for 4 weeks.
Results
Fifty-seven percent of patients (n=138) had at least 1 serious adverse event. About 5% (n=11) were considered treatment-related, and 1.7% (n=4) led to study discontinuation. There was 1 infusion reaction.
Thirty-four percent of patients (n=81) died through day 100, and 2.5% (n=6) experienced a relapse of their underlying disease.
At day 28 after treatment, the overall response rate was 65%, with a complete response rate of 14% and partial response rate of 51%. Responses were observed for all aGVHD grades and did not differ by baseline organ involvement.
When remestemcel-L was used as front-line therapy following steroid failure, the response rate was 81%. In patients with gastrointestinal and liver disease, the overall response rates were 65% and 62%, respectively.
Children who achieved a response at day 28 had significantly improved survival, compared to those who did not—82% and 39%, respectively (P<0.0001).
Extending therapy beyond day 28 in children who had a mixed response at day 28 resulted in significantly improved survival as well. Survival was 72% for these patients, compared to 18% for patients with a mixed response who did not receive additional therapy (P=0.003).
Mesoblast is now conducting a 60-patient, open label, phase 3 trial using remestemcel-L as front-line therapy in children with steroid-refractory aGVHD.
Poverty tied to early relapse in kids with ALL
Photo by Logan Tuttle
A new study suggests children with acute lymphoblastic leukemia (ALL) are more likely to suffer early relapse if they live in high-poverty areas.
All of the children studied received the same treatment, and the rates of relapse were similar regardless of poverty level.
But early relapse was more common among children from poorer areas. These children also had a lower rate of 5-year overall survival, but the difference was not significant.
Kira Bona, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues reported these results in Pediatric Blood & Cancer.
The team examined outcomes for 575 children, ages 1 to 18, with newly diagnosed ALL who were treated on Dana-Farber Cancer Institute ALL Consortium Protocols at 7 major academic medical centers in the US between 2000 and 2010.
Using US Census Bureau criteria, the investigators defined high-poverty areas as zip codes where 20% or more of residents have incomes below the federal poverty level. For a family of 4, this translates to an annual income of $24,250 or less.
Dr Bona and her colleagues found the overall rates of relapse were similar between children from low-poverty areas and those from high-poverty areas.
However, the timing of relapse differed significantly. Ninety-two percent of children from high-poverty areas who relapsed suffered early relapse (less than 36 months after first achieving complete remission), while 48% of the other children who relapsed did so early (P=0.008).
The 5-year overall survival was 85% for children from high-poverty areas and 92% for children from low-poverty areas. This difference is statistically significant when considered on its own (P=0.02) but not when the analysis is adjusted for other factors (P=0.07).
Still, the investigators said this suggests a possible disparity in survival.
“These children are getting the same best possible care at well-resourced institutions from highly trained clinicians, and we’re still seeing disparities,” Dr Bona said. “In trying to improve cure rates, we, as a field, have focused almost exclusively on biology. If we want to move forward, we also have to look at social determinants.”
Next steps
Dr Bona and her colleagues are undertaking further research designed to delve deeper into the relationship between socioeconomic status and outcomes and to allow for the development of poverty-targeted interventions.
As part of a prospective trial for children with ALL, the researchers will investigate associations between disease outcomes and the socioeconomic status of patients’ families, using a targetable measure of socioeconomic status called material hardship (food, housing, and/or energy insecurity).
The researchers will also investigate possible mechanisms underlying the relationship between socioeconomic status and early relapse, including adherence to oral chemotherapy and delays or dose reductions in chemotherapy due to a child’s underlying health.
In another study, investigators will conduct in-depth interviews with patients’ families, probing their knowledge and experience to pinpoint factors that might explain the disparity in outcomes and identify factors that can be targeted with interventions.
“Doing these next 2 studies is incredibly important,” Dr Bona said. “This study told us that simply providing the current best treatment regimen is not good enough if our goal is to cure every child with cancer.”
“At the same time that we develop new drugs and new treatment protocols, we need to address social determinants of health. Findings from these next studies will help us develop specific interventions to address disparities in outcomes. That’s an amazing opportunity.”
Photo by Logan Tuttle
A new study suggests children with acute lymphoblastic leukemia (ALL) are more likely to suffer early relapse if they live in high-poverty areas.
All of the children studied received the same treatment, and the rates of relapse were similar regardless of poverty level.
But early relapse was more common among children from poorer areas. These children also had a lower rate of 5-year overall survival, but the difference was not significant.
Kira Bona, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues reported these results in Pediatric Blood & Cancer.
The team examined outcomes for 575 children, ages 1 to 18, with newly diagnosed ALL who were treated on Dana-Farber Cancer Institute ALL Consortium Protocols at 7 major academic medical centers in the US between 2000 and 2010.
Using US Census Bureau criteria, the investigators defined high-poverty areas as zip codes where 20% or more of residents have incomes below the federal poverty level. For a family of 4, this translates to an annual income of $24,250 or less.
Dr Bona and her colleagues found the overall rates of relapse were similar between children from low-poverty areas and those from high-poverty areas.
However, the timing of relapse differed significantly. Ninety-two percent of children from high-poverty areas who relapsed suffered early relapse (less than 36 months after first achieving complete remission), while 48% of the other children who relapsed did so early (P=0.008).
The 5-year overall survival was 85% for children from high-poverty areas and 92% for children from low-poverty areas. This difference is statistically significant when considered on its own (P=0.02) but not when the analysis is adjusted for other factors (P=0.07).
Still, the investigators said this suggests a possible disparity in survival.
“These children are getting the same best possible care at well-resourced institutions from highly trained clinicians, and we’re still seeing disparities,” Dr Bona said. “In trying to improve cure rates, we, as a field, have focused almost exclusively on biology. If we want to move forward, we also have to look at social determinants.”
Next steps
Dr Bona and her colleagues are undertaking further research designed to delve deeper into the relationship between socioeconomic status and outcomes and to allow for the development of poverty-targeted interventions.
As part of a prospective trial for children with ALL, the researchers will investigate associations between disease outcomes and the socioeconomic status of patients’ families, using a targetable measure of socioeconomic status called material hardship (food, housing, and/or energy insecurity).
The researchers will also investigate possible mechanisms underlying the relationship between socioeconomic status and early relapse, including adherence to oral chemotherapy and delays or dose reductions in chemotherapy due to a child’s underlying health.
In another study, investigators will conduct in-depth interviews with patients’ families, probing their knowledge and experience to pinpoint factors that might explain the disparity in outcomes and identify factors that can be targeted with interventions.
“Doing these next 2 studies is incredibly important,” Dr Bona said. “This study told us that simply providing the current best treatment regimen is not good enough if our goal is to cure every child with cancer.”
“At the same time that we develop new drugs and new treatment protocols, we need to address social determinants of health. Findings from these next studies will help us develop specific interventions to address disparities in outcomes. That’s an amazing opportunity.”
Photo by Logan Tuttle
A new study suggests children with acute lymphoblastic leukemia (ALL) are more likely to suffer early relapse if they live in high-poverty areas.
All of the children studied received the same treatment, and the rates of relapse were similar regardless of poverty level.
But early relapse was more common among children from poorer areas. These children also had a lower rate of 5-year overall survival, but the difference was not significant.
Kira Bona, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues reported these results in Pediatric Blood & Cancer.
The team examined outcomes for 575 children, ages 1 to 18, with newly diagnosed ALL who were treated on Dana-Farber Cancer Institute ALL Consortium Protocols at 7 major academic medical centers in the US between 2000 and 2010.
Using US Census Bureau criteria, the investigators defined high-poverty areas as zip codes where 20% or more of residents have incomes below the federal poverty level. For a family of 4, this translates to an annual income of $24,250 or less.
Dr Bona and her colleagues found the overall rates of relapse were similar between children from low-poverty areas and those from high-poverty areas.
However, the timing of relapse differed significantly. Ninety-two percent of children from high-poverty areas who relapsed suffered early relapse (less than 36 months after first achieving complete remission), while 48% of the other children who relapsed did so early (P=0.008).
The 5-year overall survival was 85% for children from high-poverty areas and 92% for children from low-poverty areas. This difference is statistically significant when considered on its own (P=0.02) but not when the analysis is adjusted for other factors (P=0.07).
Still, the investigators said this suggests a possible disparity in survival.
“These children are getting the same best possible care at well-resourced institutions from highly trained clinicians, and we’re still seeing disparities,” Dr Bona said. “In trying to improve cure rates, we, as a field, have focused almost exclusively on biology. If we want to move forward, we also have to look at social determinants.”
Next steps
Dr Bona and her colleagues are undertaking further research designed to delve deeper into the relationship between socioeconomic status and outcomes and to allow for the development of poverty-targeted interventions.
As part of a prospective trial for children with ALL, the researchers will investigate associations between disease outcomes and the socioeconomic status of patients’ families, using a targetable measure of socioeconomic status called material hardship (food, housing, and/or energy insecurity).
The researchers will also investigate possible mechanisms underlying the relationship between socioeconomic status and early relapse, including adherence to oral chemotherapy and delays or dose reductions in chemotherapy due to a child’s underlying health.
In another study, investigators will conduct in-depth interviews with patients’ families, probing their knowledge and experience to pinpoint factors that might explain the disparity in outcomes and identify factors that can be targeted with interventions.
“Doing these next 2 studies is incredibly important,” Dr Bona said. “This study told us that simply providing the current best treatment regimen is not good enough if our goal is to cure every child with cancer.”
“At the same time that we develop new drugs and new treatment protocols, we need to address social determinants of health. Findings from these next studies will help us develop specific interventions to address disparities in outcomes. That’s an amazing opportunity.”
Product approved to treat hemophilia A in EU
The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.
The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.
The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.
LEOPOLD I
LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.
The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD II
LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).
The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD Kids
LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.
For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.
Safety results
For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.
The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.
The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).
None of the patients developed factor VIII inhibitors.
The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.
The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.
The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.
LEOPOLD I
LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.
The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD II
LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).
The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD Kids
LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.
For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.
Safety results
For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.
The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.
The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).
None of the patients developed factor VIII inhibitors.
The European Commission has approved a full-length recombinant factor VIII product for the treatment and prevention of bleeding in hemophilia A patients of all ages.
The product, Kovaltry (formerly BAY 81-8973), will be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The approval of Kovaltry is based on results from the LEOPOLD trials—3 multinational trials of patients with severe hemophilia A.
The trials were supported by Bayer HealthCare AG, the company developing Kovaltry.
LEOPOLD I
LEOPOLD I is an open-label, cross-over, phase 3 study of males, ages 12 to 65, with severe hemophilia A. Sixty-two patients were assigned to either 2- or 3-times-weekly dosing with Kovaltry, based on each patient’s phenotype, prior bleeding history, and other factors.
The median annualized bleeding rate (ABR) was 1.0 for all the patients who received Kovaltry prophylaxis, 1.0 for patients who received twice-weekly prophylaxis, and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD II
LEOPOLD II is a randomized, cross-over, open-label trial conducted in males ages 12 to 65. In this phase 3 study, 80 subjects were randomized to receive Kovaltry as a low-dose prophylaxis regimen (n=28) twice per week, high-dose prophylaxis (n=31) 3 times a week, or on-demand treatment (n=21).
The median ABR was significantly lower in patients who received either prophylactic regimen than those who received on-demand treatment—2.0 and 60.0, respectively (P<0.0001). The median ABR was 4.0 for patients who received twice-weekly prophylaxis and 2.0 for patients who received thrice-weekly prophylaxis.
LEOPOLD Kids
LEOPOLD Kids is an open-label, non-randomized, phase 3 study designed to evaluate Kovaltry in children age 12 and younger. The study is divided into 2 parts. Part A enrolled only previously treated children, and part B, which is ongoing, includes only untreated children.
For part A, 51 children received Kovaltry twice a week, 3 times a week, or every other day (according to investigator decision) for at least 50 exposure days. The median ABR within 48 hours of prophylactic injection was 0, and the median ABR independent of the time of injection was 1.9.
Safety results
For all 3 trials, 193 patients were evaluable for safety. Adverse reactions were defined as treatment-emergent adverse events with at least a reasonable suspected causal relationship to Kovaltry.
The researchers said the frequency, type, and severity of adverse reactions in children were similar to those observed in adults and adolescents.
The adverse reactions included headache (7.3%), pyrexia (4.1%), pruritus (3.1%), injection site reactions (2.6%), insomnia (2.6%), rash (2.6%), abdominal pain (2.1%), dyspepsia (2.1%), abdominal discomfort (1.6%), lymphadenopathy (1%), dizziness (1%), allergic dermatitis (1%), heart palpitations (1%), sinus tachycardia (1%), chest discomfort (1%), hypersensitivity (0.5%), dysgeusia (0.5%), urticaria (0.5%), and flushing (0.5%).
None of the patients developed factor VIII inhibitors.
Antiplatelet agent approved for long-term use
Photo courtesy of the CDC
The European Commission has approved use of the antiplatelet agent ticagrelor (Brilique) at a 60 mg dose to treat patients beyond the first year after a heart attack who are at high risk of developing a further atherothrombotic event.
The treatment may be used as continuation therapy after an initial 1-year treatment with 90 mg ticagrelor plus aspirin or after a year of other dual antiplatelet therapy.
This approval is applicable to all 28 European Union (EU) member countries plus Iceland, Norway, and Liechtenstein.
Ticagrelor at a 90 mg dose is already approved in the EU for the prevention of atherothrombotic events in adults with acute coronary syndrome (ACS). In the management of ACS, the recommended maintenance dose of ticagrelor is 90 mg twice daily during the first year after an ACS event.
Now, after the first year, patients with a history of heart attack can continue to be treated with ticagrelor at 60 mg twice daily, which should be taken with a daily maintenance dose of aspirin at 75 mg to 150 mg.
Trial results
The latest EU approval of ticagrelor was based on results from the PEGASUS TIMI-54 study. This trial, which involved more than 21,000 patients, was presented at the American College of Cardiology Congress in March 2015 and simultaneously published in NEJM.
Investigators compared ticagrelor (at 60 mg or 90 mg) plus low-dose aspirin to placebo plus low-dose aspirin in patients who had experienced a heart attack 1 to 3 years prior to study enrollment.
The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke.
The investigators found that patients in either ticagrelor arm were significantly less likely to achieve this endpoint than placebo-treated patients.
At 3 years, the proportion of patients meeting the primary endpoint was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).
Patients receiving ticagrelor also had a significantly higher incidence of major bleeding and dyspnea. The rate of TIMI major bleeding was 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).
The rate of dyspnea was 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for both comparisons). The rate of dyspnea leading to treatment discontinuation was 6.5%, 4.55%, and 0.79%, respectively (P<0.001 for both comparisons).
Ticagrelor has been approved in more than 100 countries. The drug is under development by AstraZeneca.
Photo courtesy of the CDC
The European Commission has approved use of the antiplatelet agent ticagrelor (Brilique) at a 60 mg dose to treat patients beyond the first year after a heart attack who are at high risk of developing a further atherothrombotic event.
The treatment may be used as continuation therapy after an initial 1-year treatment with 90 mg ticagrelor plus aspirin or after a year of other dual antiplatelet therapy.
This approval is applicable to all 28 European Union (EU) member countries plus Iceland, Norway, and Liechtenstein.
Ticagrelor at a 90 mg dose is already approved in the EU for the prevention of atherothrombotic events in adults with acute coronary syndrome (ACS). In the management of ACS, the recommended maintenance dose of ticagrelor is 90 mg twice daily during the first year after an ACS event.
Now, after the first year, patients with a history of heart attack can continue to be treated with ticagrelor at 60 mg twice daily, which should be taken with a daily maintenance dose of aspirin at 75 mg to 150 mg.
Trial results
The latest EU approval of ticagrelor was based on results from the PEGASUS TIMI-54 study. This trial, which involved more than 21,000 patients, was presented at the American College of Cardiology Congress in March 2015 and simultaneously published in NEJM.
Investigators compared ticagrelor (at 60 mg or 90 mg) plus low-dose aspirin to placebo plus low-dose aspirin in patients who had experienced a heart attack 1 to 3 years prior to study enrollment.
The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke.
The investigators found that patients in either ticagrelor arm were significantly less likely to achieve this endpoint than placebo-treated patients.
At 3 years, the proportion of patients meeting the primary endpoint was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).
Patients receiving ticagrelor also had a significantly higher incidence of major bleeding and dyspnea. The rate of TIMI major bleeding was 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).
The rate of dyspnea was 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for both comparisons). The rate of dyspnea leading to treatment discontinuation was 6.5%, 4.55%, and 0.79%, respectively (P<0.001 for both comparisons).
Ticagrelor has been approved in more than 100 countries. The drug is under development by AstraZeneca.
Photo courtesy of the CDC
The European Commission has approved use of the antiplatelet agent ticagrelor (Brilique) at a 60 mg dose to treat patients beyond the first year after a heart attack who are at high risk of developing a further atherothrombotic event.
The treatment may be used as continuation therapy after an initial 1-year treatment with 90 mg ticagrelor plus aspirin or after a year of other dual antiplatelet therapy.
This approval is applicable to all 28 European Union (EU) member countries plus Iceland, Norway, and Liechtenstein.
Ticagrelor at a 90 mg dose is already approved in the EU for the prevention of atherothrombotic events in adults with acute coronary syndrome (ACS). In the management of ACS, the recommended maintenance dose of ticagrelor is 90 mg twice daily during the first year after an ACS event.
Now, after the first year, patients with a history of heart attack can continue to be treated with ticagrelor at 60 mg twice daily, which should be taken with a daily maintenance dose of aspirin at 75 mg to 150 mg.
Trial results
The latest EU approval of ticagrelor was based on results from the PEGASUS TIMI-54 study. This trial, which involved more than 21,000 patients, was presented at the American College of Cardiology Congress in March 2015 and simultaneously published in NEJM.
Investigators compared ticagrelor (at 60 mg or 90 mg) plus low-dose aspirin to placebo plus low-dose aspirin in patients who had experienced a heart attack 1 to 3 years prior to study enrollment.
The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, or stroke.
The investigators found that patients in either ticagrelor arm were significantly less likely to achieve this endpoint than placebo-treated patients.
At 3 years, the proportion of patients meeting the primary endpoint was 7.85% in the 90 mg group, 7.77% in the 60 mg group, and 9.04% in the placebo group (P=0.008 for 90 mg vs placebo and P=0.004 for 60 mg vs placebo).
Patients receiving ticagrelor also had a significantly higher incidence of major bleeding and dyspnea. The rate of TIMI major bleeding was 2.60% in the 90 mg group, 2.30% in the 60 mg group, and 1.06% in the placebo group (P<0.001 for each ticagrelor dose vs placebo).
The rate of dyspnea was 18.93% in the 90 mg group, 15.84% in 60 mg group, and 6.38% in the placebo group (P<0.001 for both comparisons). The rate of dyspnea leading to treatment discontinuation was 6.5%, 4.55%, and 0.79%, respectively (P<0.001 for both comparisons).
Ticagrelor has been approved in more than 100 countries. The drug is under development by AstraZeneca.
How an anticancer drug fights lymphoid malignancies
Photo by Cameron Wells,
Walter and Eliza Hall
Institute of Medical Research
Research published in Cell Reports helps explain how the anticancer agent Nutlin3a fights lymphoma and other hematologic malignancies.
Nutlin3a is known to activate the tumor suppressor p53, but it hasn’t been clear exactly which p53 target genes are essential for the drug’s therapeutic activity.
The new research revealed that PUMA-mediated apoptosis—not p21-mediated cell-cycle arrest or senescence—is responsible for Nutlin3a’s therapeutic activity in lymphoid malignancies.
“By understanding how nutlins are killing cancer cells, we can begin to formulate their best possible use, including choosing the best partner drugs to combine the nutlins with,” said study author Andreas Strasser, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.
With this study, Dr Strasser and his colleagues first found that Nutlin3a activates p53 target gene expression and causes cell-cycle arrest and apoptosis in non-transformed mouse lymphoid cells in vitro.
The team then showed that Nutlin3a-mediated killing of these cells requires PUMA but not p21. In vivo, loss of PUMA protected non-transformed mouse lymphoid cells against Nutlin3a-induced killing. Loss of p21 did not provide the same protection.
Next, the researchers found that malignant Eµ-Myc lymphoma cells were much more sensitive to Nutlin3a than were non-transformed lymphoid cells. In vitro experiments with Eµ-Myc lymphoma cells showed that Nutlin3a promotes p53 accumulation and downstream effector pathway activation.
As in previous experiments, PUMA (not p21) proved critical for Nutlin3a-induced killing of Eµ-Myc lymphoma cells in vitro. And loss of PUMA (but not p21) impaired the regression of Eµ-Myc lymphomas induced by Nutlin3a in vivo.
Finally, the researchers found that PUMA contributed to Nutlin3a-induced apoptosis in myeloid leukemia, multiple myeloma, and Burkitt lymphoma cell lines.
The team noted that, because PUMA, a pro-apoptotic BH3-only protein, is critical for the therapeutic impact of Nutlin3a, it may be possible to boost the drug’s efficacy by combining it with BH3 mimetic drugs such as navitoclax or venetoclax.
Photo by Cameron Wells,
Walter and Eliza Hall
Institute of Medical Research
Research published in Cell Reports helps explain how the anticancer agent Nutlin3a fights lymphoma and other hematologic malignancies.
Nutlin3a is known to activate the tumor suppressor p53, but it hasn’t been clear exactly which p53 target genes are essential for the drug’s therapeutic activity.
The new research revealed that PUMA-mediated apoptosis—not p21-mediated cell-cycle arrest or senescence—is responsible for Nutlin3a’s therapeutic activity in lymphoid malignancies.
“By understanding how nutlins are killing cancer cells, we can begin to formulate their best possible use, including choosing the best partner drugs to combine the nutlins with,” said study author Andreas Strasser, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.
With this study, Dr Strasser and his colleagues first found that Nutlin3a activates p53 target gene expression and causes cell-cycle arrest and apoptosis in non-transformed mouse lymphoid cells in vitro.
The team then showed that Nutlin3a-mediated killing of these cells requires PUMA but not p21. In vivo, loss of PUMA protected non-transformed mouse lymphoid cells against Nutlin3a-induced killing. Loss of p21 did not provide the same protection.
Next, the researchers found that malignant Eµ-Myc lymphoma cells were much more sensitive to Nutlin3a than were non-transformed lymphoid cells. In vitro experiments with Eµ-Myc lymphoma cells showed that Nutlin3a promotes p53 accumulation and downstream effector pathway activation.
As in previous experiments, PUMA (not p21) proved critical for Nutlin3a-induced killing of Eµ-Myc lymphoma cells in vitro. And loss of PUMA (but not p21) impaired the regression of Eµ-Myc lymphomas induced by Nutlin3a in vivo.
Finally, the researchers found that PUMA contributed to Nutlin3a-induced apoptosis in myeloid leukemia, multiple myeloma, and Burkitt lymphoma cell lines.
The team noted that, because PUMA, a pro-apoptotic BH3-only protein, is critical for the therapeutic impact of Nutlin3a, it may be possible to boost the drug’s efficacy by combining it with BH3 mimetic drugs such as navitoclax or venetoclax.
Photo by Cameron Wells,
Walter and Eliza Hall
Institute of Medical Research
Research published in Cell Reports helps explain how the anticancer agent Nutlin3a fights lymphoma and other hematologic malignancies.
Nutlin3a is known to activate the tumor suppressor p53, but it hasn’t been clear exactly which p53 target genes are essential for the drug’s therapeutic activity.
The new research revealed that PUMA-mediated apoptosis—not p21-mediated cell-cycle arrest or senescence—is responsible for Nutlin3a’s therapeutic activity in lymphoid malignancies.
“By understanding how nutlins are killing cancer cells, we can begin to formulate their best possible use, including choosing the best partner drugs to combine the nutlins with,” said study author Andreas Strasser, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.
With this study, Dr Strasser and his colleagues first found that Nutlin3a activates p53 target gene expression and causes cell-cycle arrest and apoptosis in non-transformed mouse lymphoid cells in vitro.
The team then showed that Nutlin3a-mediated killing of these cells requires PUMA but not p21. In vivo, loss of PUMA protected non-transformed mouse lymphoid cells against Nutlin3a-induced killing. Loss of p21 did not provide the same protection.
Next, the researchers found that malignant Eµ-Myc lymphoma cells were much more sensitive to Nutlin3a than were non-transformed lymphoid cells. In vitro experiments with Eµ-Myc lymphoma cells showed that Nutlin3a promotes p53 accumulation and downstream effector pathway activation.
As in previous experiments, PUMA (not p21) proved critical for Nutlin3a-induced killing of Eµ-Myc lymphoma cells in vitro. And loss of PUMA (but not p21) impaired the regression of Eµ-Myc lymphomas induced by Nutlin3a in vivo.
Finally, the researchers found that PUMA contributed to Nutlin3a-induced apoptosis in myeloid leukemia, multiple myeloma, and Burkitt lymphoma cell lines.
The team noted that, because PUMA, a pro-apoptotic BH3-only protein, is critical for the therapeutic impact of Nutlin3a, it may be possible to boost the drug’s efficacy by combining it with BH3 mimetic drugs such as navitoclax or venetoclax.
Drug may still be viable as CMV prophylaxis
Photo by Chad McNeeley
HONOLULU—Despite disappointing results in a phase 3 trial, investigators believe the oral nucleotide analog brincidofovir may still be viable as cytomegalovirus (CMV) prophylaxis in patients undergoing hematopoietic stem cell transplant (HSCT).
As reported last December, brincidofovir did not meet the primary endpoint of the phase 3 SUPPRESS trial, which was to prevent clinically significant CMV infection at week 24 after HSCT.
However, trial investigators said the drug did prevent CMV through week 14, which was the end of the treatment period.
The team believes they have an explanation for these findings, which were presented at the 2016 BMT Tandem Meetings (abstract 5). The trial was supported by Chimerix, the company developing brincidofovir.
The SUPPRESS trial included 452 subjects at high risk for CMV who were randomized to receive brincidofovir or placebo twice weekly for up to 14 weeks following allogeneic HSCT. They were then followed for 10 weeks after treatment.
Baseline characteristics were similar between the treatment arms, although there were more males in the placebo arm than the brincidofovir arm—66% and 54%, respectively. The median age was 56 in the brincidofovir arm and 54 in the placebo arm (overall range, 18-77).
Key results
The primary endpoint was assessed at week 24. At that time, the proportion of patients with clinically significant CMV infection was similar in the brincidofovir and placebo arms—51% and 52%, respectively.
However, the investigators did note that brincidofovir exhibited an antiviral effect during the trial. At the end of the on-treatment period at week 14, patients who received brincidofovir had fewer clinically significant CMV infections than patients in the placebo group—24% and 38%, respectively (P=0.002).
The investigators said the failure to meet the primary endpoint at week 24 appears to be associated with CMV events in the post-treatment period among subjects on the brincidofovir arm, driven by higher use of corticosteroids and other immunosuppressive therapies for the treatment of presumptive graft-versus-host disease (GVHD).
Diarrhea can be a symptom of GVHD in the gut and is also a known side effect of brincidofovir that can be managed by a temporary dose interruption, as described in the safety monitoring and management plan (SMMP) developed during the phase 2 trial of the drug (then known as CMX001).
In the SUPPRESS trial, diarrhea in brincidofovir-treated patients was more frequent and often presumed to be gut GVHD. So patients were treated with corticosteroids rather than undergoing temporary treatment interruption according to the SMMP. Among patients who were managed according to the SMMP, the investigators observed significantly fewer CMV infections (P=0.03) and lower mortality (P<0.001).
There was an 8-fold increase in the use of corticosteroids through week 14 in the brincidofovir arm compared to the placebo arm. The median cumulative dose of prednisone-equivalent corticosteroids was 26 mg/kg and 3 mg/kg, respectively.
The use of corticosteroids and other immunosuppressive therapies for the treatment of GVHD is known to increase the risk of infections, including CMV infections that occur when patients discontinue antiviral therapy.
Among patients who either underwent T-cell depletion or received alemtuzumab/ATG to decrease the risk of GVHD, those who were randomized to receive brincidofovir showed a lower incidence of CMV when compared to placebo, at a rate consistent with what was observed in the phase 2 study.
Additional endpoints
Brincidofovir did not prevent infection with non-CMV DNA viruses, such as BK virus.
And there was no significant difference between the treatment arms with regard to all-cause mortality. The rate was 15.5% in the brincidofovir arm and 10.1% in the placebo arm (P=0.12).
The investigators said the numerical differences in mortality appear to be driven by higher use of corticosteroids and other immunosuppressive therapies in the subjects who received brincidofovir.
The rate of treatment-emergent adverse events (AEs) was 100% in the brincidofovir arm and 98% in the placebo arm. The rate of grade 3 or higher AEs was 67% and 38%, respectively. The rate of serious AEs was 57% and 38%, respectively.
The rate of AEs leading to treatment discontinuation was 26% and 7%, respectively. And the rate of AEs leading to treatment change or interruption was 45% and 15%, respectively.
The most common AEs in the brincidofovir arm were diarrhea (61%), acute GVHD (57%), abdominal pain (34%), nausea (31%), vomiting (24%), peripheral edema (17%), hyperglycemia (16%), hypokalemia (16%), hypomagnesemia (13%), and ALT elevation (11%). There was no evidence of bone marrow toxicity, kidney toxicity, or viral resistance to brincidofovir.
Brincidofovir development
Chimerix said it will discuss the SUPPRESS data in full with the US Food and Drug Administration and other regulators, including the benefit-to-risk profile in specific subpopulations, as well as the current adenovirus and smallpox data, to determine next steps for the brincidofovir clinical programs.
The development of an intravenous (IV) formulation of brincidofovir is progressing toward clinical testing and has the potential to avoid the gastrointestinal side effects of orally administered brincidofovir.
Preclinical studies of IV brincidofovir have shown a lower risk of gastrointestinal effects based on maintained body weight during dosing and no evidence of injury in preliminary review of the gastrointestinal tract.
If human studies continue to support these findings, IV dosing during the first few weeks after transplant when patients are recovering from conditioning chemotherapy could be explored, with oral brincidofovir therapy available as patients are discharged home.
As there is no preventive therapy approved for CMV in HSCT recipients, Chimerix said it is committed to moving brincidofovir forward in this indication. Plans for brincidofovir in HSCT recipients will be the subject of further discussions with regulators.
Photo by Chad McNeeley
HONOLULU—Despite disappointing results in a phase 3 trial, investigators believe the oral nucleotide analog brincidofovir may still be viable as cytomegalovirus (CMV) prophylaxis in patients undergoing hematopoietic stem cell transplant (HSCT).
As reported last December, brincidofovir did not meet the primary endpoint of the phase 3 SUPPRESS trial, which was to prevent clinically significant CMV infection at week 24 after HSCT.
However, trial investigators said the drug did prevent CMV through week 14, which was the end of the treatment period.
The team believes they have an explanation for these findings, which were presented at the 2016 BMT Tandem Meetings (abstract 5). The trial was supported by Chimerix, the company developing brincidofovir.
The SUPPRESS trial included 452 subjects at high risk for CMV who were randomized to receive brincidofovir or placebo twice weekly for up to 14 weeks following allogeneic HSCT. They were then followed for 10 weeks after treatment.
Baseline characteristics were similar between the treatment arms, although there were more males in the placebo arm than the brincidofovir arm—66% and 54%, respectively. The median age was 56 in the brincidofovir arm and 54 in the placebo arm (overall range, 18-77).
Key results
The primary endpoint was assessed at week 24. At that time, the proportion of patients with clinically significant CMV infection was similar in the brincidofovir and placebo arms—51% and 52%, respectively.
However, the investigators did note that brincidofovir exhibited an antiviral effect during the trial. At the end of the on-treatment period at week 14, patients who received brincidofovir had fewer clinically significant CMV infections than patients in the placebo group—24% and 38%, respectively (P=0.002).
The investigators said the failure to meet the primary endpoint at week 24 appears to be associated with CMV events in the post-treatment period among subjects on the brincidofovir arm, driven by higher use of corticosteroids and other immunosuppressive therapies for the treatment of presumptive graft-versus-host disease (GVHD).
Diarrhea can be a symptom of GVHD in the gut and is also a known side effect of brincidofovir that can be managed by a temporary dose interruption, as described in the safety monitoring and management plan (SMMP) developed during the phase 2 trial of the drug (then known as CMX001).
In the SUPPRESS trial, diarrhea in brincidofovir-treated patients was more frequent and often presumed to be gut GVHD. So patients were treated with corticosteroids rather than undergoing temporary treatment interruption according to the SMMP. Among patients who were managed according to the SMMP, the investigators observed significantly fewer CMV infections (P=0.03) and lower mortality (P<0.001).
There was an 8-fold increase in the use of corticosteroids through week 14 in the brincidofovir arm compared to the placebo arm. The median cumulative dose of prednisone-equivalent corticosteroids was 26 mg/kg and 3 mg/kg, respectively.
The use of corticosteroids and other immunosuppressive therapies for the treatment of GVHD is known to increase the risk of infections, including CMV infections that occur when patients discontinue antiviral therapy.
Among patients who either underwent T-cell depletion or received alemtuzumab/ATG to decrease the risk of GVHD, those who were randomized to receive brincidofovir showed a lower incidence of CMV when compared to placebo, at a rate consistent with what was observed in the phase 2 study.
Additional endpoints
Brincidofovir did not prevent infection with non-CMV DNA viruses, such as BK virus.
And there was no significant difference between the treatment arms with regard to all-cause mortality. The rate was 15.5% in the brincidofovir arm and 10.1% in the placebo arm (P=0.12).
The investigators said the numerical differences in mortality appear to be driven by higher use of corticosteroids and other immunosuppressive therapies in the subjects who received brincidofovir.
The rate of treatment-emergent adverse events (AEs) was 100% in the brincidofovir arm and 98% in the placebo arm. The rate of grade 3 or higher AEs was 67% and 38%, respectively. The rate of serious AEs was 57% and 38%, respectively.
The rate of AEs leading to treatment discontinuation was 26% and 7%, respectively. And the rate of AEs leading to treatment change or interruption was 45% and 15%, respectively.
The most common AEs in the brincidofovir arm were diarrhea (61%), acute GVHD (57%), abdominal pain (34%), nausea (31%), vomiting (24%), peripheral edema (17%), hyperglycemia (16%), hypokalemia (16%), hypomagnesemia (13%), and ALT elevation (11%). There was no evidence of bone marrow toxicity, kidney toxicity, or viral resistance to brincidofovir.
Brincidofovir development
Chimerix said it will discuss the SUPPRESS data in full with the US Food and Drug Administration and other regulators, including the benefit-to-risk profile in specific subpopulations, as well as the current adenovirus and smallpox data, to determine next steps for the brincidofovir clinical programs.
The development of an intravenous (IV) formulation of brincidofovir is progressing toward clinical testing and has the potential to avoid the gastrointestinal side effects of orally administered brincidofovir.
Preclinical studies of IV brincidofovir have shown a lower risk of gastrointestinal effects based on maintained body weight during dosing and no evidence of injury in preliminary review of the gastrointestinal tract.
If human studies continue to support these findings, IV dosing during the first few weeks after transplant when patients are recovering from conditioning chemotherapy could be explored, with oral brincidofovir therapy available as patients are discharged home.
As there is no preventive therapy approved for CMV in HSCT recipients, Chimerix said it is committed to moving brincidofovir forward in this indication. Plans for brincidofovir in HSCT recipients will be the subject of further discussions with regulators.
Photo by Chad McNeeley
HONOLULU—Despite disappointing results in a phase 3 trial, investigators believe the oral nucleotide analog brincidofovir may still be viable as cytomegalovirus (CMV) prophylaxis in patients undergoing hematopoietic stem cell transplant (HSCT).
As reported last December, brincidofovir did not meet the primary endpoint of the phase 3 SUPPRESS trial, which was to prevent clinically significant CMV infection at week 24 after HSCT.
However, trial investigators said the drug did prevent CMV through week 14, which was the end of the treatment period.
The team believes they have an explanation for these findings, which were presented at the 2016 BMT Tandem Meetings (abstract 5). The trial was supported by Chimerix, the company developing brincidofovir.
The SUPPRESS trial included 452 subjects at high risk for CMV who were randomized to receive brincidofovir or placebo twice weekly for up to 14 weeks following allogeneic HSCT. They were then followed for 10 weeks after treatment.
Baseline characteristics were similar between the treatment arms, although there were more males in the placebo arm than the brincidofovir arm—66% and 54%, respectively. The median age was 56 in the brincidofovir arm and 54 in the placebo arm (overall range, 18-77).
Key results
The primary endpoint was assessed at week 24. At that time, the proportion of patients with clinically significant CMV infection was similar in the brincidofovir and placebo arms—51% and 52%, respectively.
However, the investigators did note that brincidofovir exhibited an antiviral effect during the trial. At the end of the on-treatment period at week 14, patients who received brincidofovir had fewer clinically significant CMV infections than patients in the placebo group—24% and 38%, respectively (P=0.002).
The investigators said the failure to meet the primary endpoint at week 24 appears to be associated with CMV events in the post-treatment period among subjects on the brincidofovir arm, driven by higher use of corticosteroids and other immunosuppressive therapies for the treatment of presumptive graft-versus-host disease (GVHD).
Diarrhea can be a symptom of GVHD in the gut and is also a known side effect of brincidofovir that can be managed by a temporary dose interruption, as described in the safety monitoring and management plan (SMMP) developed during the phase 2 trial of the drug (then known as CMX001).
In the SUPPRESS trial, diarrhea in brincidofovir-treated patients was more frequent and often presumed to be gut GVHD. So patients were treated with corticosteroids rather than undergoing temporary treatment interruption according to the SMMP. Among patients who were managed according to the SMMP, the investigators observed significantly fewer CMV infections (P=0.03) and lower mortality (P<0.001).
There was an 8-fold increase in the use of corticosteroids through week 14 in the brincidofovir arm compared to the placebo arm. The median cumulative dose of prednisone-equivalent corticosteroids was 26 mg/kg and 3 mg/kg, respectively.
The use of corticosteroids and other immunosuppressive therapies for the treatment of GVHD is known to increase the risk of infections, including CMV infections that occur when patients discontinue antiviral therapy.
Among patients who either underwent T-cell depletion or received alemtuzumab/ATG to decrease the risk of GVHD, those who were randomized to receive brincidofovir showed a lower incidence of CMV when compared to placebo, at a rate consistent with what was observed in the phase 2 study.
Additional endpoints
Brincidofovir did not prevent infection with non-CMV DNA viruses, such as BK virus.
And there was no significant difference between the treatment arms with regard to all-cause mortality. The rate was 15.5% in the brincidofovir arm and 10.1% in the placebo arm (P=0.12).
The investigators said the numerical differences in mortality appear to be driven by higher use of corticosteroids and other immunosuppressive therapies in the subjects who received brincidofovir.
The rate of treatment-emergent adverse events (AEs) was 100% in the brincidofovir arm and 98% in the placebo arm. The rate of grade 3 or higher AEs was 67% and 38%, respectively. The rate of serious AEs was 57% and 38%, respectively.
The rate of AEs leading to treatment discontinuation was 26% and 7%, respectively. And the rate of AEs leading to treatment change or interruption was 45% and 15%, respectively.
The most common AEs in the brincidofovir arm were diarrhea (61%), acute GVHD (57%), abdominal pain (34%), nausea (31%), vomiting (24%), peripheral edema (17%), hyperglycemia (16%), hypokalemia (16%), hypomagnesemia (13%), and ALT elevation (11%). There was no evidence of bone marrow toxicity, kidney toxicity, or viral resistance to brincidofovir.
Brincidofovir development
Chimerix said it will discuss the SUPPRESS data in full with the US Food and Drug Administration and other regulators, including the benefit-to-risk profile in specific subpopulations, as well as the current adenovirus and smallpox data, to determine next steps for the brincidofovir clinical programs.
The development of an intravenous (IV) formulation of brincidofovir is progressing toward clinical testing and has the potential to avoid the gastrointestinal side effects of orally administered brincidofovir.
Preclinical studies of IV brincidofovir have shown a lower risk of gastrointestinal effects based on maintained body weight during dosing and no evidence of injury in preliminary review of the gastrointestinal tract.
If human studies continue to support these findings, IV dosing during the first few weeks after transplant when patients are recovering from conditioning chemotherapy could be explored, with oral brincidofovir therapy available as patients are discharged home.
As there is no preventive therapy approved for CMV in HSCT recipients, Chimerix said it is committed to moving brincidofovir forward in this indication. Plans for brincidofovir in HSCT recipients will be the subject of further discussions with regulators.
Teens’ weight, height linked to risk of NHL
A new analysis indicates that having a higher body weight and taller stature during adolescence may increase the risk of developing non-Hodgkin lymphoma (NHL).
Global rates of NHL have been on the rise in recent years, and research suggests that rising rates of obesity may be contributing to this trend.
With this in mind, investigators examined whether adolescent weight and height might be associated with the risk of developing NHL later in life.
They reported their results in Cancer.
The study included 2,352,988 subjects, ages 16 to 19, who were examined between 1967 and 2011. Their information was linked to the Israel National Cancer Registry, which included 4021 cases of NHL from 1967 through 2012.
The data showed that being overweight or obese in adolescence was associated with an increased risk of NHL later in life. When compared to adolescents of normal weight, the hazard ratio (HR) was 1.25 for subjects who were overweight or obese. The HR for underweight individuals was 0.98.
Being overweight or obese in adolescence was a significant predictor for marginal zone lymphoma (HR=1.70), primary cutaneous lymphoma (PCL, HR=1.44), and diffuse large B-cell lymphoma (DLBCL, HR=1.31). Excess weight was a borderline predictor for follicular lymphoma (HR=1.28).
“It is important to be aware that overweight and obesity are not risk factors only for diabetes and cardiovascular disease but also for lymphomas,” said study author Merav Leiba, MD, of the Sheba Medical Center in Israel.
Dr Leiba and her colleagues also observed an increased risk of NHL corresponding with increases in subjects’ height. When compared with the mid-range height category, shorter individuals had an HR of 1.25, and the tallest individuals had an HR of 1.28.
The strongest associations between taller height and NHL were observed for primary cutaneous lymphoma and diffuse large B-cell lymphoma. The HRs for the tallest group, compared to the shortest group, were 3.19 for PCL and 2.21 for DLBCL.
The investigators said additional research is needed to help explain the links between height, weight, and NHL.
A new analysis indicates that having a higher body weight and taller stature during adolescence may increase the risk of developing non-Hodgkin lymphoma (NHL).
Global rates of NHL have been on the rise in recent years, and research suggests that rising rates of obesity may be contributing to this trend.
With this in mind, investigators examined whether adolescent weight and height might be associated with the risk of developing NHL later in life.
They reported their results in Cancer.
The study included 2,352,988 subjects, ages 16 to 19, who were examined between 1967 and 2011. Their information was linked to the Israel National Cancer Registry, which included 4021 cases of NHL from 1967 through 2012.
The data showed that being overweight or obese in adolescence was associated with an increased risk of NHL later in life. When compared to adolescents of normal weight, the hazard ratio (HR) was 1.25 for subjects who were overweight or obese. The HR for underweight individuals was 0.98.
Being overweight or obese in adolescence was a significant predictor for marginal zone lymphoma (HR=1.70), primary cutaneous lymphoma (PCL, HR=1.44), and diffuse large B-cell lymphoma (DLBCL, HR=1.31). Excess weight was a borderline predictor for follicular lymphoma (HR=1.28).
“It is important to be aware that overweight and obesity are not risk factors only for diabetes and cardiovascular disease but also for lymphomas,” said study author Merav Leiba, MD, of the Sheba Medical Center in Israel.
Dr Leiba and her colleagues also observed an increased risk of NHL corresponding with increases in subjects’ height. When compared with the mid-range height category, shorter individuals had an HR of 1.25, and the tallest individuals had an HR of 1.28.
The strongest associations between taller height and NHL were observed for primary cutaneous lymphoma and diffuse large B-cell lymphoma. The HRs for the tallest group, compared to the shortest group, were 3.19 for PCL and 2.21 for DLBCL.
The investigators said additional research is needed to help explain the links between height, weight, and NHL.
A new analysis indicates that having a higher body weight and taller stature during adolescence may increase the risk of developing non-Hodgkin lymphoma (NHL).
Global rates of NHL have been on the rise in recent years, and research suggests that rising rates of obesity may be contributing to this trend.
With this in mind, investigators examined whether adolescent weight and height might be associated with the risk of developing NHL later in life.
They reported their results in Cancer.
The study included 2,352,988 subjects, ages 16 to 19, who were examined between 1967 and 2011. Their information was linked to the Israel National Cancer Registry, which included 4021 cases of NHL from 1967 through 2012.
The data showed that being overweight or obese in adolescence was associated with an increased risk of NHL later in life. When compared to adolescents of normal weight, the hazard ratio (HR) was 1.25 for subjects who were overweight or obese. The HR for underweight individuals was 0.98.
Being overweight or obese in adolescence was a significant predictor for marginal zone lymphoma (HR=1.70), primary cutaneous lymphoma (PCL, HR=1.44), and diffuse large B-cell lymphoma (DLBCL, HR=1.31). Excess weight was a borderline predictor for follicular lymphoma (HR=1.28).
“It is important to be aware that overweight and obesity are not risk factors only for diabetes and cardiovascular disease but also for lymphomas,” said study author Merav Leiba, MD, of the Sheba Medical Center in Israel.
Dr Leiba and her colleagues also observed an increased risk of NHL corresponding with increases in subjects’ height. When compared with the mid-range height category, shorter individuals had an HR of 1.25, and the tallest individuals had an HR of 1.28.
The strongest associations between taller height and NHL were observed for primary cutaneous lymphoma and diffuse large B-cell lymphoma. The HRs for the tallest group, compared to the shortest group, were 3.19 for PCL and 2.21 for DLBCL.
The investigators said additional research is needed to help explain the links between height, weight, and NHL.