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Slowing the progression of sickle cell disease
Image courtesy of the
University of Michigan
Activating the antioxidant regulator Nrf2 may slow the progression of sickle cell disease (SCD), according to preclinical research published in JCI Insight.
Investigators found the severity of hemolytic anemia, vascular inflammation, and lung injury increased with age in mice with SCD.
However, activating Nrf2 in young animals had a prophylactic effect, reducing the severity of these adverse effects and improving survival.
To uncover these findings, Solomon Ofori-Acquah, PhD, of the University of Pittsburgh in Pennsylvania, and his colleagues conducted a 10-month longitudinal observational study of mice with SCD.
The team found that, in mice with homozygous SCD (SS), there was a link between intravascular hemolysis, vascular inflammation, lung injury, and early death.
Mice as young as 2 months showed exacerbation of intravascular hemolysis. And additional investigation linked worsening intravascular hemolysis and oxidative stress to the release of VE-cadherin and progressive lung damage in aging SS mice.
The investigators knew that Nrf2 regulates the expression of genes that protect against the effects of intravascular hemolysis. So they decided to see if activating Nrf2 in young mice with SCD would slow the disease progression that occurs with age.
The team took SS mice that were about a month old and randomized them to receive 3H-1, 2-dithiole-3-thione (D3T) or a DMSO vehicle for 3 months or longer.
Treatment with D3T stabilized the concentration of hemoglobin, increased white blood cell counts, increased reticulocyte counts (though not significantly), kept HO-1 levels stable, increased levels of NQO1 and ferritin, and impeded the progression of endothelial dysfunction.
The investigators also looked at the role of Nrf2 in nonhematopoietic tissues and were surprised to find that Nrf2 deficiency in nonhematopoietic tissues exacerbated anemia and caused premature pulmonary edema in mice with SCD.
The team said this suggests a dominant protective role for nonhematopoietic Nrf2 against tissue damage in both erythroid and nonerythroid tissues in SCD.
And, when taken together, the results of this research indicate that activating Nrf2 can impede the onset of the severe adult phenotype of SCD in mice. 
Image courtesy of the
University of Michigan
Activating the antioxidant regulator Nrf2 may slow the progression of sickle cell disease (SCD), according to preclinical research published in JCI Insight.
Investigators found the severity of hemolytic anemia, vascular inflammation, and lung injury increased with age in mice with SCD.
However, activating Nrf2 in young animals had a prophylactic effect, reducing the severity of these adverse effects and improving survival.
To uncover these findings, Solomon Ofori-Acquah, PhD, of the University of Pittsburgh in Pennsylvania, and his colleagues conducted a 10-month longitudinal observational study of mice with SCD.
The team found that, in mice with homozygous SCD (SS), there was a link between intravascular hemolysis, vascular inflammation, lung injury, and early death.
Mice as young as 2 months showed exacerbation of intravascular hemolysis. And additional investigation linked worsening intravascular hemolysis and oxidative stress to the release of VE-cadherin and progressive lung damage in aging SS mice.
The investigators knew that Nrf2 regulates the expression of genes that protect against the effects of intravascular hemolysis. So they decided to see if activating Nrf2 in young mice with SCD would slow the disease progression that occurs with age.
The team took SS mice that were about a month old and randomized them to receive 3H-1, 2-dithiole-3-thione (D3T) or a DMSO vehicle for 3 months or longer.
Treatment with D3T stabilized the concentration of hemoglobin, increased white blood cell counts, increased reticulocyte counts (though not significantly), kept HO-1 levels stable, increased levels of NQO1 and ferritin, and impeded the progression of endothelial dysfunction.
The investigators also looked at the role of Nrf2 in nonhematopoietic tissues and were surprised to find that Nrf2 deficiency in nonhematopoietic tissues exacerbated anemia and caused premature pulmonary edema in mice with SCD.
The team said this suggests a dominant protective role for nonhematopoietic Nrf2 against tissue damage in both erythroid and nonerythroid tissues in SCD.
And, when taken together, the results of this research indicate that activating Nrf2 can impede the onset of the severe adult phenotype of SCD in mice.
Image courtesy of the
University of Michigan
Activating the antioxidant regulator Nrf2 may slow the progression of sickle cell disease (SCD), according to preclinical research published in JCI Insight.
Investigators found the severity of hemolytic anemia, vascular inflammation, and lung injury increased with age in mice with SCD.
However, activating Nrf2 in young animals had a prophylactic effect, reducing the severity of these adverse effects and improving survival.
To uncover these findings, Solomon Ofori-Acquah, PhD, of the University of Pittsburgh in Pennsylvania, and his colleagues conducted a 10-month longitudinal observational study of mice with SCD.
The team found that, in mice with homozygous SCD (SS), there was a link between intravascular hemolysis, vascular inflammation, lung injury, and early death.
Mice as young as 2 months showed exacerbation of intravascular hemolysis. And additional investigation linked worsening intravascular hemolysis and oxidative stress to the release of VE-cadherin and progressive lung damage in aging SS mice.
The investigators knew that Nrf2 regulates the expression of genes that protect against the effects of intravascular hemolysis. So they decided to see if activating Nrf2 in young mice with SCD would slow the disease progression that occurs with age.
The team took SS mice that were about a month old and randomized them to receive 3H-1, 2-dithiole-3-thione (D3T) or a DMSO vehicle for 3 months or longer.
Treatment with D3T stabilized the concentration of hemoglobin, increased white blood cell counts, increased reticulocyte counts (though not significantly), kept HO-1 levels stable, increased levels of NQO1 and ferritin, and impeded the progression of endothelial dysfunction.
The investigators also looked at the role of Nrf2 in nonhematopoietic tissues and were surprised to find that Nrf2 deficiency in nonhematopoietic tissues exacerbated anemia and caused premature pulmonary edema in mice with SCD.
The team said this suggests a dominant protective role for nonhematopoietic Nrf2 against tissue damage in both erythroid and nonerythroid tissues in SCD.
And, when taken together, the results of this research indicate that activating Nrf2 can impede the onset of the severe adult phenotype of SCD in mice.
EC approves drug for pediatric ITP
Photo by Logan Tuttle
The European Commission (EC) has approved eltrombopag (Revolade), a once-daily oral thrombopoietin receptor agonist, to treat pediatric patients (age 1 and older) with chronic immune thrombocytopenia (ITP) that is refractory to other therapies.
This approval includes the use of tablets and a new oral suspension formulation of eltrombopag, which is designed for younger children who may not be able to swallow tablets.
The approval applies to all 28 member states of the European Union plus Iceland, Norway, and Liechtenstein.
Eltrombopag was previously approved by the EC for use in adults with refractory chronic ITP. The drug is also approved in the EC to treat adults with severe aplastic anemia and adults with chronic hepatitis C virus infection who have thrombocytopenia.
Eltrombopag is made by Novartis. For more details on the drug, see the full Summary of Product Characteristics, available on the European Medicines Agency’s website.
The EC’s latest approval of eltrombopag was based on data from 2 double-blind, placebo-controlled trials—the phase 2 PETIT trial and the phase 3 PETIT2 trial.
PETIT trials: Efficacy
The PETIT trial included 67 ITP patients stratified by age cohort (12-17 years, 6-11 years, and 1-5 years). They were randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 109/L or higher at least once between days 8 and 43 of the randomized period of the study.
Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).
The PETIT2 trial enrolled 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 109/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.
Significantly more patients in the eltrombopag arm met this endpoint—41.3%—compared to 3.4% of patients in the placebo arm (P<0.001).
PETIT trials: Safety
For both trials, there were 107 eltrombopag-treated patients evaluable for safety.
The most common adverse events that occurred more frequently in the eltrombopag arms than the placebo arms were upper respiratory tract infection, nasopharyngitis, cough, diarrhea, pyrexia, rhinitis, abdominal pain, oropharyngeal pain, toothache, increased ALT/AST, rash, and rhinorrhea.
Serious adverse events were reported in 8% of patients during the randomized part of both trials, although no serious adverse event occurred in more than 1 patient.
An ALT elevation of at least 3 times the upper limit of normal occurred in 5% of eltrombopag-treated patients. Of those patients, 2% had ALT increases of at least 5 times the upper limit of normal.
There were no deaths or thromboembolic events during either study.
Photo by Logan Tuttle
The European Commission (EC) has approved eltrombopag (Revolade), a once-daily oral thrombopoietin receptor agonist, to treat pediatric patients (age 1 and older) with chronic immune thrombocytopenia (ITP) that is refractory to other therapies.
This approval includes the use of tablets and a new oral suspension formulation of eltrombopag, which is designed for younger children who may not be able to swallow tablets.
The approval applies to all 28 member states of the European Union plus Iceland, Norway, and Liechtenstein.
Eltrombopag was previously approved by the EC for use in adults with refractory chronic ITP. The drug is also approved in the EC to treat adults with severe aplastic anemia and adults with chronic hepatitis C virus infection who have thrombocytopenia.
Eltrombopag is made by Novartis. For more details on the drug, see the full Summary of Product Characteristics, available on the European Medicines Agency’s website.
The EC’s latest approval of eltrombopag was based on data from 2 double-blind, placebo-controlled trials—the phase 2 PETIT trial and the phase 3 PETIT2 trial.
PETIT trials: Efficacy
The PETIT trial included 67 ITP patients stratified by age cohort (12-17 years, 6-11 years, and 1-5 years). They were randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 109/L or higher at least once between days 8 and 43 of the randomized period of the study.
Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).
The PETIT2 trial enrolled 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 109/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.
Significantly more patients in the eltrombopag arm met this endpoint—41.3%—compared to 3.4% of patients in the placebo arm (P<0.001).
PETIT trials: Safety
For both trials, there were 107 eltrombopag-treated patients evaluable for safety.
The most common adverse events that occurred more frequently in the eltrombopag arms than the placebo arms were upper respiratory tract infection, nasopharyngitis, cough, diarrhea, pyrexia, rhinitis, abdominal pain, oropharyngeal pain, toothache, increased ALT/AST, rash, and rhinorrhea.
Serious adverse events were reported in 8% of patients during the randomized part of both trials, although no serious adverse event occurred in more than 1 patient.
An ALT elevation of at least 3 times the upper limit of normal occurred in 5% of eltrombopag-treated patients. Of those patients, 2% had ALT increases of at least 5 times the upper limit of normal.
There were no deaths or thromboembolic events during either study.
Photo by Logan Tuttle
The European Commission (EC) has approved eltrombopag (Revolade), a once-daily oral thrombopoietin receptor agonist, to treat pediatric patients (age 1 and older) with chronic immune thrombocytopenia (ITP) that is refractory to other therapies.
This approval includes the use of tablets and a new oral suspension formulation of eltrombopag, which is designed for younger children who may not be able to swallow tablets.
The approval applies to all 28 member states of the European Union plus Iceland, Norway, and Liechtenstein.
Eltrombopag was previously approved by the EC for use in adults with refractory chronic ITP. The drug is also approved in the EC to treat adults with severe aplastic anemia and adults with chronic hepatitis C virus infection who have thrombocytopenia.
Eltrombopag is made by Novartis. For more details on the drug, see the full Summary of Product Characteristics, available on the European Medicines Agency’s website.
The EC’s latest approval of eltrombopag was based on data from 2 double-blind, placebo-controlled trials—the phase 2 PETIT trial and the phase 3 PETIT2 trial.
PETIT trials: Efficacy
The PETIT trial included 67 ITP patients stratified by age cohort (12-17 years, 6-11 years, and 1-5 years). They were randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 109/L or higher at least once between days 8 and 43 of the randomized period of the study.
Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).
The PETIT2 trial enrolled 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 109/L.
The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 109/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.
Significantly more patients in the eltrombopag arm met this endpoint—41.3%—compared to 3.4% of patients in the placebo arm (P<0.001).
PETIT trials: Safety
For both trials, there were 107 eltrombopag-treated patients evaluable for safety.
The most common adverse events that occurred more frequently in the eltrombopag arms than the placebo arms were upper respiratory tract infection, nasopharyngitis, cough, diarrhea, pyrexia, rhinitis, abdominal pain, oropharyngeal pain, toothache, increased ALT/AST, rash, and rhinorrhea.
Serious adverse events were reported in 8% of patients during the randomized part of both trials, although no serious adverse event occurred in more than 1 patient.
An ALT elevation of at least 3 times the upper limit of normal occurred in 5% of eltrombopag-treated patients. Of those patients, 2% had ALT increases of at least 5 times the upper limit of normal.
There were no deaths or thromboembolic events during either study.
Study suggests iPSCs pose no cancer risk
Image from the Salk Institute
In tracking the mutational history of somatic cells and induced pluripotent stem cells (iPSCs), researchers found that somatic cells accumulate mutations more frequently than iPSCs.
And none of the mutations found in iPSCs were associated with cancers.
“None of the mutations we found in induced pluripotent stem cells were cancer-driver mutations or mutations in cancer-causing genes,” said Foad Rouhani, of the Wellcome Trust Sanger Institute in the UK.
“We didn’t find anything that would preclude the use of [iPSCs] in therapeutic medicine.”
Rouhani and his colleagues reported these findings in PLOS Genetics.
The researchers generated iPSCs using cells from healthy individuals, then sequenced the genomes of the somatic cells and the derived iPSCs.
They found that somatic cells had a mutation rate of 14 single nucleotide variants per cell per generation, and the mutation rate for iPSCs was 10-fold lower.
The researchers said this is the first time that mutation rates of both types of cells, the donor cell and iPSC, have been calculated and compared.
“Until now, the question of whether generating [iPSCs] and growing them in cell culture creates mutations has not been addressed in detail,” said study author Allan Bradley, PhD, of the Wellcome Trust Sanger Institute.
“If human cells are really to be reprogrammed on a large scale for use in regenerative medicine, then understanding the mutations the donor cells carry will be a crucial step. We now have the tools to do this.”
The researchers also used the iPSCs to trace the history of every mutation that one endothelial progenitor cell had developed from the time it was a fertilized egg to the moment it was taken out of the body.
They said the ability to track the genetic changes in cells over a lifetime could improve scientists’ understanding of how, when, and why mutations lead to cancer.
Image from the Salk Institute
In tracking the mutational history of somatic cells and induced pluripotent stem cells (iPSCs), researchers found that somatic cells accumulate mutations more frequently than iPSCs.
And none of the mutations found in iPSCs were associated with cancers.
“None of the mutations we found in induced pluripotent stem cells were cancer-driver mutations or mutations in cancer-causing genes,” said Foad Rouhani, of the Wellcome Trust Sanger Institute in the UK.
“We didn’t find anything that would preclude the use of [iPSCs] in therapeutic medicine.”
Rouhani and his colleagues reported these findings in PLOS Genetics.
The researchers generated iPSCs using cells from healthy individuals, then sequenced the genomes of the somatic cells and the derived iPSCs.
They found that somatic cells had a mutation rate of 14 single nucleotide variants per cell per generation, and the mutation rate for iPSCs was 10-fold lower.
The researchers said this is the first time that mutation rates of both types of cells, the donor cell and iPSC, have been calculated and compared.
“Until now, the question of whether generating [iPSCs] and growing them in cell culture creates mutations has not been addressed in detail,” said study author Allan Bradley, PhD, of the Wellcome Trust Sanger Institute.
“If human cells are really to be reprogrammed on a large scale for use in regenerative medicine, then understanding the mutations the donor cells carry will be a crucial step. We now have the tools to do this.”
The researchers also used the iPSCs to trace the history of every mutation that one endothelial progenitor cell had developed from the time it was a fertilized egg to the moment it was taken out of the body.
They said the ability to track the genetic changes in cells over a lifetime could improve scientists’ understanding of how, when, and why mutations lead to cancer.
Image from the Salk Institute
In tracking the mutational history of somatic cells and induced pluripotent stem cells (iPSCs), researchers found that somatic cells accumulate mutations more frequently than iPSCs.
And none of the mutations found in iPSCs were associated with cancers.
“None of the mutations we found in induced pluripotent stem cells were cancer-driver mutations or mutations in cancer-causing genes,” said Foad Rouhani, of the Wellcome Trust Sanger Institute in the UK.
“We didn’t find anything that would preclude the use of [iPSCs] in therapeutic medicine.”
Rouhani and his colleagues reported these findings in PLOS Genetics.
The researchers generated iPSCs using cells from healthy individuals, then sequenced the genomes of the somatic cells and the derived iPSCs.
They found that somatic cells had a mutation rate of 14 single nucleotide variants per cell per generation, and the mutation rate for iPSCs was 10-fold lower.
The researchers said this is the first time that mutation rates of both types of cells, the donor cell and iPSC, have been calculated and compared.
“Until now, the question of whether generating [iPSCs] and growing them in cell culture creates mutations has not been addressed in detail,” said study author Allan Bradley, PhD, of the Wellcome Trust Sanger Institute.
“If human cells are really to be reprogrammed on a large scale for use in regenerative medicine, then understanding the mutations the donor cells carry will be a crucial step. We now have the tools to do this.”
The researchers also used the iPSCs to trace the history of every mutation that one endothelial progenitor cell had developed from the time it was a fertilized egg to the moment it was taken out of the body.
They said the ability to track the genetic changes in cells over a lifetime could improve scientists’ understanding of how, when, and why mutations lead to cancer.
Expanded UCB product provides clinical benefit
Photo courtesy of NHS
VALENCIA, SPAIN—The expanded umbilical cord blood (UCB) product NiCord can provide clinical benefits in patients with high-risk hematologic malignancies, according to data presented at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation.
NiCord consists of cells from a single UCB unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.
The data showed that patients transplanted with NiCord had fewer moderate to severe bacterial infections and shorter hospital stays than patients who received standard UCB transplants.
“We saw a significant reduction in serious bacterial infections during the first 100 days in the NiCord group,” said Mitchell Horwitz, MD, of the Duke University School of Medicine in Durham, North Carolina.
“This is encouraging because this type of infection is a major cause of early death following UCB transplantation. We also saw a significant reduction in hospitalization time in the NiCord group, indicating a faster recovery of these patients in comparison to those transplanted with standard umbilical cord blood.”
These results were presented at the meeting as abstract O090. The research was funded by Gamida Cell, the company developing NiCord.
Dr Horwitz and his colleagues analyzed 18 patients with high-risk hematologic malignancies—most with acute leukemia or myelodysplastic syndromes (90%)—who were transplanted with NiCord.
Ten of the patients received NiCord with a second, unmanipulated UCB unit, and 8 patients received NiCord as a single UCB graft.
The researchers compared these patients to 101 patients who received standard single or double UCB transplants at Duke University from January 2005 to March 2015.
Patients in both groups received a total body irradiation-based myeloablative preparative regimen.
The median time to neutrophil engraftment was significantly shorter in the NiCord group than the control group—12.5 days and 27 days, respectively (P<0.001).
All 18 patients in the Nicord group and 100 patients in the control group had at least 1 infection.
Patients in the NiCord group had a significantly lower incidence of grade 2-3 bacterial infections than patients in the control group—22% and 54%, respectively (P=0.015).
However, there was no significant difference between the groups with regard to grade 2-3 viral infections (39% and 35%, respectively, P=0.729), fungal infections (0% and 5%, respectively, P=1.0), or non-microbiologically defined infections (0% and 17%, respectively, P=0.072).
In the first 100 days after transplant, patients in the NiCord group spent significantly more days out of the hospital than patients in the control group. The median number of days for each group was 74 and 53, respectively (P=0.002).
“These results demonstrate that the rapid hematopoietic recovery from NiCord transplantation results in clinical benefit, in comparison to similar site controls,” Dr Horwitz concluded.
Photo courtesy of NHS
VALENCIA, SPAIN—The expanded umbilical cord blood (UCB) product NiCord can provide clinical benefits in patients with high-risk hematologic malignancies, according to data presented at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation.
NiCord consists of cells from a single UCB unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.
The data showed that patients transplanted with NiCord had fewer moderate to severe bacterial infections and shorter hospital stays than patients who received standard UCB transplants.
“We saw a significant reduction in serious bacterial infections during the first 100 days in the NiCord group,” said Mitchell Horwitz, MD, of the Duke University School of Medicine in Durham, North Carolina.
“This is encouraging because this type of infection is a major cause of early death following UCB transplantation. We also saw a significant reduction in hospitalization time in the NiCord group, indicating a faster recovery of these patients in comparison to those transplanted with standard umbilical cord blood.”
These results were presented at the meeting as abstract O090. The research was funded by Gamida Cell, the company developing NiCord.
Dr Horwitz and his colleagues analyzed 18 patients with high-risk hematologic malignancies—most with acute leukemia or myelodysplastic syndromes (90%)—who were transplanted with NiCord.
Ten of the patients received NiCord with a second, unmanipulated UCB unit, and 8 patients received NiCord as a single UCB graft.
The researchers compared these patients to 101 patients who received standard single or double UCB transplants at Duke University from January 2005 to March 2015.
Patients in both groups received a total body irradiation-based myeloablative preparative regimen.
The median time to neutrophil engraftment was significantly shorter in the NiCord group than the control group—12.5 days and 27 days, respectively (P<0.001).
All 18 patients in the Nicord group and 100 patients in the control group had at least 1 infection.
Patients in the NiCord group had a significantly lower incidence of grade 2-3 bacterial infections than patients in the control group—22% and 54%, respectively (P=0.015).
However, there was no significant difference between the groups with regard to grade 2-3 viral infections (39% and 35%, respectively, P=0.729), fungal infections (0% and 5%, respectively, P=1.0), or non-microbiologically defined infections (0% and 17%, respectively, P=0.072).
In the first 100 days after transplant, patients in the NiCord group spent significantly more days out of the hospital than patients in the control group. The median number of days for each group was 74 and 53, respectively (P=0.002).
“These results demonstrate that the rapid hematopoietic recovery from NiCord transplantation results in clinical benefit, in comparison to similar site controls,” Dr Horwitz concluded.
Photo courtesy of NHS
VALENCIA, SPAIN—The expanded umbilical cord blood (UCB) product NiCord can provide clinical benefits in patients with high-risk hematologic malignancies, according to data presented at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation.
NiCord consists of cells from a single UCB unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.
The data showed that patients transplanted with NiCord had fewer moderate to severe bacterial infections and shorter hospital stays than patients who received standard UCB transplants.
“We saw a significant reduction in serious bacterial infections during the first 100 days in the NiCord group,” said Mitchell Horwitz, MD, of the Duke University School of Medicine in Durham, North Carolina.
“This is encouraging because this type of infection is a major cause of early death following UCB transplantation. We also saw a significant reduction in hospitalization time in the NiCord group, indicating a faster recovery of these patients in comparison to those transplanted with standard umbilical cord blood.”
These results were presented at the meeting as abstract O090. The research was funded by Gamida Cell, the company developing NiCord.
Dr Horwitz and his colleagues analyzed 18 patients with high-risk hematologic malignancies—most with acute leukemia or myelodysplastic syndromes (90%)—who were transplanted with NiCord.
Ten of the patients received NiCord with a second, unmanipulated UCB unit, and 8 patients received NiCord as a single UCB graft.
The researchers compared these patients to 101 patients who received standard single or double UCB transplants at Duke University from January 2005 to March 2015.
Patients in both groups received a total body irradiation-based myeloablative preparative regimen.
The median time to neutrophil engraftment was significantly shorter in the NiCord group than the control group—12.5 days and 27 days, respectively (P<0.001).
All 18 patients in the Nicord group and 100 patients in the control group had at least 1 infection.
Patients in the NiCord group had a significantly lower incidence of grade 2-3 bacterial infections than patients in the control group—22% and 54%, respectively (P=0.015).
However, there was no significant difference between the groups with regard to grade 2-3 viral infections (39% and 35%, respectively, P=0.729), fungal infections (0% and 5%, respectively, P=1.0), or non-microbiologically defined infections (0% and 17%, respectively, P=0.072).
In the first 100 days after transplant, patients in the NiCord group spent significantly more days out of the hospital than patients in the control group. The median number of days for each group was 74 and 53, respectively (P=0.002).
“These results demonstrate that the rapid hematopoietic recovery from NiCord transplantation results in clinical benefit, in comparison to similar site controls,” Dr Horwitz concluded.
Subgroup benefits from long-term DAPT
Photo courtesy of AstraZeneca
CHICAGO—Long-term use of dual antiplatelet therapy (DAPT) can benefit patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), according to data presented at the American College of Cardiology’s 65th Annual Scientific Session.
The data were from a subanalysis of the PEGASUS-TIMI 54 trial, in which researchers evaluated long-term use of aspirin, with or without the antiplatelet agent ticagrelor, in patients with a history of MI and at least 1 additional risk factor for thrombotic cardiovascular (CV) events.
The analysis suggested that, in stable patients with a history of MI, concomitant PAD is associated with a higher risk of major adverse cardiac events (MACE).
However, long-term DAPT with ticagrelor and aspirin can reduce the incidence of MACE in these patients, when compared to aspirin plus a placebo.
These results were presented as abstract 907-04 and simultaneously published in the Journal of American College of Cardiology. The trial was sponsored by AstraZeneca, the company developing ticagrelor.
Patients in the PEGASUS-TIMI 54 trial were randomized to receive aspirin plus twice-daily doses of ticagrelor at 90 mg, ticagrelor at 60 mg, or placebo.
The study’s primary efficacy endpoint was the incidence of MACE, which was defined as a composite of CV death, MI, or stroke.
The subanalysis showed that the 1143 patients with a prior MI and PAD had a higher incidence of MACE at 3 years than patients without PAD—19.3% and 8.4%, respectively (P<0.001).
The increased risk of MACE in patients with PAD persisted after the researchers adjusted for differences in patient characteristics at baseline. The hazard ratio (HR) was 1.60 (95% CI 1.20-2.13, P=0.0013).
Patients with PAD had a higher risk of CV death (HR 1.84, 95% CI 1.16-2.94, P=0.0102), stroke (HR 2.31, 95% CI 1.26–4.25, P=0.0071), and mortality (HR 2.05, 95% CI 1.43-2.94, P<0.001) than patients without PAD.
Patients who received DAPT (ticagrelor at either dose plus aspirin) had a lower risk of MACE at 3 years than patients who received placebo plus aspirin. This was true for patients with PAD (HR 0.75, 95% CI 0.55-1.01) and without it (HR 0.86, 95% CI 0.77-0.96, P-interaction=0.41).
However, because of their higher absolute risk of MACE, patients with PAD had a greater absolute risk reduction (4.1%) than patients without PAD.
The risk of TIMI major bleeding was not significantly higher in patients with PAD than in those without it (HR 1.57, 95% CI 0.47-5.22, P=0.46).
For patients with PAD, TIMI major bleeding occurred more frequently with ticagrelor at 90 mg plus aspirin than with placebo plus aspirin (HR 1.46, 95% CI 0.39-5.43, P=0.57) and with ticagrelor at 60 mg plus aspirin than with placebo plus aspirin (HR 1.18, 95% CI 0.29-4.70, P=0.82), though the differences were not significant.
“Patients with prior MI and PAD are at further heightened risk of ischemic events relative to patients with prior MI and no PAD, even when accounting for other risk factors,” said study investigator Marc Bonaca, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“Because of their heightened ischemic risk, patients in the subgroup analysis with a prior MI and PAD appear to have a higher absolute risk reduction with ticagrelor than those without. These findings may be helpful to clinicians in identifying patients with prior MI who they feel could benefit from prolonged therapy with ticagrelor.”
Photo courtesy of AstraZeneca
CHICAGO—Long-term use of dual antiplatelet therapy (DAPT) can benefit patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), according to data presented at the American College of Cardiology’s 65th Annual Scientific Session.
The data were from a subanalysis of the PEGASUS-TIMI 54 trial, in which researchers evaluated long-term use of aspirin, with or without the antiplatelet agent ticagrelor, in patients with a history of MI and at least 1 additional risk factor for thrombotic cardiovascular (CV) events.
The analysis suggested that, in stable patients with a history of MI, concomitant PAD is associated with a higher risk of major adverse cardiac events (MACE).
However, long-term DAPT with ticagrelor and aspirin can reduce the incidence of MACE in these patients, when compared to aspirin plus a placebo.
These results were presented as abstract 907-04 and simultaneously published in the Journal of American College of Cardiology. The trial was sponsored by AstraZeneca, the company developing ticagrelor.
Patients in the PEGASUS-TIMI 54 trial were randomized to receive aspirin plus twice-daily doses of ticagrelor at 90 mg, ticagrelor at 60 mg, or placebo.
The study’s primary efficacy endpoint was the incidence of MACE, which was defined as a composite of CV death, MI, or stroke.
The subanalysis showed that the 1143 patients with a prior MI and PAD had a higher incidence of MACE at 3 years than patients without PAD—19.3% and 8.4%, respectively (P<0.001).
The increased risk of MACE in patients with PAD persisted after the researchers adjusted for differences in patient characteristics at baseline. The hazard ratio (HR) was 1.60 (95% CI 1.20-2.13, P=0.0013).
Patients with PAD had a higher risk of CV death (HR 1.84, 95% CI 1.16-2.94, P=0.0102), stroke (HR 2.31, 95% CI 1.26–4.25, P=0.0071), and mortality (HR 2.05, 95% CI 1.43-2.94, P<0.001) than patients without PAD.
Patients who received DAPT (ticagrelor at either dose plus aspirin) had a lower risk of MACE at 3 years than patients who received placebo plus aspirin. This was true for patients with PAD (HR 0.75, 95% CI 0.55-1.01) and without it (HR 0.86, 95% CI 0.77-0.96, P-interaction=0.41).
However, because of their higher absolute risk of MACE, patients with PAD had a greater absolute risk reduction (4.1%) than patients without PAD.
The risk of TIMI major bleeding was not significantly higher in patients with PAD than in those without it (HR 1.57, 95% CI 0.47-5.22, P=0.46).
For patients with PAD, TIMI major bleeding occurred more frequently with ticagrelor at 90 mg plus aspirin than with placebo plus aspirin (HR 1.46, 95% CI 0.39-5.43, P=0.57) and with ticagrelor at 60 mg plus aspirin than with placebo plus aspirin (HR 1.18, 95% CI 0.29-4.70, P=0.82), though the differences were not significant.
“Patients with prior MI and PAD are at further heightened risk of ischemic events relative to patients with prior MI and no PAD, even when accounting for other risk factors,” said study investigator Marc Bonaca, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“Because of their heightened ischemic risk, patients in the subgroup analysis with a prior MI and PAD appear to have a higher absolute risk reduction with ticagrelor than those without. These findings may be helpful to clinicians in identifying patients with prior MI who they feel could benefit from prolonged therapy with ticagrelor.”
Photo courtesy of AstraZeneca
CHICAGO—Long-term use of dual antiplatelet therapy (DAPT) can benefit patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), according to data presented at the American College of Cardiology’s 65th Annual Scientific Session.
The data were from a subanalysis of the PEGASUS-TIMI 54 trial, in which researchers evaluated long-term use of aspirin, with or without the antiplatelet agent ticagrelor, in patients with a history of MI and at least 1 additional risk factor for thrombotic cardiovascular (CV) events.
The analysis suggested that, in stable patients with a history of MI, concomitant PAD is associated with a higher risk of major adverse cardiac events (MACE).
However, long-term DAPT with ticagrelor and aspirin can reduce the incidence of MACE in these patients, when compared to aspirin plus a placebo.
These results were presented as abstract 907-04 and simultaneously published in the Journal of American College of Cardiology. The trial was sponsored by AstraZeneca, the company developing ticagrelor.
Patients in the PEGASUS-TIMI 54 trial were randomized to receive aspirin plus twice-daily doses of ticagrelor at 90 mg, ticagrelor at 60 mg, or placebo.
The study’s primary efficacy endpoint was the incidence of MACE, which was defined as a composite of CV death, MI, or stroke.
The subanalysis showed that the 1143 patients with a prior MI and PAD had a higher incidence of MACE at 3 years than patients without PAD—19.3% and 8.4%, respectively (P<0.001).
The increased risk of MACE in patients with PAD persisted after the researchers adjusted for differences in patient characteristics at baseline. The hazard ratio (HR) was 1.60 (95% CI 1.20-2.13, P=0.0013).
Patients with PAD had a higher risk of CV death (HR 1.84, 95% CI 1.16-2.94, P=0.0102), stroke (HR 2.31, 95% CI 1.26–4.25, P=0.0071), and mortality (HR 2.05, 95% CI 1.43-2.94, P<0.001) than patients without PAD.
Patients who received DAPT (ticagrelor at either dose plus aspirin) had a lower risk of MACE at 3 years than patients who received placebo plus aspirin. This was true for patients with PAD (HR 0.75, 95% CI 0.55-1.01) and without it (HR 0.86, 95% CI 0.77-0.96, P-interaction=0.41).
However, because of their higher absolute risk of MACE, patients with PAD had a greater absolute risk reduction (4.1%) than patients without PAD.
The risk of TIMI major bleeding was not significantly higher in patients with PAD than in those without it (HR 1.57, 95% CI 0.47-5.22, P=0.46).
For patients with PAD, TIMI major bleeding occurred more frequently with ticagrelor at 90 mg plus aspirin than with placebo plus aspirin (HR 1.46, 95% CI 0.39-5.43, P=0.57) and with ticagrelor at 60 mg plus aspirin than with placebo plus aspirin (HR 1.18, 95% CI 0.29-4.70, P=0.82), though the differences were not significant.
“Patients with prior MI and PAD are at further heightened risk of ischemic events relative to patients with prior MI and no PAD, even when accounting for other risk factors,” said study investigator Marc Bonaca, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“Because of their heightened ischemic risk, patients in the subgroup analysis with a prior MI and PAD appear to have a higher absolute risk reduction with ticagrelor than those without. These findings may be helpful to clinicians in identifying patients with prior MI who they feel could benefit from prolonged therapy with ticagrelor.”
Combos produce similar 10-year OS, PFS in HL
Photo by Bill Branson
Long-term results of the HD2000 trial reveal similar survival rates in patients with previously untreated, aggressive Hodgkin lymphoma (HL) who received 3 different combination treatment regimens.
At 10 years of follow-up, there was no significant difference in overall survival (OS) or progression-free survival (PFS) whether patients received ABVD, BEACOPP, or CEC.
However, patients who received ABVD were significantly less likely than those who received BEACOPP or CEC to develop second malignancies.
Francesco Merli, MD, of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Italy, and his colleagues reported these results in the Journal of Clinical Oncology.
The trial enrolled 307 patients with advanced-stage HL. Patients were randomized to receive 1 of 3 treatment regimens:
- Six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)
- Four escalated plus 2 standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)
- Six cycles of CEC (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin).
Some patients also received radiotherapy, but there was no significant difference in the proportion of patients receiving radiotherapy across the treatment arms—46% in the ABVD arm, 44% in the BEACOPP arm, and 43% in the CEC arm (P=0.871).
Results
At the end of all therapy, the complete response rate was 84% with ABVD, 91% with BEACOPP, and 83% with CEC.
There were 84 patients who did not achieve a complete response, and salvage data were available for 73 of these patients. Three patients (4%) died before salvage therapy could begin, 26 (36%) received conventional chemotherapy, 40 (55%) received a hematopoietic stem cell transplant, and 4 (5%) received radiotherapy.
The median follow-up was 120 months (range, 4 to 169 months), and 295 patients were evaluable.
In a previous analysis, at a median follow-up of 42 months, patients who received BEACOPP had superior PFS compared to patients who received ABVD.
However, in the current analysis, there was no significant difference in PFS between the 3 treatment arms. The 10-year PFS was 69% in the ABVD arm, 75% in the BEACOPP arm, and 76% in the CEC arm (P=0.471).
Likewise, there was no significant difference in OS between the treatment arms. The 10-year OS was 85% in the ABVD arm, 84% in the BEACOPP arm, and 86% in the CEC arm (P=0.892).
There were a total of 13 second malignancies—1 in the ABVD arm and 6 each in the BEACOPP and CEC arms.
The cumulative risk of developing a second malignancy at 10 years was 0.9% in the ABVD arm, 6.6% in the BEACOPP arm, and 6% in the CEC arm. So the risk with either BEACOPP or CEC was significantly higher than with ABVD (P=0.027 and 0.02, respectively).
The researchers said these results suggest BEACOPP provides better disease control than ABVD, but this benefit is counterbalanced by a higher rate of late major events with BEACOPP, particularly second malignancies, which resulted in patient deaths.
So the team concluded that BEACOPP is a viable treatment option for advanced HL, but it should not be considered the standard for all patients because 70% of these patients may be cured with ABVD and limited radiotherapy. A careful assessment of the risk-benefit ratio of the initial treatment choice is warranted.
Photo by Bill Branson
Long-term results of the HD2000 trial reveal similar survival rates in patients with previously untreated, aggressive Hodgkin lymphoma (HL) who received 3 different combination treatment regimens.
At 10 years of follow-up, there was no significant difference in overall survival (OS) or progression-free survival (PFS) whether patients received ABVD, BEACOPP, or CEC.
However, patients who received ABVD were significantly less likely than those who received BEACOPP or CEC to develop second malignancies.
Francesco Merli, MD, of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Italy, and his colleagues reported these results in the Journal of Clinical Oncology.
The trial enrolled 307 patients with advanced-stage HL. Patients were randomized to receive 1 of 3 treatment regimens:
- Six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)
- Four escalated plus 2 standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)
- Six cycles of CEC (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin).
Some patients also received radiotherapy, but there was no significant difference in the proportion of patients receiving radiotherapy across the treatment arms—46% in the ABVD arm, 44% in the BEACOPP arm, and 43% in the CEC arm (P=0.871).
Results
At the end of all therapy, the complete response rate was 84% with ABVD, 91% with BEACOPP, and 83% with CEC.
There were 84 patients who did not achieve a complete response, and salvage data were available for 73 of these patients. Three patients (4%) died before salvage therapy could begin, 26 (36%) received conventional chemotherapy, 40 (55%) received a hematopoietic stem cell transplant, and 4 (5%) received radiotherapy.
The median follow-up was 120 months (range, 4 to 169 months), and 295 patients were evaluable.
In a previous analysis, at a median follow-up of 42 months, patients who received BEACOPP had superior PFS compared to patients who received ABVD.
However, in the current analysis, there was no significant difference in PFS between the 3 treatment arms. The 10-year PFS was 69% in the ABVD arm, 75% in the BEACOPP arm, and 76% in the CEC arm (P=0.471).
Likewise, there was no significant difference in OS between the treatment arms. The 10-year OS was 85% in the ABVD arm, 84% in the BEACOPP arm, and 86% in the CEC arm (P=0.892).
There were a total of 13 second malignancies—1 in the ABVD arm and 6 each in the BEACOPP and CEC arms.
The cumulative risk of developing a second malignancy at 10 years was 0.9% in the ABVD arm, 6.6% in the BEACOPP arm, and 6% in the CEC arm. So the risk with either BEACOPP or CEC was significantly higher than with ABVD (P=0.027 and 0.02, respectively).
The researchers said these results suggest BEACOPP provides better disease control than ABVD, but this benefit is counterbalanced by a higher rate of late major events with BEACOPP, particularly second malignancies, which resulted in patient deaths.
So the team concluded that BEACOPP is a viable treatment option for advanced HL, but it should not be considered the standard for all patients because 70% of these patients may be cured with ABVD and limited radiotherapy. A careful assessment of the risk-benefit ratio of the initial treatment choice is warranted.
Photo by Bill Branson
Long-term results of the HD2000 trial reveal similar survival rates in patients with previously untreated, aggressive Hodgkin lymphoma (HL) who received 3 different combination treatment regimens.
At 10 years of follow-up, there was no significant difference in overall survival (OS) or progression-free survival (PFS) whether patients received ABVD, BEACOPP, or CEC.
However, patients who received ABVD were significantly less likely than those who received BEACOPP or CEC to develop second malignancies.
Francesco Merli, MD, of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Italy, and his colleagues reported these results in the Journal of Clinical Oncology.
The trial enrolled 307 patients with advanced-stage HL. Patients were randomized to receive 1 of 3 treatment regimens:
- Six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)
- Four escalated plus 2 standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)
- Six cycles of CEC (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin).
Some patients also received radiotherapy, but there was no significant difference in the proportion of patients receiving radiotherapy across the treatment arms—46% in the ABVD arm, 44% in the BEACOPP arm, and 43% in the CEC arm (P=0.871).
Results
At the end of all therapy, the complete response rate was 84% with ABVD, 91% with BEACOPP, and 83% with CEC.
There were 84 patients who did not achieve a complete response, and salvage data were available for 73 of these patients. Three patients (4%) died before salvage therapy could begin, 26 (36%) received conventional chemotherapy, 40 (55%) received a hematopoietic stem cell transplant, and 4 (5%) received radiotherapy.
The median follow-up was 120 months (range, 4 to 169 months), and 295 patients were evaluable.
In a previous analysis, at a median follow-up of 42 months, patients who received BEACOPP had superior PFS compared to patients who received ABVD.
However, in the current analysis, there was no significant difference in PFS between the 3 treatment arms. The 10-year PFS was 69% in the ABVD arm, 75% in the BEACOPP arm, and 76% in the CEC arm (P=0.471).
Likewise, there was no significant difference in OS between the treatment arms. The 10-year OS was 85% in the ABVD arm, 84% in the BEACOPP arm, and 86% in the CEC arm (P=0.892).
There were a total of 13 second malignancies—1 in the ABVD arm and 6 each in the BEACOPP and CEC arms.
The cumulative risk of developing a second malignancy at 10 years was 0.9% in the ABVD arm, 6.6% in the BEACOPP arm, and 6% in the CEC arm. So the risk with either BEACOPP or CEC was significantly higher than with ABVD (P=0.027 and 0.02, respectively).
The researchers said these results suggest BEACOPP provides better disease control than ABVD, but this benefit is counterbalanced by a higher rate of late major events with BEACOPP, particularly second malignancies, which resulted in patient deaths.
So the team concluded that BEACOPP is a viable treatment option for advanced HL, but it should not be considered the standard for all patients because 70% of these patients may be cured with ABVD and limited radiotherapy. A careful assessment of the risk-benefit ratio of the initial treatment choice is warranted.
Drug can reverse anticoagulant effect in emergencies
Photo by Piotr Bodzek
CHICAGO—Updated results from the RE-VERSE AD trial suggest idarucizumab, a humanized antibody fragment, can reverse the anticoagulant effect of dabigatran in emergency settings.
In this ongoing phase 3 trial, idarucizumab has normalized diluted thrombin time (dTT) and ecarin clotting time (ECT) in a majority of patients with uncontrolled or life-threatening bleeding and patients who required emergency surgery or an invasive procedure.
In addition, researchers said there have been no safety concerns related to idarucizumab in this trial.
These results were presented at the American College of Cardiology’s 65th Annual Scientific Session (abstract 1130M-05). The study was sponsored by Boehringer Ingelheim, the company that developed idarucizumab and dabigatran.
“The data from this new RE-VERSE AD interim analysis, of the first 123 patients, support earlier findings that show idarucizumab reverses the anticoagulant effect of dabigatran, including reversal in critically ill, high-risk patients in emergency care,” said Charles Pollack, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
Dr Pollack and his colleagues presented data on 123 patients—66 with uncontrolled or life-threatening bleeding complications (Group A) and 57 patients requiring emergency surgery or an invasive procedure (Group B).
All of these patients received 5 g of idarucizumab. The primary endpoint of the study is the degree to which idarucizumab reversed the anticoagulant effect of dabigatran within 4 hours, measured by dTT and ECT.
Overall, 94 patients were evaluable for dTT and 112 for ECT. So 97% of evaluable patients (91/94) achieved full reversal of dTT, and 87% (97/112) achieved full reversal of ECT.
Among evaluable patients in Group A (n=48), the median subjective investigator-reported time to cessation of bleeding was 9.8 hours. For 92% of patients (44/48), bleeding stopped within 72 hours of idarucizumab administration.
Among evaluable patients in Group B (n=52), the mean time to surgery was 1.7 hours after receiving idarucizumab. Normal hemostasis during surgery was reported in 92% of patients (48/52).
Thromboembolic events occurred in 5 patients after idarucizumab administration—1 each at 48 hours, 7 days, 9 days, 13 days, and 24 days. None of these patients were receiving antithrombotic therapy at the time of their event.
However, most patients in both groups restarted anticoagulation after receiving idarucizumab—47 of 66 patients in Group A and 49 of 57 patients in Group B.
There were a total of 26 deaths—13 in each group. All of the deaths appeared to be related to the original reason for emergency admission to the hospital and/or to comorbidities.
Photo by Piotr Bodzek
CHICAGO—Updated results from the RE-VERSE AD trial suggest idarucizumab, a humanized antibody fragment, can reverse the anticoagulant effect of dabigatran in emergency settings.
In this ongoing phase 3 trial, idarucizumab has normalized diluted thrombin time (dTT) and ecarin clotting time (ECT) in a majority of patients with uncontrolled or life-threatening bleeding and patients who required emergency surgery or an invasive procedure.
In addition, researchers said there have been no safety concerns related to idarucizumab in this trial.
These results were presented at the American College of Cardiology’s 65th Annual Scientific Session (abstract 1130M-05). The study was sponsored by Boehringer Ingelheim, the company that developed idarucizumab and dabigatran.
“The data from this new RE-VERSE AD interim analysis, of the first 123 patients, support earlier findings that show idarucizumab reverses the anticoagulant effect of dabigatran, including reversal in critically ill, high-risk patients in emergency care,” said Charles Pollack, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
Dr Pollack and his colleagues presented data on 123 patients—66 with uncontrolled or life-threatening bleeding complications (Group A) and 57 patients requiring emergency surgery or an invasive procedure (Group B).
All of these patients received 5 g of idarucizumab. The primary endpoint of the study is the degree to which idarucizumab reversed the anticoagulant effect of dabigatran within 4 hours, measured by dTT and ECT.
Overall, 94 patients were evaluable for dTT and 112 for ECT. So 97% of evaluable patients (91/94) achieved full reversal of dTT, and 87% (97/112) achieved full reversal of ECT.
Among evaluable patients in Group A (n=48), the median subjective investigator-reported time to cessation of bleeding was 9.8 hours. For 92% of patients (44/48), bleeding stopped within 72 hours of idarucizumab administration.
Among evaluable patients in Group B (n=52), the mean time to surgery was 1.7 hours after receiving idarucizumab. Normal hemostasis during surgery was reported in 92% of patients (48/52).
Thromboembolic events occurred in 5 patients after idarucizumab administration—1 each at 48 hours, 7 days, 9 days, 13 days, and 24 days. None of these patients were receiving antithrombotic therapy at the time of their event.
However, most patients in both groups restarted anticoagulation after receiving idarucizumab—47 of 66 patients in Group A and 49 of 57 patients in Group B.
There were a total of 26 deaths—13 in each group. All of the deaths appeared to be related to the original reason for emergency admission to the hospital and/or to comorbidities.
Photo by Piotr Bodzek
CHICAGO—Updated results from the RE-VERSE AD trial suggest idarucizumab, a humanized antibody fragment, can reverse the anticoagulant effect of dabigatran in emergency settings.
In this ongoing phase 3 trial, idarucizumab has normalized diluted thrombin time (dTT) and ecarin clotting time (ECT) in a majority of patients with uncontrolled or life-threatening bleeding and patients who required emergency surgery or an invasive procedure.
In addition, researchers said there have been no safety concerns related to idarucizumab in this trial.
These results were presented at the American College of Cardiology’s 65th Annual Scientific Session (abstract 1130M-05). The study was sponsored by Boehringer Ingelheim, the company that developed idarucizumab and dabigatran.
“The data from this new RE-VERSE AD interim analysis, of the first 123 patients, support earlier findings that show idarucizumab reverses the anticoagulant effect of dabigatran, including reversal in critically ill, high-risk patients in emergency care,” said Charles Pollack, MD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
Dr Pollack and his colleagues presented data on 123 patients—66 with uncontrolled or life-threatening bleeding complications (Group A) and 57 patients requiring emergency surgery or an invasive procedure (Group B).
All of these patients received 5 g of idarucizumab. The primary endpoint of the study is the degree to which idarucizumab reversed the anticoagulant effect of dabigatran within 4 hours, measured by dTT and ECT.
Overall, 94 patients were evaluable for dTT and 112 for ECT. So 97% of evaluable patients (91/94) achieved full reversal of dTT, and 87% (97/112) achieved full reversal of ECT.
Among evaluable patients in Group A (n=48), the median subjective investigator-reported time to cessation of bleeding was 9.8 hours. For 92% of patients (44/48), bleeding stopped within 72 hours of idarucizumab administration.
Among evaluable patients in Group B (n=52), the mean time to surgery was 1.7 hours after receiving idarucizumab. Normal hemostasis during surgery was reported in 92% of patients (48/52).
Thromboembolic events occurred in 5 patients after idarucizumab administration—1 each at 48 hours, 7 days, 9 days, 13 days, and 24 days. None of these patients were receiving antithrombotic therapy at the time of their event.
However, most patients in both groups restarted anticoagulation after receiving idarucizumab—47 of 66 patients in Group A and 49 of 57 patients in Group B.
There were a total of 26 deaths—13 in each group. All of the deaths appeared to be related to the original reason for emergency admission to the hospital and/or to comorbidities.
Team produces heparin using human cells
Photo by Daniel Sone
SAN DIEGO—Researchers say they have discovered a way to make the anticoagulant heparin using human cells.
The team found they could produce heparin from human embryonic kidney cells transfected with the serglycin gene.
They believe this new method could offer a safer alternative to current heparin production methods, which rely on animal byproducts that are largely sourced in China.
However, the researchers noted that their recombinant human heparin was substantially less potent than porcine heparin. So more work must be done to increase the anticoagulant activity of the human heparin.
John Whitelock, PhD, of the University of New South Wales in Sydney, Australia, and his colleagues generated the recombinant human heparin and described their work in a poster presented at Experimental Biology 2016.
“What we’ve done is looked at the way our cells naturally make heparin in our bodies, taken that gene, and expressed it in cells in the laboratory,” Dr Whitelock explained. “The result is a natural product that is not synthetic, which makes it safer than the animal-sourced material.”
Specifically, the researchers increased the expression of serglycin in human embryonic kidney (HEK-293) cells and were able to produce heparin.
The team compared the anticoagulant activity of this heparin and unfractionated porcine mucosal heparin, and they found the porcine heparin was approximately 20 times more potent than the human heparin, on a weight basis.
However, the recombinant human heparin was able to significantly delay fibrin clot formation in plasma when compared to no heparin.
“Frankly, we were surprised that there was any anticoagulant effect at all,” Dr Whitelock said. “People in this field have been working with serglycin for upwards of 20 years, and, usually, you get a sort of heparin ‘cousin’ but not real heparin. It’s been a great source of frustration, and our study is an important step toward an alternative source of heparin that could have distinct advantages for patient safety.”
The team’s next steps are to refine the engineered cells to increase the amount and potency of the heparin they produce.
Dr Whitelock estimates heparin produced with the new method could hit the market within 10 to 15 years, although he cautioned that the drug will likely be more expensive than traditional animal-derived heparin because of the economies of scale that are already built into the existing supply chain.
However, human-cell-derived heparin could potentially be safer, less prone to contamination and adverse reactions, and a better option for patients who cannot use animal-derived heparin due to religious or dietary restrictions.
Photo by Daniel Sone
SAN DIEGO—Researchers say they have discovered a way to make the anticoagulant heparin using human cells.
The team found they could produce heparin from human embryonic kidney cells transfected with the serglycin gene.
They believe this new method could offer a safer alternative to current heparin production methods, which rely on animal byproducts that are largely sourced in China.
However, the researchers noted that their recombinant human heparin was substantially less potent than porcine heparin. So more work must be done to increase the anticoagulant activity of the human heparin.
John Whitelock, PhD, of the University of New South Wales in Sydney, Australia, and his colleagues generated the recombinant human heparin and described their work in a poster presented at Experimental Biology 2016.
“What we’ve done is looked at the way our cells naturally make heparin in our bodies, taken that gene, and expressed it in cells in the laboratory,” Dr Whitelock explained. “The result is a natural product that is not synthetic, which makes it safer than the animal-sourced material.”
Specifically, the researchers increased the expression of serglycin in human embryonic kidney (HEK-293) cells and were able to produce heparin.
The team compared the anticoagulant activity of this heparin and unfractionated porcine mucosal heparin, and they found the porcine heparin was approximately 20 times more potent than the human heparin, on a weight basis.
However, the recombinant human heparin was able to significantly delay fibrin clot formation in plasma when compared to no heparin.
“Frankly, we were surprised that there was any anticoagulant effect at all,” Dr Whitelock said. “People in this field have been working with serglycin for upwards of 20 years, and, usually, you get a sort of heparin ‘cousin’ but not real heparin. It’s been a great source of frustration, and our study is an important step toward an alternative source of heparin that could have distinct advantages for patient safety.”
The team’s next steps are to refine the engineered cells to increase the amount and potency of the heparin they produce.
Dr Whitelock estimates heparin produced with the new method could hit the market within 10 to 15 years, although he cautioned that the drug will likely be more expensive than traditional animal-derived heparin because of the economies of scale that are already built into the existing supply chain.
However, human-cell-derived heparin could potentially be safer, less prone to contamination and adverse reactions, and a better option for patients who cannot use animal-derived heparin due to religious or dietary restrictions.
Photo by Daniel Sone
SAN DIEGO—Researchers say they have discovered a way to make the anticoagulant heparin using human cells.
The team found they could produce heparin from human embryonic kidney cells transfected with the serglycin gene.
They believe this new method could offer a safer alternative to current heparin production methods, which rely on animal byproducts that are largely sourced in China.
However, the researchers noted that their recombinant human heparin was substantially less potent than porcine heparin. So more work must be done to increase the anticoagulant activity of the human heparin.
John Whitelock, PhD, of the University of New South Wales in Sydney, Australia, and his colleagues generated the recombinant human heparin and described their work in a poster presented at Experimental Biology 2016.
“What we’ve done is looked at the way our cells naturally make heparin in our bodies, taken that gene, and expressed it in cells in the laboratory,” Dr Whitelock explained. “The result is a natural product that is not synthetic, which makes it safer than the animal-sourced material.”
Specifically, the researchers increased the expression of serglycin in human embryonic kidney (HEK-293) cells and were able to produce heparin.
The team compared the anticoagulant activity of this heparin and unfractionated porcine mucosal heparin, and they found the porcine heparin was approximately 20 times more potent than the human heparin, on a weight basis.
However, the recombinant human heparin was able to significantly delay fibrin clot formation in plasma when compared to no heparin.
“Frankly, we were surprised that there was any anticoagulant effect at all,” Dr Whitelock said. “People in this field have been working with serglycin for upwards of 20 years, and, usually, you get a sort of heparin ‘cousin’ but not real heparin. It’s been a great source of frustration, and our study is an important step toward an alternative source of heparin that could have distinct advantages for patient safety.”
The team’s next steps are to refine the engineered cells to increase the amount and potency of the heparin they produce.
Dr Whitelock estimates heparin produced with the new method could hit the market within 10 to 15 years, although he cautioned that the drug will likely be more expensive than traditional animal-derived heparin because of the economies of scale that are already built into the existing supply chain.
However, human-cell-derived heparin could potentially be safer, less prone to contamination and adverse reactions, and a better option for patients who cannot use animal-derived heparin due to religious or dietary restrictions.
EMA recommends orphan designation for cancer vaccine
The European Medicines Agency (EMA) has recommended orphan designation for the WT1 cancer vaccine galinpepimut-S as a treatment for patients
with acute myeloid leukemia (AML) and patients with malignant pleural mesothelioma (MPM).
The EMA’s opinion has been forwarded to the European Commission (EC), which makes the final decision.
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.
Orphan designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is approved for use.
About the vaccine
The WT1 vaccine consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the WT1 antigen. The vaccine is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.
Based on the vaccine’s mechanism and the accumulating evidence of activity in mid-stage trials, researchers believe the WT1 vaccine may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors.
The WT1 vaccine could potentially target more than 20 cancers that overexpress WT1, many of which are associated with relapse rates of up to 80% or more, as seen in patients with AML and MPM.
The vaccine is being developed by SELLAS Life Sciences Group. The company said that, in a phase 1 study, AML patients treated with the vaccine had a median overall survival of more than 3 years.
In a phase 2 trial of the vaccine, adult AML patients had a median overall survival of around 4 years. Data from the phase 2 trial are scheduled to be presented at the 2016 ASCO Annual Meeting.
SELLAS said it expects to begin a phase 3 trial of the vaccine in AML patients later this year.
The European Medicines Agency (EMA) has recommended orphan designation for the WT1 cancer vaccine galinpepimut-S as a treatment for patients
with acute myeloid leukemia (AML) and patients with malignant pleural mesothelioma (MPM).
The EMA’s opinion has been forwarded to the European Commission (EC), which makes the final decision.
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.
Orphan designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is approved for use.
About the vaccine
The WT1 vaccine consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the WT1 antigen. The vaccine is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.
Based on the vaccine’s mechanism and the accumulating evidence of activity in mid-stage trials, researchers believe the WT1 vaccine may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors.
The WT1 vaccine could potentially target more than 20 cancers that overexpress WT1, many of which are associated with relapse rates of up to 80% or more, as seen in patients with AML and MPM.
The vaccine is being developed by SELLAS Life Sciences Group. The company said that, in a phase 1 study, AML patients treated with the vaccine had a median overall survival of more than 3 years.
In a phase 2 trial of the vaccine, adult AML patients had a median overall survival of around 4 years. Data from the phase 2 trial are scheduled to be presented at the 2016 ASCO Annual Meeting.
SELLAS said it expects to begin a phase 3 trial of the vaccine in AML patients later this year.
The European Medicines Agency (EMA) has recommended orphan designation for the WT1 cancer vaccine galinpepimut-S as a treatment for patients
with acute myeloid leukemia (AML) and patients with malignant pleural mesothelioma (MPM).
The EMA’s opinion has been forwarded to the European Commission (EC), which makes the final decision.
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.
Orphan designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is approved for use.
About the vaccine
The WT1 vaccine consists of 4 modified peptide chains that induce an innate immune response (CD4+/CD8+ T cells) against the WT1 antigen. The vaccine is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.
Based on the vaccine’s mechanism and the accumulating evidence of activity in mid-stage trials, researchers believe the WT1 vaccine may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors.
The WT1 vaccine could potentially target more than 20 cancers that overexpress WT1, many of which are associated with relapse rates of up to 80% or more, as seen in patients with AML and MPM.
The vaccine is being developed by SELLAS Life Sciences Group. The company said that, in a phase 1 study, AML patients treated with the vaccine had a median overall survival of more than 3 years.
In a phase 2 trial of the vaccine, adult AML patients had a median overall survival of around 4 years. Data from the phase 2 trial are scheduled to be presented at the 2016 ASCO Annual Meeting.
SELLAS said it expects to begin a phase 3 trial of the vaccine in AML patients later this year.
Haplo-HSCT approach appears safe, effective for nonmalignant disorders
Image courtesy of NIAID
VALENCIA, SPAIN—Interim results of a phase 1/2 trial suggest the adjunct T-cell therapy BPX-501 can safely accelerate immune recovery after haploidentical hematopoietic stem cell transplant (haplo-HSCT) in pediatric patients with nonmalignant disorders.
Twenty-four such patients received BPX-501 after haplo-HSCT on this trial.
At a median follow-up of 7 months, all 24 were still alive and disease-free.
In addition, the incidence of graft-versus-host disease (GVHD) was considered “very low.”
Pietro Merli, MD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results during the Presidential Symposium of the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) as abstract O007.*
The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.
About BPX-501
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 goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.
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. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.
About BP-004
In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.
At the EBMT meeting, investigators reported results in 41 patients treated on this trial.
Dr Merli presented data on the 24 patients with nonmalignant disorders, including Fanconi anemia (n=5), beta-thalassemia major (n=5), severe combined immunodeficiency (n=5), Wiskott-Aldrich syndrome (n=4), Diamond-Blackfan anemia (n=1), hemophagocytic lymphohistiocytosis (n=1), immune deficiency due to mutation of XIAP gene (n=1), osteopetrosis (n=1), and sickle cell disease (n=1).
All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis.
The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 105, 5 x 105, and 1 x 106 cells/kg.
In the phase 2 portion, patients received 1 X 106 BPX-501 cells/kg. Rimiducid was only to be used in the event of uncontrollable GVHD.
Results
The median time to platelet recovery was 10 days (range, 7-16), and the median time to neutrophil recovery was 15 days (range, 10-33).
At a median follow-up of 220 days (range, 61-486), there were no reports of transplant-related mortality.
All 24 patients were still alive and disease-free. And none of the patients developed post-transplant lymphoproliferative disorder.
The cumulative incidence of skin-only acute GVHD was 16.6% (n=4), and the cumulative incidence of mild chronic GVHD was 5% (n=1).
This trial also included 17 patients with acute leukemias. Results in these patients were presented at the EBMT meeting as abstract WP16.
*Information in the abstract differs from that presented at the meeting.
Image courtesy of NIAID
VALENCIA, SPAIN—Interim results of a phase 1/2 trial suggest the adjunct T-cell therapy BPX-501 can safely accelerate immune recovery after haploidentical hematopoietic stem cell transplant (haplo-HSCT) in pediatric patients with nonmalignant disorders.
Twenty-four such patients received BPX-501 after haplo-HSCT on this trial.
At a median follow-up of 7 months, all 24 were still alive and disease-free.
In addition, the incidence of graft-versus-host disease (GVHD) was considered “very low.”
Pietro Merli, MD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results during the Presidential Symposium of the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) as abstract O007.*
The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.
About BPX-501
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 goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.
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. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.
About BP-004
In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.
At the EBMT meeting, investigators reported results in 41 patients treated on this trial.
Dr Merli presented data on the 24 patients with nonmalignant disorders, including Fanconi anemia (n=5), beta-thalassemia major (n=5), severe combined immunodeficiency (n=5), Wiskott-Aldrich syndrome (n=4), Diamond-Blackfan anemia (n=1), hemophagocytic lymphohistiocytosis (n=1), immune deficiency due to mutation of XIAP gene (n=1), osteopetrosis (n=1), and sickle cell disease (n=1).
All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis.
The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 105, 5 x 105, and 1 x 106 cells/kg.
In the phase 2 portion, patients received 1 X 106 BPX-501 cells/kg. Rimiducid was only to be used in the event of uncontrollable GVHD.
Results
The median time to platelet recovery was 10 days (range, 7-16), and the median time to neutrophil recovery was 15 days (range, 10-33).
At a median follow-up of 220 days (range, 61-486), there were no reports of transplant-related mortality.
All 24 patients were still alive and disease-free. And none of the patients developed post-transplant lymphoproliferative disorder.
The cumulative incidence of skin-only acute GVHD was 16.6% (n=4), and the cumulative incidence of mild chronic GVHD was 5% (n=1).
This trial also included 17 patients with acute leukemias. Results in these patients were presented at the EBMT meeting as abstract WP16.
*Information in the abstract differs from that presented at the meeting.
Image courtesy of NIAID
VALENCIA, SPAIN—Interim results of a phase 1/2 trial suggest the adjunct T-cell therapy BPX-501 can safely accelerate immune recovery after haploidentical hematopoietic stem cell transplant (haplo-HSCT) in pediatric patients with nonmalignant disorders.
Twenty-four such patients received BPX-501 after haplo-HSCT on this trial.
At a median follow-up of 7 months, all 24 were still alive and disease-free.
In addition, the incidence of graft-versus-host disease (GVHD) was considered “very low.”
Pietro Merli, MD, of Bambino Gesù Children’s Hospital in Rome, Italy, presented these results during the Presidential Symposium of the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) as abstract O007.*
The trial, known as BP-004, was sponsored by Bellicum Pharmaceuticals, the company developing BPX-501.
About BPX-501
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 goal is to allow physicians to more safely perform haplo-HSCTs by giving patients BPX-501 to speed immune reconstitution and provide control over viral infections. But the technology is designed to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs.
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. The idea is that, if a patient develops severe GVHD, he can receive an infusion with the small molecule rimiducid. And this will trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.
About BP-004
In late 2014, Bellicum initiated BP-004, a phase 1/2 trial in children with leukemias, lymphomas, or orphan inherited blood disorders. The trial is being conducted in European and US pediatric transplant centers and is set to enroll up to 90 patients.
At the EBMT meeting, investigators reported results in 41 patients treated on this trial.
Dr Merli presented data on the 24 patients with nonmalignant disorders, including Fanconi anemia (n=5), beta-thalassemia major (n=5), severe combined immunodeficiency (n=5), Wiskott-Aldrich syndrome (n=4), Diamond-Blackfan anemia (n=1), hemophagocytic lymphohistiocytosis (n=1), immune deficiency due to mutation of XIAP gene (n=1), osteopetrosis (n=1), and sickle cell disease (n=1).
All of these patients received a T-cell-depleted haplo-HSCT without post-transplant GVHD prophylaxis.
The patients received BPX-501 within 14 ± 4 days after haplo-HSCT. The phase 1 portion of the trial consisted of a classical 3+3 design, with 3 cohorts receiving escalating doses of BPX-501 cells—2.5 x 105, 5 x 105, and 1 x 106 cells/kg.
In the phase 2 portion, patients received 1 X 106 BPX-501 cells/kg. Rimiducid was only to be used in the event of uncontrollable GVHD.
Results
The median time to platelet recovery was 10 days (range, 7-16), and the median time to neutrophil recovery was 15 days (range, 10-33).
At a median follow-up of 220 days (range, 61-486), there were no reports of transplant-related mortality.
All 24 patients were still alive and disease-free. And none of the patients developed post-transplant lymphoproliferative disorder.
The cumulative incidence of skin-only acute GVHD was 16.6% (n=4), and the cumulative incidence of mild chronic GVHD was 5% (n=1).
This trial also included 17 patients with acute leukemias. Results in these patients were presented at the EBMT meeting as abstract WP16.
*Information in the abstract differs from that presented at the meeting.