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CAR T-cell therapy granted orphan designation
The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for several hematologic malignancies.
This includes primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).
KTE-C19 previously received orphan designation from the FDA for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity.
KTE-C19 also has breakthrough therapy designation from the FDA as a treatment for DLBCL, PMBCL, and transformed FL.
About KTE-C19
KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target CD19. The product is being developed by Kite Pharma, Inc.
In a study published in the Journal of Clinical Oncology, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.
The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Thirteen patients were evaluable for response. The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with DLBCL, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.
Of the 4 patients with CLL, 3 had a CR, and 1 had a PR. All 3 CRs were ongoing at the time of publication, with the duration ranging from 14 months to 23 months.
Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the CR was 11 months at the time of publication.
KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.
Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.
KTE-C19 is currently under investigation in a phase 2 trial of refractory DLBCL, PMBCL, and transformed FL (ZUMA-1), a phase 2 trial of relapsed/refractory MCL (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult ALL (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric ALL (ZUMA-4).
Results from ZUMA-1 were recently presented at the 2016 AACR Annual Meeting (abstract CT135). 
The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for several hematologic malignancies.
This includes primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).
KTE-C19 previously received orphan designation from the FDA for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity.
KTE-C19 also has breakthrough therapy designation from the FDA as a treatment for DLBCL, PMBCL, and transformed FL.
About KTE-C19
KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target CD19. The product is being developed by Kite Pharma, Inc.
In a study published in the Journal of Clinical Oncology, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.
The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Thirteen patients were evaluable for response. The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with DLBCL, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.
Of the 4 patients with CLL, 3 had a CR, and 1 had a PR. All 3 CRs were ongoing at the time of publication, with the duration ranging from 14 months to 23 months.
Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the CR was 11 months at the time of publication.
KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.
Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.
KTE-C19 is currently under investigation in a phase 2 trial of refractory DLBCL, PMBCL, and transformed FL (ZUMA-1), a phase 2 trial of relapsed/refractory MCL (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult ALL (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric ALL (ZUMA-4).
Results from ZUMA-1 were recently presented at the 2016 AACR Annual Meeting (abstract CT135).
The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for several hematologic malignancies.
This includes primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).
KTE-C19 previously received orphan designation from the FDA for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity.
KTE-C19 also has breakthrough therapy designation from the FDA as a treatment for DLBCL, PMBCL, and transformed FL.
About KTE-C19
KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target CD19. The product is being developed by Kite Pharma, Inc.
In a study published in the Journal of Clinical Oncology, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.
The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Thirteen patients were evaluable for response. The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with DLBCL, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.
Of the 4 patients with CLL, 3 had a CR, and 1 had a PR. All 3 CRs were ongoing at the time of publication, with the duration ranging from 14 months to 23 months.
Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the CR was 11 months at the time of publication.
KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.
Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.
KTE-C19 is currently under investigation in a phase 2 trial of refractory DLBCL, PMBCL, and transformed FL (ZUMA-1), a phase 2 trial of relapsed/refractory MCL (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult ALL (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric ALL (ZUMA-4).
Results from ZUMA-1 were recently presented at the 2016 AACR Annual Meeting (abstract CT135).
Pre-treatment gut bacteria may predict risk of BSI
A new study suggests the composition of a cancer patient’s intestinal microbiome before treatment may predict his risk of developing a bloodstream infection (BSI) after treatment.
Researchers analyzed fecal samples from patients with non-Hodgkin lymphoma who were set to receive an allogeneic hematopoietic stem cell transplant (allo-HSCT) with myeloablative conditioning.
The team found that patients with less diversity in their fecal samples before this treatment were more likely to develop a BSI after.
Emmanuel Montassier, MD, PhD, of Nantes University Hospital in France, and his colleagues conducted this study and reported the result in Genome Medicine.
A previous study suggested that intestinal domination—when a single bacterial taxon occupies at least 30% of the microbiota—is associated with BSIs in patients undergoing allo-HSCT. However, the role of the intestinal microbiome before treatment was not clear.
So Dr Montassier and his colleagues set out to characterize the fecal microbiome before treatment. To do this, they sequenced the bacterial DNA of fecal samples from 28 patients with non-Hodgkin lymphoma.
The team collected the samples before patients began a 5-day myeloablative conditioning regimen (high-dose carmustine, etoposide, aracytine, and melphalan), followed by allo-HSCT on the seventh day.
Eleven of these patients developed a BSI at a mean of 12 days after sample collection. Two patients (18.2%) developed Enterococcus BSI, 4 (36.4%) developed Escherichia coli BSI, and 5 (45.5%) developed other Gammaproteobacteria BSI.
The researchers said that alpha diversity in samples from these patients was significantly lower than alpha diversity from patients who did not develop a BSI, with reduced evenness (Shannon index, Monte Carlo permuted t-test two-sided P value = 0.004) and reduced richness (Observed species, Monte Carlo permuted t-test two-sided P value = 0.001)
The team also noted that, compared to patients who did not develop a BSI, those who did had decreased abundance of Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella.
Using this information, the researchers developed a BSI risk index that could predict the likelihood of a BSI with 90% sensitivity and specificity.
“This method worked even better than we expected because we found a consistent difference between the gut bacteria in those who developed infections and those who did not,” said study author Dan Knights, PhD, of the University of Minnesota in Minneapolis.
“This research is an early demonstration that we may be able to use the bugs in our gut to predict infections and possibly develop new prognostic models in other diseases.”
Still, the researchers said these findings are based on a limited number of patients treated with the same regimen at a single clinic. So the next step for this research is to validate the findings in a much larger cohort including patients with different cancer types, different treatment types, and from multiple treatment centers.
“We still need to determine if these bacteria are playing any kind of causal role in the infections or if they are simply acting as biomarkers for some other predisposing condition in the patient,” Dr Montassier said.
A new study suggests the composition of a cancer patient’s intestinal microbiome before treatment may predict his risk of developing a bloodstream infection (BSI) after treatment.
Researchers analyzed fecal samples from patients with non-Hodgkin lymphoma who were set to receive an allogeneic hematopoietic stem cell transplant (allo-HSCT) with myeloablative conditioning.
The team found that patients with less diversity in their fecal samples before this treatment were more likely to develop a BSI after.
Emmanuel Montassier, MD, PhD, of Nantes University Hospital in France, and his colleagues conducted this study and reported the result in Genome Medicine.
A previous study suggested that intestinal domination—when a single bacterial taxon occupies at least 30% of the microbiota—is associated with BSIs in patients undergoing allo-HSCT. However, the role of the intestinal microbiome before treatment was not clear.
So Dr Montassier and his colleagues set out to characterize the fecal microbiome before treatment. To do this, they sequenced the bacterial DNA of fecal samples from 28 patients with non-Hodgkin lymphoma.
The team collected the samples before patients began a 5-day myeloablative conditioning regimen (high-dose carmustine, etoposide, aracytine, and melphalan), followed by allo-HSCT on the seventh day.
Eleven of these patients developed a BSI at a mean of 12 days after sample collection. Two patients (18.2%) developed Enterococcus BSI, 4 (36.4%) developed Escherichia coli BSI, and 5 (45.5%) developed other Gammaproteobacteria BSI.
The researchers said that alpha diversity in samples from these patients was significantly lower than alpha diversity from patients who did not develop a BSI, with reduced evenness (Shannon index, Monte Carlo permuted t-test two-sided P value = 0.004) and reduced richness (Observed species, Monte Carlo permuted t-test two-sided P value = 0.001)
The team also noted that, compared to patients who did not develop a BSI, those who did had decreased abundance of Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella.
Using this information, the researchers developed a BSI risk index that could predict the likelihood of a BSI with 90% sensitivity and specificity.
“This method worked even better than we expected because we found a consistent difference between the gut bacteria in those who developed infections and those who did not,” said study author Dan Knights, PhD, of the University of Minnesota in Minneapolis.
“This research is an early demonstration that we may be able to use the bugs in our gut to predict infections and possibly develop new prognostic models in other diseases.”
Still, the researchers said these findings are based on a limited number of patients treated with the same regimen at a single clinic. So the next step for this research is to validate the findings in a much larger cohort including patients with different cancer types, different treatment types, and from multiple treatment centers.
“We still need to determine if these bacteria are playing any kind of causal role in the infections or if they are simply acting as biomarkers for some other predisposing condition in the patient,” Dr Montassier said.
A new study suggests the composition of a cancer patient’s intestinal microbiome before treatment may predict his risk of developing a bloodstream infection (BSI) after treatment.
Researchers analyzed fecal samples from patients with non-Hodgkin lymphoma who were set to receive an allogeneic hematopoietic stem cell transplant (allo-HSCT) with myeloablative conditioning.
The team found that patients with less diversity in their fecal samples before this treatment were more likely to develop a BSI after.
Emmanuel Montassier, MD, PhD, of Nantes University Hospital in France, and his colleagues conducted this study and reported the result in Genome Medicine.
A previous study suggested that intestinal domination—when a single bacterial taxon occupies at least 30% of the microbiota—is associated with BSIs in patients undergoing allo-HSCT. However, the role of the intestinal microbiome before treatment was not clear.
So Dr Montassier and his colleagues set out to characterize the fecal microbiome before treatment. To do this, they sequenced the bacterial DNA of fecal samples from 28 patients with non-Hodgkin lymphoma.
The team collected the samples before patients began a 5-day myeloablative conditioning regimen (high-dose carmustine, etoposide, aracytine, and melphalan), followed by allo-HSCT on the seventh day.
Eleven of these patients developed a BSI at a mean of 12 days after sample collection. Two patients (18.2%) developed Enterococcus BSI, 4 (36.4%) developed Escherichia coli BSI, and 5 (45.5%) developed other Gammaproteobacteria BSI.
The researchers said that alpha diversity in samples from these patients was significantly lower than alpha diversity from patients who did not develop a BSI, with reduced evenness (Shannon index, Monte Carlo permuted t-test two-sided P value = 0.004) and reduced richness (Observed species, Monte Carlo permuted t-test two-sided P value = 0.001)
The team also noted that, compared to patients who did not develop a BSI, those who did had decreased abundance of Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella.
Using this information, the researchers developed a BSI risk index that could predict the likelihood of a BSI with 90% sensitivity and specificity.
“This method worked even better than we expected because we found a consistent difference between the gut bacteria in those who developed infections and those who did not,” said study author Dan Knights, PhD, of the University of Minnesota in Minneapolis.
“This research is an early demonstration that we may be able to use the bugs in our gut to predict infections and possibly develop new prognostic models in other diseases.”
Still, the researchers said these findings are based on a limited number of patients treated with the same regimen at a single clinic. So the next step for this research is to validate the findings in a much larger cohort including patients with different cancer types, different treatment types, and from multiple treatment centers.
“We still need to determine if these bacteria are playing any kind of causal role in the infections or if they are simply acting as biomarkers for some other predisposing condition in the patient,” Dr Montassier said.
Current cancer drug discovery method flawed, team says
Image courtesy of PNAS
The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.
Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.
They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.
“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.
“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”
For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.
However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.
“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”
In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.
Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.
The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.
In one cell line, the team found a stark disagreement between the two metrics.
“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.
“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”
The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”
These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.
The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.
“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”
Image courtesy of PNAS
The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.
Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.
They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.
“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.
“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”
For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.
However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.
“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”
In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.
Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.
The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.
In one cell line, the team found a stark disagreement between the two metrics.
“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.
“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”
The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”
These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.
The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.
“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”
Image courtesy of PNAS
The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.
Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.
They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.
“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.
“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”
For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.
However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.
“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”
In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.
Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.
The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.
In one cell line, the team found a stark disagreement between the two metrics.
“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.
“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”
The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”
These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.
The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.
“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”
Therapy may reduce memory problems related to chemo
patient and her father
Photo by Rhoda Baer
A type of cognitive behavioral therapy may help prevent some of the long-term memory issues caused by chemotherapy, according to research published in Cancer.
The therapy is called “Memory and Attention Adaptation Training” (MAAT).
It’s designed to help cancer survivors increase awareness of situations where memory problems can arise and develop skills to either prevent memory failure or compensate for memory dysfunction.
MAAT was developed by Robert Ferguson, PhD, of the University of Pittsburgh Cancer Institute in Pennsylvania, and his colleagues.
The researchers tested MAAT in a small, randomized study of 47 Caucasian breast cancer survivors who were an average of 4 years post-chemotherapy.
The patients were assigned to 8 visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for an identical time span. The intent of the supportive therapy was to control for the simple effects of interacting with a supportive clinician, or “behavioral placebo.”
Both treatments were delivered over a videoconference network between health centers to minimize patient travel.
All participants completed questionnaires assessing perceived memory difficulty and anxiety about memory problems. They were also tested over the phone with neuropsychological tests of verbal memory and processing speed, or the ability to automatically and fluently perform relatively easy cognitive tasks.
Participants were evaluated again after the 8 MAAT and supportive therapy videoconference visits, as well as 2 months after the conclusion of these therapies.
Compared with participants who received supportive therapy, MAAT participants reported significantly fewer memory problems (P=0.02) and improved processing speed post-treatment (P=0.03).
MAAT participants also reported less anxiety about cognitive problems compared with supportive therapy participants 2 months after MAAT concluded, but this was not a statistically significant finding.
“This is what we believe is the first randomized study with an active control condition that demonstrates improvement in cognitive symptoms in breast cancer survivors with long-term memory complaints,” Dr Ferguson said. “MAAT participants reported reduced anxiety and high satisfaction with this cognitive behavioral, non-drug approach.”
“Because treatment was delivered over videoconference device, this study demonstrates MAAT can be delivered electronically and survivors can reduce or eliminate travel to a cancer center. This can improve access to survivorship care.”
Dr Ferguson also noted that more research on MAAT is needed using a larger number of individuals with varied ethnic and cultural backgrounds and multiple clinicians delivering treatment.
patient and her father
Photo by Rhoda Baer
A type of cognitive behavioral therapy may help prevent some of the long-term memory issues caused by chemotherapy, according to research published in Cancer.
The therapy is called “Memory and Attention Adaptation Training” (MAAT).
It’s designed to help cancer survivors increase awareness of situations where memory problems can arise and develop skills to either prevent memory failure or compensate for memory dysfunction.
MAAT was developed by Robert Ferguson, PhD, of the University of Pittsburgh Cancer Institute in Pennsylvania, and his colleagues.
The researchers tested MAAT in a small, randomized study of 47 Caucasian breast cancer survivors who were an average of 4 years post-chemotherapy.
The patients were assigned to 8 visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for an identical time span. The intent of the supportive therapy was to control for the simple effects of interacting with a supportive clinician, or “behavioral placebo.”
Both treatments were delivered over a videoconference network between health centers to minimize patient travel.
All participants completed questionnaires assessing perceived memory difficulty and anxiety about memory problems. They were also tested over the phone with neuropsychological tests of verbal memory and processing speed, or the ability to automatically and fluently perform relatively easy cognitive tasks.
Participants were evaluated again after the 8 MAAT and supportive therapy videoconference visits, as well as 2 months after the conclusion of these therapies.
Compared with participants who received supportive therapy, MAAT participants reported significantly fewer memory problems (P=0.02) and improved processing speed post-treatment (P=0.03).
MAAT participants also reported less anxiety about cognitive problems compared with supportive therapy participants 2 months after MAAT concluded, but this was not a statistically significant finding.
“This is what we believe is the first randomized study with an active control condition that demonstrates improvement in cognitive symptoms in breast cancer survivors with long-term memory complaints,” Dr Ferguson said. “MAAT participants reported reduced anxiety and high satisfaction with this cognitive behavioral, non-drug approach.”
“Because treatment was delivered over videoconference device, this study demonstrates MAAT can be delivered electronically and survivors can reduce or eliminate travel to a cancer center. This can improve access to survivorship care.”
Dr Ferguson also noted that more research on MAAT is needed using a larger number of individuals with varied ethnic and cultural backgrounds and multiple clinicians delivering treatment.
patient and her father
Photo by Rhoda Baer
A type of cognitive behavioral therapy may help prevent some of the long-term memory issues caused by chemotherapy, according to research published in Cancer.
The therapy is called “Memory and Attention Adaptation Training” (MAAT).
It’s designed to help cancer survivors increase awareness of situations where memory problems can arise and develop skills to either prevent memory failure or compensate for memory dysfunction.
MAAT was developed by Robert Ferguson, PhD, of the University of Pittsburgh Cancer Institute in Pennsylvania, and his colleagues.
The researchers tested MAAT in a small, randomized study of 47 Caucasian breast cancer survivors who were an average of 4 years post-chemotherapy.
The patients were assigned to 8 visits of MAAT (30 to 45 minutes each visit) or supportive talk therapy for an identical time span. The intent of the supportive therapy was to control for the simple effects of interacting with a supportive clinician, or “behavioral placebo.”
Both treatments were delivered over a videoconference network between health centers to minimize patient travel.
All participants completed questionnaires assessing perceived memory difficulty and anxiety about memory problems. They were also tested over the phone with neuropsychological tests of verbal memory and processing speed, or the ability to automatically and fluently perform relatively easy cognitive tasks.
Participants were evaluated again after the 8 MAAT and supportive therapy videoconference visits, as well as 2 months after the conclusion of these therapies.
Compared with participants who received supportive therapy, MAAT participants reported significantly fewer memory problems (P=0.02) and improved processing speed post-treatment (P=0.03).
MAAT participants also reported less anxiety about cognitive problems compared with supportive therapy participants 2 months after MAAT concluded, but this was not a statistically significant finding.
“This is what we believe is the first randomized study with an active control condition that demonstrates improvement in cognitive symptoms in breast cancer survivors with long-term memory complaints,” Dr Ferguson said. “MAAT participants reported reduced anxiety and high satisfaction with this cognitive behavioral, non-drug approach.”
“Because treatment was delivered over videoconference device, this study demonstrates MAAT can be delivered electronically and survivors can reduce or eliminate travel to a cancer center. This can improve access to survivorship care.”
Dr Ferguson also noted that more research on MAAT is needed using a larger number of individuals with varied ethnic and cultural backgrounds and multiple clinicians delivering treatment.
Current cancer drug discovery method flawed, team says
Image courtesy of PNAS
The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.
Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.
They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.
“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.
“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”
For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.
However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.
“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”
In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.
Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.
The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.
In one cell line, the team found a stark disagreement between the two metrics.
“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.
“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”
The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”
These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.
The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.
“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”
Image courtesy of PNAS
The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.
Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.
They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.
“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.
“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”
For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.
However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.
“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”
In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.
Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.
The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.
In one cell line, the team found a stark disagreement between the two metrics.
“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.
“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”
The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”
These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.
The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.
“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”
Image courtesy of PNAS
The primary method used to test compounds for anticancer activity in vitro may produce inaccurate results, according to researchers.
Therefore, they have developed a new metric to evaluate a compound’s effect on cell proliferation—the drug-induced proliferation (DIP) rate.
They believe this metric, described in Nature Methods, overcomes the time-dependent bias of traditional proliferation assays.
“More than 90% of candidate cancer drugs fail in late-stage clinical trials, costing hundreds of millions of dollars,” said study author Vito Quaranta, MD, of Vanderbilt University School of Medicine in Nashville, Tennessee.
“The flawed in vitro drug discovery metric may not be the only responsible factor, but it may be worth pursuing an estimate of its impact.”
For more than 30 years, scientists have evaluated the ability of a compound to kill cells by adding the compound and counting how many cells are alive after 72 hours.
However, these proliferation assays, which measure cell number at a single time point, don’t take into account the bias introduced by exponential cell proliferation, even in the presence of the drug, said study author Darren Tyson, PhD, of Vanderbilt University School of Medicine.
“Cells are not uniform,” added Dr Quaranta. “They all proliferate exponentially but at different rates. At 72 hours, some cells will have doubled 3 times, and others will not have doubled at all.”
In addition, he noted, drugs don’t all behave the same way on every cell line. For example, a drug might have an immediate effect on one cell line and a delayed effect on another.
Therefore, he and his colleagues used a systems biology approach to demonstrate the time-dependent bias in static proliferation assays and to develop the time-independent DIP rate metric.
The researchers evaluated the responses of 4 different melanoma cell lines to the drug vemurafenib, currently used to treat melanoma, with the standard metric and with the DIP rate.
In one cell line, the team found a stark disagreement between the two metrics.
“The static metric says that the cell line is very sensitive to vemurafenib,” said Leonard Harris, PhD, of Vanderbilt University School of Medicine.
“However, our analysis shows this is not the case. A brief period of drug sensitivity, quickly followed by rebound, fools the static metric but not the DIP rate.”
The findings “suggest we should expect melanoma tumors treated with this drug to come back, and that’s what has happened, puzzling investigators,” Dr Quaranta said. “DIP rate analyses may help solve this conundrum, leading to better treatment strategies.”
These findings have particular importance in light of recent international efforts to generate data sets that include the responses of “thousands of cell lines to hundreds of compounds,” Dr Quaranta said.
The Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases include drug response data along with genomic and proteomic data that detail each cell line’s molecular makeup.
“The idea is to look for statistical correlations—these particular cell lines with this particular makeup are sensitive to these types of compounds—to use these large databases as discovery tools for new therapeutic targets in cancer,” Dr Quaranta said. “If the metric by which you’ve evaluated the drug sensitivity of the cells is wrong, your statistical correlations are basically no good.”
Radiotherapy trial results going unpublished
woman for radiotherapy
Photo by Rhoda Baer
TURIN, ITALY—Results from many phase 3 radiotherapy trials conducted in the US are not being published on ClincalTrials.gov, according to a study presented at ESTRO 35.
Since 2007, it has been mandatory to publish the results of clinical trials carried out in the US on ClinicalTrials.gov within 12 months of trial completion.
However, an analysis of more than 800 radiotherapy trials revealed that more than 80% did not meet this requirement.
Jaime Pérez-Alija, of Hospital Plató in Barcelona, Spain, and his colleagues presented these results at ESTRO 35 as abstract PV-0087.
In 2007, the Food and Drug Administration Amendments Act (FDAAA) mandated that sponsors of most US trials begin registering and reporting basic summary results on ClinicalTrials.gov so the American public could have access to the resulting data.
The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.
To investigate how well this mandate has been followed by sponsors of phase 3 radiotherapy trials, Pérez-Alija and his colleagues analyzed 802 trials with a primary completion date prior to January 1, 2013.
The team found that 81.7% of these trials (n=655) did not have even summary results published on ClinicalTrials.gov.
The researchers also looked specifically at those trials that began after the 2007 act was passed and found that 76.4% of these trials (422/552) did not have results published.
When the researchers looked at publication by cancer type, they found that 78% of lymphoma trial results were unpublished.
The most-published cancer type was glioblastoma, with 62.5% of results unpublished. And the least-published cancer types were anal and testicular cancers, for which 100% of trial results were unpublished.
“These findings came as a surprise for many reasons, not least of which was that many of the trials had been funded by the US National Institutes of Health,” Pérez-Alija said.
“Interestingly, we found that company-funded trials are far better at complying with the rules than academic trials—55% and 30% respectively. However, only one-third of all the trials we studied were company trials. Since we know that clinical trials produce the best data for decision-making in modern evidenced-based medicine, it is particularly worrying that the law is being ignored on such a wide scale.”
One possible reason for non-publication, according to the researchers, is that some of the trials may have been granted a deadline extension. However, if this is the case, it is not publicly known.
“Therefore, our first problem is that we do not know with any certainty whether a trial is truly overdue,” Pérez-Alija said. “The registry says clearly that all dates must be updated if an extension has been allowed, but it seems likely that this is not happening in many cases.”
The researchers are investigating the issue further to see, for example, how many of the trials registered in ClinicalTrials.gov or in other databases are being published in medical journals.
They intend to email principal investigators to ask why the mandatory deposition of results did not take place and to enquire about the reasons for non-publication in medical journals of those trials where there is a published deposition.
“We have shown that a large number of study participants are routinely exposed to the risks of trial participation without the benefits that sharing and publishing results would have for patients in the future,” Pérez-Alija said.
“Information about what was done and what was found in these trials could be lost forever, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated unnecessarily. This situation should not be allowed to continue.”
woman for radiotherapy
Photo by Rhoda Baer
TURIN, ITALY—Results from many phase 3 radiotherapy trials conducted in the US are not being published on ClincalTrials.gov, according to a study presented at ESTRO 35.
Since 2007, it has been mandatory to publish the results of clinical trials carried out in the US on ClinicalTrials.gov within 12 months of trial completion.
However, an analysis of more than 800 radiotherapy trials revealed that more than 80% did not meet this requirement.
Jaime Pérez-Alija, of Hospital Plató in Barcelona, Spain, and his colleagues presented these results at ESTRO 35 as abstract PV-0087.
In 2007, the Food and Drug Administration Amendments Act (FDAAA) mandated that sponsors of most US trials begin registering and reporting basic summary results on ClinicalTrials.gov so the American public could have access to the resulting data.
The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.
To investigate how well this mandate has been followed by sponsors of phase 3 radiotherapy trials, Pérez-Alija and his colleagues analyzed 802 trials with a primary completion date prior to January 1, 2013.
The team found that 81.7% of these trials (n=655) did not have even summary results published on ClinicalTrials.gov.
The researchers also looked specifically at those trials that began after the 2007 act was passed and found that 76.4% of these trials (422/552) did not have results published.
When the researchers looked at publication by cancer type, they found that 78% of lymphoma trial results were unpublished.
The most-published cancer type was glioblastoma, with 62.5% of results unpublished. And the least-published cancer types were anal and testicular cancers, for which 100% of trial results were unpublished.
“These findings came as a surprise for many reasons, not least of which was that many of the trials had been funded by the US National Institutes of Health,” Pérez-Alija said.
“Interestingly, we found that company-funded trials are far better at complying with the rules than academic trials—55% and 30% respectively. However, only one-third of all the trials we studied were company trials. Since we know that clinical trials produce the best data for decision-making in modern evidenced-based medicine, it is particularly worrying that the law is being ignored on such a wide scale.”
One possible reason for non-publication, according to the researchers, is that some of the trials may have been granted a deadline extension. However, if this is the case, it is not publicly known.
“Therefore, our first problem is that we do not know with any certainty whether a trial is truly overdue,” Pérez-Alija said. “The registry says clearly that all dates must be updated if an extension has been allowed, but it seems likely that this is not happening in many cases.”
The researchers are investigating the issue further to see, for example, how many of the trials registered in ClinicalTrials.gov or in other databases are being published in medical journals.
They intend to email principal investigators to ask why the mandatory deposition of results did not take place and to enquire about the reasons for non-publication in medical journals of those trials where there is a published deposition.
“We have shown that a large number of study participants are routinely exposed to the risks of trial participation without the benefits that sharing and publishing results would have for patients in the future,” Pérez-Alija said.
“Information about what was done and what was found in these trials could be lost forever, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated unnecessarily. This situation should not be allowed to continue.”
woman for radiotherapy
Photo by Rhoda Baer
TURIN, ITALY—Results from many phase 3 radiotherapy trials conducted in the US are not being published on ClincalTrials.gov, according to a study presented at ESTRO 35.
Since 2007, it has been mandatory to publish the results of clinical trials carried out in the US on ClinicalTrials.gov within 12 months of trial completion.
However, an analysis of more than 800 radiotherapy trials revealed that more than 80% did not meet this requirement.
Jaime Pérez-Alija, of Hospital Plató in Barcelona, Spain, and his colleagues presented these results at ESTRO 35 as abstract PV-0087.
In 2007, the Food and Drug Administration Amendments Act (FDAAA) mandated that sponsors of most US trials begin registering and reporting basic summary results on ClinicalTrials.gov so the American public could have access to the resulting data.
The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.
To investigate how well this mandate has been followed by sponsors of phase 3 radiotherapy trials, Pérez-Alija and his colleagues analyzed 802 trials with a primary completion date prior to January 1, 2013.
The team found that 81.7% of these trials (n=655) did not have even summary results published on ClinicalTrials.gov.
The researchers also looked specifically at those trials that began after the 2007 act was passed and found that 76.4% of these trials (422/552) did not have results published.
When the researchers looked at publication by cancer type, they found that 78% of lymphoma trial results were unpublished.
The most-published cancer type was glioblastoma, with 62.5% of results unpublished. And the least-published cancer types were anal and testicular cancers, for which 100% of trial results were unpublished.
“These findings came as a surprise for many reasons, not least of which was that many of the trials had been funded by the US National Institutes of Health,” Pérez-Alija said.
“Interestingly, we found that company-funded trials are far better at complying with the rules than academic trials—55% and 30% respectively. However, only one-third of all the trials we studied were company trials. Since we know that clinical trials produce the best data for decision-making in modern evidenced-based medicine, it is particularly worrying that the law is being ignored on such a wide scale.”
One possible reason for non-publication, according to the researchers, is that some of the trials may have been granted a deadline extension. However, if this is the case, it is not publicly known.
“Therefore, our first problem is that we do not know with any certainty whether a trial is truly overdue,” Pérez-Alija said. “The registry says clearly that all dates must be updated if an extension has been allowed, but it seems likely that this is not happening in many cases.”
The researchers are investigating the issue further to see, for example, how many of the trials registered in ClinicalTrials.gov or in other databases are being published in medical journals.
They intend to email principal investigators to ask why the mandatory deposition of results did not take place and to enquire about the reasons for non-publication in medical journals of those trials where there is a published deposition.
“We have shown that a large number of study participants are routinely exposed to the risks of trial participation without the benefits that sharing and publishing results would have for patients in the future,” Pérez-Alija said.
“Information about what was done and what was found in these trials could be lost forever, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated unnecessarily. This situation should not be allowed to continue.”
Study links radon and hematologic cancers in women
New research suggests there is a significant positive association between high levels of residential radon and the risk of hematologic malignancies in women.
The study is the first prospective, population-based study of residential radon exposure and hematologic malignancy risk.
Therefore, the researchers caution that it requires replication to better understand the association and whether it truly differs by sex.
Lauren Teras, PhD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in Environmental Research.
Radon is a naturally occurring byproduct of the decay of radium and is a known human lung carcinogen. It is the second-leading cause of lung cancer in the US.
Modeling studies have shown that radon delivers a non-negligible dose of alpha radiation to the bone marrow and therefore could increase the risk of hematologic malignancies. However, studies investigating the link between radon and hematologic malignancies have produced inconsistent results.
For the current study, Dr Teras and her colleagues used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort to examine the association between county-level residential radon exposure and the risk of hematologic cancer.
The analysis included 140,652 participants, including 3019 who had hematologic malignancies during 19 years of follow-up (1992 to 2011).
The researchers found that women living in counties with the highest mean radon concentration (> 148 Bq/m3) had a significantly higher risk of developing a hematologic malignancy than women living in counties with the lowest radon levels (< 74 Bq/m3).
The adjusted hazard ratio (adjusted for age, race, family history of hematologic malignancy, etc.) was 1.63 (P=0.0010).
The researchers also found evidence of a dose-response relationship, with an adjusted hazard ratio of 1.38 (P=0.001).
The team said there was evidence of a positive exposure-response relationship between radon concentration and the risk of all lymphoid malignancy subtypes in women. But the highest risk was observed for follicular lymphoma, with an adjusted hazard ratio of 2.74 (P=0.02).
On the other hand, there was a non-significant inverse association between radon and myeloid leukemias in women.
There was no association between hematologic malignancy and radon exposure among the men.
The researchers said a possible explanation for this finding is that men may have a higher baseline risk of hematologic malignancy, possibly because of more exposure to occupational or other risk factors, which would reduce the impact of any additional risk from residential radon.
In women, who have a smaller baseline risk, residential radon exposure might be a larger contributor to overall risk.
Another reason for the sex difference observed in this study may be that the women of this generation spent more time in their homes, so they had more residential exposure than men.
“The overall lifetime risk of hematological cancers in the United States is about 2%, so even a 60% relative increase would still mean a relatively small absolute risk,” Dr Teras noted.
“Nonetheless, radon is already associated with lung cancer, and if other studies confirm the link to blood cancers, we think it would warrant strengthened public health efforts to mitigate residential radon risks.”
New research suggests there is a significant positive association between high levels of residential radon and the risk of hematologic malignancies in women.
The study is the first prospective, population-based study of residential radon exposure and hematologic malignancy risk.
Therefore, the researchers caution that it requires replication to better understand the association and whether it truly differs by sex.
Lauren Teras, PhD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in Environmental Research.
Radon is a naturally occurring byproduct of the decay of radium and is a known human lung carcinogen. It is the second-leading cause of lung cancer in the US.
Modeling studies have shown that radon delivers a non-negligible dose of alpha radiation to the bone marrow and therefore could increase the risk of hematologic malignancies. However, studies investigating the link between radon and hematologic malignancies have produced inconsistent results.
For the current study, Dr Teras and her colleagues used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort to examine the association between county-level residential radon exposure and the risk of hematologic cancer.
The analysis included 140,652 participants, including 3019 who had hematologic malignancies during 19 years of follow-up (1992 to 2011).
The researchers found that women living in counties with the highest mean radon concentration (> 148 Bq/m3) had a significantly higher risk of developing a hematologic malignancy than women living in counties with the lowest radon levels (< 74 Bq/m3).
The adjusted hazard ratio (adjusted for age, race, family history of hematologic malignancy, etc.) was 1.63 (P=0.0010).
The researchers also found evidence of a dose-response relationship, with an adjusted hazard ratio of 1.38 (P=0.001).
The team said there was evidence of a positive exposure-response relationship between radon concentration and the risk of all lymphoid malignancy subtypes in women. But the highest risk was observed for follicular lymphoma, with an adjusted hazard ratio of 2.74 (P=0.02).
On the other hand, there was a non-significant inverse association between radon and myeloid leukemias in women.
There was no association between hematologic malignancy and radon exposure among the men.
The researchers said a possible explanation for this finding is that men may have a higher baseline risk of hematologic malignancy, possibly because of more exposure to occupational or other risk factors, which would reduce the impact of any additional risk from residential radon.
In women, who have a smaller baseline risk, residential radon exposure might be a larger contributor to overall risk.
Another reason for the sex difference observed in this study may be that the women of this generation spent more time in their homes, so they had more residential exposure than men.
“The overall lifetime risk of hematological cancers in the United States is about 2%, so even a 60% relative increase would still mean a relatively small absolute risk,” Dr Teras noted.
“Nonetheless, radon is already associated with lung cancer, and if other studies confirm the link to blood cancers, we think it would warrant strengthened public health efforts to mitigate residential radon risks.”
New research suggests there is a significant positive association between high levels of residential radon and the risk of hematologic malignancies in women.
The study is the first prospective, population-based study of residential radon exposure and hematologic malignancy risk.
Therefore, the researchers caution that it requires replication to better understand the association and whether it truly differs by sex.
Lauren Teras, PhD, of the American Cancer Society in Atlanta, Georgia, and her colleagues conducted this study and reported the results in Environmental Research.
Radon is a naturally occurring byproduct of the decay of radium and is a known human lung carcinogen. It is the second-leading cause of lung cancer in the US.
Modeling studies have shown that radon delivers a non-negligible dose of alpha radiation to the bone marrow and therefore could increase the risk of hematologic malignancies. However, studies investigating the link between radon and hematologic malignancies have produced inconsistent results.
For the current study, Dr Teras and her colleagues used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort to examine the association between county-level residential radon exposure and the risk of hematologic cancer.
The analysis included 140,652 participants, including 3019 who had hematologic malignancies during 19 years of follow-up (1992 to 2011).
The researchers found that women living in counties with the highest mean radon concentration (> 148 Bq/m3) had a significantly higher risk of developing a hematologic malignancy than women living in counties with the lowest radon levels (< 74 Bq/m3).
The adjusted hazard ratio (adjusted for age, race, family history of hematologic malignancy, etc.) was 1.63 (P=0.0010).
The researchers also found evidence of a dose-response relationship, with an adjusted hazard ratio of 1.38 (P=0.001).
The team said there was evidence of a positive exposure-response relationship between radon concentration and the risk of all lymphoid malignancy subtypes in women. But the highest risk was observed for follicular lymphoma, with an adjusted hazard ratio of 2.74 (P=0.02).
On the other hand, there was a non-significant inverse association between radon and myeloid leukemias in women.
There was no association between hematologic malignancy and radon exposure among the men.
The researchers said a possible explanation for this finding is that men may have a higher baseline risk of hematologic malignancy, possibly because of more exposure to occupational or other risk factors, which would reduce the impact of any additional risk from residential radon.
In women, who have a smaller baseline risk, residential radon exposure might be a larger contributor to overall risk.
Another reason for the sex difference observed in this study may be that the women of this generation spent more time in their homes, so they had more residential exposure than men.
“The overall lifetime risk of hematological cancers in the United States is about 2%, so even a 60% relative increase would still mean a relatively small absolute risk,” Dr Teras noted.
“Nonetheless, radon is already associated with lung cancer, and if other studies confirm the link to blood cancers, we think it would warrant strengthened public health efforts to mitigate residential radon risks.”
CHMP recommends approving drug to treat FL
The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody, be approved for use in patients with follicular lymphoma (FL).
The recommended indication is for obinutuzumab to be given first in combination with bendamustine and then as maintenance therapy in FL patients who did not respond to, progressed during, or progressed up to 6 months after treatment with rituximab or a rituximab-containing regimen.
Based on the CHMP’s recommendation, a final decision regarding the approval of obinutuzumab in FL is expected from the European Commission in the coming months.
Obinutuzumab is already approved in the European Union for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
Obinutuzumab is being developed by Roche.
GADOLIN trial
The CHMP’s recommendation to approve obinutuzumab in FL is based on results from the phase 3 GADOLIN trial. The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.
The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.
Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.
Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).
The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.
The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.
The median overall survival has not yet been reached in either study arm.
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).
The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).
The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody, be approved for use in patients with follicular lymphoma (FL).
The recommended indication is for obinutuzumab to be given first in combination with bendamustine and then as maintenance therapy in FL patients who did not respond to, progressed during, or progressed up to 6 months after treatment with rituximab or a rituximab-containing regimen.
Based on the CHMP’s recommendation, a final decision regarding the approval of obinutuzumab in FL is expected from the European Commission in the coming months.
Obinutuzumab is already approved in the European Union for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
Obinutuzumab is being developed by Roche.
GADOLIN trial
The CHMP’s recommendation to approve obinutuzumab in FL is based on results from the phase 3 GADOLIN trial. The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.
The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.
Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.
Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).
The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.
The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.
The median overall survival has not yet been reached in either study arm.
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).
The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).
The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody, be approved for use in patients with follicular lymphoma (FL).
The recommended indication is for obinutuzumab to be given first in combination with bendamustine and then as maintenance therapy in FL patients who did not respond to, progressed during, or progressed up to 6 months after treatment with rituximab or a rituximab-containing regimen.
Based on the CHMP’s recommendation, a final decision regarding the approval of obinutuzumab in FL is expected from the European Commission in the coming months.
Obinutuzumab is already approved in the European Union for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
Obinutuzumab is being developed by Roche.
GADOLIN trial
The CHMP’s recommendation to approve obinutuzumab in FL is based on results from the phase 3 GADOLIN trial. The study included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.
The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.
Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.
Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).
The best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.
The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.
The median overall survival has not yet been reached in either study arm.
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).
The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).
FDA authorizes first commercial Zika test
Photo by Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for another test designed to detect Zika virus infection.
The test, Zika Virus RNA Qualitative Real-Time RT-PCR test (Zika RT-PCR test), is intended for the qualitative detection of RNA from the Zika virus in human serum specimens from patients meeting criteria for testing outlined by the Centers for Disease Control and Prevention (CDC).
The Zika RT-PCR test is the first test from a commercial laboratory provider to be granted an EUA for testing patients for Zika virus RNA. The test was developed by Focus Diagnostics, Inc., a subsidiary of Quest Diagnostics.
About the EUA
The Zika RT-PCR test has not been FDA cleared or approved. An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The FDA issued the EUA for the Zika RT-PCR test based on data submitted by Focus Diagnostics, Inc., and on the US Secretary of Health and Human Services’ (HHS) declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and/or diagnosis of Zika virus infection.
This EUA will terminate when the HHS Secretary’s declaration terminates, unless the FDA revokes it sooner.
Until now, the only Zika tests authorized by the FDA under EUA were available from the CDC and were only used in qualified laboratories designated by the CDC. These are the Trioplex Real-time RT-PCR Assay and the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).
About the test
Quest Diagnostics plans to make the Zika RT-PCR test broadly available for patient testing early in the week of May 2.
The Zika RT-PCR test is intended for use by clinical laboratory personnel qualified by state and federal regulations who have received specific training on the use of the test in qualified laboratories designated by Focus Diagnostics, Inc., and certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high-complexity tests.
The test can potentially be performed at any CLIA high-complexity laboratory in the Quest Diagnostics network, which includes several dozen CLIA high-complexity labs in the US, including in Toa Baja, Puerto Rico.
Within the US, positive results of this test must be reported to the CDC.
The CDC recommends RT-PCR testing for Zika infection during approximately the first 7 days of the onset of symptoms for certain patients, including:
- Individuals with symptoms suggestive of Zika infection who have traveled within the last 2 weeks to an area with ongoing transmission
- Asymptomatic pregnant women with a history of residence in or travel to areas of active Zika infection
- Asymptomatic pregnant women whose male sexual partners have traveled to or lived in an area of active Zika infection
- Infants born to mothers who live in or traveled to areas with Zika virus transmission during their pregnancy, including both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection.
A negative test result does not preclude infection, and additional serological testing to evaluate the body’s immune response to infection may be considered within 2 to 12 weeks after symptom onset.
For more information on the Zika RT-PCR test, visit www.QuestDiagnostics.com/Zika.
Photo by Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for another test designed to detect Zika virus infection.
The test, Zika Virus RNA Qualitative Real-Time RT-PCR test (Zika RT-PCR test), is intended for the qualitative detection of RNA from the Zika virus in human serum specimens from patients meeting criteria for testing outlined by the Centers for Disease Control and Prevention (CDC).
The Zika RT-PCR test is the first test from a commercial laboratory provider to be granted an EUA for testing patients for Zika virus RNA. The test was developed by Focus Diagnostics, Inc., a subsidiary of Quest Diagnostics.
About the EUA
The Zika RT-PCR test has not been FDA cleared or approved. An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The FDA issued the EUA for the Zika RT-PCR test based on data submitted by Focus Diagnostics, Inc., and on the US Secretary of Health and Human Services’ (HHS) declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and/or diagnosis of Zika virus infection.
This EUA will terminate when the HHS Secretary’s declaration terminates, unless the FDA revokes it sooner.
Until now, the only Zika tests authorized by the FDA under EUA were available from the CDC and were only used in qualified laboratories designated by the CDC. These are the Trioplex Real-time RT-PCR Assay and the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).
About the test
Quest Diagnostics plans to make the Zika RT-PCR test broadly available for patient testing early in the week of May 2.
The Zika RT-PCR test is intended for use by clinical laboratory personnel qualified by state and federal regulations who have received specific training on the use of the test in qualified laboratories designated by Focus Diagnostics, Inc., and certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high-complexity tests.
The test can potentially be performed at any CLIA high-complexity laboratory in the Quest Diagnostics network, which includes several dozen CLIA high-complexity labs in the US, including in Toa Baja, Puerto Rico.
Within the US, positive results of this test must be reported to the CDC.
The CDC recommends RT-PCR testing for Zika infection during approximately the first 7 days of the onset of symptoms for certain patients, including:
- Individuals with symptoms suggestive of Zika infection who have traveled within the last 2 weeks to an area with ongoing transmission
- Asymptomatic pregnant women with a history of residence in or travel to areas of active Zika infection
- Asymptomatic pregnant women whose male sexual partners have traveled to or lived in an area of active Zika infection
- Infants born to mothers who live in or traveled to areas with Zika virus transmission during their pregnancy, including both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection.
A negative test result does not preclude infection, and additional serological testing to evaluate the body’s immune response to infection may be considered within 2 to 12 weeks after symptom onset.
For more information on the Zika RT-PCR test, visit www.QuestDiagnostics.com/Zika.
Photo by Juan D. Alfonso
The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for another test designed to detect Zika virus infection.
The test, Zika Virus RNA Qualitative Real-Time RT-PCR test (Zika RT-PCR test), is intended for the qualitative detection of RNA from the Zika virus in human serum specimens from patients meeting criteria for testing outlined by the Centers for Disease Control and Prevention (CDC).
The Zika RT-PCR test is the first test from a commercial laboratory provider to be granted an EUA for testing patients for Zika virus RNA. The test was developed by Focus Diagnostics, Inc., a subsidiary of Quest Diagnostics.
About the EUA
The Zika RT-PCR test has not been FDA cleared or approved. An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The FDA issued the EUA for the Zika RT-PCR test based on data submitted by Focus Diagnostics, Inc., and on the US Secretary of Health and Human Services’ (HHS) declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and/or diagnosis of Zika virus infection.
This EUA will terminate when the HHS Secretary’s declaration terminates, unless the FDA revokes it sooner.
Until now, the only Zika tests authorized by the FDA under EUA were available from the CDC and were only used in qualified laboratories designated by the CDC. These are the Trioplex Real-time RT-PCR Assay and the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).
About the test
Quest Diagnostics plans to make the Zika RT-PCR test broadly available for patient testing early in the week of May 2.
The Zika RT-PCR test is intended for use by clinical laboratory personnel qualified by state and federal regulations who have received specific training on the use of the test in qualified laboratories designated by Focus Diagnostics, Inc., and certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high-complexity tests.
The test can potentially be performed at any CLIA high-complexity laboratory in the Quest Diagnostics network, which includes several dozen CLIA high-complexity labs in the US, including in Toa Baja, Puerto Rico.
Within the US, positive results of this test must be reported to the CDC.
The CDC recommends RT-PCR testing for Zika infection during approximately the first 7 days of the onset of symptoms for certain patients, including:
- Individuals with symptoms suggestive of Zika infection who have traveled within the last 2 weeks to an area with ongoing transmission
- Asymptomatic pregnant women with a history of residence in or travel to areas of active Zika infection
- Asymptomatic pregnant women whose male sexual partners have traveled to or lived in an area of active Zika infection
- Infants born to mothers who live in or traveled to areas with Zika virus transmission during their pregnancy, including both molecular and serologic testing of infants who are being evaluated for evidence of a congenital Zika virus infection.
A negative test result does not preclude infection, and additional serological testing to evaluate the body’s immune response to infection may be considered within 2 to 12 weeks after symptom onset.
For more information on the Zika RT-PCR test, visit www.QuestDiagnostics.com/Zika.
All-oral combo extends PFS in rel/ref MM
Photo courtesy of ASH
In the phase 3 TOURMALINE-MM1 trial, adding the oral proteasome inhibitor ixazomib to treatment with lenalidomide and dexamethasone significantly extended progression-free survival (PFS), with limited additional toxicity, in patients with relapsed/refractory multiple myeloma (MM).
The median PFS was about 21 months for patients who received ixazomib, lenalidomide, and dexamethasone (IRd) and about 15 months for those who received placebo, lenalidomide, and dexamethasone (Rd).
Gastrointestinal adverse events (AEs), rash, and grade 3/4 thrombocytopenia were more common in the IRd arm than the Rd arm.
These results were published in NEJM. The study was sponsored by Millennium Pharmaceuticals, Inc. Results from this trial were previously presented at ASH 2015, but the data in NEJM differ slightly from that presentation.
“NEJM has published the results of the first phase 3 study supporting an all-oral triplet regimen containing a proteasome inhibitor in multiple myeloma,” said study author Philippe Moreau, MD, of University of Nantes in France.
“The TOURMALINE-MM1 results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma.”
TOURMALINE-MM1 enrolled 722 patients with relapsed (77%), refractory (11%), relapsed and refractory (12%), or primary refractory (6%) MM.
The patients were randomized to receive IRd (n=360) or Rd (n=362). Baseline patient characteristics were similar between the treatment arms. The median age was 66 in both arms (overall range, 30-91), and nearly 60% of patients were male.
About 60% of patients in both arms had received 1 prior therapy, roughly 30% had received 2, and about 10% had received 3. Seventy percent of patients in both arms had received prior treatment with a proteasome inhibitor, and about 55% had received an immunomodulatory drug.
Efficacy
The study’s primary endpoint was PFS. And the researchers saw a significant improvement in PFS for the IRd arm compared to the Rd arm. The median PFS was 20.6 months and 14.7 months, respectively. The hazard ratio was 0.74 (P=0.01).
There was a benefit in PFS in the IRd arm across pre-specified patient subgroups, including patients with poor prognosis, such as elderly patients, those who had received 2 or 3 prior therapies, those with advanced stage disease, and those with high-risk cytogenetic abnormalities.
At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.
The overall response rates were 78% in the IRd arm and 72% in the Rd arm. The complete response rates were 12% and 7%, respectively, and the stringent complete response rates were 2% and <1%, respectively.
The median time to response was 1.1 months in the IRd arm and 1.9 months in the Rd arm. The median duration of response was 20.5 months and 15.0 months, respectively.
Safety
AEs occurred in 98% of patients in the IRd arm and 99% in the Rd arm. Grade 3 or higher AEs occurred in 74% and 69% of patients, respectively, serious AEs occurred in 47% and 49%, respectively, and on-study deaths occurred in 4% and 6%, respectively.
Grade 3 and 4 thrombocytopenia was more frequent in the IRd arm (12% and 7%, respectively) than in the Rd arm (5% and 4%, respectively). Rash also occurred more frequently in the IRd arm than in the Rd arm (36% and 23%, respectively).
Gastrointestinal AEs were more frequent in the IRd arm than the Rd arm, including diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), and vomiting (23% vs 12%).
The incidence of peripheral neuropathy was 27% in the IRd arm and 22% in the Rd arm. Grade 3 events occurred in 2% of patients in each arm, and no grade 4 events were reported.
Roughly the same percentage of patients developed new primary malignant tumors—5% in the IRd arm and 4% in the Rd arm.
Photo courtesy of ASH
In the phase 3 TOURMALINE-MM1 trial, adding the oral proteasome inhibitor ixazomib to treatment with lenalidomide and dexamethasone significantly extended progression-free survival (PFS), with limited additional toxicity, in patients with relapsed/refractory multiple myeloma (MM).
The median PFS was about 21 months for patients who received ixazomib, lenalidomide, and dexamethasone (IRd) and about 15 months for those who received placebo, lenalidomide, and dexamethasone (Rd).
Gastrointestinal adverse events (AEs), rash, and grade 3/4 thrombocytopenia were more common in the IRd arm than the Rd arm.
These results were published in NEJM. The study was sponsored by Millennium Pharmaceuticals, Inc. Results from this trial were previously presented at ASH 2015, but the data in NEJM differ slightly from that presentation.
“NEJM has published the results of the first phase 3 study supporting an all-oral triplet regimen containing a proteasome inhibitor in multiple myeloma,” said study author Philippe Moreau, MD, of University of Nantes in France.
“The TOURMALINE-MM1 results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma.”
TOURMALINE-MM1 enrolled 722 patients with relapsed (77%), refractory (11%), relapsed and refractory (12%), or primary refractory (6%) MM.
The patients were randomized to receive IRd (n=360) or Rd (n=362). Baseline patient characteristics were similar between the treatment arms. The median age was 66 in both arms (overall range, 30-91), and nearly 60% of patients were male.
About 60% of patients in both arms had received 1 prior therapy, roughly 30% had received 2, and about 10% had received 3. Seventy percent of patients in both arms had received prior treatment with a proteasome inhibitor, and about 55% had received an immunomodulatory drug.
Efficacy
The study’s primary endpoint was PFS. And the researchers saw a significant improvement in PFS for the IRd arm compared to the Rd arm. The median PFS was 20.6 months and 14.7 months, respectively. The hazard ratio was 0.74 (P=0.01).
There was a benefit in PFS in the IRd arm across pre-specified patient subgroups, including patients with poor prognosis, such as elderly patients, those who had received 2 or 3 prior therapies, those with advanced stage disease, and those with high-risk cytogenetic abnormalities.
At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.
The overall response rates were 78% in the IRd arm and 72% in the Rd arm. The complete response rates were 12% and 7%, respectively, and the stringent complete response rates were 2% and <1%, respectively.
The median time to response was 1.1 months in the IRd arm and 1.9 months in the Rd arm. The median duration of response was 20.5 months and 15.0 months, respectively.
Safety
AEs occurred in 98% of patients in the IRd arm and 99% in the Rd arm. Grade 3 or higher AEs occurred in 74% and 69% of patients, respectively, serious AEs occurred in 47% and 49%, respectively, and on-study deaths occurred in 4% and 6%, respectively.
Grade 3 and 4 thrombocytopenia was more frequent in the IRd arm (12% and 7%, respectively) than in the Rd arm (5% and 4%, respectively). Rash also occurred more frequently in the IRd arm than in the Rd arm (36% and 23%, respectively).
Gastrointestinal AEs were more frequent in the IRd arm than the Rd arm, including diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), and vomiting (23% vs 12%).
The incidence of peripheral neuropathy was 27% in the IRd arm and 22% in the Rd arm. Grade 3 events occurred in 2% of patients in each arm, and no grade 4 events were reported.
Roughly the same percentage of patients developed new primary malignant tumors—5% in the IRd arm and 4% in the Rd arm.
Photo courtesy of ASH
In the phase 3 TOURMALINE-MM1 trial, adding the oral proteasome inhibitor ixazomib to treatment with lenalidomide and dexamethasone significantly extended progression-free survival (PFS), with limited additional toxicity, in patients with relapsed/refractory multiple myeloma (MM).
The median PFS was about 21 months for patients who received ixazomib, lenalidomide, and dexamethasone (IRd) and about 15 months for those who received placebo, lenalidomide, and dexamethasone (Rd).
Gastrointestinal adverse events (AEs), rash, and grade 3/4 thrombocytopenia were more common in the IRd arm than the Rd arm.
These results were published in NEJM. The study was sponsored by Millennium Pharmaceuticals, Inc. Results from this trial were previously presented at ASH 2015, but the data in NEJM differ slightly from that presentation.
“NEJM has published the results of the first phase 3 study supporting an all-oral triplet regimen containing a proteasome inhibitor in multiple myeloma,” said study author Philippe Moreau, MD, of University of Nantes in France.
“The TOURMALINE-MM1 results demonstrated that ixazomib in combination with lenalidomide and dexamethasone is an effective and tolerable oral regimen with a manageable safety profile for patients with relapsed and/or refractory multiple myeloma.”
TOURMALINE-MM1 enrolled 722 patients with relapsed (77%), refractory (11%), relapsed and refractory (12%), or primary refractory (6%) MM.
The patients were randomized to receive IRd (n=360) or Rd (n=362). Baseline patient characteristics were similar between the treatment arms. The median age was 66 in both arms (overall range, 30-91), and nearly 60% of patients were male.
About 60% of patients in both arms had received 1 prior therapy, roughly 30% had received 2, and about 10% had received 3. Seventy percent of patients in both arms had received prior treatment with a proteasome inhibitor, and about 55% had received an immunomodulatory drug.
Efficacy
The study’s primary endpoint was PFS. And the researchers saw a significant improvement in PFS for the IRd arm compared to the Rd arm. The median PFS was 20.6 months and 14.7 months, respectively. The hazard ratio was 0.74 (P=0.01).
There was a benefit in PFS in the IRd arm across pre-specified patient subgroups, including patients with poor prognosis, such as elderly patients, those who had received 2 or 3 prior therapies, those with advanced stage disease, and those with high-risk cytogenetic abnormalities.
At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.
The overall response rates were 78% in the IRd arm and 72% in the Rd arm. The complete response rates were 12% and 7%, respectively, and the stringent complete response rates were 2% and <1%, respectively.
The median time to response was 1.1 months in the IRd arm and 1.9 months in the Rd arm. The median duration of response was 20.5 months and 15.0 months, respectively.
Safety
AEs occurred in 98% of patients in the IRd arm and 99% in the Rd arm. Grade 3 or higher AEs occurred in 74% and 69% of patients, respectively, serious AEs occurred in 47% and 49%, respectively, and on-study deaths occurred in 4% and 6%, respectively.
Grade 3 and 4 thrombocytopenia was more frequent in the IRd arm (12% and 7%, respectively) than in the Rd arm (5% and 4%, respectively). Rash also occurred more frequently in the IRd arm than in the Rd arm (36% and 23%, respectively).
Gastrointestinal AEs were more frequent in the IRd arm than the Rd arm, including diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), and vomiting (23% vs 12%).
The incidence of peripheral neuropathy was 27% in the IRd arm and 22% in the Rd arm. Grade 3 events occurred in 2% of patients in each arm, and no grade 4 events were reported.
Roughly the same percentage of patients developed new primary malignant tumors—5% in the IRd arm and 4% in the Rd arm.