HT Staff

Parenteral nutrition source

A parenteral nutrition source can reduce the toxicity and increase the bioavailability of platinum-based anticancer nanodrugs, according to preclinical research published in Scientific Reports.

Many of the side effects of platinum-based drugs occur when they settle in healthy tissue.

To deliver these drugs in a more targeted way, researchers have created nanoscale delivery systems engineered to make the drugs accumulate at tumor sites.

However, tests of these nanodrugs show that between 1% and 10% of the drugs are delivered to the tumor site, with most of the remainder being diverted to the liver and spleen.

“The body’s immune system, especially the liver and spleen, has been one of the biggest stumbling blocks in developing nanoscale chemotherapy drug delivery systems,” said Chien Ho, PhD, of Carnegie Mellon University in Pittsburg, Pennsylvania.

“When the drugs collect in those organs, they become less available to treat the cancer and can also cause toxicity.”

But Dr Ho and his colleagues have found evidence to suggest that Intralipid, a fat emulsion used as a parenteral nutrition source, can help prevent that.

While developing cellular nanotags to help detect organ rejection, Dr Ho noticed that Intralipid reduced the amount of nanoparticles that were being cleared by the liver and spleen by about 50%. As a result, the nanoparticles remained in the bloodstream for longer periods of time.

So he and his colleagues decided to see if Intralipid had the same effect on platinum-based anticancer nanodrugs.

In the newly published study, the researchers administered a single, clinical dose of Intralipid to Sprague Dawley rats. One hour later, they administered a dose of a platinum-based chemotherapy drug that had been incorporated into a nanoparticle to both Intralipid-treated rats and controls.

Twenty-four hours after the drug was administered, rats pretreated with Intralipid had experienced reduced accumulation of the platinum-based drug compared to controls.

Drug accumulation decreased by 20.4% in the liver, 42.5% in the spleen, and 31.2% in the kidney. Consequently, in these organs, the toxic side effects of the nanodrug were significantly decreased compared to controls.

Furthermore, Intralipid pretreatment allowed more of the drug to remain available and active in the body for longer periods of time.

After 5 hours, the drug’s bioavailability increased by 18.7% in Intralipid-treated mice compared to controls. After 24 hours, bioavailability was 9.4% higher in Intralipid-treated mice than in controls.

The researchers believe this increased bioavailability will allow more of the drug to reach the tumor site and could perhaps allow clinicians to reduce the dosage needed to treat a patient. The team is now investigating the possibility of bringing this research to a clinical trial.

Parenteral nutrition source

A parenteral nutrition source can reduce the toxicity and increase the bioavailability of platinum-based anticancer nanodrugs, according to preclinical research published in Scientific Reports.

Many of the side effects of platinum-based drugs occur when they settle in healthy tissue.

To deliver these drugs in a more targeted way, researchers have created nanoscale delivery systems engineered to make the drugs accumulate at tumor sites.

However, tests of these nanodrugs show that between 1% and 10% of the drugs are delivered to the tumor site, with most of the remainder being diverted to the liver and spleen.

“The body’s immune system, especially the liver and spleen, has been one of the biggest stumbling blocks in developing nanoscale chemotherapy drug delivery systems,” said Chien Ho, PhD, of Carnegie Mellon University in Pittsburg, Pennsylvania.

“When the drugs collect in those organs, they become less available to treat the cancer and can also cause toxicity.”

But Dr Ho and his colleagues have found evidence to suggest that Intralipid, a fat emulsion used as a parenteral nutrition source, can help prevent that.

While developing cellular nanotags to help detect organ rejection, Dr Ho noticed that Intralipid reduced the amount of nanoparticles that were being cleared by the liver and spleen by about 50%. As a result, the nanoparticles remained in the bloodstream for longer periods of time.

So he and his colleagues decided to see if Intralipid had the same effect on platinum-based anticancer nanodrugs.

In the newly published study, the researchers administered a single, clinical dose of Intralipid to Sprague Dawley rats. One hour later, they administered a dose of a platinum-based chemotherapy drug that had been incorporated into a nanoparticle to both Intralipid-treated rats and controls.

Twenty-four hours after the drug was administered, rats pretreated with Intralipid had experienced reduced accumulation of the platinum-based drug compared to controls.

Drug accumulation decreased by 20.4% in the liver, 42.5% in the spleen, and 31.2% in the kidney. Consequently, in these organs, the toxic side effects of the nanodrug were significantly decreased compared to controls.

Furthermore, Intralipid pretreatment allowed more of the drug to remain available and active in the body for longer periods of time.

After 5 hours, the drug’s bioavailability increased by 18.7% in Intralipid-treated mice compared to controls. After 24 hours, bioavailability was 9.4% higher in Intralipid-treated mice than in controls.

The researchers believe this increased bioavailability will allow more of the drug to reach the tumor site and could perhaps allow clinicians to reduce the dosage needed to treat a patient. The team is now investigating the possibility of bringing this research to a clinical trial.

Parenteral nutrition source

A parenteral nutrition source can reduce the toxicity and increase the bioavailability of platinum-based anticancer nanodrugs, according to preclinical research published in Scientific Reports.

Many of the side effects of platinum-based drugs occur when they settle in healthy tissue.

To deliver these drugs in a more targeted way, researchers have created nanoscale delivery systems engineered to make the drugs accumulate at tumor sites.

However, tests of these nanodrugs show that between 1% and 10% of the drugs are delivered to the tumor site, with most of the remainder being diverted to the liver and spleen.

“The body’s immune system, especially the liver and spleen, has been one of the biggest stumbling blocks in developing nanoscale chemotherapy drug delivery systems,” said Chien Ho, PhD, of Carnegie Mellon University in Pittsburg, Pennsylvania.

“When the drugs collect in those organs, they become less available to treat the cancer and can also cause toxicity.”

But Dr Ho and his colleagues have found evidence to suggest that Intralipid, a fat emulsion used as a parenteral nutrition source, can help prevent that.

While developing cellular nanotags to help detect organ rejection, Dr Ho noticed that Intralipid reduced the amount of nanoparticles that were being cleared by the liver and spleen by about 50%. As a result, the nanoparticles remained in the bloodstream for longer periods of time.

So he and his colleagues decided to see if Intralipid had the same effect on platinum-based anticancer nanodrugs.

In the newly published study, the researchers administered a single, clinical dose of Intralipid to Sprague Dawley rats. One hour later, they administered a dose of a platinum-based chemotherapy drug that had been incorporated into a nanoparticle to both Intralipid-treated rats and controls.

Twenty-four hours after the drug was administered, rats pretreated with Intralipid had experienced reduced accumulation of the platinum-based drug compared to controls.

Drug accumulation decreased by 20.4% in the liver, 42.5% in the spleen, and 31.2% in the kidney. Consequently, in these organs, the toxic side effects of the nanodrug were significantly decreased compared to controls.

Furthermore, Intralipid pretreatment allowed more of the drug to remain available and active in the body for longer periods of time.

After 5 hours, the drug’s bioavailability increased by 18.7% in Intralipid-treated mice compared to controls. After 24 hours, bioavailability was 9.4% higher in Intralipid-treated mice than in controls.

The researchers believe this increased bioavailability will allow more of the drug to reach the tumor site and could perhaps allow clinicians to reduce the dosage needed to treat a patient. The team is now investigating the possibility of bringing this research to a clinical trial.

Sagar Lonial, MD

© ASCO/Todd Buchanan

CHICAGO—The anti-CD38 monoclonal antibody daratumumab can be effective as a stand-alone therapy for some heavily pretreated patients with multiple myeloma (MM), results of an ongoing phase 2 trial suggest.

The study, known as SIRIUS or MMY2002, included more than 100 patients who had received 3 or more prior lines of therapy.

Roughly 30% of these subjects responded to daratumumab, with a median response duration of about 7 months.

The median progression-free survival was close to 4 months, and the estimated 1-year overall survival rate was 65%.

Serious adverse events (AEs) occurred in 30% of patients.

“These findings speak to the potential of daratumumab as an effective and tolerable option for people with multiple myeloma who have exhausted other available treatment options,” said study investigator Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.

Dr Lonial presented these findings at the 2015 ASCO Annual Meeting (abstract LBA8512). The research was funded by Janssen Research & Development, the company developing daratumumab.

In part 1 of this study, 34 patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.

In part 2, an additional 90 patients were enrolled to receive 16 mg/kg of daratumumab on the same dosing schedule as in part 1.

Dr Lonial reported results for all patients in parts 1 and 2 who received 16 mg/kg of daratumumab. These 106 patients had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.

According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response. The median duration of response was 7.4 months.

“It is particularly noteworthy to see this level of response with a single-agent in this heavily pretreated population,” Dr Lonial said. “Ninety-seven percent of patients in this study were refractory to their last line of therapy, and 95% were double-refractory to both a [proteasome inhibitor] and an [immunomodulatory drug].”

The median overall survival has not been reached, and the estimated 1-year overall survival rate is 65%. The median progression-free survival was 3.7 months.

After a median follow up of 9.4 months, 45.2% of responders remain on therapy.

The most common AEs were fatigue (39.6%), anemia (33%), nausea (29.2%), thrombocytopenia (25.5%), neutropenia (22.6%), back pain (22.6%), and cough (20.8%).

Thirty percent of patients experienced serious AEs. And 4.7% of patients discontinued treatment due to AEs, none of which were considered drug-related.

Infusion-related reactions (IRR) were reported in 42.5% of patients and were predominantly grade 1 or 2 (4.7% grade 3; no grade 4). These occurred mainly during the first infusion.

The most common IRRs included nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.

Sagar Lonial, MD

© ASCO/Todd Buchanan

CHICAGO—The anti-CD38 monoclonal antibody daratumumab can be effective as a stand-alone therapy for some heavily pretreated patients with multiple myeloma (MM), results of an ongoing phase 2 trial suggest.

The study, known as SIRIUS or MMY2002, included more than 100 patients who had received 3 or more prior lines of therapy.

Roughly 30% of these subjects responded to daratumumab, with a median response duration of about 7 months.

The median progression-free survival was close to 4 months, and the estimated 1-year overall survival rate was 65%.

Serious adverse events (AEs) occurred in 30% of patients.

“These findings speak to the potential of daratumumab as an effective and tolerable option for people with multiple myeloma who have exhausted other available treatment options,” said study investigator Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.

Dr Lonial presented these findings at the 2015 ASCO Annual Meeting (abstract LBA8512). The research was funded by Janssen Research & Development, the company developing daratumumab.

In part 1 of this study, 34 patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.

In part 2, an additional 90 patients were enrolled to receive 16 mg/kg of daratumumab on the same dosing schedule as in part 1.

Dr Lonial reported results for all patients in parts 1 and 2 who received 16 mg/kg of daratumumab. These 106 patients had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.

According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response. The median duration of response was 7.4 months.

“It is particularly noteworthy to see this level of response with a single-agent in this heavily pretreated population,” Dr Lonial said. “Ninety-seven percent of patients in this study were refractory to their last line of therapy, and 95% were double-refractory to both a [proteasome inhibitor] and an [immunomodulatory drug].”

The median overall survival has not been reached, and the estimated 1-year overall survival rate is 65%. The median progression-free survival was 3.7 months.

After a median follow up of 9.4 months, 45.2% of responders remain on therapy.

The most common AEs were fatigue (39.6%), anemia (33%), nausea (29.2%), thrombocytopenia (25.5%), neutropenia (22.6%), back pain (22.6%), and cough (20.8%).

Thirty percent of patients experienced serious AEs. And 4.7% of patients discontinued treatment due to AEs, none of which were considered drug-related.

Infusion-related reactions (IRR) were reported in 42.5% of patients and were predominantly grade 1 or 2 (4.7% grade 3; no grade 4). These occurred mainly during the first infusion.

The most common IRRs included nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.

Sagar Lonial, MD

© ASCO/Todd Buchanan

CHICAGO—The anti-CD38 monoclonal antibody daratumumab can be effective as a stand-alone therapy for some heavily pretreated patients with multiple myeloma (MM), results of an ongoing phase 2 trial suggest.

The study, known as SIRIUS or MMY2002, included more than 100 patients who had received 3 or more prior lines of therapy.

Roughly 30% of these subjects responded to daratumumab, with a median response duration of about 7 months.

The median progression-free survival was close to 4 months, and the estimated 1-year overall survival rate was 65%.

Serious adverse events (AEs) occurred in 30% of patients.

“These findings speak to the potential of daratumumab as an effective and tolerable option for people with multiple myeloma who have exhausted other available treatment options,” said study investigator Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.

Dr Lonial presented these findings at the 2015 ASCO Annual Meeting (abstract LBA8512). The research was funded by Janssen Research & Development, the company developing daratumumab.

In part 1 of this study, 34 patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.

In part 2, an additional 90 patients were enrolled to receive 16 mg/kg of daratumumab on the same dosing schedule as in part 1.

Dr Lonial reported results for all patients in parts 1 and 2 who received 16 mg/kg of daratumumab. These 106 patients had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.

According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response. The median duration of response was 7.4 months.

“It is particularly noteworthy to see this level of response with a single-agent in this heavily pretreated population,” Dr Lonial said. “Ninety-seven percent of patients in this study were refractory to their last line of therapy, and 95% were double-refractory to both a [proteasome inhibitor] and an [immunomodulatory drug].”

The median overall survival has not been reached, and the estimated 1-year overall survival rate is 65%. The median progression-free survival was 3.7 months.

After a median follow up of 9.4 months, 45.2% of responders remain on therapy.

The most common AEs were fatigue (39.6%), anemia (33%), nausea (29.2%), thrombocytopenia (25.5%), neutropenia (22.6%), back pain (22.6%), and cough (20.8%).

Thirty percent of patients experienced serious AEs. And 4.7% of patients discontinued treatment due to AEs, none of which were considered drug-related.

Infusion-related reactions (IRR) were reported in 42.5% of patients and were predominantly grade 1 or 2 (4.7% grade 3; no grade 4). These occurred mainly during the first infusion.

The most common IRRs included nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Cancer survivors’ moods are impacted—both positively and negatively—by their spouses’ moods, according to research published in Cancer Epidemiology, Biomarkers & Prevention.

In the study, cancer survivors whose spouses reported depressed moods were more likely to be depressed after about a year of follow-up, and survivors whose spouses reported better mental and physical health-related quality of life (HRQOL) were less likely to be depressed.

However, survivors’ moods did not have the same impact on their spouses.

“We were surprised that the effects of the spouses on the survivors were so much larger in this study than the effect of the survivors on their spouses,” said study author Kristin Litzelman, PhD, of the National Cancer Institute in Bethesda, Maryland. “We expected to see a more reciprocal relationship.”

Dr Litzelman and her colleagues conducted this research in an attempt to understand how cancer survivors and their families influence one another. The team hoped to identify ways to improve the healthcare both parties receive and thereby improve their health and well-being.

The researchers analyzed data from 910 cancer patients and their spouses, comparing them to 910 couples without any kind of cancer-related health problem.

The team used statistical models to assess how each spouse’s quality of life or depression at one time point was associated with his or her partner’s risk of depression around 11 months later. The researchers took into account a person’s previously reported mood, demographic characteristics, and other factors.

The results showed that, when spouses reported feeling depressed, cancer survivors were about 4 times more likely to report being depressed 11 months later (odds ratio [OR]=4.27). This association was stronger among female cancer survivors (OR=9.49) than male survivors (OR=3.98).

Cancer survivors whose spouses reported better HRQOL had a 30% decrease in depressed mood per 10-point improvement in HRQOL score. The ORs were 0.72 for mental health and 0.68 for physical health. The associations between spousal HRQOL and survivor depressed mood were similar for male and female survivors.

The researchers noted that cancer survivors’ moods did not have a significant impact on their spouses’ risk of depressed mood 11 months later.

And the team did not see mood associations in couples without any cancer-related health problems.

“This finding certainly needs to be backed up by other studies, but it highlights the importance of family well-being in cancer survivor outcomes,” Dr Litzelman said. “Our research highlights that spouses need to take care of themselves, not just for their own sake, but also for the sake of the cancer survivor.”

“Our findings also suggest that, when caring for cancer survivors, clinicians may want to assess the well-being of spousal caregivers. Future research could test whether including caregivers in the survivorship care plan might help to improve outcomes for both caregivers and for cancer survivors.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Cancer survivors’ moods are impacted—both positively and negatively—by their spouses’ moods, according to research published in Cancer Epidemiology, Biomarkers & Prevention.

In the study, cancer survivors whose spouses reported depressed moods were more likely to be depressed after about a year of follow-up, and survivors whose spouses reported better mental and physical health-related quality of life (HRQOL) were less likely to be depressed.

However, survivors’ moods did not have the same impact on their spouses.

“We were surprised that the effects of the spouses on the survivors were so much larger in this study than the effect of the survivors on their spouses,” said study author Kristin Litzelman, PhD, of the National Cancer Institute in Bethesda, Maryland. “We expected to see a more reciprocal relationship.”

Dr Litzelman and her colleagues conducted this research in an attempt to understand how cancer survivors and their families influence one another. The team hoped to identify ways to improve the healthcare both parties receive and thereby improve their health and well-being.

The researchers analyzed data from 910 cancer patients and their spouses, comparing them to 910 couples without any kind of cancer-related health problem.

The team used statistical models to assess how each spouse’s quality of life or depression at one time point was associated with his or her partner’s risk of depression around 11 months later. The researchers took into account a person’s previously reported mood, demographic characteristics, and other factors.

The results showed that, when spouses reported feeling depressed, cancer survivors were about 4 times more likely to report being depressed 11 months later (odds ratio [OR]=4.27). This association was stronger among female cancer survivors (OR=9.49) than male survivors (OR=3.98).

Cancer survivors whose spouses reported better HRQOL had a 30% decrease in depressed mood per 10-point improvement in HRQOL score. The ORs were 0.72 for mental health and 0.68 for physical health. The associations between spousal HRQOL and survivor depressed mood were similar for male and female survivors.

The researchers noted that cancer survivors’ moods did not have a significant impact on their spouses’ risk of depressed mood 11 months later.

And the team did not see mood associations in couples without any cancer-related health problems.

“This finding certainly needs to be backed up by other studies, but it highlights the importance of family well-being in cancer survivor outcomes,” Dr Litzelman said. “Our research highlights that spouses need to take care of themselves, not just for their own sake, but also for the sake of the cancer survivor.”

“Our findings also suggest that, when caring for cancer survivors, clinicians may want to assess the well-being of spousal caregivers. Future research could test whether including caregivers in the survivorship care plan might help to improve outcomes for both caregivers and for cancer survivors.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Cancer survivors’ moods are impacted—both positively and negatively—by their spouses’ moods, according to research published in Cancer Epidemiology, Biomarkers & Prevention.

In the study, cancer survivors whose spouses reported depressed moods were more likely to be depressed after about a year of follow-up, and survivors whose spouses reported better mental and physical health-related quality of life (HRQOL) were less likely to be depressed.

However, survivors’ moods did not have the same impact on their spouses.

“We were surprised that the effects of the spouses on the survivors were so much larger in this study than the effect of the survivors on their spouses,” said study author Kristin Litzelman, PhD, of the National Cancer Institute in Bethesda, Maryland. “We expected to see a more reciprocal relationship.”

Dr Litzelman and her colleagues conducted this research in an attempt to understand how cancer survivors and their families influence one another. The team hoped to identify ways to improve the healthcare both parties receive and thereby improve their health and well-being.

The researchers analyzed data from 910 cancer patients and their spouses, comparing them to 910 couples without any kind of cancer-related health problem.

The team used statistical models to assess how each spouse’s quality of life or depression at one time point was associated with his or her partner’s risk of depression around 11 months later. The researchers took into account a person’s previously reported mood, demographic characteristics, and other factors.

The results showed that, when spouses reported feeling depressed, cancer survivors were about 4 times more likely to report being depressed 11 months later (odds ratio [OR]=4.27). This association was stronger among female cancer survivors (OR=9.49) than male survivors (OR=3.98).

Cancer survivors whose spouses reported better HRQOL had a 30% decrease in depressed mood per 10-point improvement in HRQOL score. The ORs were 0.72 for mental health and 0.68 for physical health. The associations between spousal HRQOL and survivor depressed mood were similar for male and female survivors.

The researchers noted that cancer survivors’ moods did not have a significant impact on their spouses’ risk of depressed mood 11 months later.

And the team did not see mood associations in couples without any cancer-related health problems.

“This finding certainly needs to be backed up by other studies, but it highlights the importance of family well-being in cancer survivor outcomes,” Dr Litzelman said. “Our research highlights that spouses need to take care of themselves, not just for their own sake, but also for the sake of the cancer survivor.”

“Our findings also suggest that, when caring for cancer survivors, clinicians may want to assess the well-being of spousal caregivers. Future research could test whether including caregivers in the survivorship care plan might help to improve outcomes for both caregivers and for cancer survivors.”

Doctor and patient

Photo courtesy of NIH

Tools that help physicians decide whether to use diagnostic imaging can help reduce the use of unnecessary tests.

But new research suggests these tools may not be able to determine which tests are necessary most of the time.

The tools in question are computerized clinical decision support (CDS) systems, which match a patient’s characteristics against appropriateness

criteria to produce algorithmic treatment recommendations.

In a study published in JAMA, CDS systems did increase orders of imaging tests rated as “appropriate.”

However, the systems were not able to assign appropriateness ratings for a majority of tests because no appropriateness criteria were available for a particular test, or because the systems themselves were not able to find matching criteria.

“The increase in orders rated as appropriate is promising, but the number of tests that were not rated indicates there is room for further improvement of these tools,” said study author Peter S. Hussey, PhD, of the RAND Corporation in Boston, Massachusetts.

Study details

Dr Hussey and his colleagues used data from the Medicare Imaging Demonstration to evaluate the relationship of CDS system use with the proportion of imaging orders matched to appropriateness criteria, the appropriateness of ordered images, and the proportion of orders that changed after feedback.

The team compared 2 time periods during which clinicians used computerized radiology order entry systems and CDS systems for MRI, CT, and nuclear medicine procedures.

During a 6-month baseline period, the CDS systems tracked whether orders were linked with appropriateness criteria but did not provide clinicians with feedback on the appropriateness of orders.

During the 18-month intervention period, the CDS systems provided feedback indicating whether the order was linked to appropriateness criteria and, if so, the appropriateness rating, any recommendations for alternative orders, and a link to documentation supporting each rating.

National medical specialty societies developed the appropriateness criteria using expert panels that reviewed evidence and completed a structured rating process. The same appropriateness criteria were loaded into the CDS systems tools for all participating clinicians.

In all, 3340 clinicians placed 117,348 orders for advanced diagnostic imaging procedures.

Results

The CDS systems could not match most orders to appropriateness criteria. The systems did not identify relevant criteria for 63.3% of orders made during the baseline period and 66.5% of orders made during the intervention period.

Of the orders CDS systems could rate, 73.7% ordered during the baseline period and 81% ordered during the intervention period were rated as appropriate, and 11.1% and 6.4%, respectively, were rated inappropriate.

Of the orders that were initially rated as inappropriate, 4.8% were changed, and 1.9% were canceled.

When the CDS systems suggested an alternative for inappropriate orders, 9.9% of the orders were changed, and 0.4% were canceled. When the systems did not provide an alternative, 1.4% of inappropriate orders were changed, and 2.8% were canceled.

“In response to these findings, we recommend that clinical decision support efforts should focus on tools that help clinicians perform their work more efficiently and effectively,” said study author Katherine Kahn, MD, of the University of California, Los Angeles.

“We need a more comprehensive set of evidence-based guidelines that cover a greater proportion of advanced imaging orders for Medicare patients, and provide better methods for communicating feedback to clinicians.”

Doctor and patient

Photo courtesy of NIH

Tools that help physicians decide whether to use diagnostic imaging can help reduce the use of unnecessary tests.

But new research suggests these tools may not be able to determine which tests are necessary most of the time.

The tools in question are computerized clinical decision support (CDS) systems, which match a patient’s characteristics against appropriateness

criteria to produce algorithmic treatment recommendations.

In a study published in JAMA, CDS systems did increase orders of imaging tests rated as “appropriate.”

However, the systems were not able to assign appropriateness ratings for a majority of tests because no appropriateness criteria were available for a particular test, or because the systems themselves were not able to find matching criteria.

“The increase in orders rated as appropriate is promising, but the number of tests that were not rated indicates there is room for further improvement of these tools,” said study author Peter S. Hussey, PhD, of the RAND Corporation in Boston, Massachusetts.

Study details

Dr Hussey and his colleagues used data from the Medicare Imaging Demonstration to evaluate the relationship of CDS system use with the proportion of imaging orders matched to appropriateness criteria, the appropriateness of ordered images, and the proportion of orders that changed after feedback.

The team compared 2 time periods during which clinicians used computerized radiology order entry systems and CDS systems for MRI, CT, and nuclear medicine procedures.

During a 6-month baseline period, the CDS systems tracked whether orders were linked with appropriateness criteria but did not provide clinicians with feedback on the appropriateness of orders.

During the 18-month intervention period, the CDS systems provided feedback indicating whether the order was linked to appropriateness criteria and, if so, the appropriateness rating, any recommendations for alternative orders, and a link to documentation supporting each rating.

National medical specialty societies developed the appropriateness criteria using expert panels that reviewed evidence and completed a structured rating process. The same appropriateness criteria were loaded into the CDS systems tools for all participating clinicians.

In all, 3340 clinicians placed 117,348 orders for advanced diagnostic imaging procedures.

Results

The CDS systems could not match most orders to appropriateness criteria. The systems did not identify relevant criteria for 63.3% of orders made during the baseline period and 66.5% of orders made during the intervention period.

Of the orders CDS systems could rate, 73.7% ordered during the baseline period and 81% ordered during the intervention period were rated as appropriate, and 11.1% and 6.4%, respectively, were rated inappropriate.

Of the orders that were initially rated as inappropriate, 4.8% were changed, and 1.9% were canceled.

When the CDS systems suggested an alternative for inappropriate orders, 9.9% of the orders were changed, and 0.4% were canceled. When the systems did not provide an alternative, 1.4% of inappropriate orders were changed, and 2.8% were canceled.

“In response to these findings, we recommend that clinical decision support efforts should focus on tools that help clinicians perform their work more efficiently and effectively,” said study author Katherine Kahn, MD, of the University of California, Los Angeles.

“We need a more comprehensive set of evidence-based guidelines that cover a greater proportion of advanced imaging orders for Medicare patients, and provide better methods for communicating feedback to clinicians.”

Doctor and patient

Photo courtesy of NIH

Tools that help physicians decide whether to use diagnostic imaging can help reduce the use of unnecessary tests.

But new research suggests these tools may not be able to determine which tests are necessary most of the time.

The tools in question are computerized clinical decision support (CDS) systems, which match a patient’s characteristics against appropriateness

criteria to produce algorithmic treatment recommendations.

In a study published in JAMA, CDS systems did increase orders of imaging tests rated as “appropriate.”

However, the systems were not able to assign appropriateness ratings for a majority of tests because no appropriateness criteria were available for a particular test, or because the systems themselves were not able to find matching criteria.

“The increase in orders rated as appropriate is promising, but the number of tests that were not rated indicates there is room for further improvement of these tools,” said study author Peter S. Hussey, PhD, of the RAND Corporation in Boston, Massachusetts.

Study details

Dr Hussey and his colleagues used data from the Medicare Imaging Demonstration to evaluate the relationship of CDS system use with the proportion of imaging orders matched to appropriateness criteria, the appropriateness of ordered images, and the proportion of orders that changed after feedback.

The team compared 2 time periods during which clinicians used computerized radiology order entry systems and CDS systems for MRI, CT, and nuclear medicine procedures.

During a 6-month baseline period, the CDS systems tracked whether orders were linked with appropriateness criteria but did not provide clinicians with feedback on the appropriateness of orders.

During the 18-month intervention period, the CDS systems provided feedback indicating whether the order was linked to appropriateness criteria and, if so, the appropriateness rating, any recommendations for alternative orders, and a link to documentation supporting each rating.

National medical specialty societies developed the appropriateness criteria using expert panels that reviewed evidence and completed a structured rating process. The same appropriateness criteria were loaded into the CDS systems tools for all participating clinicians.

In all, 3340 clinicians placed 117,348 orders for advanced diagnostic imaging procedures.

Results

The CDS systems could not match most orders to appropriateness criteria. The systems did not identify relevant criteria for 63.3% of orders made during the baseline period and 66.5% of orders made during the intervention period.

Of the orders CDS systems could rate, 73.7% ordered during the baseline period and 81% ordered during the intervention period were rated as appropriate, and 11.1% and 6.4%, respectively, were rated inappropriate.

Of the orders that were initially rated as inappropriate, 4.8% were changed, and 1.9% were canceled.

When the CDS systems suggested an alternative for inappropriate orders, 9.9% of the orders were changed, and 0.4% were canceled. When the systems did not provide an alternative, 1.4% of inappropriate orders were changed, and 2.8% were canceled.

“In response to these findings, we recommend that clinical decision support efforts should focus on tools that help clinicians perform their work more efficiently and effectively,” said study author Katherine Kahn, MD, of the University of California, Los Angeles.

“We need a more comprehensive set of evidence-based guidelines that cover a greater proportion of advanced imaging orders for Medicare patients, and provide better methods for communicating feedback to clinicians.”

Robbie Loewith, PhD

Photo courtesy of

University of Geneva

A group of researchers has developed a new tool to study the structure and function of target of rapamycin complex 2 (TORC2), which helps explain why rapamycin cannot access the TOR protein in this complex.

TOR is essential for the growth of normal cells but is hyperactive in tumor cells. Rapamycin is an immunosuppressant and anticancer agent that inactivates TOR in TORC1 but not in TORC2.

“In order to more easily study TORC2, we wanted to learn how to make this complex sensitive to rapamycin,” said Robbie Loewith, PhD, of the University of Geneva in Switzerland.

So Dr Loewith and a team of scientists from Switzerland, France, and the UK set out to elucidate how TORC2 works. The team reported their findings in Molecular Cell.

Using crosslinking-mass spectrometry and electron microscopy, they discovered that TORC2 has 3 features in common with TORC1: a rhomboid shape, 2-fold symmetry, and a central cavity delimited by the interface of its protein chains.

The 2 complexes differ markedly, however, in overall size, surface area of the interface, and the volume and shape of the central cavity.

By determining the structure of TORC2, the team could observe which subunit within TORC2 was obstructing the rapamycin binding site on TOR.

“By deleting part of this subunit, we generated a variant of TORC2 sensitive to rapamycin,” said Manoel Prouteau, PhD, also of the University of Geneva.

This allowed the researchers to study how TORC2 acts to stimulate cell growth.

Now, they hope to identify a specific inhibitor of endogenous TORC2 that could also be an effective anticancer agent.

“Our discovery that TORC2 inhibition alone is sufficient to block the cell cycle suggests that mTORC2-specific inhibitors may provide new and potentially better therapeutic alternatives,” the team concluded.

Robbie Loewith, PhD

Photo courtesy of

University of Geneva

A group of researchers has developed a new tool to study the structure and function of target of rapamycin complex 2 (TORC2), which helps explain why rapamycin cannot access the TOR protein in this complex.

TOR is essential for the growth of normal cells but is hyperactive in tumor cells. Rapamycin is an immunosuppressant and anticancer agent that inactivates TOR in TORC1 but not in TORC2.

“In order to more easily study TORC2, we wanted to learn how to make this complex sensitive to rapamycin,” said Robbie Loewith, PhD, of the University of Geneva in Switzerland.

So Dr Loewith and a team of scientists from Switzerland, France, and the UK set out to elucidate how TORC2 works. The team reported their findings in Molecular Cell.

Using crosslinking-mass spectrometry and electron microscopy, they discovered that TORC2 has 3 features in common with TORC1: a rhomboid shape, 2-fold symmetry, and a central cavity delimited by the interface of its protein chains.

The 2 complexes differ markedly, however, in overall size, surface area of the interface, and the volume and shape of the central cavity.

By determining the structure of TORC2, the team could observe which subunit within TORC2 was obstructing the rapamycin binding site on TOR.

“By deleting part of this subunit, we generated a variant of TORC2 sensitive to rapamycin,” said Manoel Prouteau, PhD, also of the University of Geneva.

This allowed the researchers to study how TORC2 acts to stimulate cell growth.

Now, they hope to identify a specific inhibitor of endogenous TORC2 that could also be an effective anticancer agent.

“Our discovery that TORC2 inhibition alone is sufficient to block the cell cycle suggests that mTORC2-specific inhibitors may provide new and potentially better therapeutic alternatives,” the team concluded.

Robbie Loewith, PhD

Photo courtesy of

University of Geneva

A group of researchers has developed a new tool to study the structure and function of target of rapamycin complex 2 (TORC2), which helps explain why rapamycin cannot access the TOR protein in this complex.

TOR is essential for the growth of normal cells but is hyperactive in tumor cells. Rapamycin is an immunosuppressant and anticancer agent that inactivates TOR in TORC1 but not in TORC2.

“In order to more easily study TORC2, we wanted to learn how to make this complex sensitive to rapamycin,” said Robbie Loewith, PhD, of the University of Geneva in Switzerland.

So Dr Loewith and a team of scientists from Switzerland, France, and the UK set out to elucidate how TORC2 works. The team reported their findings in Molecular Cell.

Using crosslinking-mass spectrometry and electron microscopy, they discovered that TORC2 has 3 features in common with TORC1: a rhomboid shape, 2-fold symmetry, and a central cavity delimited by the interface of its protein chains.

The 2 complexes differ markedly, however, in overall size, surface area of the interface, and the volume and shape of the central cavity.

By determining the structure of TORC2, the team could observe which subunit within TORC2 was obstructing the rapamycin binding site on TOR.

“By deleting part of this subunit, we generated a variant of TORC2 sensitive to rapamycin,” said Manoel Prouteau, PhD, also of the University of Geneva.

This allowed the researchers to study how TORC2 acts to stimulate cell growth.

Now, they hope to identify a specific inhibitor of endogenous TORC2 that could also be an effective anticancer agent.

“Our discovery that TORC2 inhibition alone is sufficient to block the cell cycle suggests that mTORC2-specific inhibitors may provide new and potentially better therapeutic alternatives,” the team concluded.

 

 

Inside McCormick Place, site of

the 2015 ASCO Annual Meeting

 

CHICAGO—Adding obinutuzumab to treatment with bendamustine improves progression-free survival (PFS) in patients with rituximab-refractory, indolent non-Hodgkin lymphoma (NHL), interim results of the phase 3 GADOLIN trial suggest.

Study investigators said patients who received obinutuzumab and bendamustine followed by obinutuzumab maintenance had roughly double the PFS of patients who received bendamustine alone.

There was no significant difference between the treatment groups with regard to response rates or overall survival (OS), but the investigators said longer follow-up is needed to determine if obinutuzumab confers a benefit in OS.

This trial was stopped before its protocol-specified final analysis because of the PFS benefit observed in the obinutuzumab arm.

Laurie Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, presented these results at the 2015 ASCO Annual Meeting (abstract LBA8502). Genentech Inc. and F. Hoffmann-La Roche Ltd. funded this research.

The trial included 413 patients with rituximab-refractory NHL, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenstrom’s macroglobulinemia (WM).

The patients were randomized to receive bendamustine alone (120 mg/m²/day on days 1 and 2 for up to six 28-day cycles) or a combination of bendamustine (90 mg/m²/day on days 1 and 2 for up to six 28-day cycles) plus obinutuzumab (1000 mg on days 1, 8, and 15 for cycle 1, followed by 1 dose for up to six 28-day cycles), followed by obinutuzumab maintenance (1000 mg every 2 months for 2 years or until progression).

Dr Sehn said there were no significant differences in baseline characteristics between the treatment arms. Patients in both arms had received a median of 2 prior treatments, and the median time from last treatment was about 4 months.

Of the 194 patients randomized to treatment in the obinutuzumab-bendamustine (OB) arm, 79.9% had FL, 13.9% had MZL, and 6.2% had SLL. Of the 202 patients randomized to the bendamustine-alone (control) arm, 82.2% had FL, 9.4% had MZL, 7.9% had SLL, and 0.5% had WM.

Ultimately, 156 patients completed induction in the OB arm, as did 129 patients in the control arm. Thirty-six patients completed maintenance with obinutuzumab, and 46 were still receiving maintenance at the time of analysis.

Safety results

Dr Sehn said there were no unexpected safety signals among patients in the OB arm.

About 99% of patients in the OB arm experienced at least 1 adverse event (AE), as did 98% of patients in the control arm. Severe AEs occurred in 38.1% and 32.8% of patients, respectively, and grade 3/4 AEs occurred in 67% and 62.1%, respectively.

AEs leading to treatment withdrawal occurred in 18% and 15.7% of patients, respectively. And AEs leading to death occurred in 6.2% and 6.1%, respectively.

Grade 3/4 AEs that occurred in at least 2% of patients in the OB and control arms, respectively, were neutropenia (33% vs 26.3%), thrombocytopenia (10.8% vs 16.2%), infusion-related reactions (10.8% vs 5.6%), anemia (7.7% vs 10.1%), febrile neutropenia (4.6% vs 3.5%), nausea (1% vs 3%), fatigue (1.5% vs 2.5%), diarrhea (1% vs 2.5%), and vomiting (2.1% vs 1%).

Response and survival

According to an independent radiology facility, 69.2% of patients in the OB arm had responded to treatment at the end of induction, as had 63% of the control arm. The best overall response by the 12-month mark was 78.7% and 76.6%, respectively.

The median follow-up was 21 months. At that point, the median PFS had not been reached in the OB arm but was 14.9 months in the control arm (P<0.0001), according to the independent radiology facility.

According to investigators, the median PFS was 29.2 months and 14 months, respectively (P<0.0001).

The median OS has not been reached in either arm (P=0.4017). Thirty-four patients (18%) in the OB arm died, as did 41 (20%) in the control arm.

Dr Sehn said longer follow-up is needed to determine the potential OS benefit associated with obinutuzumab, but the PFS benefit of OB is clinically meaningful.

“The fact that this new approach doubled average remission time marks a major step forward for our patients,” she said. “Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy.”

 

 

Inside McCormick Place, site of

the 2015 ASCO Annual Meeting

 

CHICAGO—Adding obinutuzumab to treatment with bendamustine improves progression-free survival (PFS) in patients with rituximab-refractory, indolent non-Hodgkin lymphoma (NHL), interim results of the phase 3 GADOLIN trial suggest.

Study investigators said patients who received obinutuzumab and bendamustine followed by obinutuzumab maintenance had roughly double the PFS of patients who received bendamustine alone.

There was no significant difference between the treatment groups with regard to response rates or overall survival (OS), but the investigators said longer follow-up is needed to determine if obinutuzumab confers a benefit in OS.

This trial was stopped before its protocol-specified final analysis because of the PFS benefit observed in the obinutuzumab arm.

Laurie Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, presented these results at the 2015 ASCO Annual Meeting (abstract LBA8502). Genentech Inc. and F. Hoffmann-La Roche Ltd. funded this research.

The trial included 413 patients with rituximab-refractory NHL, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenstrom’s macroglobulinemia (WM).

The patients were randomized to receive bendamustine alone (120 mg/m²/day on days 1 and 2 for up to six 28-day cycles) or a combination of bendamustine (90 mg/m²/day on days 1 and 2 for up to six 28-day cycles) plus obinutuzumab (1000 mg on days 1, 8, and 15 for cycle 1, followed by 1 dose for up to six 28-day cycles), followed by obinutuzumab maintenance (1000 mg every 2 months for 2 years or until progression).

Dr Sehn said there were no significant differences in baseline characteristics between the treatment arms. Patients in both arms had received a median of 2 prior treatments, and the median time from last treatment was about 4 months.

Of the 194 patients randomized to treatment in the obinutuzumab-bendamustine (OB) arm, 79.9% had FL, 13.9% had MZL, and 6.2% had SLL. Of the 202 patients randomized to the bendamustine-alone (control) arm, 82.2% had FL, 9.4% had MZL, 7.9% had SLL, and 0.5% had WM.

Ultimately, 156 patients completed induction in the OB arm, as did 129 patients in the control arm. Thirty-six patients completed maintenance with obinutuzumab, and 46 were still receiving maintenance at the time of analysis.

Safety results

Dr Sehn said there were no unexpected safety signals among patients in the OB arm.

About 99% of patients in the OB arm experienced at least 1 adverse event (AE), as did 98% of patients in the control arm. Severe AEs occurred in 38.1% and 32.8% of patients, respectively, and grade 3/4 AEs occurred in 67% and 62.1%, respectively.

AEs leading to treatment withdrawal occurred in 18% and 15.7% of patients, respectively. And AEs leading to death occurred in 6.2% and 6.1%, respectively.

Grade 3/4 AEs that occurred in at least 2% of patients in the OB and control arms, respectively, were neutropenia (33% vs 26.3%), thrombocytopenia (10.8% vs 16.2%), infusion-related reactions (10.8% vs 5.6%), anemia (7.7% vs 10.1%), febrile neutropenia (4.6% vs 3.5%), nausea (1% vs 3%), fatigue (1.5% vs 2.5%), diarrhea (1% vs 2.5%), and vomiting (2.1% vs 1%).

Response and survival

According to an independent radiology facility, 69.2% of patients in the OB arm had responded to treatment at the end of induction, as had 63% of the control arm. The best overall response by the 12-month mark was 78.7% and 76.6%, respectively.

The median follow-up was 21 months. At that point, the median PFS had not been reached in the OB arm but was 14.9 months in the control arm (P<0.0001), according to the independent radiology facility.

According to investigators, the median PFS was 29.2 months and 14 months, respectively (P<0.0001).

The median OS has not been reached in either arm (P=0.4017). Thirty-four patients (18%) in the OB arm died, as did 41 (20%) in the control arm.

Dr Sehn said longer follow-up is needed to determine the potential OS benefit associated with obinutuzumab, but the PFS benefit of OB is clinically meaningful.

“The fact that this new approach doubled average remission time marks a major step forward for our patients,” she said. “Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy.”

 

 

Inside McCormick Place, site of

the 2015 ASCO Annual Meeting

 

CHICAGO—Adding obinutuzumab to treatment with bendamustine improves progression-free survival (PFS) in patients with rituximab-refractory, indolent non-Hodgkin lymphoma (NHL), interim results of the phase 3 GADOLIN trial suggest.

Study investigators said patients who received obinutuzumab and bendamustine followed by obinutuzumab maintenance had roughly double the PFS of patients who received bendamustine alone.

There was no significant difference between the treatment groups with regard to response rates or overall survival (OS), but the investigators said longer follow-up is needed to determine if obinutuzumab confers a benefit in OS.

This trial was stopped before its protocol-specified final analysis because of the PFS benefit observed in the obinutuzumab arm.

Laurie Sehn, MD, of the BC Cancer Agency in Vancouver, Canada, presented these results at the 2015 ASCO Annual Meeting (abstract LBA8502). Genentech Inc. and F. Hoffmann-La Roche Ltd. funded this research.

The trial included 413 patients with rituximab-refractory NHL, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenstrom’s macroglobulinemia (WM).

The patients were randomized to receive bendamustine alone (120 mg/m²/day on days 1 and 2 for up to six 28-day cycles) or a combination of bendamustine (90 mg/m²/day on days 1 and 2 for up to six 28-day cycles) plus obinutuzumab (1000 mg on days 1, 8, and 15 for cycle 1, followed by 1 dose for up to six 28-day cycles), followed by obinutuzumab maintenance (1000 mg every 2 months for 2 years or until progression).

Dr Sehn said there were no significant differences in baseline characteristics between the treatment arms. Patients in both arms had received a median of 2 prior treatments, and the median time from last treatment was about 4 months.

Of the 194 patients randomized to treatment in the obinutuzumab-bendamustine (OB) arm, 79.9% had FL, 13.9% had MZL, and 6.2% had SLL. Of the 202 patients randomized to the bendamustine-alone (control) arm, 82.2% had FL, 9.4% had MZL, 7.9% had SLL, and 0.5% had WM.

Ultimately, 156 patients completed induction in the OB arm, as did 129 patients in the control arm. Thirty-six patients completed maintenance with obinutuzumab, and 46 were still receiving maintenance at the time of analysis.

Safety results

Dr Sehn said there were no unexpected safety signals among patients in the OB arm.

About 99% of patients in the OB arm experienced at least 1 adverse event (AE), as did 98% of patients in the control arm. Severe AEs occurred in 38.1% and 32.8% of patients, respectively, and grade 3/4 AEs occurred in 67% and 62.1%, respectively.

AEs leading to treatment withdrawal occurred in 18% and 15.7% of patients, respectively. And AEs leading to death occurred in 6.2% and 6.1%, respectively.

Grade 3/4 AEs that occurred in at least 2% of patients in the OB and control arms, respectively, were neutropenia (33% vs 26.3%), thrombocytopenia (10.8% vs 16.2%), infusion-related reactions (10.8% vs 5.6%), anemia (7.7% vs 10.1%), febrile neutropenia (4.6% vs 3.5%), nausea (1% vs 3%), fatigue (1.5% vs 2.5%), diarrhea (1% vs 2.5%), and vomiting (2.1% vs 1%).

Response and survival

According to an independent radiology facility, 69.2% of patients in the OB arm had responded to treatment at the end of induction, as had 63% of the control arm. The best overall response by the 12-month mark was 78.7% and 76.6%, respectively.

The median follow-up was 21 months. At that point, the median PFS had not been reached in the OB arm but was 14.9 months in the control arm (P<0.0001), according to the independent radiology facility.

According to investigators, the median PFS was 29.2 months and 14 months, respectively (P<0.0001).

The median OS has not been reached in either arm (P=0.4017). Thirty-four patients (18%) in the OB arm died, as did 41 (20%) in the control arm.

Dr Sehn said longer follow-up is needed to determine the potential OS benefit associated with obinutuzumab, but the PFS benefit of OB is clinically meaningful.

“The fact that this new approach doubled average remission time marks a major step forward for our patients,” she said. “Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy.”

Breastfeeding baby

Photo by Petr Kratochvil

Breastfeeding a child may reduce his risk of developing acute lymphoblastic leukemia (ALL) but perhaps not acute myeloid leukemia (AML), according to a review published in JAMA Pediatrics.

Researchers found that breastfeeding a child for 6 months or longer was associated with a 19% lower risk of childhood leukemia, compared with no

breastfeeding or breastfeeding for a shorter period of time.

And children who were breastfed for any amount of time had an 11% lower risk of childhood leukemia than children who were never breastfed.

However, when the researchers analyzed studies of ALL and AML separately, they found that breastfeeding was not associated with a significantly lower risk of AML.

Efrat L. Amitay, PhD, and Lital Keinan-Boker, MD, PhD, of the University of Haifa in Israel, conducted this research.

In a review of 18 studies, the pair found that breastfeeding a child for 6 months or longer was associated with a significantly lower risk of childhood leukemia, compared with no breastfeeding or breastfeeding for a shorter period of time (odds ratio [OR]=0.81).

And a separate analysis of 15 studies showed that children who were breastfed for any amount of time had a lower risk of childhood leukemia than children who were never breastfed (OR=0.89).

The researchers also conducted meta-analyses of AML studies and ALL studies separately—11 ALL and 6 AML studies. And they found a significant inverse association between breastfeeding for 6 months or more and ALL risk (OR=0.82) but no significant association for AML risk (OR=0.74).

The researchers said several biological mechanisms may explain the association between breastfeeding and a reduced risk of childhood leukemia. However, more high-quality studies are needed to clarify those mechanisms.

Breastfeeding baby

Photo by Petr Kratochvil

Breastfeeding a child may reduce his risk of developing acute lymphoblastic leukemia (ALL) but perhaps not acute myeloid leukemia (AML), according to a review published in JAMA Pediatrics.

Researchers found that breastfeeding a child for 6 months or longer was associated with a 19% lower risk of childhood leukemia, compared with no

breastfeeding or breastfeeding for a shorter period of time.

And children who were breastfed for any amount of time had an 11% lower risk of childhood leukemia than children who were never breastfed.

However, when the researchers analyzed studies of ALL and AML separately, they found that breastfeeding was not associated with a significantly lower risk of AML.

Efrat L. Amitay, PhD, and Lital Keinan-Boker, MD, PhD, of the University of Haifa in Israel, conducted this research.

In a review of 18 studies, the pair found that breastfeeding a child for 6 months or longer was associated with a significantly lower risk of childhood leukemia, compared with no breastfeeding or breastfeeding for a shorter period of time (odds ratio [OR]=0.81).

And a separate analysis of 15 studies showed that children who were breastfed for any amount of time had a lower risk of childhood leukemia than children who were never breastfed (OR=0.89).

The researchers also conducted meta-analyses of AML studies and ALL studies separately—11 ALL and 6 AML studies. And they found a significant inverse association between breastfeeding for 6 months or more and ALL risk (OR=0.82) but no significant association for AML risk (OR=0.74).

The researchers said several biological mechanisms may explain the association between breastfeeding and a reduced risk of childhood leukemia. However, more high-quality studies are needed to clarify those mechanisms.

Breastfeeding baby

Photo by Petr Kratochvil

Breastfeeding a child may reduce his risk of developing acute lymphoblastic leukemia (ALL) but perhaps not acute myeloid leukemia (AML), according to a review published in JAMA Pediatrics.

Researchers found that breastfeeding a child for 6 months or longer was associated with a 19% lower risk of childhood leukemia, compared with no

breastfeeding or breastfeeding for a shorter period of time.

And children who were breastfed for any amount of time had an 11% lower risk of childhood leukemia than children who were never breastfed.

However, when the researchers analyzed studies of ALL and AML separately, they found that breastfeeding was not associated with a significantly lower risk of AML.

Efrat L. Amitay, PhD, and Lital Keinan-Boker, MD, PhD, of the University of Haifa in Israel, conducted this research.

In a review of 18 studies, the pair found that breastfeeding a child for 6 months or longer was associated with a significantly lower risk of childhood leukemia, compared with no breastfeeding or breastfeeding for a shorter period of time (odds ratio [OR]=0.81).

And a separate analysis of 15 studies showed that children who were breastfed for any amount of time had a lower risk of childhood leukemia than children who were never breastfed (OR=0.89).

The researchers also conducted meta-analyses of AML studies and ALL studies separately—11 ALL and 6 AML studies. And they found a significant inverse association between breastfeeding for 6 months or more and ALL risk (OR=0.82) but no significant association for AML risk (OR=0.74).

The researchers said several biological mechanisms may explain the association between breastfeeding and a reduced risk of childhood leukemia. However, more high-quality studies are needed to clarify those mechanisms.

Warfarin tablets

A meta-analysis of 92,816 people taking anticoagulants has shown that the risk of gastrointestinal (GI) bleeding related to the newer oral anticoagulants dabigatran and rivaroxaban is similar to that for warfarin.

But for patients older than 65, the risk of GI bleeding increases. By age 76, the risk may be 3 to 5 times higher when taking the newer anticoagulants compared to warfarin.

These findings were published in BMJ.

“The new anticoagulants have really been popular with patients who have previously only had one choice of oral anticoagulant,” said study author Neena S. Abraham, MD, of the Mayo Clinic in Scottsdale, Arizona.

“However, they may not be the right choice for everyone. Our findings definitely point toward important age-related risk that merit consideration when doctors are making treatment recommendations.”

Dr Abraham and her colleagues compared the risk of GI bleeding with newer anticoagulants and warfarin using national data available on privately insured patients and Medicare Advantage enrollees from the Optum Labs Data Warehouse.

Data on apixaban were not included in the study because there were too few patients prescribed apixaban in the dataset during the period of observation, from November 1, 2010, to September 30, 2013.

The cohort included 8578 (9.2%) patients on dabigatran, 16,253 (17.5%) on rivaroxaban, and 67,985 (73.2%) on warfarin. Patients were 18 years of age or older.

The researchers found that, among atrial fibrillation (AF) patients older than 75, the risk of GI bleeding was higher than with warfarin. The hazard ratios (HRs) were 2.49 (95% confidence interval [CI] 1.61 to 3.83) and 1.62 (95% CI 1.02 to 2.58), respectively.

However, among older patients without AF, the risk of GI bleeding was comparable with dabigatran and warfarin. The HRs were 1.56 (95% CI 0.42 to 5.80) and 2.73 (95% CI 0.83 to 8.94), respectively.

Older AF patients taking rivaroxaban had an increased risk of GI bleeding compared to patients taking warfarin. The HRs were 2.91 (95% CI 1.65 to 4.81) and 2.05 (95% CI 1.17 to 3.59), respectively.

And older patients without AF had an increased risk of GI bleeding with rivaroxaban compared to warfarin. The HRs were 4.58 (95% CI 2.40 to 8.72) and 4.40 (95% CI 2.43 to 7.96), respectively.

The researchers also found that, for those patients under 65, the newer agents seemed to confer a lower risk of GI bleeding than warfarin.

Warfarin tablets

A meta-analysis of 92,816 people taking anticoagulants has shown that the risk of gastrointestinal (GI) bleeding related to the newer oral anticoagulants dabigatran and rivaroxaban is similar to that for warfarin.

But for patients older than 65, the risk of GI bleeding increases. By age 76, the risk may be 3 to 5 times higher when taking the newer anticoagulants compared to warfarin.

These findings were published in BMJ.

“The new anticoagulants have really been popular with patients who have previously only had one choice of oral anticoagulant,” said study author Neena S. Abraham, MD, of the Mayo Clinic in Scottsdale, Arizona.

“However, they may not be the right choice for everyone. Our findings definitely point toward important age-related risk that merit consideration when doctors are making treatment recommendations.”

Dr Abraham and her colleagues compared the risk of GI bleeding with newer anticoagulants and warfarin using national data available on privately insured patients and Medicare Advantage enrollees from the Optum Labs Data Warehouse.

Data on apixaban were not included in the study because there were too few patients prescribed apixaban in the dataset during the period of observation, from November 1, 2010, to September 30, 2013.

The cohort included 8578 (9.2%) patients on dabigatran, 16,253 (17.5%) on rivaroxaban, and 67,985 (73.2%) on warfarin. Patients were 18 years of age or older.

The researchers found that, among atrial fibrillation (AF) patients older than 75, the risk of GI bleeding was higher than with warfarin. The hazard ratios (HRs) were 2.49 (95% confidence interval [CI] 1.61 to 3.83) and 1.62 (95% CI 1.02 to 2.58), respectively.

However, among older patients without AF, the risk of GI bleeding was comparable with dabigatran and warfarin. The HRs were 1.56 (95% CI 0.42 to 5.80) and 2.73 (95% CI 0.83 to 8.94), respectively.

Older AF patients taking rivaroxaban had an increased risk of GI bleeding compared to patients taking warfarin. The HRs were 2.91 (95% CI 1.65 to 4.81) and 2.05 (95% CI 1.17 to 3.59), respectively.

And older patients without AF had an increased risk of GI bleeding with rivaroxaban compared to warfarin. The HRs were 4.58 (95% CI 2.40 to 8.72) and 4.40 (95% CI 2.43 to 7.96), respectively.

The researchers also found that, for those patients under 65, the newer agents seemed to confer a lower risk of GI bleeding than warfarin.

Warfarin tablets

A meta-analysis of 92,816 people taking anticoagulants has shown that the risk of gastrointestinal (GI) bleeding related to the newer oral anticoagulants dabigatran and rivaroxaban is similar to that for warfarin.

But for patients older than 65, the risk of GI bleeding increases. By age 76, the risk may be 3 to 5 times higher when taking the newer anticoagulants compared to warfarin.

These findings were published in BMJ.

“The new anticoagulants have really been popular with patients who have previously only had one choice of oral anticoagulant,” said study author Neena S. Abraham, MD, of the Mayo Clinic in Scottsdale, Arizona.

“However, they may not be the right choice for everyone. Our findings definitely point toward important age-related risk that merit consideration when doctors are making treatment recommendations.”

Dr Abraham and her colleagues compared the risk of GI bleeding with newer anticoagulants and warfarin using national data available on privately insured patients and Medicare Advantage enrollees from the Optum Labs Data Warehouse.

Data on apixaban were not included in the study because there were too few patients prescribed apixaban in the dataset during the period of observation, from November 1, 2010, to September 30, 2013.

The cohort included 8578 (9.2%) patients on dabigatran, 16,253 (17.5%) on rivaroxaban, and 67,985 (73.2%) on warfarin. Patients were 18 years of age or older.

The researchers found that, among atrial fibrillation (AF) patients older than 75, the risk of GI bleeding was higher than with warfarin. The hazard ratios (HRs) were 2.49 (95% confidence interval [CI] 1.61 to 3.83) and 1.62 (95% CI 1.02 to 2.58), respectively.

However, among older patients without AF, the risk of GI bleeding was comparable with dabigatran and warfarin. The HRs were 1.56 (95% CI 0.42 to 5.80) and 2.73 (95% CI 0.83 to 8.94), respectively.

Older AF patients taking rivaroxaban had an increased risk of GI bleeding compared to patients taking warfarin. The HRs were 2.91 (95% CI 1.65 to 4.81) and 2.05 (95% CI 1.17 to 3.59), respectively.

And older patients without AF had an increased risk of GI bleeding with rivaroxaban compared to warfarin. The HRs were 4.58 (95% CI 2.40 to 8.72) and 4.40 (95% CI 2.43 to 7.96), respectively.

The researchers also found that, for those patients under 65, the newer agents seemed to confer a lower risk of GI bleeding than warfarin.

Ruben Mesa, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—The JAK2/FLT3 inhibitor pacritinib may fulfill an unmet need in the treatment of myelofibrosis (MF), according to a speaker at the 2015 ASCO Annual Meeting.

Results of the phase 3 PERSIST-1 trial indicate that pacritinib is safe and effective for MF patients with thrombocytopenia.

“Thrombocytopenia is a common feature in people with advanced [MF], and current treatment options have not been able to concurrently improve splenomegaly symptoms and cytopenias in these patients,” said study investigator Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center in Scottsdale, Arizona.

But PERSIST-1 showed that pacritinib can accomplish this. And the drug proved more effective than best available therapy (BAT), excluding JAK inhibitors, in reducing spleen volume and alleviating MF symptoms in the entire cohort of MF patients.

Dr Mesa presented these results at ASCO as abstract LBA7006. The study was funded by CTI BioPharma Corp., the company developing pacritinib.

The trial included 327 patients who were randomized to receive pacritinib (n=220) or BAT (n=107).

Patients in the BAT arm received therapies that are routinely prescribed off-label for MF, such as erythropoietin-stimulating agents, immunomodulatory drugs, and hydroxyurea. Ruxolitinib was intentionally excluded from this trial because the study included patients with thrombocytopenia.

Dr Mesa said the patients’ baseline characteristics “demonstrate a group of individuals with advanced myelofibrosis, a heavy percentage of those with primary myelofibrosis, the vast majority having intermediate-2 or high-risk disease, with very significant splenomegaly, and the vast majority having the JAK2 mutation.”

“About half the individuals were anemic or transfusion-dependent,” he noted. “And a full third were thrombocytopenic, under 100,000 [platelets/µL], with 16% under 50,000 [platelets/µL]. This was the first phase 3 study of myelofibrosis that allowed individuals with a platelet count of less than 100,000 to be enrolled.”

Fifty-six percent of patients remained on pacritinib at the time of analysis, as did 8% of patients on BAT. Seventy-nine percent of patients crossed over from the BAT arm to the pacritinib arm.

Spleen reduction

The study’s primary endpoint was a reduction in spleen volume of 35% or greater.

In the intent-to-treat (ITT) population, 19.1% of patients in the pacritinib arm met this endpoint, as did 4.7% of patients in the BAT arm (P=0.0003). In the evaluable population—165 patients in the pacritinib arm and 85 patients in the BAT arm—the rates were 25% and 5.9%, respectively (P=0.0001).

Dr Mesa noted that pacritinib was able to reduce spleen volume in all subgroups of patients, including those with thrombocytopenia.

“Both the group [with platelet counts] under 100,000 as well as under 50,000 uniquely responded only on the pacritinib arm, with no responses on the BAT arm,” he said.

In the ITT population, 16.7% of patients with platelet counts under 100,000/µL and 22.9% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values, in the comparison with the BAT arm, were 0.0451 and 0.0086, respectively.

In the evaluable population, 23.5% of patients with platelet counts under 100,000/µL and 33.3% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values were 0.0370 and 0.0072, respectively.

“It is too early to know if pacritinib has an impact on survival, but that is clearly our expectation [based on the spleen responses observed],” Dr Mesa said.

TSS and transfusion

The study’s secondary endpoint was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to week 24. TSS was measured by patient responses on the Myeloproliferative Neoplasm Symptom Assessment Form.

In the ITT population, 24.5% of pacritinib-treated patients and 6.5% of BAT-treated patients had a 50% or greater reduction in TSS score (P<0.0001). In the evaluable population, 40.9% and 9.9% of patients, respectively (P<0.0001), met this endpoint.

Dr Mesa also pointed out that 25.7% of pacritinib-treated patients who were severely anemic and transfusion-dependent—requiring at least 6 units of blood in the 90 days prior to study entry—became transfusion independent. But none of the BAT-treated patients did so (P<0.043).

Adverse events

“The most common adverse events [in the pacritinib arm] were consistent with the earlier studies,” Dr Mesa said. “Gastrointestinal toxicities were most common, although typically at low grades.”

“As expected, we saw very few individuals with any significant thrombocytopenia or anemia as drug-emergent. There were individuals who enrolled in the study as a grade 4, so some of those remained.”

The most common adverse events of any grade were diarrhea (53.2% in the pacritinib arm and 12.3% in the BAT arm), nausea (26.8% vs 6.6%), anemia (22.3% vs 19.8%), thrombocytopenia (16.8% vs 13.2%), and vomiting (15.9% vs 5.7%).

Ten percent of patients in the pacritinib arm required dose reductions due to adverse events. Diarrhea prompted dose interruptions in 13 patients and discontinuation in 3 patients. But pacritinib-associated diarrhea typically resolved in a little over a week.

“Based on these preliminary results, pacritinib may represent a very important agent for individuals with advanced disease and may have an impact on the disease course,” Dr Mesa concluded.

Ruben Mesa, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—The JAK2/FLT3 inhibitor pacritinib may fulfill an unmet need in the treatment of myelofibrosis (MF), according to a speaker at the 2015 ASCO Annual Meeting.

Results of the phase 3 PERSIST-1 trial indicate that pacritinib is safe and effective for MF patients with thrombocytopenia.

“Thrombocytopenia is a common feature in people with advanced [MF], and current treatment options have not been able to concurrently improve splenomegaly symptoms and cytopenias in these patients,” said study investigator Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center in Scottsdale, Arizona.

But PERSIST-1 showed that pacritinib can accomplish this. And the drug proved more effective than best available therapy (BAT), excluding JAK inhibitors, in reducing spleen volume and alleviating MF symptoms in the entire cohort of MF patients.

Dr Mesa presented these results at ASCO as abstract LBA7006. The study was funded by CTI BioPharma Corp., the company developing pacritinib.

The trial included 327 patients who were randomized to receive pacritinib (n=220) or BAT (n=107).

Patients in the BAT arm received therapies that are routinely prescribed off-label for MF, such as erythropoietin-stimulating agents, immunomodulatory drugs, and hydroxyurea. Ruxolitinib was intentionally excluded from this trial because the study included patients with thrombocytopenia.

Dr Mesa said the patients’ baseline characteristics “demonstrate a group of individuals with advanced myelofibrosis, a heavy percentage of those with primary myelofibrosis, the vast majority having intermediate-2 or high-risk disease, with very significant splenomegaly, and the vast majority having the JAK2 mutation.”

“About half the individuals were anemic or transfusion-dependent,” he noted. “And a full third were thrombocytopenic, under 100,000 [platelets/µL], with 16% under 50,000 [platelets/µL]. This was the first phase 3 study of myelofibrosis that allowed individuals with a platelet count of less than 100,000 to be enrolled.”

Fifty-six percent of patients remained on pacritinib at the time of analysis, as did 8% of patients on BAT. Seventy-nine percent of patients crossed over from the BAT arm to the pacritinib arm.

Spleen reduction

The study’s primary endpoint was a reduction in spleen volume of 35% or greater.

In the intent-to-treat (ITT) population, 19.1% of patients in the pacritinib arm met this endpoint, as did 4.7% of patients in the BAT arm (P=0.0003). In the evaluable population—165 patients in the pacritinib arm and 85 patients in the BAT arm—the rates were 25% and 5.9%, respectively (P=0.0001).

Dr Mesa noted that pacritinib was able to reduce spleen volume in all subgroups of patients, including those with thrombocytopenia.

“Both the group [with platelet counts] under 100,000 as well as under 50,000 uniquely responded only on the pacritinib arm, with no responses on the BAT arm,” he said.

In the ITT population, 16.7% of patients with platelet counts under 100,000/µL and 22.9% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values, in the comparison with the BAT arm, were 0.0451 and 0.0086, respectively.

In the evaluable population, 23.5% of patients with platelet counts under 100,000/µL and 33.3% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values were 0.0370 and 0.0072, respectively.

“It is too early to know if pacritinib has an impact on survival, but that is clearly our expectation [based on the spleen responses observed],” Dr Mesa said.

TSS and transfusion

The study’s secondary endpoint was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to week 24. TSS was measured by patient responses on the Myeloproliferative Neoplasm Symptom Assessment Form.

In the ITT population, 24.5% of pacritinib-treated patients and 6.5% of BAT-treated patients had a 50% or greater reduction in TSS score (P<0.0001). In the evaluable population, 40.9% and 9.9% of patients, respectively (P<0.0001), met this endpoint.

Dr Mesa also pointed out that 25.7% of pacritinib-treated patients who were severely anemic and transfusion-dependent—requiring at least 6 units of blood in the 90 days prior to study entry—became transfusion independent. But none of the BAT-treated patients did so (P<0.043).

Adverse events

“The most common adverse events [in the pacritinib arm] were consistent with the earlier studies,” Dr Mesa said. “Gastrointestinal toxicities were most common, although typically at low grades.”

“As expected, we saw very few individuals with any significant thrombocytopenia or anemia as drug-emergent. There were individuals who enrolled in the study as a grade 4, so some of those remained.”

The most common adverse events of any grade were diarrhea (53.2% in the pacritinib arm and 12.3% in the BAT arm), nausea (26.8% vs 6.6%), anemia (22.3% vs 19.8%), thrombocytopenia (16.8% vs 13.2%), and vomiting (15.9% vs 5.7%).

Ten percent of patients in the pacritinib arm required dose reductions due to adverse events. Diarrhea prompted dose interruptions in 13 patients and discontinuation in 3 patients. But pacritinib-associated diarrhea typically resolved in a little over a week.

“Based on these preliminary results, pacritinib may represent a very important agent for individuals with advanced disease and may have an impact on the disease course,” Dr Mesa concluded.

Ruben Mesa, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—The JAK2/FLT3 inhibitor pacritinib may fulfill an unmet need in the treatment of myelofibrosis (MF), according to a speaker at the 2015 ASCO Annual Meeting.

Results of the phase 3 PERSIST-1 trial indicate that pacritinib is safe and effective for MF patients with thrombocytopenia.

“Thrombocytopenia is a common feature in people with advanced [MF], and current treatment options have not been able to concurrently improve splenomegaly symptoms and cytopenias in these patients,” said study investigator Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center in Scottsdale, Arizona.

But PERSIST-1 showed that pacritinib can accomplish this. And the drug proved more effective than best available therapy (BAT), excluding JAK inhibitors, in reducing spleen volume and alleviating MF symptoms in the entire cohort of MF patients.

Dr Mesa presented these results at ASCO as abstract LBA7006. The study was funded by CTI BioPharma Corp., the company developing pacritinib.

The trial included 327 patients who were randomized to receive pacritinib (n=220) or BAT (n=107).

Patients in the BAT arm received therapies that are routinely prescribed off-label for MF, such as erythropoietin-stimulating agents, immunomodulatory drugs, and hydroxyurea. Ruxolitinib was intentionally excluded from this trial because the study included patients with thrombocytopenia.

Dr Mesa said the patients’ baseline characteristics “demonstrate a group of individuals with advanced myelofibrosis, a heavy percentage of those with primary myelofibrosis, the vast majority having intermediate-2 or high-risk disease, with very significant splenomegaly, and the vast majority having the JAK2 mutation.”

“About half the individuals were anemic or transfusion-dependent,” he noted. “And a full third were thrombocytopenic, under 100,000 [platelets/µL], with 16% under 50,000 [platelets/µL]. This was the first phase 3 study of myelofibrosis that allowed individuals with a platelet count of less than 100,000 to be enrolled.”

Fifty-six percent of patients remained on pacritinib at the time of analysis, as did 8% of patients on BAT. Seventy-nine percent of patients crossed over from the BAT arm to the pacritinib arm.

Spleen reduction

The study’s primary endpoint was a reduction in spleen volume of 35% or greater.

In the intent-to-treat (ITT) population, 19.1% of patients in the pacritinib arm met this endpoint, as did 4.7% of patients in the BAT arm (P=0.0003). In the evaluable population—165 patients in the pacritinib arm and 85 patients in the BAT arm—the rates were 25% and 5.9%, respectively (P=0.0001).

Dr Mesa noted that pacritinib was able to reduce spleen volume in all subgroups of patients, including those with thrombocytopenia.

“Both the group [with platelet counts] under 100,000 as well as under 50,000 uniquely responded only on the pacritinib arm, with no responses on the BAT arm,” he said.

In the ITT population, 16.7% of patients with platelet counts under 100,000/µL and 22.9% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values, in the comparison with the BAT arm, were 0.0451 and 0.0086, respectively.

In the evaluable population, 23.5% of patients with platelet counts under 100,000/µL and 33.3% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values were 0.0370 and 0.0072, respectively.

“It is too early to know if pacritinib has an impact on survival, but that is clearly our expectation [based on the spleen responses observed],” Dr Mesa said.

TSS and transfusion

The study’s secondary endpoint was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to week 24. TSS was measured by patient responses on the Myeloproliferative Neoplasm Symptom Assessment Form.

In the ITT population, 24.5% of pacritinib-treated patients and 6.5% of BAT-treated patients had a 50% or greater reduction in TSS score (P<0.0001). In the evaluable population, 40.9% and 9.9% of patients, respectively (P<0.0001), met this endpoint.

Dr Mesa also pointed out that 25.7% of pacritinib-treated patients who were severely anemic and transfusion-dependent—requiring at least 6 units of blood in the 90 days prior to study entry—became transfusion independent. But none of the BAT-treated patients did so (P<0.043).

Adverse events

“The most common adverse events [in the pacritinib arm] were consistent with the earlier studies,” Dr Mesa said. “Gastrointestinal toxicities were most common, although typically at low grades.”

“As expected, we saw very few individuals with any significant thrombocytopenia or anemia as drug-emergent. There were individuals who enrolled in the study as a grade 4, so some of those remained.”

The most common adverse events of any grade were diarrhea (53.2% in the pacritinib arm and 12.3% in the BAT arm), nausea (26.8% vs 6.6%), anemia (22.3% vs 19.8%), thrombocytopenia (16.8% vs 13.2%), and vomiting (15.9% vs 5.7%).

Ten percent of patients in the pacritinib arm required dose reductions due to adverse events. Diarrhea prompted dose interruptions in 13 patients and discontinuation in 3 patients. But pacritinib-associated diarrhea typically resolved in a little over a week.

“Based on these preliminary results, pacritinib may represent a very important agent for individuals with advanced disease and may have an impact on the disease course,” Dr Mesa concluded.

Asher Alban Akmal

Chanan-Khan, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.

There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.

“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.

Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.

The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.

Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.

“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”

Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).

Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.

Response and survival

The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).

At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).

“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”

Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.

The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.

The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).

Adverse events

Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.

The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).

The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).

Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.

The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.

Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.

Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.

“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”

Asher Alban Akmal

Chanan-Khan, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.

There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.

“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.

Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.

The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.

Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.

“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”

Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).

Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.

Response and survival

The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).

At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).

“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”

Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.

The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.

The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).

Adverse events

Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.

The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).

The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).

Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.

The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.

Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.

Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.

“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”

Asher Alban Akmal

Chanan-Khan, MD

© ASCO/Zach Boyden-Holmes

CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.

There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.

“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.

Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.

The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.

Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.

“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”

Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).

Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.

Response and survival

The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).

At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).

“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”

Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.

The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.

The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).

Adverse events

Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.

The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).

The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).

Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.

The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.

Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.

Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.

“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”