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Young adults with hypertension may be at higher CVD risk
a pair of recent studies published in JAMA suggest.
In one study, investigators applied the 2017 American College of Cardiology/American Heart Association blood pressure criteria to nearly 5,000 U.S. young adults followed for approximately 20 years and who had up to a 3.5-fold risk associated with hypertension versus normal blood pressure.
The second study of almost 2.5 million Korean young adults, followed for 10 years, similarly found increased risks of cardiovascular disease later in life for those who had stage 1 or 2 hypertension between the ages of 20 and 39 years.
“These findings from a second country on the opposite side of the globe are consistent with those of the U.S. study, providing further support for the ACC/AHA guideline definitions of hypertension,” Naomi D.L. Fisher, MD, deputy editor, JAMA, and Gregory Curfman, MD, Brigham and Women’s Hospital, Boston, said in an editorial also appearing in JAMA.
Disagreement over the ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults threatens to distract from their potential benefits, Dr. Fisher and Dr. Curfman wrote in that editorial.
By redefining stage 1 hypertension as 130/80 mm Hg or higher, down from 140/90 mm Hg or higher, the 2017 ACC/AHA increased the prevalence of hypertension in the United States from 31.9% to 45.6%, they noted.
“Given the magnitude and reach of the global problem of hypertension, it is imperative that dedicated control efforts at the population level intensify,” they said.
U.S. study
The U.S. study, described in JAMA by Yuichiro Yano, MD, PhD, department of community and family medicine, Duke University, Durham, N.C., and his colleagues, was based on analysis of a prospective cohort study, CARDIA (Coronary Artery Risk Development in Young Adults Study), which started in 1985 and enrolled 5,115 black and white adults aged 18-30 years.
They applied the ACC/AHA blood pressure criteria based on each participants’ highest measurement before the age of 40 years, and correlated that with incident cardiovascular disease events that occurred over a median follow-up of 18.8 years.
Patients with normal blood pressure had a cardiovascular disease incidence rate of 1.37/1,000 person-years, compared with 2.74/1,000 person-years for those with elevated blood pressure, 3.15 for stage 1 hypertension, and 8.04 for stage 2 hypertension, investigators found.
That translated into increased risks of cardiovascular disease for those with elevated blood pressure versus those with normal blood pressure. After multivariable adjustment, the hazard ratio for cardiovascular disease was 1.67 (95% confidence interval, 1.01-2.77) for elevated blood pressure, 1.75 (95% CI, 1.22-2.53) for stage 1 hypertension, and 3.49 (95% CI, 2.42-5.05) for stage 2, Dr. Yano and his colleagues reported.
“The ACC/AHA blood pressure classification system may help identify young adults at higher risk for CVD events,” they concluded.
South Korean study
Similar findings were shown in a population-based cohort study, also published in JAMA, that included 2,488,101 adults aged 20-39 years in Korean National Health Insurance Service records.
The investigators looked at mean blood pressure levels from an initial health examination that took place during 2002-2003 and a second examination during 2004-2005.
Follow-up was shorter than the U.S. study, with a median duration of 10 years, reported Joung Sik Son, MD, department of family medicine and biomedical sciences, Seoul (South Korea) National University, and coauthors.
Even so, investigators detected an elevated risk of cardiovascular events for individuals with stage 1 or 2 hypertension versus those with normal blood pressure.
For men with baseline stage 1 hypertension based on the mean values and using the latest ACC/AHA blood pressure criteria, the incidence of cardiovascular disease was 215/100,000 person-years, versus 164 for those with normal blood pressure, with an adjusted hazard ratio of 1.25 (95% CI, 1.21-1.28), the authors said. Likewise, women with stage 1 hypertension had an incidence of 131/100,000 person-years versus 40 for women with normal blood pressure, with a hazard ratio of 1.27 (95% CI, 1.21-1.34).
Men with stage 2 hypertension likewise had a higher cardiovascular disease incidence than did those with normal blood pressure (336 vs. 164 per 100,000 person-years; adjusted HR 1.76), with similar findings seen in women, the report shows.
“Despite the relatively low absolute risk, the difference in absolute risk and the fact that sustained hypertension during longer durations is associated with higher risk of CVD [cardiovascular disease] indicate that early blood pressure management among young adults may lead to significant public health benefits by reducing CVD risk later in life,” Dr. Son and colleagues wrote in a discussion of the results.
Authors of the U.S. study reported disclosures related to Amarin, Amgen, and Novartis outside of the submitted work, as well as grants from the National Heart, Lung, and Blood Institute and National Institutes of Health during the conduct of the study.
Authors of the South Korean study reported no conflict of interest disclosures. That study was supported by the Ministry of Health and Welfare and the Ministry of Education of Korea, along with grants from the National Research Foundation of Korea.
SOURCES: Yano Y et al. JAMA. 2018;302(17):1774-82; Son JS et al. JAMA. 2018;302(17):1783-92.
These two studies suggest that a higher blood pressure level in young adulthood is associated with a greater hazard of premature cardiovascular disease, according to Ramachandran S. Vasan, MD.
However, observing an elevated risk of premature cardiovascular disease does necessarily prove causality, or establish that intervening to lower blood pressure in this age group would lessen that risk, he said in an editorial.
The studies are notable for showing that half to nearly 60% of younger adults had levels of blood pressure considered not normal, he added in the editorial, which appears in JAMA.
It is not clear why so many young adults would manifest higher blood pressure levels in these studies, he said, noting that the umbrella of young adults with hypertension likely includes patients with a variety of subtypes. Those including white-coat hypertension, peripheral amplification with normal central blood pressure, hyperadrenergic state, isolated systolic hypertension, and a smaller subset with secondary hypertension.
“These distinct pathophenotypes may have varying natural histories and their management approaches may be distinctive, suggesting the importance and potential role of subphenotyping of elevated blood pressure in young adults to facilitate treatment decisions,” he wrote in his editorial.
The two studies raise key questions, such as whether there are modifiable social, behavioral, or cultural factors that could prevent elevated blood pressure in younger people, he said.
To date, a substantial body of evidence does suggest that blood pressure levels evolve over the course of life, driven by environmental factors superimposed on genetic risks, and modified by sex and race.
“Overall, these data emphasize that primary prevention of higher blood pressure levels must begin in childhood,” he said.
Ramachandran S. Vasan, MD, is with the section of preventive medicine and epidemiology at Boston University. He reported no conflict of interest disclosures related to his editorial, which was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and a grant from the National Institutes of Health. JAMA. 2018;320(17):1760-3. doi:10.1001/jama.2018.16068.
These two studies suggest that a higher blood pressure level in young adulthood is associated with a greater hazard of premature cardiovascular disease, according to Ramachandran S. Vasan, MD.
However, observing an elevated risk of premature cardiovascular disease does necessarily prove causality, or establish that intervening to lower blood pressure in this age group would lessen that risk, he said in an editorial.
The studies are notable for showing that half to nearly 60% of younger adults had levels of blood pressure considered not normal, he added in the editorial, which appears in JAMA.
It is not clear why so many young adults would manifest higher blood pressure levels in these studies, he said, noting that the umbrella of young adults with hypertension likely includes patients with a variety of subtypes. Those including white-coat hypertension, peripheral amplification with normal central blood pressure, hyperadrenergic state, isolated systolic hypertension, and a smaller subset with secondary hypertension.
“These distinct pathophenotypes may have varying natural histories and their management approaches may be distinctive, suggesting the importance and potential role of subphenotyping of elevated blood pressure in young adults to facilitate treatment decisions,” he wrote in his editorial.
The two studies raise key questions, such as whether there are modifiable social, behavioral, or cultural factors that could prevent elevated blood pressure in younger people, he said.
To date, a substantial body of evidence does suggest that blood pressure levels evolve over the course of life, driven by environmental factors superimposed on genetic risks, and modified by sex and race.
“Overall, these data emphasize that primary prevention of higher blood pressure levels must begin in childhood,” he said.
Ramachandran S. Vasan, MD, is with the section of preventive medicine and epidemiology at Boston University. He reported no conflict of interest disclosures related to his editorial, which was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and a grant from the National Institutes of Health. JAMA. 2018;320(17):1760-3. doi:10.1001/jama.2018.16068.
These two studies suggest that a higher blood pressure level in young adulthood is associated with a greater hazard of premature cardiovascular disease, according to Ramachandran S. Vasan, MD.
However, observing an elevated risk of premature cardiovascular disease does necessarily prove causality, or establish that intervening to lower blood pressure in this age group would lessen that risk, he said in an editorial.
The studies are notable for showing that half to nearly 60% of younger adults had levels of blood pressure considered not normal, he added in the editorial, which appears in JAMA.
It is not clear why so many young adults would manifest higher blood pressure levels in these studies, he said, noting that the umbrella of young adults with hypertension likely includes patients with a variety of subtypes. Those including white-coat hypertension, peripheral amplification with normal central blood pressure, hyperadrenergic state, isolated systolic hypertension, and a smaller subset with secondary hypertension.
“These distinct pathophenotypes may have varying natural histories and their management approaches may be distinctive, suggesting the importance and potential role of subphenotyping of elevated blood pressure in young adults to facilitate treatment decisions,” he wrote in his editorial.
The two studies raise key questions, such as whether there are modifiable social, behavioral, or cultural factors that could prevent elevated blood pressure in younger people, he said.
To date, a substantial body of evidence does suggest that blood pressure levels evolve over the course of life, driven by environmental factors superimposed on genetic risks, and modified by sex and race.
“Overall, these data emphasize that primary prevention of higher blood pressure levels must begin in childhood,” he said.
Ramachandran S. Vasan, MD, is with the section of preventive medicine and epidemiology at Boston University. He reported no conflict of interest disclosures related to his editorial, which was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study and a grant from the National Institutes of Health. JAMA. 2018;320(17):1760-3. doi:10.1001/jama.2018.16068.
a pair of recent studies published in JAMA suggest.
In one study, investigators applied the 2017 American College of Cardiology/American Heart Association blood pressure criteria to nearly 5,000 U.S. young adults followed for approximately 20 years and who had up to a 3.5-fold risk associated with hypertension versus normal blood pressure.
The second study of almost 2.5 million Korean young adults, followed for 10 years, similarly found increased risks of cardiovascular disease later in life for those who had stage 1 or 2 hypertension between the ages of 20 and 39 years.
“These findings from a second country on the opposite side of the globe are consistent with those of the U.S. study, providing further support for the ACC/AHA guideline definitions of hypertension,” Naomi D.L. Fisher, MD, deputy editor, JAMA, and Gregory Curfman, MD, Brigham and Women’s Hospital, Boston, said in an editorial also appearing in JAMA.
Disagreement over the ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults threatens to distract from their potential benefits, Dr. Fisher and Dr. Curfman wrote in that editorial.
By redefining stage 1 hypertension as 130/80 mm Hg or higher, down from 140/90 mm Hg or higher, the 2017 ACC/AHA increased the prevalence of hypertension in the United States from 31.9% to 45.6%, they noted.
“Given the magnitude and reach of the global problem of hypertension, it is imperative that dedicated control efforts at the population level intensify,” they said.
U.S. study
The U.S. study, described in JAMA by Yuichiro Yano, MD, PhD, department of community and family medicine, Duke University, Durham, N.C., and his colleagues, was based on analysis of a prospective cohort study, CARDIA (Coronary Artery Risk Development in Young Adults Study), which started in 1985 and enrolled 5,115 black and white adults aged 18-30 years.
They applied the ACC/AHA blood pressure criteria based on each participants’ highest measurement before the age of 40 years, and correlated that with incident cardiovascular disease events that occurred over a median follow-up of 18.8 years.
Patients with normal blood pressure had a cardiovascular disease incidence rate of 1.37/1,000 person-years, compared with 2.74/1,000 person-years for those with elevated blood pressure, 3.15 for stage 1 hypertension, and 8.04 for stage 2 hypertension, investigators found.
That translated into increased risks of cardiovascular disease for those with elevated blood pressure versus those with normal blood pressure. After multivariable adjustment, the hazard ratio for cardiovascular disease was 1.67 (95% confidence interval, 1.01-2.77) for elevated blood pressure, 1.75 (95% CI, 1.22-2.53) for stage 1 hypertension, and 3.49 (95% CI, 2.42-5.05) for stage 2, Dr. Yano and his colleagues reported.
“The ACC/AHA blood pressure classification system may help identify young adults at higher risk for CVD events,” they concluded.
South Korean study
Similar findings were shown in a population-based cohort study, also published in JAMA, that included 2,488,101 adults aged 20-39 years in Korean National Health Insurance Service records.
The investigators looked at mean blood pressure levels from an initial health examination that took place during 2002-2003 and a second examination during 2004-2005.
Follow-up was shorter than the U.S. study, with a median duration of 10 years, reported Joung Sik Son, MD, department of family medicine and biomedical sciences, Seoul (South Korea) National University, and coauthors.
Even so, investigators detected an elevated risk of cardiovascular events for individuals with stage 1 or 2 hypertension versus those with normal blood pressure.
For men with baseline stage 1 hypertension based on the mean values and using the latest ACC/AHA blood pressure criteria, the incidence of cardiovascular disease was 215/100,000 person-years, versus 164 for those with normal blood pressure, with an adjusted hazard ratio of 1.25 (95% CI, 1.21-1.28), the authors said. Likewise, women with stage 1 hypertension had an incidence of 131/100,000 person-years versus 40 for women with normal blood pressure, with a hazard ratio of 1.27 (95% CI, 1.21-1.34).
Men with stage 2 hypertension likewise had a higher cardiovascular disease incidence than did those with normal blood pressure (336 vs. 164 per 100,000 person-years; adjusted HR 1.76), with similar findings seen in women, the report shows.
“Despite the relatively low absolute risk, the difference in absolute risk and the fact that sustained hypertension during longer durations is associated with higher risk of CVD [cardiovascular disease] indicate that early blood pressure management among young adults may lead to significant public health benefits by reducing CVD risk later in life,” Dr. Son and colleagues wrote in a discussion of the results.
Authors of the U.S. study reported disclosures related to Amarin, Amgen, and Novartis outside of the submitted work, as well as grants from the National Heart, Lung, and Blood Institute and National Institutes of Health during the conduct of the study.
Authors of the South Korean study reported no conflict of interest disclosures. That study was supported by the Ministry of Health and Welfare and the Ministry of Education of Korea, along with grants from the National Research Foundation of Korea.
SOURCES: Yano Y et al. JAMA. 2018;302(17):1774-82; Son JS et al. JAMA. 2018;302(17):1783-92.
a pair of recent studies published in JAMA suggest.
In one study, investigators applied the 2017 American College of Cardiology/American Heart Association blood pressure criteria to nearly 5,000 U.S. young adults followed for approximately 20 years and who had up to a 3.5-fold risk associated with hypertension versus normal blood pressure.
The second study of almost 2.5 million Korean young adults, followed for 10 years, similarly found increased risks of cardiovascular disease later in life for those who had stage 1 or 2 hypertension between the ages of 20 and 39 years.
“These findings from a second country on the opposite side of the globe are consistent with those of the U.S. study, providing further support for the ACC/AHA guideline definitions of hypertension,” Naomi D.L. Fisher, MD, deputy editor, JAMA, and Gregory Curfman, MD, Brigham and Women’s Hospital, Boston, said in an editorial also appearing in JAMA.
Disagreement over the ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults threatens to distract from their potential benefits, Dr. Fisher and Dr. Curfman wrote in that editorial.
By redefining stage 1 hypertension as 130/80 mm Hg or higher, down from 140/90 mm Hg or higher, the 2017 ACC/AHA increased the prevalence of hypertension in the United States from 31.9% to 45.6%, they noted.
“Given the magnitude and reach of the global problem of hypertension, it is imperative that dedicated control efforts at the population level intensify,” they said.
U.S. study
The U.S. study, described in JAMA by Yuichiro Yano, MD, PhD, department of community and family medicine, Duke University, Durham, N.C., and his colleagues, was based on analysis of a prospective cohort study, CARDIA (Coronary Artery Risk Development in Young Adults Study), which started in 1985 and enrolled 5,115 black and white adults aged 18-30 years.
They applied the ACC/AHA blood pressure criteria based on each participants’ highest measurement before the age of 40 years, and correlated that with incident cardiovascular disease events that occurred over a median follow-up of 18.8 years.
Patients with normal blood pressure had a cardiovascular disease incidence rate of 1.37/1,000 person-years, compared with 2.74/1,000 person-years for those with elevated blood pressure, 3.15 for stage 1 hypertension, and 8.04 for stage 2 hypertension, investigators found.
That translated into increased risks of cardiovascular disease for those with elevated blood pressure versus those with normal blood pressure. After multivariable adjustment, the hazard ratio for cardiovascular disease was 1.67 (95% confidence interval, 1.01-2.77) for elevated blood pressure, 1.75 (95% CI, 1.22-2.53) for stage 1 hypertension, and 3.49 (95% CI, 2.42-5.05) for stage 2, Dr. Yano and his colleagues reported.
“The ACC/AHA blood pressure classification system may help identify young adults at higher risk for CVD events,” they concluded.
South Korean study
Similar findings were shown in a population-based cohort study, also published in JAMA, that included 2,488,101 adults aged 20-39 years in Korean National Health Insurance Service records.
The investigators looked at mean blood pressure levels from an initial health examination that took place during 2002-2003 and a second examination during 2004-2005.
Follow-up was shorter than the U.S. study, with a median duration of 10 years, reported Joung Sik Son, MD, department of family medicine and biomedical sciences, Seoul (South Korea) National University, and coauthors.
Even so, investigators detected an elevated risk of cardiovascular events for individuals with stage 1 or 2 hypertension versus those with normal blood pressure.
For men with baseline stage 1 hypertension based on the mean values and using the latest ACC/AHA blood pressure criteria, the incidence of cardiovascular disease was 215/100,000 person-years, versus 164 for those with normal blood pressure, with an adjusted hazard ratio of 1.25 (95% CI, 1.21-1.28), the authors said. Likewise, women with stage 1 hypertension had an incidence of 131/100,000 person-years versus 40 for women with normal blood pressure, with a hazard ratio of 1.27 (95% CI, 1.21-1.34).
Men with stage 2 hypertension likewise had a higher cardiovascular disease incidence than did those with normal blood pressure (336 vs. 164 per 100,000 person-years; adjusted HR 1.76), with similar findings seen in women, the report shows.
“Despite the relatively low absolute risk, the difference in absolute risk and the fact that sustained hypertension during longer durations is associated with higher risk of CVD [cardiovascular disease] indicate that early blood pressure management among young adults may lead to significant public health benefits by reducing CVD risk later in life,” Dr. Son and colleagues wrote in a discussion of the results.
Authors of the U.S. study reported disclosures related to Amarin, Amgen, and Novartis outside of the submitted work, as well as grants from the National Heart, Lung, and Blood Institute and National Institutes of Health during the conduct of the study.
Authors of the South Korean study reported no conflict of interest disclosures. That study was supported by the Ministry of Health and Welfare and the Ministry of Education of Korea, along with grants from the National Research Foundation of Korea.
SOURCES: Yano Y et al. JAMA. 2018;302(17):1774-82; Son JS et al. JAMA. 2018;302(17):1783-92.
FROM JAMA
Combo appears safe, active in rel/ref NHL
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
Results
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
Nipple-sparing mastectomy safe in older patients
BOSTON – For women undergoing results of recent studies suggest.
The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.
“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.
The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.
“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.
Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.
The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.
The rate of unintended reoperation, at 4.9%, was not significantly different in the neoadjuvant chemotherapy and primary surgery groups, at 5.2% and 4.8%, Mr. Bartholomew said. Similarly, he found that the rate of nipple areolar complex loss of 1% overall was not different between groups.
Advanced age was likewise not associated with increased complications in the study presented by Dr. Cox, which was a retrospective review of data for patients undergoing nipple-sparing mastectomy from 1998 to 2015 at a single institution. That cohort included 38 patients age 60 years or older, and 358 younger patients.
The rate of complications was 15.5% for patients over age 60 years, and similarly, 13.0% for their younger counterparts (P = .590), Dr. Cox reported. Likewise, the rate of unintended operations was 13.3% and 15.3% for older and younger patients, respectively (P = .274).
These findings are important because advancing age has been associated with a decrease in the likelihood of nipple-sparing mastectomy, according to Dr. Cox.
For mastectomies in general, advanced age has been implicated as a potential risk factor for necrosis, technical complications, and poor outcomes with mastectomies. However, no prior studies had been done specifically to evaluate nipple-sparing mastectomies in older breast cancer patients, Dr. Cox said.
Nipple-sparing mastectomy provides both cosmetic and psychosocial benefits to patients, according to the researchers, because the procedure spares the nipple-areolar complex.
The researchers who had no relevant disclosures.
SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018
BOSTON – For women undergoing results of recent studies suggest.
The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.
“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.
The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.
“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.
Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.
The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.
The rate of unintended reoperation, at 4.9%, was not significantly different in the neoadjuvant chemotherapy and primary surgery groups, at 5.2% and 4.8%, Mr. Bartholomew said. Similarly, he found that the rate of nipple areolar complex loss of 1% overall was not different between groups.
Advanced age was likewise not associated with increased complications in the study presented by Dr. Cox, which was a retrospective review of data for patients undergoing nipple-sparing mastectomy from 1998 to 2015 at a single institution. That cohort included 38 patients age 60 years or older, and 358 younger patients.
The rate of complications was 15.5% for patients over age 60 years, and similarly, 13.0% for their younger counterparts (P = .590), Dr. Cox reported. Likewise, the rate of unintended operations was 13.3% and 15.3% for older and younger patients, respectively (P = .274).
These findings are important because advancing age has been associated with a decrease in the likelihood of nipple-sparing mastectomy, according to Dr. Cox.
For mastectomies in general, advanced age has been implicated as a potential risk factor for necrosis, technical complications, and poor outcomes with mastectomies. However, no prior studies had been done specifically to evaluate nipple-sparing mastectomies in older breast cancer patients, Dr. Cox said.
Nipple-sparing mastectomy provides both cosmetic and psychosocial benefits to patients, according to the researchers, because the procedure spares the nipple-areolar complex.
The researchers who had no relevant disclosures.
SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018
BOSTON – For women undergoing results of recent studies suggest.
The procedure was “surgically safe” in older patients, with complication rates comparable to those seen in younger patients, Solange E. Cox, MD, of MedStar Georgetown University Hospital, Washington, said in a presentation of one those two retrospective analyses at the annual clinical congress of the American College of Surgeons.
“From this, we think that eligible older patients should be offered a nipple-sparing mastectomy as a surgical option for breast cancer, and age alone should not be used as criteria to exclude these patients from the option,” she said.
The second retrospective study showed that patients undergoing neoadjuvant chemotherapy had a rate of surgical complications and unintended reoperations comparable to what was seen in women undergoing primary surgery.
“Our big-picture takeaway from this study is that receipt of neoadjuvant chemotherapy is not a contraindication for nipple-sparing mastectomy,” said investigator Alex J. Bartholomew, MS, also of Medstar Georgetown University Hospital.
Mr. Bartholomew’s conclusion was based on an analysis of the nipple-sparing mastectomy registry of the American Society of Breast Surgeons that included a total of 3,125 breasts. Neoadjuvant chemotherapy was used in 528, or 16.9%, while primary surgery was performed in 2,597, or 83.1%.
The overall rate of complications was 11%, with nonsignificant differences between the neoadjuvant chemotherapy and primary surgery groups at 12.7% and 10.7%, respectively.
The rate of unintended reoperation, at 4.9%, was not significantly different in the neoadjuvant chemotherapy and primary surgery groups, at 5.2% and 4.8%, Mr. Bartholomew said. Similarly, he found that the rate of nipple areolar complex loss of 1% overall was not different between groups.
Advanced age was likewise not associated with increased complications in the study presented by Dr. Cox, which was a retrospective review of data for patients undergoing nipple-sparing mastectomy from 1998 to 2015 at a single institution. That cohort included 38 patients age 60 years or older, and 358 younger patients.
The rate of complications was 15.5% for patients over age 60 years, and similarly, 13.0% for their younger counterparts (P = .590), Dr. Cox reported. Likewise, the rate of unintended operations was 13.3% and 15.3% for older and younger patients, respectively (P = .274).
These findings are important because advancing age has been associated with a decrease in the likelihood of nipple-sparing mastectomy, according to Dr. Cox.
For mastectomies in general, advanced age has been implicated as a potential risk factor for necrosis, technical complications, and poor outcomes with mastectomies. However, no prior studies had been done specifically to evaluate nipple-sparing mastectomies in older breast cancer patients, Dr. Cox said.
Nipple-sparing mastectomy provides both cosmetic and psychosocial benefits to patients, according to the researchers, because the procedure spares the nipple-areolar complex.
The researchers who had no relevant disclosures.
SOURCES: Cox S et al. SF310 abstract; Bartholomew AJ et al. SF310 abstract ACS Clinical Congress 2018
REPORTING FROM THE ACS CLINICAL CONGRESS
Key clinical point: Neoadjuvant chemotherapy and advancing age were not associated with increased rates of complications in women undergoing nipple-sparing mastectomy in two recent studies.
Major finding: The overall rate of complications was not significantly different for neoadjuvant chemotherapy vs. primary surgery (12.7% vs. 10.7%) or for age over 60 years vs. younger age (15.5% vs. 13.0%).
Study details: Retrospective studies of a nipple-sparing mastectomy registry including more than 3,000 breasts (neoadjuvant chemotherapy vs. primary surgery study) and a single-institution study of nearly 400 patients (older vs. younger study).
Disclosures: The authors reported no conflicts of interest.
Source: Cox S et al. and Bartholomew AJ et al. Session SF310 ACS Clinical Congress 2018.
Haploidentical transplantation holds promise in relapsed myeloma
, investigators have reported.
The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.
Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”
“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.
The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.
Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.
The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.
Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.
Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.
By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.
This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.
There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
, investigators have reported.
The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.
Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”
“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.
The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.
Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.
The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.
Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.
Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.
By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.
This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.
There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
, investigators have reported.
The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.
Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”
“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.
The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.
Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.
The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.
Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.
Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.
By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.
This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.
There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
FROM BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Key clinical point: Haploidentical allogeneic transplantation is feasible and had an acceptable rate of non-relapse mortality, setting the stage for its use in future combination strategies.
Major finding: The cumulative risk of relapse and progression at 2 years was 56%, and the 1-year nonrelapse mortality was 21%.
Study details: A retrospective analysis including 96 patients who underwent haploidentical allogeneic hematopoietic stem cell transplantation between 2008 and 2016.
Disclosures: Authors reported no conflicts of interest.
Source: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.
Antibiotics, antacids before age 2 linked to obesity
Acid-suppressing medications were also associated with childhood obesity, although to a lesser extent, according to results of the study, which included more than a quarter of a million children receiving care in the U.S. military health system.
Antibiotics and antacids are both microbiota-altering medications, researchers said, noting that obesity has been linked to variations in the native gut microbiota.
While the evidence from previous studies is conflicting on whether microbiota-altering medications may play a role in development of childhood obesity, this study does suggest such medications may lead to weight gain early in life, they said in the journal Gut.
“Providers should practice appropriate stewardship as the first-line response to these findings,” said Christopher M. Stark, MD, of the William Beaumont Army Medical Center, El Paso, Tex., and his co-authors.
This retrospective analysis included the largest cohort of pediatric patients ever studied for the link between antibiotics and obesity, according to Dr. Stark and colleagues, and was the first to look at the link between acid-suppressing medications and obesity in that age group.
The analysis included a total of 333,353 U.S. Department of Defense TRICARE beneficiaries born between October 2006 and September 2013 who were exposed to antibiotics, histamine-2-receptor antagonists (H2RAs), or proton pump inhibitors (PPIs) within the first 2 years of life.
Patients were followed past their initial exposure period, up to 8 years of age in some cases, investigators said.
Antibiotics were prescribed in 72.4% of those children, while H2RAs and PPIs were prescribed in 11.8% and 3.3%, respectively, with a substantial number of children receiving more than one of the medications of interest for this study.
A total of 46,993 (14.1%) of the children developed obesity. Of those obese children only 9,268, or 11%, had no antibiotic or acid suppressant prescriptions on record in the first 2 years of life, the reported data show.
Antibiotic prescriptions were associated with a 26% increase in obesity risk (unadjusted hazard ratio, 1.26; 95% CI, 1.23-1.28), investigators reported. That association strengthened steadily with the number of antibiotic prescriptions, with adjusted hazard ratios of 1.12 (95% CI, 1.09-1.15) for a single prescription, up to 1.42 (95% CI, 1.37-1.46) for 4 or more prescriptions
Likewise, H2RAs and PPIs were associated, albeit weakly, with an increased hazard of obesity, investigators said. The adjusted hazard ratios and 95% confidence intervals were 1.02 (1.01-1.03) for PPIs and 1.01 (1.004-1.02) for H2RA prescriptions.
The risk of obesity steadily climbed for those receiving multiple medications, researchers added, from a hazard ratio of 1.21 for one medication, 1.31 for two, and 1.42 for three, data show.
Dr. Stark and co-authors declared no competing interests related to the study.
SOURCE: Stark CM, et al. Gut. 2018 Oct 30. pii: gutjnl-2017-314971.
Acid-suppressing medications were also associated with childhood obesity, although to a lesser extent, according to results of the study, which included more than a quarter of a million children receiving care in the U.S. military health system.
Antibiotics and antacids are both microbiota-altering medications, researchers said, noting that obesity has been linked to variations in the native gut microbiota.
While the evidence from previous studies is conflicting on whether microbiota-altering medications may play a role in development of childhood obesity, this study does suggest such medications may lead to weight gain early in life, they said in the journal Gut.
“Providers should practice appropriate stewardship as the first-line response to these findings,” said Christopher M. Stark, MD, of the William Beaumont Army Medical Center, El Paso, Tex., and his co-authors.
This retrospective analysis included the largest cohort of pediatric patients ever studied for the link between antibiotics and obesity, according to Dr. Stark and colleagues, and was the first to look at the link between acid-suppressing medications and obesity in that age group.
The analysis included a total of 333,353 U.S. Department of Defense TRICARE beneficiaries born between October 2006 and September 2013 who were exposed to antibiotics, histamine-2-receptor antagonists (H2RAs), or proton pump inhibitors (PPIs) within the first 2 years of life.
Patients were followed past their initial exposure period, up to 8 years of age in some cases, investigators said.
Antibiotics were prescribed in 72.4% of those children, while H2RAs and PPIs were prescribed in 11.8% and 3.3%, respectively, with a substantial number of children receiving more than one of the medications of interest for this study.
A total of 46,993 (14.1%) of the children developed obesity. Of those obese children only 9,268, or 11%, had no antibiotic or acid suppressant prescriptions on record in the first 2 years of life, the reported data show.
Antibiotic prescriptions were associated with a 26% increase in obesity risk (unadjusted hazard ratio, 1.26; 95% CI, 1.23-1.28), investigators reported. That association strengthened steadily with the number of antibiotic prescriptions, with adjusted hazard ratios of 1.12 (95% CI, 1.09-1.15) for a single prescription, up to 1.42 (95% CI, 1.37-1.46) for 4 or more prescriptions
Likewise, H2RAs and PPIs were associated, albeit weakly, with an increased hazard of obesity, investigators said. The adjusted hazard ratios and 95% confidence intervals were 1.02 (1.01-1.03) for PPIs and 1.01 (1.004-1.02) for H2RA prescriptions.
The risk of obesity steadily climbed for those receiving multiple medications, researchers added, from a hazard ratio of 1.21 for one medication, 1.31 for two, and 1.42 for three, data show.
Dr. Stark and co-authors declared no competing interests related to the study.
SOURCE: Stark CM, et al. Gut. 2018 Oct 30. pii: gutjnl-2017-314971.
Acid-suppressing medications were also associated with childhood obesity, although to a lesser extent, according to results of the study, which included more than a quarter of a million children receiving care in the U.S. military health system.
Antibiotics and antacids are both microbiota-altering medications, researchers said, noting that obesity has been linked to variations in the native gut microbiota.
While the evidence from previous studies is conflicting on whether microbiota-altering medications may play a role in development of childhood obesity, this study does suggest such medications may lead to weight gain early in life, they said in the journal Gut.
“Providers should practice appropriate stewardship as the first-line response to these findings,” said Christopher M. Stark, MD, of the William Beaumont Army Medical Center, El Paso, Tex., and his co-authors.
This retrospective analysis included the largest cohort of pediatric patients ever studied for the link between antibiotics and obesity, according to Dr. Stark and colleagues, and was the first to look at the link between acid-suppressing medications and obesity in that age group.
The analysis included a total of 333,353 U.S. Department of Defense TRICARE beneficiaries born between October 2006 and September 2013 who were exposed to antibiotics, histamine-2-receptor antagonists (H2RAs), or proton pump inhibitors (PPIs) within the first 2 years of life.
Patients were followed past their initial exposure period, up to 8 years of age in some cases, investigators said.
Antibiotics were prescribed in 72.4% of those children, while H2RAs and PPIs were prescribed in 11.8% and 3.3%, respectively, with a substantial number of children receiving more than one of the medications of interest for this study.
A total of 46,993 (14.1%) of the children developed obesity. Of those obese children only 9,268, or 11%, had no antibiotic or acid suppressant prescriptions on record in the first 2 years of life, the reported data show.
Antibiotic prescriptions were associated with a 26% increase in obesity risk (unadjusted hazard ratio, 1.26; 95% CI, 1.23-1.28), investigators reported. That association strengthened steadily with the number of antibiotic prescriptions, with adjusted hazard ratios of 1.12 (95% CI, 1.09-1.15) for a single prescription, up to 1.42 (95% CI, 1.37-1.46) for 4 or more prescriptions
Likewise, H2RAs and PPIs were associated, albeit weakly, with an increased hazard of obesity, investigators said. The adjusted hazard ratios and 95% confidence intervals were 1.02 (1.01-1.03) for PPIs and 1.01 (1.004-1.02) for H2RA prescriptions.
The risk of obesity steadily climbed for those receiving multiple medications, researchers added, from a hazard ratio of 1.21 for one medication, 1.31 for two, and 1.42 for three, data show.
Dr. Stark and co-authors declared no competing interests related to the study.
SOURCE: Stark CM, et al. Gut. 2018 Oct 30. pii: gutjnl-2017-314971.
FROM GUT
Key clinical point: When prescribed early in life, antibiotics, and to a lesser extent antacids, were associated with childhood obesity.
Major finding: Antibiotic prescriptions were associated with a 26% increase in obesity risk (unadjusted hazard ratio, 1.26; 95% CI, 1.23-1.28).
Study details: Retrospective study of 333,353 children in the U.S. military health system exposed in the first two years of life to antibiotics, histamine-2-receptor antagonists, or proton pump inhibitors.
Disclosures: Study authors declared no competing interests related to the work.
Source: Stark CM, et al. Gut. 2018 Oct 30. pii: gutjnl-2017-314971.
Quality programs drive improvements in colorectal surgery outcomes
BOSTON – Rates of (ACS NSQIP), a recent analysis shows.
Reoperation rates have also decreased, while early-discharge rates have steadily increased, according to results of the analysis, presented at the annual clinical congress of the American College of Surgeons.
The findings underline the value of such ACS-led initiatives in improving patient care and surgical quality, said Ahmed M. Al-Mazrou, MD, a general surgery resident at New York-Presbyterian Hospital/Weill Cornell Medical Center in New York.
“Over its first decade of introduction, ACS NSQIP was associated with improved outcomes after colorectal surgery, and also introduction of colectomy-targeted data was also associated with improved outcomes,” Dr. Al-Mazrou said in his presentation describing the results.
Prior to this study, the question of whether the introduction of ACS NSQIP has improved outcomes over time had not been well characterized, according to Dr. Al-Mazrou and his colleagues.
To evaluate the impact, the investigators looked at more than 310,000 nonemergency colorectal resections in ACS NSQIP, of which about 58% were done after the introduction of colectomy-targeted variables in 2013.
They found that, over time, incidence of most complications fell, including surgical site infections, urinary tract infections, sepsis and septic shock, and venous thromboembolism, while rates of early discharge increased.
For example, surgical site infections decreased from 13.7% to 4.7% over the 10-year period, while the number of patients discharged within 5 days or fewer increased from about 8% to 47%.
Introduction of colectomy-targeted data was associated with fewer surgical site infections (odds ratio, 0.78; 95% confidence interval, 0.77-0.80), multivariable analysis showed. Likewise, there were lower rates of systemic infections (OR, 0.94; 95% CI, 0.91-0.98) and urinary tract infections (OR, 0.70; 95% CI, 0.67-0.74) after introduction of the data.
Rates of reoperation also decreased (OR, 0.88; 95% CI, 0.85-0.91) while early-discharge rates increased (OR, 1.60; 95% CI, 1.57-1.63) after colectomy data was introduced, the multivariable analysis further showed.
Principal investigator P. Ravi Kiran, MD, FACS, professor of surgery at Columbia University and chief of the medical center’s division of colorectal surgery, said the improved outcomes were attributable to a few different factors.
First, the NSQIP national data allows participants to benchmark with peer hospitals and find areas for improvement, Dr. Kiran said in an ACS press release.
That benchmarking encourages participating centers to follow evidence-based recommendations, including ACS guidelines for preventing surgical site infections, he added.
The introduction of procedure-targeted datasets in NSQIP was done in response to user requests for more clinically detailed information, according to Clifford Y. Ko, MD, FACS, director of the ACS division of research and optimal patient care.
While the NSQIP data are important in improving surgical outcomes, credit also goes to the organizations that are leading the quality improvement efforts by effectively using the data, Dr. Ko said in the press release.
Dr. Ko was not involved in the study. Dr. Al-Mazrou and Dr. Kiran reported no disclosures relevant to the study.
SOURCE: Al-Mazrou AM et al. ACS Clinical Congress. Abstract SF330.
BOSTON – Rates of (ACS NSQIP), a recent analysis shows.
Reoperation rates have also decreased, while early-discharge rates have steadily increased, according to results of the analysis, presented at the annual clinical congress of the American College of Surgeons.
The findings underline the value of such ACS-led initiatives in improving patient care and surgical quality, said Ahmed M. Al-Mazrou, MD, a general surgery resident at New York-Presbyterian Hospital/Weill Cornell Medical Center in New York.
“Over its first decade of introduction, ACS NSQIP was associated with improved outcomes after colorectal surgery, and also introduction of colectomy-targeted data was also associated with improved outcomes,” Dr. Al-Mazrou said in his presentation describing the results.
Prior to this study, the question of whether the introduction of ACS NSQIP has improved outcomes over time had not been well characterized, according to Dr. Al-Mazrou and his colleagues.
To evaluate the impact, the investigators looked at more than 310,000 nonemergency colorectal resections in ACS NSQIP, of which about 58% were done after the introduction of colectomy-targeted variables in 2013.
They found that, over time, incidence of most complications fell, including surgical site infections, urinary tract infections, sepsis and septic shock, and venous thromboembolism, while rates of early discharge increased.
For example, surgical site infections decreased from 13.7% to 4.7% over the 10-year period, while the number of patients discharged within 5 days or fewer increased from about 8% to 47%.
Introduction of colectomy-targeted data was associated with fewer surgical site infections (odds ratio, 0.78; 95% confidence interval, 0.77-0.80), multivariable analysis showed. Likewise, there were lower rates of systemic infections (OR, 0.94; 95% CI, 0.91-0.98) and urinary tract infections (OR, 0.70; 95% CI, 0.67-0.74) after introduction of the data.
Rates of reoperation also decreased (OR, 0.88; 95% CI, 0.85-0.91) while early-discharge rates increased (OR, 1.60; 95% CI, 1.57-1.63) after colectomy data was introduced, the multivariable analysis further showed.
Principal investigator P. Ravi Kiran, MD, FACS, professor of surgery at Columbia University and chief of the medical center’s division of colorectal surgery, said the improved outcomes were attributable to a few different factors.
First, the NSQIP national data allows participants to benchmark with peer hospitals and find areas for improvement, Dr. Kiran said in an ACS press release.
That benchmarking encourages participating centers to follow evidence-based recommendations, including ACS guidelines for preventing surgical site infections, he added.
The introduction of procedure-targeted datasets in NSQIP was done in response to user requests for more clinically detailed information, according to Clifford Y. Ko, MD, FACS, director of the ACS division of research and optimal patient care.
While the NSQIP data are important in improving surgical outcomes, credit also goes to the organizations that are leading the quality improvement efforts by effectively using the data, Dr. Ko said in the press release.
Dr. Ko was not involved in the study. Dr. Al-Mazrou and Dr. Kiran reported no disclosures relevant to the study.
SOURCE: Al-Mazrou AM et al. ACS Clinical Congress. Abstract SF330.
BOSTON – Rates of (ACS NSQIP), a recent analysis shows.
Reoperation rates have also decreased, while early-discharge rates have steadily increased, according to results of the analysis, presented at the annual clinical congress of the American College of Surgeons.
The findings underline the value of such ACS-led initiatives in improving patient care and surgical quality, said Ahmed M. Al-Mazrou, MD, a general surgery resident at New York-Presbyterian Hospital/Weill Cornell Medical Center in New York.
“Over its first decade of introduction, ACS NSQIP was associated with improved outcomes after colorectal surgery, and also introduction of colectomy-targeted data was also associated with improved outcomes,” Dr. Al-Mazrou said in his presentation describing the results.
Prior to this study, the question of whether the introduction of ACS NSQIP has improved outcomes over time had not been well characterized, according to Dr. Al-Mazrou and his colleagues.
To evaluate the impact, the investigators looked at more than 310,000 nonemergency colorectal resections in ACS NSQIP, of which about 58% were done after the introduction of colectomy-targeted variables in 2013.
They found that, over time, incidence of most complications fell, including surgical site infections, urinary tract infections, sepsis and septic shock, and venous thromboembolism, while rates of early discharge increased.
For example, surgical site infections decreased from 13.7% to 4.7% over the 10-year period, while the number of patients discharged within 5 days or fewer increased from about 8% to 47%.
Introduction of colectomy-targeted data was associated with fewer surgical site infections (odds ratio, 0.78; 95% confidence interval, 0.77-0.80), multivariable analysis showed. Likewise, there were lower rates of systemic infections (OR, 0.94; 95% CI, 0.91-0.98) and urinary tract infections (OR, 0.70; 95% CI, 0.67-0.74) after introduction of the data.
Rates of reoperation also decreased (OR, 0.88; 95% CI, 0.85-0.91) while early-discharge rates increased (OR, 1.60; 95% CI, 1.57-1.63) after colectomy data was introduced, the multivariable analysis further showed.
Principal investigator P. Ravi Kiran, MD, FACS, professor of surgery at Columbia University and chief of the medical center’s division of colorectal surgery, said the improved outcomes were attributable to a few different factors.
First, the NSQIP national data allows participants to benchmark with peer hospitals and find areas for improvement, Dr. Kiran said in an ACS press release.
That benchmarking encourages participating centers to follow evidence-based recommendations, including ACS guidelines for preventing surgical site infections, he added.
The introduction of procedure-targeted datasets in NSQIP was done in response to user requests for more clinically detailed information, according to Clifford Y. Ko, MD, FACS, director of the ACS division of research and optimal patient care.
While the NSQIP data are important in improving surgical outcomes, credit also goes to the organizations that are leading the quality improvement efforts by effectively using the data, Dr. Ko said in the press release.
Dr. Ko was not involved in the study. Dr. Al-Mazrou and Dr. Kiran reported no disclosures relevant to the study.
SOURCE: Al-Mazrou AM et al. ACS Clinical Congress. Abstract SF330.
REPORTING FROM THE ACS CLINICAL CONGRESS
Key clinical point: Rates of colorectal procedure complications have steadily decreased since the introduction of the American College of Surgeons National Surgical Quality Improvement Program.
Major finding: Surgical site infections decreased from 13.7% to 4.7% over the 10-year period, while the number of patients discharged within 5 days or fewer increased from about 8% to 47%.
Study details: Retrospective review of more than 310,000 nonemergency colorectal resections in ACS NSQIP from 2007 to 2016.
Disclosures: Study authors reported no conflicts of interest.
Source: Al-Mazrou AM et al. ACS Clinical Congress, Abstract SF330.
Palliative care guidelines relevant for hematologists, doc says
The latest edition of the national palliative care guidelines provides new clinical strategies relevant to hematology practice in the United States, according to a physician-researcher specializing in hematology.
The Clinical Practice Guidelines for Quality Palliative Care, 4th edition, represents a “blueprint for what it looks like to provide high-quality, comprehensive palliative care to people with serious illness,” said Thomas W. LeBlanc, MD, a physician-researcher at Duke University School of Medicine in Durham, North Carolina.
However, unlike previous editions, this update to the guidelines emphasizes the importance of palliative care provided by both primary care and specialty care clinicians.
“Part of this report is about trying to raise the game of everybody in medicine and provide a higher basic level of primary palliative care to all people with serious illness, but then also to figure out who has higher levels of needs where the specialists should be applied, since they are a scarce resource,” Dr. LeBlanc said.
The latest edition helps establish a foundation for gold standard palliative care for people living with serious illness, regardless of diagnosis, prognosis, setting, or age, according to The National Coalition for Hospice and Palliative Care, which published the clinical practice guidelines.
The update was developed by the National Consensus Project for Quality Palliative Care (NCP), which includes 16 national organizations with palliative care and hospice expertise, and is endorsed by more than 80 national organizations, including the American Society of Hematology.
One key reason for the update, according to NCP, was to acknowledge that today’s healthcare system may not be meeting patients’ palliative care needs.
Specifically, the guidelines call on clinicians who don’t practice palliative care to integrate palliative care principles into their routine assessment of seriously ill patients with conditions such as heart failure, lung disease, and cancer.
That differs from the way palliative care is traditionally practiced, in which specially trained doctors, nurses, and other specialists provide that support.
An issue with that traditional model is a shortage of specialized clinicians to meet palliative care needs, said Dr. LeBlanc, whose clinical practice and research focuses on palliative care needs of patients with hematologic malignancies.
“Palliative care has matured as a field such that we are now actually facing workforce shortage issues and really fundamental questions about who really needs us the most and how we increase our reach to improve the lives of more patients and families facing serious illness,” he said.
That’s a major driver behind the emphasis in the latest guidelines on providing palliative care in the community, coordinating care, and dealing with care transitions, Dr. LeBlanc added.
“I hope that this document will help to demonstrate the value and the need for palliative care specialists and for improvements in primary care in the care of patients with hematologic diseases in general,” he said. “To me, this adds increasing legitimacy to this whole field.”
The latest edition of the national palliative care guidelines provides new clinical strategies relevant to hematology practice in the United States, according to a physician-researcher specializing in hematology.
The Clinical Practice Guidelines for Quality Palliative Care, 4th edition, represents a “blueprint for what it looks like to provide high-quality, comprehensive palliative care to people with serious illness,” said Thomas W. LeBlanc, MD, a physician-researcher at Duke University School of Medicine in Durham, North Carolina.
However, unlike previous editions, this update to the guidelines emphasizes the importance of palliative care provided by both primary care and specialty care clinicians.
“Part of this report is about trying to raise the game of everybody in medicine and provide a higher basic level of primary palliative care to all people with serious illness, but then also to figure out who has higher levels of needs where the specialists should be applied, since they are a scarce resource,” Dr. LeBlanc said.
The latest edition helps establish a foundation for gold standard palliative care for people living with serious illness, regardless of diagnosis, prognosis, setting, or age, according to The National Coalition for Hospice and Palliative Care, which published the clinical practice guidelines.
The update was developed by the National Consensus Project for Quality Palliative Care (NCP), which includes 16 national organizations with palliative care and hospice expertise, and is endorsed by more than 80 national organizations, including the American Society of Hematology.
One key reason for the update, according to NCP, was to acknowledge that today’s healthcare system may not be meeting patients’ palliative care needs.
Specifically, the guidelines call on clinicians who don’t practice palliative care to integrate palliative care principles into their routine assessment of seriously ill patients with conditions such as heart failure, lung disease, and cancer.
That differs from the way palliative care is traditionally practiced, in which specially trained doctors, nurses, and other specialists provide that support.
An issue with that traditional model is a shortage of specialized clinicians to meet palliative care needs, said Dr. LeBlanc, whose clinical practice and research focuses on palliative care needs of patients with hematologic malignancies.
“Palliative care has matured as a field such that we are now actually facing workforce shortage issues and really fundamental questions about who really needs us the most and how we increase our reach to improve the lives of more patients and families facing serious illness,” he said.
That’s a major driver behind the emphasis in the latest guidelines on providing palliative care in the community, coordinating care, and dealing with care transitions, Dr. LeBlanc added.
“I hope that this document will help to demonstrate the value and the need for palliative care specialists and for improvements in primary care in the care of patients with hematologic diseases in general,” he said. “To me, this adds increasing legitimacy to this whole field.”
The latest edition of the national palliative care guidelines provides new clinical strategies relevant to hematology practice in the United States, according to a physician-researcher specializing in hematology.
The Clinical Practice Guidelines for Quality Palliative Care, 4th edition, represents a “blueprint for what it looks like to provide high-quality, comprehensive palliative care to people with serious illness,” said Thomas W. LeBlanc, MD, a physician-researcher at Duke University School of Medicine in Durham, North Carolina.
However, unlike previous editions, this update to the guidelines emphasizes the importance of palliative care provided by both primary care and specialty care clinicians.
“Part of this report is about trying to raise the game of everybody in medicine and provide a higher basic level of primary palliative care to all people with serious illness, but then also to figure out who has higher levels of needs where the specialists should be applied, since they are a scarce resource,” Dr. LeBlanc said.
The latest edition helps establish a foundation for gold standard palliative care for people living with serious illness, regardless of diagnosis, prognosis, setting, or age, according to The National Coalition for Hospice and Palliative Care, which published the clinical practice guidelines.
The update was developed by the National Consensus Project for Quality Palliative Care (NCP), which includes 16 national organizations with palliative care and hospice expertise, and is endorsed by more than 80 national organizations, including the American Society of Hematology.
One key reason for the update, according to NCP, was to acknowledge that today’s healthcare system may not be meeting patients’ palliative care needs.
Specifically, the guidelines call on clinicians who don’t practice palliative care to integrate palliative care principles into their routine assessment of seriously ill patients with conditions such as heart failure, lung disease, and cancer.
That differs from the way palliative care is traditionally practiced, in which specially trained doctors, nurses, and other specialists provide that support.
An issue with that traditional model is a shortage of specialized clinicians to meet palliative care needs, said Dr. LeBlanc, whose clinical practice and research focuses on palliative care needs of patients with hematologic malignancies.
“Palliative care has matured as a field such that we are now actually facing workforce shortage issues and really fundamental questions about who really needs us the most and how we increase our reach to improve the lives of more patients and families facing serious illness,” he said.
That’s a major driver behind the emphasis in the latest guidelines on providing palliative care in the community, coordinating care, and dealing with care transitions, Dr. LeBlanc added.
“I hope that this document will help to demonstrate the value and the need for palliative care specialists and for improvements in primary care in the care of patients with hematologic diseases in general,” he said. “To me, this adds increasing legitimacy to this whole field.”
Checkpoint inhibitor plus rituximab is active in non-Hodgkin lymphoma
A macrophage-activating immune checkpoint inhibitor, combined with rituximab therapy, was safe and produced durable complete responses in patients with relapsed or refractory non-Hodgkin lymphoma, according to results of a phase 1b study.
Mainly low-grade toxic effects were seen on treatment with Hu5F9-G4 (5F9) and rituximab, which induced responses in more than half of patients, of which more than one-third were complete responses, the study investigators reported.
Most of the responses were ongoing at the time of data cutoff, suggesting durable responses with the combination of rituximab and 5F9 – a humanized monoclonal antibody that blocks CD47, an antiphagocytic or “do not eat me” signal overexpressed by most cancers, Ranjana Advani, MD, of Stanford (Calif.) University, and her coauthors wrote.
“The macrophage-mediated activity of 5F9 plus rituximab may serve as an effective new immunotherapy for stimulating the innate immune system,” Dr. Advani and her colleagues reported in the New England Journal of Medicine.
The study included 22 patients, including 15 with diffuse large B-cell lymphoma (DLBCL) and 7 with follicular lymphoma, who had received a median of four prior therapies. Almost all of the non-Hodgkin lymphomas (21, or 95%) were refractory to rituximab.
All patients received intravenous 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10-30 mg/kg in three dose-escalation cohorts, given until disease progression or lack of clinical benefit. Intravenous rituximab at 375 mg/m2 weekly was started on the second week of the first cycle, and then monthly for cycles 2 through 6.
“Substantial antitumor activity” was seen with this chemotherapy-free regimen in a group of heavily pretreated, largely rituximab-refractory patients, Dr. Advani and her coauthors wrote in their report.
The objective response rate was 50%, including a 36% complete response rate in the intent-to-treat analysis. For DLBCL, the rates of objective and complete responses were 40% and 33%, while for follicular lymphoma, they were 71% and 43%.
The median duration of response was not reached in either disease cohort with a median follow-up of 6.2 months for DLBCL and 8.1 months for follicular lymphoma. Of the 11 patients who responded, 10 (91%) were still in response at the time of data cutoff. “Longer follow-up is needed,” the investigators wrote.
Most adverse events were seen within the first few weeks of treatment and mainly included anemia and infusion-related reactions. The anemia was an expected, on-target effect of 5F9 because of selective clearance of older red cells, which was predictable, transient, and mitigated by the maintenance dosing strategy employed in this phase 1b trial.
“As red cells age, they lose CD47 expression and gain expression of prophagocytic signals, leading to homeostatic clearance,” they wrote.
The activity of 5F9 and rituximab is “synergistic” based on the results of previous, preclinical investigations in models of lymphoma, Dr. Advani and her coauthors added.
A phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell non-Hodgkin lymphoma is ongoing, according to their report.
The study was supported by Forty Seven and the Leukemia & Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
SOURCE: Advani R et al. N Engl J Med. 2018;379:1711-21.
A macrophage-activating immune checkpoint inhibitor, combined with rituximab therapy, was safe and produced durable complete responses in patients with relapsed or refractory non-Hodgkin lymphoma, according to results of a phase 1b study.
Mainly low-grade toxic effects were seen on treatment with Hu5F9-G4 (5F9) and rituximab, which induced responses in more than half of patients, of which more than one-third were complete responses, the study investigators reported.
Most of the responses were ongoing at the time of data cutoff, suggesting durable responses with the combination of rituximab and 5F9 – a humanized monoclonal antibody that blocks CD47, an antiphagocytic or “do not eat me” signal overexpressed by most cancers, Ranjana Advani, MD, of Stanford (Calif.) University, and her coauthors wrote.
“The macrophage-mediated activity of 5F9 plus rituximab may serve as an effective new immunotherapy for stimulating the innate immune system,” Dr. Advani and her colleagues reported in the New England Journal of Medicine.
The study included 22 patients, including 15 with diffuse large B-cell lymphoma (DLBCL) and 7 with follicular lymphoma, who had received a median of four prior therapies. Almost all of the non-Hodgkin lymphomas (21, or 95%) were refractory to rituximab.
All patients received intravenous 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10-30 mg/kg in three dose-escalation cohorts, given until disease progression or lack of clinical benefit. Intravenous rituximab at 375 mg/m2 weekly was started on the second week of the first cycle, and then monthly for cycles 2 through 6.
“Substantial antitumor activity” was seen with this chemotherapy-free regimen in a group of heavily pretreated, largely rituximab-refractory patients, Dr. Advani and her coauthors wrote in their report.
The objective response rate was 50%, including a 36% complete response rate in the intent-to-treat analysis. For DLBCL, the rates of objective and complete responses were 40% and 33%, while for follicular lymphoma, they were 71% and 43%.
The median duration of response was not reached in either disease cohort with a median follow-up of 6.2 months for DLBCL and 8.1 months for follicular lymphoma. Of the 11 patients who responded, 10 (91%) were still in response at the time of data cutoff. “Longer follow-up is needed,” the investigators wrote.
Most adverse events were seen within the first few weeks of treatment and mainly included anemia and infusion-related reactions. The anemia was an expected, on-target effect of 5F9 because of selective clearance of older red cells, which was predictable, transient, and mitigated by the maintenance dosing strategy employed in this phase 1b trial.
“As red cells age, they lose CD47 expression and gain expression of prophagocytic signals, leading to homeostatic clearance,” they wrote.
The activity of 5F9 and rituximab is “synergistic” based on the results of previous, preclinical investigations in models of lymphoma, Dr. Advani and her coauthors added.
A phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell non-Hodgkin lymphoma is ongoing, according to their report.
The study was supported by Forty Seven and the Leukemia & Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
SOURCE: Advani R et al. N Engl J Med. 2018;379:1711-21.
A macrophage-activating immune checkpoint inhibitor, combined with rituximab therapy, was safe and produced durable complete responses in patients with relapsed or refractory non-Hodgkin lymphoma, according to results of a phase 1b study.
Mainly low-grade toxic effects were seen on treatment with Hu5F9-G4 (5F9) and rituximab, which induced responses in more than half of patients, of which more than one-third were complete responses, the study investigators reported.
Most of the responses were ongoing at the time of data cutoff, suggesting durable responses with the combination of rituximab and 5F9 – a humanized monoclonal antibody that blocks CD47, an antiphagocytic or “do not eat me” signal overexpressed by most cancers, Ranjana Advani, MD, of Stanford (Calif.) University, and her coauthors wrote.
“The macrophage-mediated activity of 5F9 plus rituximab may serve as an effective new immunotherapy for stimulating the innate immune system,” Dr. Advani and her colleagues reported in the New England Journal of Medicine.
The study included 22 patients, including 15 with diffuse large B-cell lymphoma (DLBCL) and 7 with follicular lymphoma, who had received a median of four prior therapies. Almost all of the non-Hodgkin lymphomas (21, or 95%) were refractory to rituximab.
All patients received intravenous 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10-30 mg/kg in three dose-escalation cohorts, given until disease progression or lack of clinical benefit. Intravenous rituximab at 375 mg/m2 weekly was started on the second week of the first cycle, and then monthly for cycles 2 through 6.
“Substantial antitumor activity” was seen with this chemotherapy-free regimen in a group of heavily pretreated, largely rituximab-refractory patients, Dr. Advani and her coauthors wrote in their report.
The objective response rate was 50%, including a 36% complete response rate in the intent-to-treat analysis. For DLBCL, the rates of objective and complete responses were 40% and 33%, while for follicular lymphoma, they were 71% and 43%.
The median duration of response was not reached in either disease cohort with a median follow-up of 6.2 months for DLBCL and 8.1 months for follicular lymphoma. Of the 11 patients who responded, 10 (91%) were still in response at the time of data cutoff. “Longer follow-up is needed,” the investigators wrote.
Most adverse events were seen within the first few weeks of treatment and mainly included anemia and infusion-related reactions. The anemia was an expected, on-target effect of 5F9 because of selective clearance of older red cells, which was predictable, transient, and mitigated by the maintenance dosing strategy employed in this phase 1b trial.
“As red cells age, they lose CD47 expression and gain expression of prophagocytic signals, leading to homeostatic clearance,” they wrote.
The activity of 5F9 and rituximab is “synergistic” based on the results of previous, preclinical investigations in models of lymphoma, Dr. Advani and her coauthors added.
A phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell non-Hodgkin lymphoma is ongoing, according to their report.
The study was supported by Forty Seven and the Leukemia & Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
SOURCE: Advani R et al. N Engl J Med. 2018;379:1711-21.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Rates of overall and complete responses were 50% and 36%, respectively, with most responses ongoing at the time of data cutoff.
Study details: A phase 1b study of 22 patients, including 15 with diffuse large B-cell lymphoma and 7 with follicular lymphoma.
Disclosures: The study was supported by Forty Seven and the Leukemia & Lymphoma Society. Study authors reported disclosures related to Forty Seven, Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.
Source: Advani R et al. N Engl J Med. 2018;379:1711-21.
ATLAS: High-risk RCC patients might benefit from adjuvant axitinib
While adjuvant axitinib failed to improve disease-free survival in a recent phase 3 renal cell carcinoma (RCC) trial, the highest-risk subgroup appeared to benefit, according to a report on the study.
The phase 3 ATLAS trial was stopped early because of a lack of benefit for axitinib versus placebo in the study, which included patients with locoregional RCC at risk of recurrence after nephrectomy.
However, a prespecified analysis showed that axitinib reduced risk of disease-free survival events by about one-third in the highest-risk subset of patients, according to investigator David I. Quinn, MD, USC Norris Comprehensive Cancer Center, Los Angeles, and colleagues.
That finding tracks with results of the earlier S-TRAC trial, in which patients at high risk of tumor recurrence after nephrectomy had significantly longer disease-free survival with sunitinib versus placebo, Dr. Quinn and coauthors said.
“Taken together, these results support that patients at highest risk for RCC recurrence benefit from adjuvant treatment,” they wrote in Annals of Oncology.
In the ATLAS trial, Dr. Quinn and coinvestigators at 137 centers in eight countries enrolled 724 adults with newly diagnosed renal cell carcinoma (greater than or equal to pT2 and/or N+, any Fuhrman grade) with Eastern Cooperative Oncology Group status of 0 or 1 and prior nephrectomy.
Patients were randomly assigned to oral, twice-daily axitinib 5 mg or placebo for up to 3 years of treatment, and at least 1 year of treatment provided there was no recurrence, substantial toxicity, or withdrawal of consent.
For the primary endpoint, disease-free survival per independent review committee assessment, the hazard ratio was 0.870 (95% confidence interval, 0.660-1.147; P = .3211), according to the report. Disease-free survival as rated by investigators showed a somewhat larger but still not statistically significant reduction in risk of an event, Dr. Quinn and colleagues said.
However, in the prespecified subgroup analyses, the patients at highest risk (pT3 with Fuhrman grade greater than or equal to 3 or pT4 and/or N+, any T, any Fuhrman grade) had a reduction of risk with hazard ratios of 0.735 per independent review committee (P = .0704) and 0.641 per investigator (P = .0051).
The ATLAS study was designed before results of the S-TRAC study were known, and so patients at lower risk of recurrence were included, said Dr. Quinn and coauthors.
Ongoing trials are looking at sorafenib, everolimus, and immune checkpoint inhibitors in the adjuvant RCC setting, they noted in their discussion of ATLAS, S-TRAC, and other investigations.
Results from these trials may provide clarification on the future of adjuvant treatment for RCC, and whether angiogenesis inhibition is the key mechanism to obtain a reduction in risk of relapse after nephrectomy,” they said.
The study was sponsored by Pfizer and SFJ Pharmaceuticals. Dr. Quinn reported providing advisory board services for Pfizer, Bayer, Novartis, Bristol-Myers Squibb, Merck, Exelixis, Genentech, Roche, AstraZeneca, and Astellas. Coauthors reported disclosures related to Bristol-Myers Squibb, Ipsen, MSD, Novartis, Pfizer, and Roche, among others.
SOURCE: Quinn DI et al. Ann Oncol. 2018 Oct 20. doi: 10.1093/annonc/mdy454.
While adjuvant axitinib failed to improve disease-free survival in a recent phase 3 renal cell carcinoma (RCC) trial, the highest-risk subgroup appeared to benefit, according to a report on the study.
The phase 3 ATLAS trial was stopped early because of a lack of benefit for axitinib versus placebo in the study, which included patients with locoregional RCC at risk of recurrence after nephrectomy.
However, a prespecified analysis showed that axitinib reduced risk of disease-free survival events by about one-third in the highest-risk subset of patients, according to investigator David I. Quinn, MD, USC Norris Comprehensive Cancer Center, Los Angeles, and colleagues.
That finding tracks with results of the earlier S-TRAC trial, in which patients at high risk of tumor recurrence after nephrectomy had significantly longer disease-free survival with sunitinib versus placebo, Dr. Quinn and coauthors said.
“Taken together, these results support that patients at highest risk for RCC recurrence benefit from adjuvant treatment,” they wrote in Annals of Oncology.
In the ATLAS trial, Dr. Quinn and coinvestigators at 137 centers in eight countries enrolled 724 adults with newly diagnosed renal cell carcinoma (greater than or equal to pT2 and/or N+, any Fuhrman grade) with Eastern Cooperative Oncology Group status of 0 or 1 and prior nephrectomy.
Patients were randomly assigned to oral, twice-daily axitinib 5 mg or placebo for up to 3 years of treatment, and at least 1 year of treatment provided there was no recurrence, substantial toxicity, or withdrawal of consent.
For the primary endpoint, disease-free survival per independent review committee assessment, the hazard ratio was 0.870 (95% confidence interval, 0.660-1.147; P = .3211), according to the report. Disease-free survival as rated by investigators showed a somewhat larger but still not statistically significant reduction in risk of an event, Dr. Quinn and colleagues said.
However, in the prespecified subgroup analyses, the patients at highest risk (pT3 with Fuhrman grade greater than or equal to 3 or pT4 and/or N+, any T, any Fuhrman grade) had a reduction of risk with hazard ratios of 0.735 per independent review committee (P = .0704) and 0.641 per investigator (P = .0051).
The ATLAS study was designed before results of the S-TRAC study were known, and so patients at lower risk of recurrence were included, said Dr. Quinn and coauthors.
Ongoing trials are looking at sorafenib, everolimus, and immune checkpoint inhibitors in the adjuvant RCC setting, they noted in their discussion of ATLAS, S-TRAC, and other investigations.
Results from these trials may provide clarification on the future of adjuvant treatment for RCC, and whether angiogenesis inhibition is the key mechanism to obtain a reduction in risk of relapse after nephrectomy,” they said.
The study was sponsored by Pfizer and SFJ Pharmaceuticals. Dr. Quinn reported providing advisory board services for Pfizer, Bayer, Novartis, Bristol-Myers Squibb, Merck, Exelixis, Genentech, Roche, AstraZeneca, and Astellas. Coauthors reported disclosures related to Bristol-Myers Squibb, Ipsen, MSD, Novartis, Pfizer, and Roche, among others.
SOURCE: Quinn DI et al. Ann Oncol. 2018 Oct 20. doi: 10.1093/annonc/mdy454.
While adjuvant axitinib failed to improve disease-free survival in a recent phase 3 renal cell carcinoma (RCC) trial, the highest-risk subgroup appeared to benefit, according to a report on the study.
The phase 3 ATLAS trial was stopped early because of a lack of benefit for axitinib versus placebo in the study, which included patients with locoregional RCC at risk of recurrence after nephrectomy.
However, a prespecified analysis showed that axitinib reduced risk of disease-free survival events by about one-third in the highest-risk subset of patients, according to investigator David I. Quinn, MD, USC Norris Comprehensive Cancer Center, Los Angeles, and colleagues.
That finding tracks with results of the earlier S-TRAC trial, in which patients at high risk of tumor recurrence after nephrectomy had significantly longer disease-free survival with sunitinib versus placebo, Dr. Quinn and coauthors said.
“Taken together, these results support that patients at highest risk for RCC recurrence benefit from adjuvant treatment,” they wrote in Annals of Oncology.
In the ATLAS trial, Dr. Quinn and coinvestigators at 137 centers in eight countries enrolled 724 adults with newly diagnosed renal cell carcinoma (greater than or equal to pT2 and/or N+, any Fuhrman grade) with Eastern Cooperative Oncology Group status of 0 or 1 and prior nephrectomy.
Patients were randomly assigned to oral, twice-daily axitinib 5 mg or placebo for up to 3 years of treatment, and at least 1 year of treatment provided there was no recurrence, substantial toxicity, or withdrawal of consent.
For the primary endpoint, disease-free survival per independent review committee assessment, the hazard ratio was 0.870 (95% confidence interval, 0.660-1.147; P = .3211), according to the report. Disease-free survival as rated by investigators showed a somewhat larger but still not statistically significant reduction in risk of an event, Dr. Quinn and colleagues said.
However, in the prespecified subgroup analyses, the patients at highest risk (pT3 with Fuhrman grade greater than or equal to 3 or pT4 and/or N+, any T, any Fuhrman grade) had a reduction of risk with hazard ratios of 0.735 per independent review committee (P = .0704) and 0.641 per investigator (P = .0051).
The ATLAS study was designed before results of the S-TRAC study were known, and so patients at lower risk of recurrence were included, said Dr. Quinn and coauthors.
Ongoing trials are looking at sorafenib, everolimus, and immune checkpoint inhibitors in the adjuvant RCC setting, they noted in their discussion of ATLAS, S-TRAC, and other investigations.
Results from these trials may provide clarification on the future of adjuvant treatment for RCC, and whether angiogenesis inhibition is the key mechanism to obtain a reduction in risk of relapse after nephrectomy,” they said.
The study was sponsored by Pfizer and SFJ Pharmaceuticals. Dr. Quinn reported providing advisory board services for Pfizer, Bayer, Novartis, Bristol-Myers Squibb, Merck, Exelixis, Genentech, Roche, AstraZeneca, and Astellas. Coauthors reported disclosures related to Bristol-Myers Squibb, Ipsen, MSD, Novartis, Pfizer, and Roche, among others.
SOURCE: Quinn DI et al. Ann Oncol. 2018 Oct 20. doi: 10.1093/annonc/mdy454.
FROM ANNALS OF ONCOLOGY
Key clinical point: While adjuvant axitinib failed to improve disease-free survival in a recent phase 3 renal cell carcinoma trial, the highest-risk subgroup appeared to benefit.
Major finding: The highest-risk subpopulation (pT3 with Fuhrman grade greater than or equal to 3 or pT4 and/or N+, any T, any Fuhrman grade) had a reduction of risk per assessments by independent review committee (HR, 0.735; P = .0704) and investigators (HR, 0.641; P = .0051).
Study details: Results from ATLAS, a phase 3, randomized trial including 724 patients with locoregional RCC.
Disclosures: The study was sponsored by Pfizer and SFJ Pharmaceuticals. Study authors reported disclosures related to Pfizer, Bayer, Novartis, Bristol-Myers Squibb, Merck, Exelixis, Genentech, Roche, AstraZeneca, and Astellas, among others.
Source: Quinn DI et al. Ann Oncol. 2018 Oct 20. doi: 10.1093/annonc/mdy454.
Bleeding score could help identify hemophilia
Bleeding scores may be helpful in identifying hemophilia patients, regardless of whether or not clotting factor levels are known, results of a recent investigation suggest.
Both hemophilia A and B patients had significantly higher bleeding scores as assessed by the ISTH-BAT (International Society on Thrombosis and Hemostasis–Bleeding Assessment Tool), compared with control subjects, according to results of the study.
Moreover, hemophilia patients classified as severe had significantly higher ISTH-BAT scores compared with those classified as mild, reported by Munira Borhany, MD, of the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, Pakistan, and her colleagues.
“The ISTH-BAT can be easily used in the clinics by physicians and can help to identify those patients who should be further investigated,” Dr. Borhany and her coauthors reported in the journal Transfusion and Apheresis Science.
The ISTH-BAT, established to standardize the reporting of bleeding symptoms, scores symptoms from 0, which indicates absent or trivial, to 4, meaning a symptom that requires medical intervention. Total scores considered abnormal are 4 or greater in men, 6 and greater in women, and 3 and greater in children, according to previously published reports.
In the present cross-sectional study, Dr. Borhany and her colleagues evaluated bleeding scores for 115 adult and pediatric patients – 78 with hemophilia A and 37 with hemophilia B – who were treated in Pakistan between 2014 and 2016.
Bleeding scores were a mean of 13.5 and 13.2 for hemophilia A and B patients, respectively, and 0.8 for 100 healthy male controls also included in the study. Scores were significantly higher in hemophilia patients versus controls (P less than .001), but not different between hemophilia A and B patients, the investigators reported.
Further results suggested a correlation between factor levels and clinical presentation of bleeding symptoms, according to the investigators. Statistically significant differences in bleeding scores also were seen between patients with severe and mild disease, and between severe and moderate disease, but not between the mild and moderate groups, they added.
Most studies of bleeding questionnaires to date have been in patients with von Willebrand disease or platelet disorders, with very little data on hemophilia.
“Apart from one recent study using ISTH-BAT in hemophilia carriers as part of assessing quality of life, we are unaware of other studies examining this assessment tool in hemophilia,” the researchers wrote.
This study cohort was unique, according to the investigators, because it included a substantial number of adults who were new patients with bleeding symptoms who had no previous diagnosis of hemophilia. “This allowed assessing whether investigators may tend to apply a higher score when knowing very low factor levels in hemophilia patients,” they said.
In fact, there was no major difference in bleeding scores for those newly diagnosed patients versus already diagnosed patients.
Results of an ongoing study will determine whether the ISTH BAT bleeding score can predict risk of bleeding in hemophilia patients, according to Dr. Borhany and her coauthors.
They reported having no conflicts of interest.
SOURCE: Borhany M et al. Transfus Apher Sci. 2018 Aug;57(4):556-60.
Bleeding scores may be helpful in identifying hemophilia patients, regardless of whether or not clotting factor levels are known, results of a recent investigation suggest.
Both hemophilia A and B patients had significantly higher bleeding scores as assessed by the ISTH-BAT (International Society on Thrombosis and Hemostasis–Bleeding Assessment Tool), compared with control subjects, according to results of the study.
Moreover, hemophilia patients classified as severe had significantly higher ISTH-BAT scores compared with those classified as mild, reported by Munira Borhany, MD, of the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, Pakistan, and her colleagues.
“The ISTH-BAT can be easily used in the clinics by physicians and can help to identify those patients who should be further investigated,” Dr. Borhany and her coauthors reported in the journal Transfusion and Apheresis Science.
The ISTH-BAT, established to standardize the reporting of bleeding symptoms, scores symptoms from 0, which indicates absent or trivial, to 4, meaning a symptom that requires medical intervention. Total scores considered abnormal are 4 or greater in men, 6 and greater in women, and 3 and greater in children, according to previously published reports.
In the present cross-sectional study, Dr. Borhany and her colleagues evaluated bleeding scores for 115 adult and pediatric patients – 78 with hemophilia A and 37 with hemophilia B – who were treated in Pakistan between 2014 and 2016.
Bleeding scores were a mean of 13.5 and 13.2 for hemophilia A and B patients, respectively, and 0.8 for 100 healthy male controls also included in the study. Scores were significantly higher in hemophilia patients versus controls (P less than .001), but not different between hemophilia A and B patients, the investigators reported.
Further results suggested a correlation between factor levels and clinical presentation of bleeding symptoms, according to the investigators. Statistically significant differences in bleeding scores also were seen between patients with severe and mild disease, and between severe and moderate disease, but not between the mild and moderate groups, they added.
Most studies of bleeding questionnaires to date have been in patients with von Willebrand disease or platelet disorders, with very little data on hemophilia.
“Apart from one recent study using ISTH-BAT in hemophilia carriers as part of assessing quality of life, we are unaware of other studies examining this assessment tool in hemophilia,” the researchers wrote.
This study cohort was unique, according to the investigators, because it included a substantial number of adults who were new patients with bleeding symptoms who had no previous diagnosis of hemophilia. “This allowed assessing whether investigators may tend to apply a higher score when knowing very low factor levels in hemophilia patients,” they said.
In fact, there was no major difference in bleeding scores for those newly diagnosed patients versus already diagnosed patients.
Results of an ongoing study will determine whether the ISTH BAT bleeding score can predict risk of bleeding in hemophilia patients, according to Dr. Borhany and her coauthors.
They reported having no conflicts of interest.
SOURCE: Borhany M et al. Transfus Apher Sci. 2018 Aug;57(4):556-60.
Bleeding scores may be helpful in identifying hemophilia patients, regardless of whether or not clotting factor levels are known, results of a recent investigation suggest.
Both hemophilia A and B patients had significantly higher bleeding scores as assessed by the ISTH-BAT (International Society on Thrombosis and Hemostasis–Bleeding Assessment Tool), compared with control subjects, according to results of the study.
Moreover, hemophilia patients classified as severe had significantly higher ISTH-BAT scores compared with those classified as mild, reported by Munira Borhany, MD, of the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, Pakistan, and her colleagues.
“The ISTH-BAT can be easily used in the clinics by physicians and can help to identify those patients who should be further investigated,” Dr. Borhany and her coauthors reported in the journal Transfusion and Apheresis Science.
The ISTH-BAT, established to standardize the reporting of bleeding symptoms, scores symptoms from 0, which indicates absent or trivial, to 4, meaning a symptom that requires medical intervention. Total scores considered abnormal are 4 or greater in men, 6 and greater in women, and 3 and greater in children, according to previously published reports.
In the present cross-sectional study, Dr. Borhany and her colleagues evaluated bleeding scores for 115 adult and pediatric patients – 78 with hemophilia A and 37 with hemophilia B – who were treated in Pakistan between 2014 and 2016.
Bleeding scores were a mean of 13.5 and 13.2 for hemophilia A and B patients, respectively, and 0.8 for 100 healthy male controls also included in the study. Scores were significantly higher in hemophilia patients versus controls (P less than .001), but not different between hemophilia A and B patients, the investigators reported.
Further results suggested a correlation between factor levels and clinical presentation of bleeding symptoms, according to the investigators. Statistically significant differences in bleeding scores also were seen between patients with severe and mild disease, and between severe and moderate disease, but not between the mild and moderate groups, they added.
Most studies of bleeding questionnaires to date have been in patients with von Willebrand disease or platelet disorders, with very little data on hemophilia.
“Apart from one recent study using ISTH-BAT in hemophilia carriers as part of assessing quality of life, we are unaware of other studies examining this assessment tool in hemophilia,” the researchers wrote.
This study cohort was unique, according to the investigators, because it included a substantial number of adults who were new patients with bleeding symptoms who had no previous diagnosis of hemophilia. “This allowed assessing whether investigators may tend to apply a higher score when knowing very low factor levels in hemophilia patients,” they said.
In fact, there was no major difference in bleeding scores for those newly diagnosed patients versus already diagnosed patients.
Results of an ongoing study will determine whether the ISTH BAT bleeding score can predict risk of bleeding in hemophilia patients, according to Dr. Borhany and her coauthors.
They reported having no conflicts of interest.
SOURCE: Borhany M et al. Transfus Apher Sci. 2018 Aug;57(4):556-60.
FROM TRANSFUSION AND APHERESIS SCIENCE
Key clinical point:
Major finding: Bleeding scores were a mean of 13.5 and 13.2 for hemophilia A and B patients, respectively, and 0.8 for healthy male controls (P less than .001).
Study details: A cross-sectional study included 115 adult and pediatric patients with hemophilia A or B treated in Pakistan between 2014 and 2016.
Disclosures: The authors reported having no conflicts of interest.
Source: Borhany M et al. Transfus Apher Sci. 2018 Aug;57(4):556-60.