WASHINGTON – Low-grade dysplasia and length of Barrett’s segment are both significant predictors of neoplastic progression, investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.

Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.

Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.

Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.

Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.

Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.

“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”

The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.

Ms. Klaver and her colleagues had no financial conflicts of interest to report.

[email protected]

SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.

WASHINGTON – Low-grade dysplasia and length of Barrett’s segment are both significant predictors of neoplastic progression, investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.

Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.

Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.

Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.

Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.

Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.

“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”

The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.

Ms. Klaver and her colleagues had no financial conflicts of interest to report.

[email protected]

SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.

WASHINGTON – Low-grade dysplasia and length of Barrett’s segment are both significant predictors of neoplastic progression, investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.

Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.

Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.

Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.

Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.

Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.

“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”

The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.

Ms. Klaver and her colleagues had no financial conflicts of interest to report.

[email protected]

SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.

SAN DIEGO – For people with COPD at high risk of exacerbation, the addition of low-dose theophylline to inhaled corticosteroids conferred no overall clinical benefit, results from a large trial funded by the United Kingdom found.​

Doug Brunk/MDedge News

“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”

According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.

In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.

In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.

Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.

He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.

“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”

The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.

[email protected]

SOURCE: Price, D., et al, Abstract 7709, ATS 2018.

SAN DIEGO – For people with COPD at high risk of exacerbation, the addition of low-dose theophylline to inhaled corticosteroids conferred no overall clinical benefit, results from a large trial funded by the United Kingdom found.​

Doug Brunk/MDedge News

“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”

According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.

In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.

In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.

Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.

He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.

“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”

The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.

[email protected]

SOURCE: Price, D., et al, Abstract 7709, ATS 2018.

SAN DIEGO – For people with COPD at high risk of exacerbation, the addition of low-dose theophylline to inhaled corticosteroids conferred no overall clinical benefit, results from a large trial funded by the United Kingdom found.​

Doug Brunk/MDedge News

“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”

According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.

In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.

In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.

Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.

He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.

“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”

The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.

[email protected]

SOURCE: Price, D., et al, Abstract 7709, ATS 2018.

CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.

“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.

Susan London/MDedge News

Susan London/MDedge News

Study details

With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).

There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.

Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).

Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.

Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).

Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.

A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).

Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.

SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.

CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.

“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.

Susan London/MDedge News

Susan London/MDedge News

Study details

With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).

There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.

Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).

Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.

Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).

Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.

A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).

Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.

SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.

CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.

“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.

Susan London/MDedge News

Susan London/MDedge News

Study details

With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).

There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.

Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).

Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.

Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).

Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.

A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).

Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.

SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.

CHICAGO – The JAK 1/2 inhibitor ruxolitinib (Jakafi), in combination with lenalidomide and methylprednisolone, overcame resistance to lenalidomide in about half of 28 heavily pre-treated patients with relapsed/refractory multiple myeloma, based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.

Andrew Bowser/MDedge News

These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.

“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.

The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.

“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.

The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.

SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).

CHICAGO – The JAK 1/2 inhibitor ruxolitinib (Jakafi), in combination with lenalidomide and methylprednisolone, overcame resistance to lenalidomide in about half of 28 heavily pre-treated patients with relapsed/refractory multiple myeloma, based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.

Andrew Bowser/MDedge News

These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.

“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.

The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.

“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.

The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.

SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).

CHICAGO – The JAK 1/2 inhibitor ruxolitinib (Jakafi), in combination with lenalidomide and methylprednisolone, overcame resistance to lenalidomide in about half of 28 heavily pre-treated patients with relapsed/refractory multiple myeloma, based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.

Andrew Bowser/MDedge News

These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.

“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.

The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.

“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.

The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.

SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).

WASHINGTON – Patients with inflammatory bowel disease who used a smartphone app designed to monitor their clinical status showed significant improvements in their quality of care in a single-center randomized study with 320 patients.

Based on this success, the app will soon be made available to all of the roughly 5,000 inflammatory bowel disease (IBD) patients managed at Mount Sinai Medical Center in New York as well as IBD patients at several other North American centers that plan to adopt the app, Ashish Atreja, MD, said at the annual Digestive Disease Week.®

Home monitoring of IBD patients “is feasible with high adoption,” said Dr. Atreja, a gastroenterologist at Mount Sinai who directs the Sinai AppLab. The 162 IBD patients randomized to regularly use the HealthPROMISE app had their quality-of-care metric rise from 50% at baseline to 84% after an average follow-up of 575 days (19 months), a statistically significant improvement over the 158 control patients whose metric rose from 50% to 65% for the study’s primary endpoint, he reported. The results also showed a trend toward improved quality of life among the patients using the HealthPROMISE app, compared with the controls, who used an IBD educational app that produced less patient engagement than did the HealthPROMISE app, Dr Atreja said.

Dr. Atreja and his associates modeled the app on remote monitoring methods developed for patients with other types of chronic disease, such as diabetes and heart failure.

“You can’t provide proactive IBD care without remote monitoring,” Dr. Atreja explained in a video interview. “Reactive care is not best practice anymore. The only way to do treat-to-target is with remote monitoring.”

Care coordinators monitor the entries that IBD patients send in via the app. Dr. Atreja estimated that about five care coordinators will be able to track the inputs from the roughly 5,000 IBD patients at Mount Sinai who will soon begin using the app. The financial feasibility of this approach depends in part on the $45/patient per month reimbursement that U.S. health insurers now provide to centers that run remote monitoring programs, he said.

“The direction for managing chronic diseases is increasingly looking at home monitoring as a way to streamline costs and improve patient care,” commented Gil Y. Melmed, MD, director of Clinical Inflammatory Bowel Disease at Cedars-Sinai Medical Center in Los Angeles. The results that Dr. Atreja reported came from “a highly selected population that was well educated and largely white.” The study needs replication in different patient groups to establish its reproducibility and generalizability, Dr. Melmed said in an interview.

Dr. Melmed had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Atreja A et al. Digestive Disease Week 2018 abstract 17.

*This story was updated on June 7, 2018. 

WASHINGTON – Patients with inflammatory bowel disease who used a smartphone app designed to monitor their clinical status showed significant improvements in their quality of care in a single-center randomized study with 320 patients.

Based on this success, the app will soon be made available to all of the roughly 5,000 inflammatory bowel disease (IBD) patients managed at Mount Sinai Medical Center in New York as well as IBD patients at several other North American centers that plan to adopt the app, Ashish Atreja, MD, said at the annual Digestive Disease Week.®

Home monitoring of IBD patients “is feasible with high adoption,” said Dr. Atreja, a gastroenterologist at Mount Sinai who directs the Sinai AppLab. The 162 IBD patients randomized to regularly use the HealthPROMISE app had their quality-of-care metric rise from 50% at baseline to 84% after an average follow-up of 575 days (19 months), a statistically significant improvement over the 158 control patients whose metric rose from 50% to 65% for the study’s primary endpoint, he reported. The results also showed a trend toward improved quality of life among the patients using the HealthPROMISE app, compared with the controls, who used an IBD educational app that produced less patient engagement than did the HealthPROMISE app, Dr Atreja said.

Dr. Atreja and his associates modeled the app on remote monitoring methods developed for patients with other types of chronic disease, such as diabetes and heart failure.

“You can’t provide proactive IBD care without remote monitoring,” Dr. Atreja explained in a video interview. “Reactive care is not best practice anymore. The only way to do treat-to-target is with remote monitoring.”

Care coordinators monitor the entries that IBD patients send in via the app. Dr. Atreja estimated that about five care coordinators will be able to track the inputs from the roughly 5,000 IBD patients at Mount Sinai who will soon begin using the app. The financial feasibility of this approach depends in part on the $45/patient per month reimbursement that U.S. health insurers now provide to centers that run remote monitoring programs, he said.

“The direction for managing chronic diseases is increasingly looking at home monitoring as a way to streamline costs and improve patient care,” commented Gil Y. Melmed, MD, director of Clinical Inflammatory Bowel Disease at Cedars-Sinai Medical Center in Los Angeles. The results that Dr. Atreja reported came from “a highly selected population that was well educated and largely white.” The study needs replication in different patient groups to establish its reproducibility and generalizability, Dr. Melmed said in an interview.

Dr. Melmed had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Atreja A et al. Digestive Disease Week 2018 abstract 17.

*This story was updated on June 7, 2018. 

WASHINGTON – Patients with inflammatory bowel disease who used a smartphone app designed to monitor their clinical status showed significant improvements in their quality of care in a single-center randomized study with 320 patients.

Based on this success, the app will soon be made available to all of the roughly 5,000 inflammatory bowel disease (IBD) patients managed at Mount Sinai Medical Center in New York as well as IBD patients at several other North American centers that plan to adopt the app, Ashish Atreja, MD, said at the annual Digestive Disease Week.®

Home monitoring of IBD patients “is feasible with high adoption,” said Dr. Atreja, a gastroenterologist at Mount Sinai who directs the Sinai AppLab. The 162 IBD patients randomized to regularly use the HealthPROMISE app had their quality-of-care metric rise from 50% at baseline to 84% after an average follow-up of 575 days (19 months), a statistically significant improvement over the 158 control patients whose metric rose from 50% to 65% for the study’s primary endpoint, he reported. The results also showed a trend toward improved quality of life among the patients using the HealthPROMISE app, compared with the controls, who used an IBD educational app that produced less patient engagement than did the HealthPROMISE app, Dr Atreja said.

Dr. Atreja and his associates modeled the app on remote monitoring methods developed for patients with other types of chronic disease, such as diabetes and heart failure.

“You can’t provide proactive IBD care without remote monitoring,” Dr. Atreja explained in a video interview. “Reactive care is not best practice anymore. The only way to do treat-to-target is with remote monitoring.”

Care coordinators monitor the entries that IBD patients send in via the app. Dr. Atreja estimated that about five care coordinators will be able to track the inputs from the roughly 5,000 IBD patients at Mount Sinai who will soon begin using the app. The financial feasibility of this approach depends in part on the $45/patient per month reimbursement that U.S. health insurers now provide to centers that run remote monitoring programs, he said.

“The direction for managing chronic diseases is increasingly looking at home monitoring as a way to streamline costs and improve patient care,” commented Gil Y. Melmed, MD, director of Clinical Inflammatory Bowel Disease at Cedars-Sinai Medical Center in Los Angeles. The results that Dr. Atreja reported came from “a highly selected population that was well educated and largely white.” The study needs replication in different patient groups to establish its reproducibility and generalizability, Dr. Melmed said in an interview.

Dr. Melmed had no relevant disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Atreja A et al. Digestive Disease Week 2018 abstract 17.

*This story was updated on June 7, 2018. 

ORLANDO – There was a median 1-year delay between the onset of symptoms and diagnosis of classic dermatomyositis, and a 17-month delay before diagnosis of amyopathic dermatomyositis, based on a review of 232 dermatomyositis patients seen at the University of Pennsylvania, Philadelphia.

Just 103 (44.4%) patients were diagnosed with dermatomyositis (DM) right out of the gate. Among the other 129, 48 (37.2%) were diagnosed with lupus, 38 (29.5%) with undifferentiated connective tissue disease, 10 (7.8%) went undiagnosed, and 33 (25.5%) were diagnosed with rosacea, psoriasis, rheumatoid arthritis, fibromyalgia, lichen planus, and a number of other conditions. By the time the DM diagnosis was finally confirmed, almost every patient had Gottron’s papules or sign.

Misdiagnosis of dermatomyositis (DM) is nothing new, but the study brings home just how common the problem is, even at a major academic medical institution.

One of the take homes is that clinicians should never forget about the possibility of DM even when patients are diagnosed with other autoimmune diseases, and remain vigilant for erythema on the lateral thighs or nasolabial fold, Gottron’s papules, and other diagnostic giveaways, the researchers said.

M. Alexander Otto/MDedge News

“We saw that there was a much higher rate of misdiagnosis in patients who didn’t have any muscle disease. We have to raise awareness that amyopathic dermatomyositis is a very prevalent condition,” Dr. Patel said at the International Conference on Cutaneous Lupus Erythematosus.

“There might be some level of subclinical muscle activity where, if you did an MRI, you might see inflammation, but the patient doesn’t report any symptoms. There are also patients that don’t have any muscle findings on MRI, or elevated muscle enzymes, but still have the skin findings,” he said.

Perhaps the markedly increased risk of cancer in DM, especially within a year or 2 of symptom onset, is the strongest argument for earlier diagnosis. “There’s also a risk of interstitial lung disease, so making sure that you’re getting pulmonary function tests and age-appropriate malignancy screening in a timely fashion is very important,” Dr. Patel said.

Also, although many of the initial treatments for DM – sun protection and topical steroids and calcineurin inhibitors, for instance – are the same as for cutaneous lupus, medications like mycophenolate mofetil and methotrexate are used more readily. The sooner DM is recognized for what it is, the sooner patients can get relief, he said.

Almost all the patients were white women. The majority were 40-80 years old.

There was no industry funding for the work, and Dr. Patel didn’t have any disclosures.

[email protected]

SOURCE: da Silva DM et al. Presented at the 2018 International Conference on Cutaneous Lupus Erythematosus

ORLANDO – There was a median 1-year delay between the onset of symptoms and diagnosis of classic dermatomyositis, and a 17-month delay before diagnosis of amyopathic dermatomyositis, based on a review of 232 dermatomyositis patients seen at the University of Pennsylvania, Philadelphia.

Just 103 (44.4%) patients were diagnosed with dermatomyositis (DM) right out of the gate. Among the other 129, 48 (37.2%) were diagnosed with lupus, 38 (29.5%) with undifferentiated connective tissue disease, 10 (7.8%) went undiagnosed, and 33 (25.5%) were diagnosed with rosacea, psoriasis, rheumatoid arthritis, fibromyalgia, lichen planus, and a number of other conditions. By the time the DM diagnosis was finally confirmed, almost every patient had Gottron’s papules or sign.

Misdiagnosis of dermatomyositis (DM) is nothing new, but the study brings home just how common the problem is, even at a major academic medical institution.

One of the take homes is that clinicians should never forget about the possibility of DM even when patients are diagnosed with other autoimmune diseases, and remain vigilant for erythema on the lateral thighs or nasolabial fold, Gottron’s papules, and other diagnostic giveaways, the researchers said.

M. Alexander Otto/MDedge News

“We saw that there was a much higher rate of misdiagnosis in patients who didn’t have any muscle disease. We have to raise awareness that amyopathic dermatomyositis is a very prevalent condition,” Dr. Patel said at the International Conference on Cutaneous Lupus Erythematosus.

“There might be some level of subclinical muscle activity where, if you did an MRI, you might see inflammation, but the patient doesn’t report any symptoms. There are also patients that don’t have any muscle findings on MRI, or elevated muscle enzymes, but still have the skin findings,” he said.

Perhaps the markedly increased risk of cancer in DM, especially within a year or 2 of symptom onset, is the strongest argument for earlier diagnosis. “There’s also a risk of interstitial lung disease, so making sure that you’re getting pulmonary function tests and age-appropriate malignancy screening in a timely fashion is very important,” Dr. Patel said.

Also, although many of the initial treatments for DM – sun protection and topical steroids and calcineurin inhibitors, for instance – are the same as for cutaneous lupus, medications like mycophenolate mofetil and methotrexate are used more readily. The sooner DM is recognized for what it is, the sooner patients can get relief, he said.

Almost all the patients were white women. The majority were 40-80 years old.

There was no industry funding for the work, and Dr. Patel didn’t have any disclosures.

[email protected]

SOURCE: da Silva DM et al. Presented at the 2018 International Conference on Cutaneous Lupus Erythematosus

ORLANDO – There was a median 1-year delay between the onset of symptoms and diagnosis of classic dermatomyositis, and a 17-month delay before diagnosis of amyopathic dermatomyositis, based on a review of 232 dermatomyositis patients seen at the University of Pennsylvania, Philadelphia.

Just 103 (44.4%) patients were diagnosed with dermatomyositis (DM) right out of the gate. Among the other 129, 48 (37.2%) were diagnosed with lupus, 38 (29.5%) with undifferentiated connective tissue disease, 10 (7.8%) went undiagnosed, and 33 (25.5%) were diagnosed with rosacea, psoriasis, rheumatoid arthritis, fibromyalgia, lichen planus, and a number of other conditions. By the time the DM diagnosis was finally confirmed, almost every patient had Gottron’s papules or sign.

Misdiagnosis of dermatomyositis (DM) is nothing new, but the study brings home just how common the problem is, even at a major academic medical institution.

One of the take homes is that clinicians should never forget about the possibility of DM even when patients are diagnosed with other autoimmune diseases, and remain vigilant for erythema on the lateral thighs or nasolabial fold, Gottron’s papules, and other diagnostic giveaways, the researchers said.

M. Alexander Otto/MDedge News

“We saw that there was a much higher rate of misdiagnosis in patients who didn’t have any muscle disease. We have to raise awareness that amyopathic dermatomyositis is a very prevalent condition,” Dr. Patel said at the International Conference on Cutaneous Lupus Erythematosus.

“There might be some level of subclinical muscle activity where, if you did an MRI, you might see inflammation, but the patient doesn’t report any symptoms. There are also patients that don’t have any muscle findings on MRI, or elevated muscle enzymes, but still have the skin findings,” he said.

Perhaps the markedly increased risk of cancer in DM, especially within a year or 2 of symptom onset, is the strongest argument for earlier diagnosis. “There’s also a risk of interstitial lung disease, so making sure that you’re getting pulmonary function tests and age-appropriate malignancy screening in a timely fashion is very important,” Dr. Patel said.

Also, although many of the initial treatments for DM – sun protection and topical steroids and calcineurin inhibitors, for instance – are the same as for cutaneous lupus, medications like mycophenolate mofetil and methotrexate are used more readily. The sooner DM is recognized for what it is, the sooner patients can get relief, he said.

Almost all the patients were white women. The majority were 40-80 years old.

There was no industry funding for the work, and Dr. Patel didn’t have any disclosures.

[email protected]

SOURCE: da Silva DM et al. Presented at the 2018 International Conference on Cutaneous Lupus Erythematosus

CHICAGO – The investigational drug ivosidenib was associated with durable responses, transfusion independence, and a low rate of serious adverse events in patients with IDH1-mutated relapsed/refractory acute myeloid leukemia (AML), based on results of a phase 1 study presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Daily oral ivosidenib, which inhibits mutant IDH1 the gene that encodes for isocitrate dehydrogenase 1 and is present in 6%-10% of AML patients, was associated with a complete response rate of nearly 32%. In patients who achieved a complete response, median duration of response was 8.2 months and median overall survival was 18.8 months, Daniel A. Pollyea, MD, University of Colorado School of Medicine, Aurora, reported at the meeting.

A wide variety of study participants achieved transfusion independence, even patients who had lesser and no discernable responses, Dr. Pollyea said. “A significant minority of these patients (with lesser or no response) were able to achieve transfusion independence which is obviously a big achievement with respect to quality of life, and suggestive of the mechanism of action here with respect to differentiation.”

The conclusions of this study are “striking,” with response rates and tolerability “very similar” to results seen with the IDH2 inhibitor enasidenib, said Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y.

Ivosidenib is “likely to become the new standard of care treatment” for IDH1-mutant patients in the relapsed-refractory setting based on the data presented at ASCO, Dr. Wang said in a presentation commenting on the results.

“Given the development of ivosidenib and enasidenib, I think we should all carefully consider whether testing of IDH1 and IDH2 mutational status should also become standard of care in all relapsed and refractory patients, in order to offer them these novel and highly effective as well as well-tolerated targeted therapies,” she said.

Enasidenib was approved by the U.S. Food and Drug Administration (FDA) in 2017 for relapsed or refractory AML with an IDH2 mutation.

Here at ASCO, Dr. Pollyea reported results based on 179 patients with relapsed/refractory IDH1-mutant AML who received 500 mg of ivosidenib daily.

The overall response rate was 41.9% (75 patients), he said. The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 31.8% (57 patients), with a median of 2.0 months to CR/CRh and a median duration of CR/CRh of 8.2 months, he said.

Grade 3 or greater leukocytosis was seen in 8% of patients, and grade 3 or greater QT prolongation was seen in 10% of patients, Dr. Pollyea reported.

IHD differentiation syndrome of any grade was seen in 19 patients (10.6%), and about half of those cases (5%) were grade 3 or greater. However, cases were managed with supportive care, and there were no dose reductions, permanent treatment discontinuations, or deaths due to the condition, Dr. Pollyea said.

Moreover, the majority of those patients (10 out of 19) went on to have a response. “Supportive care and continued treatment can allow for patients ultimately to respond who are experiencing differentiation syndrome,” Dr. Pollyea said.

Results of the phase 1 study were published simultaneously in the New England Journal of Medicine.The trial was sponsored by Agios. Dr. Pollyea reported disclosures related to Agios, as well as Abbvie, argenx, Celgene, Celyad, Curis, Pfizer, and Servier.

SOURCE: Pollyea DA, et al. J Clin Oncol36, 2018 (suppl; abstr 7000).

CHICAGO – The investigational drug ivosidenib was associated with durable responses, transfusion independence, and a low rate of serious adverse events in patients with IDH1-mutated relapsed/refractory acute myeloid leukemia (AML), based on results of a phase 1 study presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Daily oral ivosidenib, which inhibits mutant IDH1 the gene that encodes for isocitrate dehydrogenase 1 and is present in 6%-10% of AML patients, was associated with a complete response rate of nearly 32%. In patients who achieved a complete response, median duration of response was 8.2 months and median overall survival was 18.8 months, Daniel A. Pollyea, MD, University of Colorado School of Medicine, Aurora, reported at the meeting.

A wide variety of study participants achieved transfusion independence, even patients who had lesser and no discernable responses, Dr. Pollyea said. “A significant minority of these patients (with lesser or no response) were able to achieve transfusion independence which is obviously a big achievement with respect to quality of life, and suggestive of the mechanism of action here with respect to differentiation.”

The conclusions of this study are “striking,” with response rates and tolerability “very similar” to results seen with the IDH2 inhibitor enasidenib, said Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y.

Ivosidenib is “likely to become the new standard of care treatment” for IDH1-mutant patients in the relapsed-refractory setting based on the data presented at ASCO, Dr. Wang said in a presentation commenting on the results.

“Given the development of ivosidenib and enasidenib, I think we should all carefully consider whether testing of IDH1 and IDH2 mutational status should also become standard of care in all relapsed and refractory patients, in order to offer them these novel and highly effective as well as well-tolerated targeted therapies,” she said.

Enasidenib was approved by the U.S. Food and Drug Administration (FDA) in 2017 for relapsed or refractory AML with an IDH2 mutation.

Here at ASCO, Dr. Pollyea reported results based on 179 patients with relapsed/refractory IDH1-mutant AML who received 500 mg of ivosidenib daily.

The overall response rate was 41.9% (75 patients), he said. The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 31.8% (57 patients), with a median of 2.0 months to CR/CRh and a median duration of CR/CRh of 8.2 months, he said.

Grade 3 or greater leukocytosis was seen in 8% of patients, and grade 3 or greater QT prolongation was seen in 10% of patients, Dr. Pollyea reported.

IHD differentiation syndrome of any grade was seen in 19 patients (10.6%), and about half of those cases (5%) were grade 3 or greater. However, cases were managed with supportive care, and there were no dose reductions, permanent treatment discontinuations, or deaths due to the condition, Dr. Pollyea said.

Moreover, the majority of those patients (10 out of 19) went on to have a response. “Supportive care and continued treatment can allow for patients ultimately to respond who are experiencing differentiation syndrome,” Dr. Pollyea said.

Results of the phase 1 study were published simultaneously in the New England Journal of Medicine.The trial was sponsored by Agios. Dr. Pollyea reported disclosures related to Agios, as well as Abbvie, argenx, Celgene, Celyad, Curis, Pfizer, and Servier.

SOURCE: Pollyea DA, et al. J Clin Oncol36, 2018 (suppl; abstr 7000).

CHICAGO – The investigational drug ivosidenib was associated with durable responses, transfusion independence, and a low rate of serious adverse events in patients with IDH1-mutated relapsed/refractory acute myeloid leukemia (AML), based on results of a phase 1 study presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Daily oral ivosidenib, which inhibits mutant IDH1 the gene that encodes for isocitrate dehydrogenase 1 and is present in 6%-10% of AML patients, was associated with a complete response rate of nearly 32%. In patients who achieved a complete response, median duration of response was 8.2 months and median overall survival was 18.8 months, Daniel A. Pollyea, MD, University of Colorado School of Medicine, Aurora, reported at the meeting.

A wide variety of study participants achieved transfusion independence, even patients who had lesser and no discernable responses, Dr. Pollyea said. “A significant minority of these patients (with lesser or no response) were able to achieve transfusion independence which is obviously a big achievement with respect to quality of life, and suggestive of the mechanism of action here with respect to differentiation.”

The conclusions of this study are “striking,” with response rates and tolerability “very similar” to results seen with the IDH2 inhibitor enasidenib, said Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y.

Ivosidenib is “likely to become the new standard of care treatment” for IDH1-mutant patients in the relapsed-refractory setting based on the data presented at ASCO, Dr. Wang said in a presentation commenting on the results.

“Given the development of ivosidenib and enasidenib, I think we should all carefully consider whether testing of IDH1 and IDH2 mutational status should also become standard of care in all relapsed and refractory patients, in order to offer them these novel and highly effective as well as well-tolerated targeted therapies,” she said.

Enasidenib was approved by the U.S. Food and Drug Administration (FDA) in 2017 for relapsed or refractory AML with an IDH2 mutation.

Here at ASCO, Dr. Pollyea reported results based on 179 patients with relapsed/refractory IDH1-mutant AML who received 500 mg of ivosidenib daily.

The overall response rate was 41.9% (75 patients), he said. The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 31.8% (57 patients), with a median of 2.0 months to CR/CRh and a median duration of CR/CRh of 8.2 months, he said.

Grade 3 or greater leukocytosis was seen in 8% of patients, and grade 3 or greater QT prolongation was seen in 10% of patients, Dr. Pollyea reported.

IHD differentiation syndrome of any grade was seen in 19 patients (10.6%), and about half of those cases (5%) were grade 3 or greater. However, cases were managed with supportive care, and there were no dose reductions, permanent treatment discontinuations, or deaths due to the condition, Dr. Pollyea said.

Moreover, the majority of those patients (10 out of 19) went on to have a response. “Supportive care and continued treatment can allow for patients ultimately to respond who are experiencing differentiation syndrome,” Dr. Pollyea said.

Results of the phase 1 study were published simultaneously in the New England Journal of Medicine.The trial was sponsored by Agios. Dr. Pollyea reported disclosures related to Agios, as well as Abbvie, argenx, Celgene, Celyad, Curis, Pfizer, and Servier.

SOURCE: Pollyea DA, et al. J Clin Oncol36, 2018 (suppl; abstr 7000).

CHICAGO – High frequency microsatellite instability (MSI-high) predicts Lynch Syndrome– and does so across more tumor types than previously expected, according to “absolutely practice changing” findings from a prospective analysis of more than 15,000 tumor samples.

Sharon Worcester/MDedge News

“The impact of these findings cannot be understated,” ASCO expert Shannon N. Westin, MD, said during a discussion of the findings presented by Zsofia K. Stadler, MD, at a press briefing at the annual meeting of the American Society of Clinical Oncology.

Lynch Syndrome (LS), an autosomal dominant inherited cancer predisposition syndrome caused by germline mutation in the DNA mismatch repair genes, is responsible for about 3% of colorectal and endometrial cancers; universal testing for tumor markers of LS is recommended in all patients with these types of cancers, said Dr. Stadler, director of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center, New York.

“This is usually done either via MSI analysis or immunohistochemical staining for the DNA mismatch repair proteins,” she said, noting that genetic testing and counseling is recommended in patients with tumors suggestive of LS, and increased surveillance and/or risk-reducing surgery is recommended in those recognized as having LS.

MSI-high is a hallmark of LS-associated cancers and has recently been implicated as a marker for response to immunotherapy. This has led to increased MSI testing in metastatic cancer regardless of cancer type.

However, the prevalence of germline mutations in the DNA mismatch repair genes diagnostic of LS across all MSI-high tumors is unknown, she said.

In 15,045 tumor samples across more than 50 cancer types, germline mutations were analyzed across tumor types and according to MSI status.

SOURCE: Schwark A et al., ASCO 2018 LBA1509.

CHICAGO – High frequency microsatellite instability (MSI-high) predicts Lynch Syndrome– and does so across more tumor types than previously expected, according to “absolutely practice changing” findings from a prospective analysis of more than 15,000 tumor samples.

Sharon Worcester/MDedge News

“The impact of these findings cannot be understated,” ASCO expert Shannon N. Westin, MD, said during a discussion of the findings presented by Zsofia K. Stadler, MD, at a press briefing at the annual meeting of the American Society of Clinical Oncology.

Lynch Syndrome (LS), an autosomal dominant inherited cancer predisposition syndrome caused by germline mutation in the DNA mismatch repair genes, is responsible for about 3% of colorectal and endometrial cancers; universal testing for tumor markers of LS is recommended in all patients with these types of cancers, said Dr. Stadler, director of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center, New York.

“This is usually done either via MSI analysis or immunohistochemical staining for the DNA mismatch repair proteins,” she said, noting that genetic testing and counseling is recommended in patients with tumors suggestive of LS, and increased surveillance and/or risk-reducing surgery is recommended in those recognized as having LS.

MSI-high is a hallmark of LS-associated cancers and has recently been implicated as a marker for response to immunotherapy. This has led to increased MSI testing in metastatic cancer regardless of cancer type.

However, the prevalence of germline mutations in the DNA mismatch repair genes diagnostic of LS across all MSI-high tumors is unknown, she said.

In 15,045 tumor samples across more than 50 cancer types, germline mutations were analyzed across tumor types and according to MSI status.

SOURCE: Schwark A et al., ASCO 2018 LBA1509.

CHICAGO – High frequency microsatellite instability (MSI-high) predicts Lynch Syndrome– and does so across more tumor types than previously expected, according to “absolutely practice changing” findings from a prospective analysis of more than 15,000 tumor samples.

Sharon Worcester/MDedge News

“The impact of these findings cannot be understated,” ASCO expert Shannon N. Westin, MD, said during a discussion of the findings presented by Zsofia K. Stadler, MD, at a press briefing at the annual meeting of the American Society of Clinical Oncology.

Lynch Syndrome (LS), an autosomal dominant inherited cancer predisposition syndrome caused by germline mutation in the DNA mismatch repair genes, is responsible for about 3% of colorectal and endometrial cancers; universal testing for tumor markers of LS is recommended in all patients with these types of cancers, said Dr. Stadler, director of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center, New York.

“This is usually done either via MSI analysis or immunohistochemical staining for the DNA mismatch repair proteins,” she said, noting that genetic testing and counseling is recommended in patients with tumors suggestive of LS, and increased surveillance and/or risk-reducing surgery is recommended in those recognized as having LS.

MSI-high is a hallmark of LS-associated cancers and has recently been implicated as a marker for response to immunotherapy. This has led to increased MSI testing in metastatic cancer regardless of cancer type.

However, the prevalence of germline mutations in the DNA mismatch repair genes diagnostic of LS across all MSI-high tumors is unknown, she said.

In 15,045 tumor samples across more than 50 cancer types, germline mutations were analyzed across tumor types and according to MSI status.

SOURCE: Schwark A et al., ASCO 2018 LBA1509.

Seventy-five percent of adults aged >75 years have hypertension.^1-3 According to the Joint National Commission 8 (JNC 8), the recommended target blood pressure (BP) is < 150/80 mm Hg for adults aged > 60 years.⁴ In 2016 the Systolic Blood Pressure Intervention Trial (SPRINT) suggested that more aggressive BP control with a goal of < 120/80 mm Hg reduced rates of cardiovascular disease and lowered the risk of death in adults aged > 50 years with hypertension.⁵ It is anticipated that as a result of the landmark SPRINT results, clinicians may attempt to treat hypertension more intensely in older patients with an increased risk of adverse consequences if BPs are not appropriately measured.

There is a standardized protocol for BP measurement, but these recommendations typically are not followed in routine office visits.^6,7 Some studies have noted that home BP measurement may be more accurate than office measurement.⁸ However, clinicians may not always trust the accuracy of home BP readings, and many patients are not adherent with home measurement. As a result, physicians usually manage hypertension in older patients based on office readings, though it is likely that most office measurements do not follow protocol on proper measurement. Office measurements have been noted to be inaccurate with high likelihood of overestimating or underestimating BP control.⁹

Office BP measurements demonstrate poor correlation with home measurements and have not been shown to be as good of a predictor for target organ damage or long-term cardiovascular outcomes compared with that of home measurements.^10,11 Although there have been studies comparing home and office BP measurements and comparing office and ambulatory BP measurement, no literature has been found that reports on the difference between routine office and standardized measurement of BP.^9,12-14

This study seeks to identify the magnitude of difference among BP measured according to a standardized protocol, routine clinical, and home BP. The authors hypothesized that there would be a significant, clinically relevant difference among the 3 BP measurement methods, especially between the routine office and standardized office measurements. This study has implications for implementing intensive treatment of hypertension based on office measurements.

Methods

Participants included 30 male veterans aged > 65 years who were actively participating in the Gerofit program at the VA Greater Los Angeles Healthcare System (VAGLAHS). The Gerofit program is a model clinical demonstration exercise and health promotion program targeting older and veterans at risk for falls or institutionalization. Gerofit was established in 1987 at the Durham VA Health System and successfully implemented in 2014 at VAGLAHS. Supervised exercise is offered 3 times per week and consists of individually tailored exercises aimed at reducing functional deficits that are identified and monitored by an initial and quarterly functional assessment. Blood pressures are checked routinely once a week as a part of the program. Gerofit was reviewed and approved by the institutional review board at VAGLAHS as a quality improvement/quality assurance project.

Data

Routine office and standardized protocol measurements were obtained by a single CasMED 740 (Branford, CT) automated BP machine and were conducted separately on different days. The CasMED 740 machine was not otherwise calibrated; however, a one-time correlation was performed between the CasMED 740 and the home BP monitor for each participant, when it was brought to VAGLAHS. Two measurements were made with the CasMed 740 automated BP machine on the arm that gave the higher BP reading throughout the standardized and routine protocol. Two subsequent measurements were made with the participant’s home automated BP cuff. Averages for the CasMED 740 and the home BP monitoring device were compared and assessed for significance by paired t test. No rest was scheduled prior to the first measurement, but there was a 1-minute rest after each subsequent measurement.

Mean values (SD) were used for participant characteristics and mean values (standard error [SE]) were used for BP measurements. Data were analyzed using Microsoft Excel (Redmond, WA) and GraphPad Prism version 7.03 (San Diego, CA). T tests were used for analysis of home BP measurements due to low sample size. Values of P < .05 were considered to be statistically significant.

Routine office protocol. Automated BP was measured to mimic routine office visits. Upon arrival, participants sat down, and the BP cuff was placed around their arm. Any rest before a measurement was incidental and not intentionally structured. Appropriate cuff size was determined by visual estimation of arm circumference. Only 1 measurement was made unless BP was > 150/90 mm Hg, in which case a repeat measurement was made after 2 to 4 minutes of rest. The BP was then determined based on the average of 2 or more readings. The BPs were recorded by hand in a weekly log. Participants had at least 12 weeks of BP readings measured by the routine method, and these BPs were averaged over 12 weeks to yield their average routine measured BP.

Standardized protocol. Automated BP was measured according to the 2015 USPSTF Guidelines and Look AHEAD trial protocol.^7,15 A participant’s arm circumference was measured, and appropriate cuff size was determined. The participant rested quietly in a chair for at least 5 minutes with feet flat on the floor and back supported. The cuff was snugly placed 2 to 3 cm above the antecubital fossa, and the arm was supported at the level of the right atrium during the measurement. Blood pressure was determined using the mean of 4 automated cuff readings, 2 on each arm, taken 1 minute apart. Participants did not necessarily have their BP measured by the standardized method immediately following the routine method but all measurements were performed during the same 12-week time period.

Home blood pressure protocol. Participants were given instructions according to the American Heart Association (AHA) recommendations for measuring home BP. Patients were instructed to use a calibrated, automated arm BP cuff. Home BP machines were not provided in advance, and each individual’s BP machine was not calibrated. They also were instructed to rest at least 5 minutes before measuring their BP. The mean home BP was determined by the cumulative average of 3 readings in the morning and evening, taken 1 minute between each reading, for a total of 6 readings/d. Participants recorded home BPs for 2 weeks before submitting their readings. Each participant affirmed clear understanding of how to measure BP by correctly demonstrating placement of the cuff 1 time under supervision.

Results

Thirty veterans aged > 65 years participated in the study. The average age (SD) was 82.7 (9.3) years. The average BMI (SD) was overweight at 29.7 kg/m² (5.7). Most (87.6%) of the study participants had been diagnosed with hypertension prior to the study, and no new diagnoses were made as a result of the study. 

Both systolic BP (SBP) and diastolic BPs (DBP) measured by the standardized method were significantly lower than those by the routine method (P < .01 and P < .01, respectively) (Figure 1). 

To determine the accuracy of the home BP monitors, the average routine VAGLAHS BP measure was compared with home BP results. For SBPs, there was a significant correlation coefficient of 0.91 (P < .01). 

Discussion

The present study demonstrated that standardized measurements of BP were lower than that of the routine method used in most office settings. These results suggest that there could be a risk of overtreatment for some patients those of whose results are higher than the SPRINT BP target of < 120/80 mm Hg. Clinicians might be treating BPs that are elevated due to improper measurement, which can lead to deleterious consequences in older adults, such as syncope and falls.¹⁶

Each participant exhibited a significantly lower BP reading with the standardized method than the routine method. The 20-point decrease in SBP and 10-point decrease in DBP are clinically significant. The routine method of measurement was intended to simulate BP measurement in outpatient settings. There is usually little time structured for rest, and because the protocol established by the AHA and other professional organizations is time consuming, it usually is not strictly followed. With guidelines proposed by JNC 8 and new findings from SPRINT, the method of BP readings should be reviewed in all clinical settings.

While changes in BP management are not necessarily immediate, the differences in recommendations proposed by SPRINT and JNC 8 can lead to confusion regarding how intensely to treat BP. These recommendations guide clinical practice, but clinicians’ best judgment ultimately determines BP management. Physicians who utilize routine office measurements likely rely on BP readings that are higher on average than are readings done under proper conditions. This leads to the prospect of overtreatment, where physicians attempt to control hypertension too aggressively, potentially leading to orthostatic hypotension, syncope, and increased risk for falls.¹⁶ With findings from SPRINT recommending even lower BPs than that by JNC 8, overtreatment risk becomes especially relevant. While BP protocol was strictly followed in SPRINT, some clinicians may not necessarily follow the same fastidious protocol.

The average differences between the home and standardized BPs were not statistically significant possibly due to the small sample size in the home BP measurements; however, the difference might represent some clinical relevance. There was a 15-point difference in SBP results between home (129 mm Hg) and standardized (115 mm Hg) measures. There also was a difference in DBP between home (69 mm Hg) and standardized (62 mm Hg) results. The close correlation between both home and BPs measured in VAGLAHS demonstrated that any difference was not due to variability in the measurement devices. Previous studies have demonstrated that home BPs are better indicators of cardiovascular risk than office BP.⁸

Despite lack of statistical significance, home BPs were lower than routine, which suggests that they still may be more reliable than routine office measurements. Definitive conclusions regarding the accuracy of the home BPs in the present study cannot be drawn due to the small sample size (n = 13). Further exploration with comparisons to ambulatory BP monitoring could yield more information on accuracy of home BP monitoring.

In this study’s cohort of older veterans, the average BMI was between 25 and 30 (overweight), which is a risk factor for hypertension.¹⁷ Every participant with hypertension was taking at least 1 antihypertensive medication and being actively managed. In this study, the authors accounted for other medications that may affect BP, such as α blockers used in patients with benign prostatic hyperplasia.¹⁸ These could have potential elevating or lowering effects on BP measurements.

An issue in this study was the lack of adherence to home BP monitoring. Many patients forgot to bring in their records or to measure their BPs at home. The difficulties highlight real-life issues. Clinicians often request that patients monitor their BP at home, but few may actually remember, let alone keep diligent records. There are many barriers between measuring and reporting home BPs, which may prevent the usefulness of monitoring BP at home.

Limitations

There were several limitations to the study. There was no specific protocol for the routine method of BP measurement, as it was intended to simulate the haphazard nature of office measurements. However, this approach limits its reproducibility. For home BP monitoring, it would have been ideal to provide the same calibrated, automated BP device to each participant. This study of older veterans may not be applicable to the general population. Finally, the relatively small number of participants in the study (n = 30) may have limited power in drawing definitive conclusions.

Future Directions

For future studies, comparing the standardized method to ambulatory BP monitoring would provide more information on accuracy. In addition, the authors would like to evaluate the effect of exercise on BP measurements in the different settings: home, standardized, and routine methods.

Seventy-five percent of adults aged >75 years have hypertension.^1-3 According to the Joint National Commission 8 (JNC 8), the recommended target blood pressure (BP) is < 150/80 mm Hg for adults aged > 60 years.⁴ In 2016 the Systolic Blood Pressure Intervention Trial (SPRINT) suggested that more aggressive BP control with a goal of < 120/80 mm Hg reduced rates of cardiovascular disease and lowered the risk of death in adults aged > 50 years with hypertension.⁵ It is anticipated that as a result of the landmark SPRINT results, clinicians may attempt to treat hypertension more intensely in older patients with an increased risk of adverse consequences if BPs are not appropriately measured.

There is a standardized protocol for BP measurement, but these recommendations typically are not followed in routine office visits.^6,7 Some studies have noted that home BP measurement may be more accurate than office measurement.⁸ However, clinicians may not always trust the accuracy of home BP readings, and many patients are not adherent with home measurement. As a result, physicians usually manage hypertension in older patients based on office readings, though it is likely that most office measurements do not follow protocol on proper measurement. Office measurements have been noted to be inaccurate with high likelihood of overestimating or underestimating BP control.⁹

Office BP measurements demonstrate poor correlation with home measurements and have not been shown to be as good of a predictor for target organ damage or long-term cardiovascular outcomes compared with that of home measurements.^10,11 Although there have been studies comparing home and office BP measurements and comparing office and ambulatory BP measurement, no literature has been found that reports on the difference between routine office and standardized measurement of BP.^9,12-14

This study seeks to identify the magnitude of difference among BP measured according to a standardized protocol, routine clinical, and home BP. The authors hypothesized that there would be a significant, clinically relevant difference among the 3 BP measurement methods, especially between the routine office and standardized office measurements. This study has implications for implementing intensive treatment of hypertension based on office measurements.

Methods

Participants included 30 male veterans aged > 65 years who were actively participating in the Gerofit program at the VA Greater Los Angeles Healthcare System (VAGLAHS). The Gerofit program is a model clinical demonstration exercise and health promotion program targeting older and veterans at risk for falls or institutionalization. Gerofit was established in 1987 at the Durham VA Health System and successfully implemented in 2014 at VAGLAHS. Supervised exercise is offered 3 times per week and consists of individually tailored exercises aimed at reducing functional deficits that are identified and monitored by an initial and quarterly functional assessment. Blood pressures are checked routinely once a week as a part of the program. Gerofit was reviewed and approved by the institutional review board at VAGLAHS as a quality improvement/quality assurance project.

Data

Routine office and standardized protocol measurements were obtained by a single CasMED 740 (Branford, CT) automated BP machine and were conducted separately on different days. The CasMED 740 machine was not otherwise calibrated; however, a one-time correlation was performed between the CasMED 740 and the home BP monitor for each participant, when it was brought to VAGLAHS. Two measurements were made with the CasMed 740 automated BP machine on the arm that gave the higher BP reading throughout the standardized and routine protocol. Two subsequent measurements were made with the participant’s home automated BP cuff. Averages for the CasMED 740 and the home BP monitoring device were compared and assessed for significance by paired t test. No rest was scheduled prior to the first measurement, but there was a 1-minute rest after each subsequent measurement.

Mean values (SD) were used for participant characteristics and mean values (standard error [SE]) were used for BP measurements. Data were analyzed using Microsoft Excel (Redmond, WA) and GraphPad Prism version 7.03 (San Diego, CA). T tests were used for analysis of home BP measurements due to low sample size. Values of P < .05 were considered to be statistically significant.

Routine office protocol. Automated BP was measured to mimic routine office visits. Upon arrival, participants sat down, and the BP cuff was placed around their arm. Any rest before a measurement was incidental and not intentionally structured. Appropriate cuff size was determined by visual estimation of arm circumference. Only 1 measurement was made unless BP was > 150/90 mm Hg, in which case a repeat measurement was made after 2 to 4 minutes of rest. The BP was then determined based on the average of 2 or more readings. The BPs were recorded by hand in a weekly log. Participants had at least 12 weeks of BP readings measured by the routine method, and these BPs were averaged over 12 weeks to yield their average routine measured BP.

Standardized protocol. Automated BP was measured according to the 2015 USPSTF Guidelines and Look AHEAD trial protocol.^7,15 A participant’s arm circumference was measured, and appropriate cuff size was determined. The participant rested quietly in a chair for at least 5 minutes with feet flat on the floor and back supported. The cuff was snugly placed 2 to 3 cm above the antecubital fossa, and the arm was supported at the level of the right atrium during the measurement. Blood pressure was determined using the mean of 4 automated cuff readings, 2 on each arm, taken 1 minute apart. Participants did not necessarily have their BP measured by the standardized method immediately following the routine method but all measurements were performed during the same 12-week time period.

Home blood pressure protocol. Participants were given instructions according to the American Heart Association (AHA) recommendations for measuring home BP. Patients were instructed to use a calibrated, automated arm BP cuff. Home BP machines were not provided in advance, and each individual’s BP machine was not calibrated. They also were instructed to rest at least 5 minutes before measuring their BP. The mean home BP was determined by the cumulative average of 3 readings in the morning and evening, taken 1 minute between each reading, for a total of 6 readings/d. Participants recorded home BPs for 2 weeks before submitting their readings. Each participant affirmed clear understanding of how to measure BP by correctly demonstrating placement of the cuff 1 time under supervision.

Results

Thirty veterans aged > 65 years participated in the study. The average age (SD) was 82.7 (9.3) years. The average BMI (SD) was overweight at 29.7 kg/m² (5.7). Most (87.6%) of the study participants had been diagnosed with hypertension prior to the study, and no new diagnoses were made as a result of the study. 

Both systolic BP (SBP) and diastolic BPs (DBP) measured by the standardized method were significantly lower than those by the routine method (P < .01 and P < .01, respectively) (Figure 1). 

To determine the accuracy of the home BP monitors, the average routine VAGLAHS BP measure was compared with home BP results. For SBPs, there was a significant correlation coefficient of 0.91 (P < .01). 

Discussion

The present study demonstrated that standardized measurements of BP were lower than that of the routine method used in most office settings. These results suggest that there could be a risk of overtreatment for some patients those of whose results are higher than the SPRINT BP target of < 120/80 mm Hg. Clinicians might be treating BPs that are elevated due to improper measurement, which can lead to deleterious consequences in older adults, such as syncope and falls.¹⁶

Each participant exhibited a significantly lower BP reading with the standardized method than the routine method. The 20-point decrease in SBP and 10-point decrease in DBP are clinically significant. The routine method of measurement was intended to simulate BP measurement in outpatient settings. There is usually little time structured for rest, and because the protocol established by the AHA and other professional organizations is time consuming, it usually is not strictly followed. With guidelines proposed by JNC 8 and new findings from SPRINT, the method of BP readings should be reviewed in all clinical settings.

While changes in BP management are not necessarily immediate, the differences in recommendations proposed by SPRINT and JNC 8 can lead to confusion regarding how intensely to treat BP. These recommendations guide clinical practice, but clinicians’ best judgment ultimately determines BP management. Physicians who utilize routine office measurements likely rely on BP readings that are higher on average than are readings done under proper conditions. This leads to the prospect of overtreatment, where physicians attempt to control hypertension too aggressively, potentially leading to orthostatic hypotension, syncope, and increased risk for falls.¹⁶ With findings from SPRINT recommending even lower BPs than that by JNC 8, overtreatment risk becomes especially relevant. While BP protocol was strictly followed in SPRINT, some clinicians may not necessarily follow the same fastidious protocol.

The average differences between the home and standardized BPs were not statistically significant possibly due to the small sample size in the home BP measurements; however, the difference might represent some clinical relevance. There was a 15-point difference in SBP results between home (129 mm Hg) and standardized (115 mm Hg) measures. There also was a difference in DBP between home (69 mm Hg) and standardized (62 mm Hg) results. The close correlation between both home and BPs measured in VAGLAHS demonstrated that any difference was not due to variability in the measurement devices. Previous studies have demonstrated that home BPs are better indicators of cardiovascular risk than office BP.⁸

Despite lack of statistical significance, home BPs were lower than routine, which suggests that they still may be more reliable than routine office measurements. Definitive conclusions regarding the accuracy of the home BPs in the present study cannot be drawn due to the small sample size (n = 13). Further exploration with comparisons to ambulatory BP monitoring could yield more information on accuracy of home BP monitoring.

In this study’s cohort of older veterans, the average BMI was between 25 and 30 (overweight), which is a risk factor for hypertension.¹⁷ Every participant with hypertension was taking at least 1 antihypertensive medication and being actively managed. In this study, the authors accounted for other medications that may affect BP, such as α blockers used in patients with benign prostatic hyperplasia.¹⁸ These could have potential elevating or lowering effects on BP measurements.

An issue in this study was the lack of adherence to home BP monitoring. Many patients forgot to bring in their records or to measure their BPs at home. The difficulties highlight real-life issues. Clinicians often request that patients monitor their BP at home, but few may actually remember, let alone keep diligent records. There are many barriers between measuring and reporting home BPs, which may prevent the usefulness of monitoring BP at home.

Limitations

There were several limitations to the study. There was no specific protocol for the routine method of BP measurement, as it was intended to simulate the haphazard nature of office measurements. However, this approach limits its reproducibility. For home BP monitoring, it would have been ideal to provide the same calibrated, automated BP device to each participant. This study of older veterans may not be applicable to the general population. Finally, the relatively small number of participants in the study (n = 30) may have limited power in drawing definitive conclusions.

Future Directions

For future studies, comparing the standardized method to ambulatory BP monitoring would provide more information on accuracy. In addition, the authors would like to evaluate the effect of exercise on BP measurements in the different settings: home, standardized, and routine methods.

Seventy-five percent of adults aged >75 years have hypertension.^1-3 According to the Joint National Commission 8 (JNC 8), the recommended target blood pressure (BP) is < 150/80 mm Hg for adults aged > 60 years.⁴ In 2016 the Systolic Blood Pressure Intervention Trial (SPRINT) suggested that more aggressive BP control with a goal of < 120/80 mm Hg reduced rates of cardiovascular disease and lowered the risk of death in adults aged > 50 years with hypertension.⁵ It is anticipated that as a result of the landmark SPRINT results, clinicians may attempt to treat hypertension more intensely in older patients with an increased risk of adverse consequences if BPs are not appropriately measured.

There is a standardized protocol for BP measurement, but these recommendations typically are not followed in routine office visits.^6,7 Some studies have noted that home BP measurement may be more accurate than office measurement.⁸ However, clinicians may not always trust the accuracy of home BP readings, and many patients are not adherent with home measurement. As a result, physicians usually manage hypertension in older patients based on office readings, though it is likely that most office measurements do not follow protocol on proper measurement. Office measurements have been noted to be inaccurate with high likelihood of overestimating or underestimating BP control.⁹

Office BP measurements demonstrate poor correlation with home measurements and have not been shown to be as good of a predictor for target organ damage or long-term cardiovascular outcomes compared with that of home measurements.^10,11 Although there have been studies comparing home and office BP measurements and comparing office and ambulatory BP measurement, no literature has been found that reports on the difference between routine office and standardized measurement of BP.^9,12-14

This study seeks to identify the magnitude of difference among BP measured according to a standardized protocol, routine clinical, and home BP. The authors hypothesized that there would be a significant, clinically relevant difference among the 3 BP measurement methods, especially between the routine office and standardized office measurements. This study has implications for implementing intensive treatment of hypertension based on office measurements.

Methods

Participants included 30 male veterans aged > 65 years who were actively participating in the Gerofit program at the VA Greater Los Angeles Healthcare System (VAGLAHS). The Gerofit program is a model clinical demonstration exercise and health promotion program targeting older and veterans at risk for falls or institutionalization. Gerofit was established in 1987 at the Durham VA Health System and successfully implemented in 2014 at VAGLAHS. Supervised exercise is offered 3 times per week and consists of individually tailored exercises aimed at reducing functional deficits that are identified and monitored by an initial and quarterly functional assessment. Blood pressures are checked routinely once a week as a part of the program. Gerofit was reviewed and approved by the institutional review board at VAGLAHS as a quality improvement/quality assurance project.

Data

Routine office and standardized protocol measurements were obtained by a single CasMED 740 (Branford, CT) automated BP machine and were conducted separately on different days. The CasMED 740 machine was not otherwise calibrated; however, a one-time correlation was performed between the CasMED 740 and the home BP monitor for each participant, when it was brought to VAGLAHS. Two measurements were made with the CasMed 740 automated BP machine on the arm that gave the higher BP reading throughout the standardized and routine protocol. Two subsequent measurements were made with the participant’s home automated BP cuff. Averages for the CasMED 740 and the home BP monitoring device were compared and assessed for significance by paired t test. No rest was scheduled prior to the first measurement, but there was a 1-minute rest after each subsequent measurement.

Mean values (SD) were used for participant characteristics and mean values (standard error [SE]) were used for BP measurements. Data were analyzed using Microsoft Excel (Redmond, WA) and GraphPad Prism version 7.03 (San Diego, CA). T tests were used for analysis of home BP measurements due to low sample size. Values of P < .05 were considered to be statistically significant.

Routine office protocol. Automated BP was measured to mimic routine office visits. Upon arrival, participants sat down, and the BP cuff was placed around their arm. Any rest before a measurement was incidental and not intentionally structured. Appropriate cuff size was determined by visual estimation of arm circumference. Only 1 measurement was made unless BP was > 150/90 mm Hg, in which case a repeat measurement was made after 2 to 4 minutes of rest. The BP was then determined based on the average of 2 or more readings. The BPs were recorded by hand in a weekly log. Participants had at least 12 weeks of BP readings measured by the routine method, and these BPs were averaged over 12 weeks to yield their average routine measured BP.

Standardized protocol. Automated BP was measured according to the 2015 USPSTF Guidelines and Look AHEAD trial protocol.^7,15 A participant’s arm circumference was measured, and appropriate cuff size was determined. The participant rested quietly in a chair for at least 5 minutes with feet flat on the floor and back supported. The cuff was snugly placed 2 to 3 cm above the antecubital fossa, and the arm was supported at the level of the right atrium during the measurement. Blood pressure was determined using the mean of 4 automated cuff readings, 2 on each arm, taken 1 minute apart. Participants did not necessarily have their BP measured by the standardized method immediately following the routine method but all measurements were performed during the same 12-week time period.

Home blood pressure protocol. Participants were given instructions according to the American Heart Association (AHA) recommendations for measuring home BP. Patients were instructed to use a calibrated, automated arm BP cuff. Home BP machines were not provided in advance, and each individual’s BP machine was not calibrated. They also were instructed to rest at least 5 minutes before measuring their BP. The mean home BP was determined by the cumulative average of 3 readings in the morning and evening, taken 1 minute between each reading, for a total of 6 readings/d. Participants recorded home BPs for 2 weeks before submitting their readings. Each participant affirmed clear understanding of how to measure BP by correctly demonstrating placement of the cuff 1 time under supervision.

Results

Thirty veterans aged > 65 years participated in the study. The average age (SD) was 82.7 (9.3) years. The average BMI (SD) was overweight at 29.7 kg/m² (5.7). Most (87.6%) of the study participants had been diagnosed with hypertension prior to the study, and no new diagnoses were made as a result of the study. 

Both systolic BP (SBP) and diastolic BPs (DBP) measured by the standardized method were significantly lower than those by the routine method (P < .01 and P < .01, respectively) (Figure 1). 

To determine the accuracy of the home BP monitors, the average routine VAGLAHS BP measure was compared with home BP results. For SBPs, there was a significant correlation coefficient of 0.91 (P < .01). 

Discussion

The present study demonstrated that standardized measurements of BP were lower than that of the routine method used in most office settings. These results suggest that there could be a risk of overtreatment for some patients those of whose results are higher than the SPRINT BP target of < 120/80 mm Hg. Clinicians might be treating BPs that are elevated due to improper measurement, which can lead to deleterious consequences in older adults, such as syncope and falls.¹⁶

Each participant exhibited a significantly lower BP reading with the standardized method than the routine method. The 20-point decrease in SBP and 10-point decrease in DBP are clinically significant. The routine method of measurement was intended to simulate BP measurement in outpatient settings. There is usually little time structured for rest, and because the protocol established by the AHA and other professional organizations is time consuming, it usually is not strictly followed. With guidelines proposed by JNC 8 and new findings from SPRINT, the method of BP readings should be reviewed in all clinical settings.

While changes in BP management are not necessarily immediate, the differences in recommendations proposed by SPRINT and JNC 8 can lead to confusion regarding how intensely to treat BP. These recommendations guide clinical practice, but clinicians’ best judgment ultimately determines BP management. Physicians who utilize routine office measurements likely rely on BP readings that are higher on average than are readings done under proper conditions. This leads to the prospect of overtreatment, where physicians attempt to control hypertension too aggressively, potentially leading to orthostatic hypotension, syncope, and increased risk for falls.¹⁶ With findings from SPRINT recommending even lower BPs than that by JNC 8, overtreatment risk becomes especially relevant. While BP protocol was strictly followed in SPRINT, some clinicians may not necessarily follow the same fastidious protocol.

The average differences between the home and standardized BPs were not statistically significant possibly due to the small sample size in the home BP measurements; however, the difference might represent some clinical relevance. There was a 15-point difference in SBP results between home (129 mm Hg) and standardized (115 mm Hg) measures. There also was a difference in DBP between home (69 mm Hg) and standardized (62 mm Hg) results. The close correlation between both home and BPs measured in VAGLAHS demonstrated that any difference was not due to variability in the measurement devices. Previous studies have demonstrated that home BPs are better indicators of cardiovascular risk than office BP.⁸

Despite lack of statistical significance, home BPs were lower than routine, which suggests that they still may be more reliable than routine office measurements. Definitive conclusions regarding the accuracy of the home BPs in the present study cannot be drawn due to the small sample size (n = 13). Further exploration with comparisons to ambulatory BP monitoring could yield more information on accuracy of home BP monitoring.

In this study’s cohort of older veterans, the average BMI was between 25 and 30 (overweight), which is a risk factor for hypertension.¹⁷ Every participant with hypertension was taking at least 1 antihypertensive medication and being actively managed. In this study, the authors accounted for other medications that may affect BP, such as α blockers used in patients with benign prostatic hyperplasia.¹⁸ These could have potential elevating or lowering effects on BP measurements.

An issue in this study was the lack of adherence to home BP monitoring. Many patients forgot to bring in their records or to measure their BPs at home. The difficulties highlight real-life issues. Clinicians often request that patients monitor their BP at home, but few may actually remember, let alone keep diligent records. There are many barriers between measuring and reporting home BPs, which may prevent the usefulness of monitoring BP at home.

Limitations

There were several limitations to the study. There was no specific protocol for the routine method of BP measurement, as it was intended to simulate the haphazard nature of office measurements. However, this approach limits its reproducibility. For home BP monitoring, it would have been ideal to provide the same calibrated, automated BP device to each participant. This study of older veterans may not be applicable to the general population. Finally, the relatively small number of participants in the study (n = 30) may have limited power in drawing definitive conclusions.

Future Directions

For future studies, comparing the standardized method to ambulatory BP monitoring would provide more information on accuracy. In addition, the authors would like to evaluate the effect of exercise on BP measurements in the different settings: home, standardized, and routine methods.

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US. 

Photo courtesy of GSK

Eltrombopag (Promacta®) in combination with standard immunosuppressive therapy (IST) has received priority review designation from the US Food and Drug Administration (FDA) for first-line treatment of severe aplastic anemia (SAA).

The drug is already approved for SAA in the refractory setting for patients who have had an insufficient response to IST.

And it is approved for adults and children with chronic immune thrombocytopenia (ITP) who are refractory to other treatments and for patients with chronic hepatitis C virus infection who are thrombocytopenic.

Eltrombopag, an oral thrombopoietin receptor agonist, had received breakthrough therapy designation from the FDA earlier this year for use in combination with IST as first-line treatment of SAA.

The priority review designation for the agent as a first-line treatment for SAA is supported by data from a phase 1/2 trial published in NEJM in April 2017 and subsequent data on file with Novartis.

The FDA intends to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Trial data

Ninety-two patients with previously untreated SAA were enrolled on the trial and received IST and eltrombopag in 3 different cohorts.

Cohorts varied by start day of eltrombopag and duration of eltrombopag therapy. Patients in cohort 1 received eltrombopag from day 14 to 6 months. Patients in cohort 2 received the drug from day 14 to 3 months. And patients in cohort 3 received eltrombopag from day 1 to 6 months.

The overall response rate (ORR) at 6 months was 80% (cohort 1), 87% (cohort 2), and 94% (cohort 3).

The complete response rate at 6 months was 33%, 26%, and 58% in the 3 cohorts, respectively.

At a median follow-up of 2 years, the overall survival rate was 97%.

In the corporate announcement of the priority review designation, Novartis reported an ORR of 85% at 6 months.

Adverse events included transient elevations in liver enzyme levels (7 patients) and 2 severe adverse events—grades 2 and 3 cutaneous eruption—related to eltrombopag that resulted in patients stopping the drug.

Eltrombopag is marketed as Revolade in countries outside the US.