Use of a clinical decision tree predicted antibiotic resistance in sepsis patients infected with gram-negative bacteria, based on data from 1,618 patients.

Increasing rates of bacterial resistance have “contributed to the unwarranted empiric administration of broad-spectrum antibiotics, further promoting resistance emergence across microbial species,” said M. Cristina Vazquez Guillamet, MD, of the University of New Mexico, Albuquerque, and her colleagues (Clin Infect Dis. cix612. 2017 Jul 10. doi: 10.1093/cid/cix612).

The researchers identified adults with sepsis or septic shock caused by bloodstream infections who were treated at a single center between 2008 and 2015. They developed clinical decision trees using the CHAID algorithm (Chi squared Automatic Interaction Detection) to analyze risk factors for resistance associated with three antibiotics: piperacillin-tazobactam (PT), cefepime (CE), and meropenem (ME).

Overall, resistance rates to PT, CE, and ME were 29%, 22%, and 9%, respectively, and 6.6% of the isolates were resistant to all three antibiotics.

Factors associated with increased resistance risk included residence in a nursing home, transfer from an outside hospital, and prior antibiotics use. Resistance to ME was associated with infection with Pseudomonas or Acinetobacter spp, the researchers noted, and resistance to PT was associated with central nervous system and central venous catheter infections.

Clinical decision trees were able to separate patients at low risk for resistance to PT and CE, as well as those with a risk greater than 30% of resistance to PT, CE, or ME. “We also found good overall agreement between the accuracies of the [multivariable logistic regression] models and the decision tree analyses for predicting antibiotic resistance,” the researchers said.

The findings were limited by several factors, including the use of data from a single center and incomplete reporting of previous antibiotic exposure, the researchers noted. However, the results “provide a framework for how empiric antibiotics can be tailored according to decision tree patient clusters,” they said.

Combining user-friendly clinical decision trees and multivariable logistic regression models may offer the best opportunities for hospitals to derive local models to help with antimicrobial prescription.

The researchers had no financial conflicts to disclose.

[email protected]

Use of a clinical decision tree predicted antibiotic resistance in sepsis patients infected with gram-negative bacteria, based on data from 1,618 patients.

Increasing rates of bacterial resistance have “contributed to the unwarranted empiric administration of broad-spectrum antibiotics, further promoting resistance emergence across microbial species,” said M. Cristina Vazquez Guillamet, MD, of the University of New Mexico, Albuquerque, and her colleagues (Clin Infect Dis. cix612. 2017 Jul 10. doi: 10.1093/cid/cix612).

The researchers identified adults with sepsis or septic shock caused by bloodstream infections who were treated at a single center between 2008 and 2015. They developed clinical decision trees using the CHAID algorithm (Chi squared Automatic Interaction Detection) to analyze risk factors for resistance associated with three antibiotics: piperacillin-tazobactam (PT), cefepime (CE), and meropenem (ME).

Overall, resistance rates to PT, CE, and ME were 29%, 22%, and 9%, respectively, and 6.6% of the isolates were resistant to all three antibiotics.

Factors associated with increased resistance risk included residence in a nursing home, transfer from an outside hospital, and prior antibiotics use. Resistance to ME was associated with infection with Pseudomonas or Acinetobacter spp, the researchers noted, and resistance to PT was associated with central nervous system and central venous catheter infections.

Clinical decision trees were able to separate patients at low risk for resistance to PT and CE, as well as those with a risk greater than 30% of resistance to PT, CE, or ME. “We also found good overall agreement between the accuracies of the [multivariable logistic regression] models and the decision tree analyses for predicting antibiotic resistance,” the researchers said.

The findings were limited by several factors, including the use of data from a single center and incomplete reporting of previous antibiotic exposure, the researchers noted. However, the results “provide a framework for how empiric antibiotics can be tailored according to decision tree patient clusters,” they said.

Combining user-friendly clinical decision trees and multivariable logistic regression models may offer the best opportunities for hospitals to derive local models to help with antimicrobial prescription.

The researchers had no financial conflicts to disclose.

[email protected]

Use of a clinical decision tree predicted antibiotic resistance in sepsis patients infected with gram-negative bacteria, based on data from 1,618 patients.

Increasing rates of bacterial resistance have “contributed to the unwarranted empiric administration of broad-spectrum antibiotics, further promoting resistance emergence across microbial species,” said M. Cristina Vazquez Guillamet, MD, of the University of New Mexico, Albuquerque, and her colleagues (Clin Infect Dis. cix612. 2017 Jul 10. doi: 10.1093/cid/cix612).

The researchers identified adults with sepsis or septic shock caused by bloodstream infections who were treated at a single center between 2008 and 2015. They developed clinical decision trees using the CHAID algorithm (Chi squared Automatic Interaction Detection) to analyze risk factors for resistance associated with three antibiotics: piperacillin-tazobactam (PT), cefepime (CE), and meropenem (ME).

Overall, resistance rates to PT, CE, and ME were 29%, 22%, and 9%, respectively, and 6.6% of the isolates were resistant to all three antibiotics.

Factors associated with increased resistance risk included residence in a nursing home, transfer from an outside hospital, and prior antibiotics use. Resistance to ME was associated with infection with Pseudomonas or Acinetobacter spp, the researchers noted, and resistance to PT was associated with central nervous system and central venous catheter infections.

Clinical decision trees were able to separate patients at low risk for resistance to PT and CE, as well as those with a risk greater than 30% of resistance to PT, CE, or ME. “We also found good overall agreement between the accuracies of the [multivariable logistic regression] models and the decision tree analyses for predicting antibiotic resistance,” the researchers said.

The findings were limited by several factors, including the use of data from a single center and incomplete reporting of previous antibiotic exposure, the researchers noted. However, the results “provide a framework for how empiric antibiotics can be tailored according to decision tree patient clusters,” they said.

Combining user-friendly clinical decision trees and multivariable logistic regression models may offer the best opportunities for hospitals to derive local models to help with antimicrobial prescription.

The researchers had no financial conflicts to disclose.

[email protected]

The VA is working to implement Government Accountability Office (GAO) recommendations on improving efficiency and reporting of health care providers, according to Carolyn Clancy, MD, deputy under secretary for organizational excellence at the VHA. Dr. Clancy told members of the House Committee on Veterans’ Affairs that the “VA concurred with GAO’s recommendations and is already working to complete them.”

In July 2017, the GAO issued the report “Improvements Needed in Data and Monitoring of Clinical Productivity and Efficiency.” The report found that “VA’s productivity metrics and efficiency models may not provide complete and accurate information on provider productivity and VAMC efficiency.” Based on its findings, the GAO recommended that the “VA develop a policy requiring VAMCs to monitor and improve clinical inefficiency through a standard process, such as establishing performance standards based on VA’s efficiency models, and develop remediation plans for addressing clinical inefficiencies.” The GAO also made 4 specific recommendations:

1. Expand existing productivity metrics to track the productivity of all providers of care to veterans, including contract physicians and some advanced practice providers;
2. Ensure the accuracy of underlying staffing and workload data by, training all providers on coding clinical procedures;
3. Create a policy for all VAMCs to monitor and improve clinical efficiency by establishing performance standards based on VA’s efficiency models and developing a remediation plan for addressing clinical inefficiency; and
4. Establish an ongoing process to systematically review VAMCs and ensure that VAMCs and VISNs are implementing those plans and addressing low clinical productivity and inefficiency.

In her testimony, Dr. Clancy took pains to reassure the House committee that she agreed with the GAO recommendations. “VA appreciates our colleagues at GAO’s efforts and the efforts of others to improve clinical efficiency and productivity,” she told the panel. “Mr. Chairman, I am proud of the health care our employees provide to our nation’s veterans. Together with Congress, I look forward to making sure that VA will be a good steward of taxpayer dollars while providing this care in a productive and efficient manner.”

Dr. Clancy explained to the Committee that the VA will expand the use of some of its measures, such as the Specialty Productivity-Access Report and Quadrant (SPARQ) tool. In addition, Dr. Clancy pledged that the VA would take up training in clinical coding for health care providers as well as an effort to improve the efficiency of specialty providers. “We have also undertaken a comprehensive education and communication plan about the specialty physician productivity and staffing standards,” she told the committee. “Our specialty physicians are committed to demonstrating and improving specialty productivity and access.”

In addition, Dr. Clancy insisted that plans to improve clinical efficiency must be developed at each VAMC and that remediation plans would be tracked at both the facility and VISN. The central office will “review the progress VAMCs are making on the remediation plans for addressing low clinical productivity twice a year with the VISN,” she said. The expected completion date for this will be March 2018.

The VA is working to implement Government Accountability Office (GAO) recommendations on improving efficiency and reporting of health care providers, according to Carolyn Clancy, MD, deputy under secretary for organizational excellence at the VHA. Dr. Clancy told members of the House Committee on Veterans’ Affairs that the “VA concurred with GAO’s recommendations and is already working to complete them.”

In July 2017, the GAO issued the report “Improvements Needed in Data and Monitoring of Clinical Productivity and Efficiency.” The report found that “VA’s productivity metrics and efficiency models may not provide complete and accurate information on provider productivity and VAMC efficiency.” Based on its findings, the GAO recommended that the “VA develop a policy requiring VAMCs to monitor and improve clinical inefficiency through a standard process, such as establishing performance standards based on VA’s efficiency models, and develop remediation plans for addressing clinical inefficiencies.” The GAO also made 4 specific recommendations:

1. Expand existing productivity metrics to track the productivity of all providers of care to veterans, including contract physicians and some advanced practice providers;
2. Ensure the accuracy of underlying staffing and workload data by, training all providers on coding clinical procedures;
3. Create a policy for all VAMCs to monitor and improve clinical efficiency by establishing performance standards based on VA’s efficiency models and developing a remediation plan for addressing clinical inefficiency; and
4. Establish an ongoing process to systematically review VAMCs and ensure that VAMCs and VISNs are implementing those plans and addressing low clinical productivity and inefficiency.

In her testimony, Dr. Clancy took pains to reassure the House committee that she agreed with the GAO recommendations. “VA appreciates our colleagues at GAO’s efforts and the efforts of others to improve clinical efficiency and productivity,” she told the panel. “Mr. Chairman, I am proud of the health care our employees provide to our nation’s veterans. Together with Congress, I look forward to making sure that VA will be a good steward of taxpayer dollars while providing this care in a productive and efficient manner.”

Dr. Clancy explained to the Committee that the VA will expand the use of some of its measures, such as the Specialty Productivity-Access Report and Quadrant (SPARQ) tool. In addition, Dr. Clancy pledged that the VA would take up training in clinical coding for health care providers as well as an effort to improve the efficiency of specialty providers. “We have also undertaken a comprehensive education and communication plan about the specialty physician productivity and staffing standards,” she told the committee. “Our specialty physicians are committed to demonstrating and improving specialty productivity and access.”

In addition, Dr. Clancy insisted that plans to improve clinical efficiency must be developed at each VAMC and that remediation plans would be tracked at both the facility and VISN. The central office will “review the progress VAMCs are making on the remediation plans for addressing low clinical productivity twice a year with the VISN,” she said. The expected completion date for this will be March 2018.

The VA is working to implement Government Accountability Office (GAO) recommendations on improving efficiency and reporting of health care providers, according to Carolyn Clancy, MD, deputy under secretary for organizational excellence at the VHA. Dr. Clancy told members of the House Committee on Veterans’ Affairs that the “VA concurred with GAO’s recommendations and is already working to complete them.”

In July 2017, the GAO issued the report “Improvements Needed in Data and Monitoring of Clinical Productivity and Efficiency.” The report found that “VA’s productivity metrics and efficiency models may not provide complete and accurate information on provider productivity and VAMC efficiency.” Based on its findings, the GAO recommended that the “VA develop a policy requiring VAMCs to monitor and improve clinical inefficiency through a standard process, such as establishing performance standards based on VA’s efficiency models, and develop remediation plans for addressing clinical inefficiencies.” The GAO also made 4 specific recommendations:

1. Expand existing productivity metrics to track the productivity of all providers of care to veterans, including contract physicians and some advanced practice providers;
2. Ensure the accuracy of underlying staffing and workload data by, training all providers on coding clinical procedures;
3. Create a policy for all VAMCs to monitor and improve clinical efficiency by establishing performance standards based on VA’s efficiency models and developing a remediation plan for addressing clinical inefficiency; and
4. Establish an ongoing process to systematically review VAMCs and ensure that VAMCs and VISNs are implementing those plans and addressing low clinical productivity and inefficiency.

In her testimony, Dr. Clancy took pains to reassure the House committee that she agreed with the GAO recommendations. “VA appreciates our colleagues at GAO’s efforts and the efforts of others to improve clinical efficiency and productivity,” she told the panel. “Mr. Chairman, I am proud of the health care our employees provide to our nation’s veterans. Together with Congress, I look forward to making sure that VA will be a good steward of taxpayer dollars while providing this care in a productive and efficient manner.”

Dr. Clancy explained to the Committee that the VA will expand the use of some of its measures, such as the Specialty Productivity-Access Report and Quadrant (SPARQ) tool. In addition, Dr. Clancy pledged that the VA would take up training in clinical coding for health care providers as well as an effort to improve the efficiency of specialty providers. “We have also undertaken a comprehensive education and communication plan about the specialty physician productivity and staffing standards,” she told the committee. “Our specialty physicians are committed to demonstrating and improving specialty productivity and access.”

In addition, Dr. Clancy insisted that plans to improve clinical efficiency must be developed at each VAMC and that remediation plans would be tracked at both the facility and VISN. The central office will “review the progress VAMCs are making on the remediation plans for addressing low clinical productivity twice a year with the VISN,” she said. The expected completion date for this will be March 2018.

A “detailed, patient-centered roadmap” for addressing the third leading cause of death in the U.S.—chronic obstructive pulmonary disease (COPD)—will provide a “cohesive tool” for health professionals, according to the National Heart, Lung, and Blood Institute (NHLBI). Together with federal and non-federal partners, NHLBI released the first-ever COPD National Action Plan in May at the American Thoracic Society International Conference in Washington, DC.

The plan was developed from comments shared at a “COPD Town Hall” by patients and their families, health care providers, academics, and industry representatives. It takes a unified approach identifying the specific work doctors, educators, researchers, federal agencies, patients, advocates, and the biomedical industry can do to make a difference, according to official at NHLBI.

An estimated 16 million Americans have COPD—and millions more may have it and not know. However COPD often is preventable and highly treatable, early diagnosis can lead to better outcomes. With that as the goal, the plan’s developers aim to:

• Empower patients, families, and caregivers to recognize and reduce the burden of COPD
• Equip health care professionals to provide comprehensive care to people with COPD
• Collect, analyze, report, and disseminate COPD data
• Increase and sustain COPD research
• Turn COPD recommendations into research and public health care actions

Involving patients and families has been “invaluable,” said James Kiley, PhD, director of NHLBI’s division of Lung Diseases. “The different perspectives brought by those who live these issues every day contributed to making this a clear, coordinated way forward for all stakeholders.”

A “detailed, patient-centered roadmap” for addressing the third leading cause of death in the U.S.—chronic obstructive pulmonary disease (COPD)—will provide a “cohesive tool” for health professionals, according to the National Heart, Lung, and Blood Institute (NHLBI). Together with federal and non-federal partners, NHLBI released the first-ever COPD National Action Plan in May at the American Thoracic Society International Conference in Washington, DC.

The plan was developed from comments shared at a “COPD Town Hall” by patients and their families, health care providers, academics, and industry representatives. It takes a unified approach identifying the specific work doctors, educators, researchers, federal agencies, patients, advocates, and the biomedical industry can do to make a difference, according to official at NHLBI.

An estimated 16 million Americans have COPD—and millions more may have it and not know. However COPD often is preventable and highly treatable, early diagnosis can lead to better outcomes. With that as the goal, the plan’s developers aim to:

• Empower patients, families, and caregivers to recognize and reduce the burden of COPD
• Equip health care professionals to provide comprehensive care to people with COPD
• Collect, analyze, report, and disseminate COPD data
• Increase and sustain COPD research
• Turn COPD recommendations into research and public health care actions

Involving patients and families has been “invaluable,” said James Kiley, PhD, director of NHLBI’s division of Lung Diseases. “The different perspectives brought by those who live these issues every day contributed to making this a clear, coordinated way forward for all stakeholders.”

A “detailed, patient-centered roadmap” for addressing the third leading cause of death in the U.S.—chronic obstructive pulmonary disease (COPD)—will provide a “cohesive tool” for health professionals, according to the National Heart, Lung, and Blood Institute (NHLBI). Together with federal and non-federal partners, NHLBI released the first-ever COPD National Action Plan in May at the American Thoracic Society International Conference in Washington, DC.

The plan was developed from comments shared at a “COPD Town Hall” by patients and their families, health care providers, academics, and industry representatives. It takes a unified approach identifying the specific work doctors, educators, researchers, federal agencies, patients, advocates, and the biomedical industry can do to make a difference, according to official at NHLBI.

An estimated 16 million Americans have COPD—and millions more may have it and not know. However COPD often is preventable and highly treatable, early diagnosis can lead to better outcomes. With that as the goal, the plan’s developers aim to:

• Empower patients, families, and caregivers to recognize and reduce the burden of COPD
• Equip health care professionals to provide comprehensive care to people with COPD
• Collect, analyze, report, and disseminate COPD data
• Increase and sustain COPD research
• Turn COPD recommendations into research and public health care actions

Involving patients and families has been “invaluable,” said James Kiley, PhD, director of NHLBI’s division of Lung Diseases. “The different perspectives brought by those who live these issues every day contributed to making this a clear, coordinated way forward for all stakeholders.”

Research Center

A chimeric antigen receptor (CAR) T-cell therapy is “highly effective” in high-risk patients with chronic lymphocytic leukemia (CLL), according to researchers.

The CD19 CAR T-cell therapy, JCAR014, produced an overall response rate of 71% and a complete response (CR) rate of 17% in a phase 1/2 trial of patients with relapsed/refractory CLL.

Eighty-three percent of patients experienced cytokine release syndrome (CRS), and 33% developed neurotoxicity. One patient died of CRS/neurotoxicity.

Researchers reported these results in The Journal of Clinical Oncology.

The study was supported by Juno Therapeutics, Life Science Discovery Fund, the Bezos Family, the University of British Columbia Clinical Investigator Program, and grants from the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.

The trial included 24 patients with relapsed or refractory CLL. The patients’ median age was 61 (range, 40-73), and they had received a median of 5 prior therapies (range, 3-9). Nineteen patients had progressed while on ibrutinib, and 3 could not tolerate the drug.

“It was not known whether CAR T cells could be used to treat these high-risk CLL patients,” said study author Cameron Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

“Our study shows that CD19 CAR T cells are a highly promising treatment for CLL patients who have failed ibrutinib.”

Treatment and safety

All 24 patients received lymphodepletion prior to JCAR014. Lymphodepleting regimens consisted of cyclophosphamide, fludarabine, or both.

Patients received JCAR014 at 1 of 3 dose levels—2 x 10⁵, 2 x 10⁶, or 2 x 10⁷ CAR T cells/kg.

Twenty patients (83%) developed CRS—18 with grade 1/2, 1 with grade 4, and 1 with grade 5 CRS.

Eight patients (33%) developed neurotoxicity, all of whom also had CRS. Five patients had grade 3 neurotoxicity, and 1 had grade 5 (same patient with grade 5 CRS).

Initial response

The overall response rate, according to IWCLL criteria, was 71%. Seventeen patients responded, 4 with CRs and 13 with partial responses (PRs).

One of the patients who achieved a CR had received a second dose of JCAR014, without lymphodepletion, 14 days after the first dose.

One of the patients with a PR initially had stable disease (SD) at the 4-week assessment but was in PR 8 weeks later.

Twenty-one patients had a bone marrow evaluation 4 weeks after treatment with JCAR014. Seventeen of these patients (81%) had no residual disease according to high-resolution flow cytometry.

The researchers also performed IGH sequencing of bone marrow in 12 patients with no residual disease by flow cytometry. Seven of these patients (58%) had no detectable malignant IGH sequences 4 weeks after receiving JCAR014.

Second dose

Six patients who had persistent disease or who relapsed after receiving JCAR014 received a second cycle of lymphodepletion and JCAR014 at the same dose (n=1) or a 10-fold higher dose (n=5).

Four of these patients developed CRS (2 grade 3 or higher), and 1 developed reversible neurotoxicity (grade 3).

Two patients achieved a CR and had no residual disease by flow cytometry or IGH sequencing.

Survival

Responders had significantly superior progression-free survival (PFS) and overall survival (OS) compared to non-responders.

The median PFS was 9.8 months in patients who achieved a CR, was not reached in those with a PR, and was 1.1 months in patients with progressive disease (PD) or SD (P=0.0068 for CR/PR vs SD/PD).

The median OS was not reached in patients who achieved a CR or a PR, but it was 11.2 months in patients with SD or PD (P=0.0011 for CR/PR vs SD/PD).

The researchers also found that IGH sequencing revealed patients with durable PFS.

The median PFS was not reached in patients with no malignant IGH sequences, but it was 8.5 months in IGH-positive patients (P=0.253). The median OS was not reached in either group (P=0.25).

Research Center

A chimeric antigen receptor (CAR) T-cell therapy is “highly effective” in high-risk patients with chronic lymphocytic leukemia (CLL), according to researchers.

The CD19 CAR T-cell therapy, JCAR014, produced an overall response rate of 71% and a complete response (CR) rate of 17% in a phase 1/2 trial of patients with relapsed/refractory CLL.

Eighty-three percent of patients experienced cytokine release syndrome (CRS), and 33% developed neurotoxicity. One patient died of CRS/neurotoxicity.

Researchers reported these results in The Journal of Clinical Oncology.

The study was supported by Juno Therapeutics, Life Science Discovery Fund, the Bezos Family, the University of British Columbia Clinical Investigator Program, and grants from the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.

The trial included 24 patients with relapsed or refractory CLL. The patients’ median age was 61 (range, 40-73), and they had received a median of 5 prior therapies (range, 3-9). Nineteen patients had progressed while on ibrutinib, and 3 could not tolerate the drug.

“It was not known whether CAR T cells could be used to treat these high-risk CLL patients,” said study author Cameron Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

“Our study shows that CD19 CAR T cells are a highly promising treatment for CLL patients who have failed ibrutinib.”

Treatment and safety

All 24 patients received lymphodepletion prior to JCAR014. Lymphodepleting regimens consisted of cyclophosphamide, fludarabine, or both.

Patients received JCAR014 at 1 of 3 dose levels—2 x 10⁵, 2 x 10⁶, or 2 x 10⁷ CAR T cells/kg.

Twenty patients (83%) developed CRS—18 with grade 1/2, 1 with grade 4, and 1 with grade 5 CRS.

Eight patients (33%) developed neurotoxicity, all of whom also had CRS. Five patients had grade 3 neurotoxicity, and 1 had grade 5 (same patient with grade 5 CRS).

Initial response

The overall response rate, according to IWCLL criteria, was 71%. Seventeen patients responded, 4 with CRs and 13 with partial responses (PRs).

One of the patients who achieved a CR had received a second dose of JCAR014, without lymphodepletion, 14 days after the first dose.

One of the patients with a PR initially had stable disease (SD) at the 4-week assessment but was in PR 8 weeks later.

Twenty-one patients had a bone marrow evaluation 4 weeks after treatment with JCAR014. Seventeen of these patients (81%) had no residual disease according to high-resolution flow cytometry.

The researchers also performed IGH sequencing of bone marrow in 12 patients with no residual disease by flow cytometry. Seven of these patients (58%) had no detectable malignant IGH sequences 4 weeks after receiving JCAR014.

Second dose

Six patients who had persistent disease or who relapsed after receiving JCAR014 received a second cycle of lymphodepletion and JCAR014 at the same dose (n=1) or a 10-fold higher dose (n=5).

Four of these patients developed CRS (2 grade 3 or higher), and 1 developed reversible neurotoxicity (grade 3).

Two patients achieved a CR and had no residual disease by flow cytometry or IGH sequencing.

Survival

Responders had significantly superior progression-free survival (PFS) and overall survival (OS) compared to non-responders.

The median PFS was 9.8 months in patients who achieved a CR, was not reached in those with a PR, and was 1.1 months in patients with progressive disease (PD) or SD (P=0.0068 for CR/PR vs SD/PD).

The median OS was not reached in patients who achieved a CR or a PR, but it was 11.2 months in patients with SD or PD (P=0.0011 for CR/PR vs SD/PD).

The researchers also found that IGH sequencing revealed patients with durable PFS.

The median PFS was not reached in patients with no malignant IGH sequences, but it was 8.5 months in IGH-positive patients (P=0.253). The median OS was not reached in either group (P=0.25).

Research Center

A chimeric antigen receptor (CAR) T-cell therapy is “highly effective” in high-risk patients with chronic lymphocytic leukemia (CLL), according to researchers.

The CD19 CAR T-cell therapy, JCAR014, produced an overall response rate of 71% and a complete response (CR) rate of 17% in a phase 1/2 trial of patients with relapsed/refractory CLL.

Eighty-three percent of patients experienced cytokine release syndrome (CRS), and 33% developed neurotoxicity. One patient died of CRS/neurotoxicity.

Researchers reported these results in The Journal of Clinical Oncology.

The study was supported by Juno Therapeutics, Life Science Discovery Fund, the Bezos Family, the University of British Columbia Clinical Investigator Program, and grants from the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.

The trial included 24 patients with relapsed or refractory CLL. The patients’ median age was 61 (range, 40-73), and they had received a median of 5 prior therapies (range, 3-9). Nineteen patients had progressed while on ibrutinib, and 3 could not tolerate the drug.

“It was not known whether CAR T cells could be used to treat these high-risk CLL patients,” said study author Cameron Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

“Our study shows that CD19 CAR T cells are a highly promising treatment for CLL patients who have failed ibrutinib.”

Treatment and safety

All 24 patients received lymphodepletion prior to JCAR014. Lymphodepleting regimens consisted of cyclophosphamide, fludarabine, or both.

Patients received JCAR014 at 1 of 3 dose levels—2 x 10⁵, 2 x 10⁶, or 2 x 10⁷ CAR T cells/kg.

Twenty patients (83%) developed CRS—18 with grade 1/2, 1 with grade 4, and 1 with grade 5 CRS.

Eight patients (33%) developed neurotoxicity, all of whom also had CRS. Five patients had grade 3 neurotoxicity, and 1 had grade 5 (same patient with grade 5 CRS).

Initial response

The overall response rate, according to IWCLL criteria, was 71%. Seventeen patients responded, 4 with CRs and 13 with partial responses (PRs).

One of the patients who achieved a CR had received a second dose of JCAR014, without lymphodepletion, 14 days after the first dose.

One of the patients with a PR initially had stable disease (SD) at the 4-week assessment but was in PR 8 weeks later.

Twenty-one patients had a bone marrow evaluation 4 weeks after treatment with JCAR014. Seventeen of these patients (81%) had no residual disease according to high-resolution flow cytometry.

The researchers also performed IGH sequencing of bone marrow in 12 patients with no residual disease by flow cytometry. Seven of these patients (58%) had no detectable malignant IGH sequences 4 weeks after receiving JCAR014.

Second dose

Six patients who had persistent disease or who relapsed after receiving JCAR014 received a second cycle of lymphodepletion and JCAR014 at the same dose (n=1) or a 10-fold higher dose (n=5).

Four of these patients developed CRS (2 grade 3 or higher), and 1 developed reversible neurotoxicity (grade 3).

Two patients achieved a CR and had no residual disease by flow cytometry or IGH sequencing.

Survival

Responders had significantly superior progression-free survival (PFS) and overall survival (OS) compared to non-responders.

The median PFS was 9.8 months in patients who achieved a CR, was not reached in those with a PR, and was 1.1 months in patients with progressive disease (PD) or SD (P=0.0068 for CR/PR vs SD/PD).

The median OS was not reached in patients who achieved a CR or a PR, but it was 11.2 months in patients with SD or PD (P=0.0011 for CR/PR vs SD/PD).

The researchers also found that IGH sequencing revealed patients with durable PFS.

The median PFS was not reached in patients with no malignant IGH sequences, but it was 8.5 months in IGH-positive patients (P=0.253). The median OS was not reached in either group (P=0.25).

Boehringer Ingelheim

BERLIN—Data from the GARFIELD-VTE registry showed that, in the first 6 months after a patient was diagnosed with venous thromboembolism (VTE), death was the most frequent major adverse outcome.

More than half of the deaths were related to cancer, with small percentages of patients dying from VTE complications and bleeding events.

GARFIELD-VTE is a prospective registry designed to provide insight into the management of VTE in everyday clinical practice.

Six-month results from the registry were presented in a poster at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress (PB 1196).

The GARFIELD-VTE registry has enrolled more than 10,000 patients with acute VTE—including deep vein thrombosis (DVT) and pulmonary embolism (PE)—from across 415 sites in 28 countries.

Alexander G. G. Turpie, MD, of McMaster University in Hamilton, Ontario, Canada, and his colleagues presented data on 10,315 patients with at least 6 months of follow-up.

Baseline characteristics

The patients’ median age was 60.2 (range, 46.2-71.7), and 49.9% were female. Most patients were white (69.3%), 19.6% were Asian, 4.4% were black, 0.6% were multiracial, 4.3% were classified as “other,” and 1.9% were of unknown race.

Six percent of patients had a family history of VTE (first-degree relatives), 15.1% had a prior episode of DVT and/or PE themselves, and 37.5% had at least 1 provoking factor for VTE.

Most patients (61.8%) had DVT alone, but 38.3% had PE with or without DVT.

The registry included patients with active cancer (9.1%), a history of cancer (10.7%), thrombophilia (2.9%), chronic immobilization (5.6%), heart failure (3.2%), and renal insufficiency (3.5%).

Outcomes

Over 6 months of follow-up, the following events were reported:

• Any bleeding—622 total bleeds or 13.6 per 100 person-years
• All-cause mortality—460 total deaths or 9.7 per 100 person-years
• Recurrent VTE—169 events or 3.6 per 100 person-years
• Major bleeding—106 events or 2.2 per 100 person-years
• Myocardial infarction—42 events or 0.9 per 100 person-years
• Stroke/transient ischemic attack—38 events or 0.8 per 100 person-years.

Nearly 5% of patients died (4.5%, n=460). More than half (54.3%, n=250) of these deaths were cancer-related.

Other causes of death included:

• Cardiac death—7.0% (n=32)
• PE—3.5% (n=16)
• Bleeding—3.3% (n=15)
• VTE complications—1.3% (n=6)
• Stroke—1.1%  (n=5)
• Other cause—17.8% (n=82)
• Unknown cause—11.7% (n=54).

Additional data from the GARFIELD-VTE registry were presented at ISTH 2017 as posters (PB 460 and PB 1188) and in an oral presentation (ASY 35.4). The next set of data from the registry is slated to be presented at the 2017 ASH Annual Meeting.

GARFIELD-VTE is supported by an unrestricted educational grant from Bayer AG. For further information on the registry, visit http://www.garfieldregistry.org.

Boehringer Ingelheim

BERLIN—Data from the GARFIELD-VTE registry showed that, in the first 6 months after a patient was diagnosed with venous thromboembolism (VTE), death was the most frequent major adverse outcome.

More than half of the deaths were related to cancer, with small percentages of patients dying from VTE complications and bleeding events.

GARFIELD-VTE is a prospective registry designed to provide insight into the management of VTE in everyday clinical practice.

Six-month results from the registry were presented in a poster at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress (PB 1196).

The GARFIELD-VTE registry has enrolled more than 10,000 patients with acute VTE—including deep vein thrombosis (DVT) and pulmonary embolism (PE)—from across 415 sites in 28 countries.

Alexander G. G. Turpie, MD, of McMaster University in Hamilton, Ontario, Canada, and his colleagues presented data on 10,315 patients with at least 6 months of follow-up.

Baseline characteristics

The patients’ median age was 60.2 (range, 46.2-71.7), and 49.9% were female. Most patients were white (69.3%), 19.6% were Asian, 4.4% were black, 0.6% were multiracial, 4.3% were classified as “other,” and 1.9% were of unknown race.

Six percent of patients had a family history of VTE (first-degree relatives), 15.1% had a prior episode of DVT and/or PE themselves, and 37.5% had at least 1 provoking factor for VTE.

Most patients (61.8%) had DVT alone, but 38.3% had PE with or without DVT.

The registry included patients with active cancer (9.1%), a history of cancer (10.7%), thrombophilia (2.9%), chronic immobilization (5.6%), heart failure (3.2%), and renal insufficiency (3.5%).

Outcomes

Over 6 months of follow-up, the following events were reported:

• Any bleeding—622 total bleeds or 13.6 per 100 person-years
• All-cause mortality—460 total deaths or 9.7 per 100 person-years
• Recurrent VTE—169 events or 3.6 per 100 person-years
• Major bleeding—106 events or 2.2 per 100 person-years
• Myocardial infarction—42 events or 0.9 per 100 person-years
• Stroke/transient ischemic attack—38 events or 0.8 per 100 person-years.

Nearly 5% of patients died (4.5%, n=460). More than half (54.3%, n=250) of these deaths were cancer-related.

Other causes of death included:

• Cardiac death—7.0% (n=32)
• PE—3.5% (n=16)
• Bleeding—3.3% (n=15)
• VTE complications—1.3% (n=6)
• Stroke—1.1%  (n=5)
• Other cause—17.8% (n=82)
• Unknown cause—11.7% (n=54).

Additional data from the GARFIELD-VTE registry were presented at ISTH 2017 as posters (PB 460 and PB 1188) and in an oral presentation (ASY 35.4). The next set of data from the registry is slated to be presented at the 2017 ASH Annual Meeting.

GARFIELD-VTE is supported by an unrestricted educational grant from Bayer AG. For further information on the registry, visit http://www.garfieldregistry.org.

Boehringer Ingelheim

BERLIN—Data from the GARFIELD-VTE registry showed that, in the first 6 months after a patient was diagnosed with venous thromboembolism (VTE), death was the most frequent major adverse outcome.

More than half of the deaths were related to cancer, with small percentages of patients dying from VTE complications and bleeding events.

GARFIELD-VTE is a prospective registry designed to provide insight into the management of VTE in everyday clinical practice.

Six-month results from the registry were presented in a poster at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress (PB 1196).

The GARFIELD-VTE registry has enrolled more than 10,000 patients with acute VTE—including deep vein thrombosis (DVT) and pulmonary embolism (PE)—from across 415 sites in 28 countries.

Alexander G. G. Turpie, MD, of McMaster University in Hamilton, Ontario, Canada, and his colleagues presented data on 10,315 patients with at least 6 months of follow-up.

Baseline characteristics

The patients’ median age was 60.2 (range, 46.2-71.7), and 49.9% were female. Most patients were white (69.3%), 19.6% were Asian, 4.4% were black, 0.6% were multiracial, 4.3% were classified as “other,” and 1.9% were of unknown race.

Six percent of patients had a family history of VTE (first-degree relatives), 15.1% had a prior episode of DVT and/or PE themselves, and 37.5% had at least 1 provoking factor for VTE.

Most patients (61.8%) had DVT alone, but 38.3% had PE with or without DVT.

The registry included patients with active cancer (9.1%), a history of cancer (10.7%), thrombophilia (2.9%), chronic immobilization (5.6%), heart failure (3.2%), and renal insufficiency (3.5%).

Outcomes

Over 6 months of follow-up, the following events were reported:

• Any bleeding—622 total bleeds or 13.6 per 100 person-years
• All-cause mortality—460 total deaths or 9.7 per 100 person-years
• Recurrent VTE—169 events or 3.6 per 100 person-years
• Major bleeding—106 events or 2.2 per 100 person-years
• Myocardial infarction—42 events or 0.9 per 100 person-years
• Stroke/transient ischemic attack—38 events or 0.8 per 100 person-years.

Nearly 5% of patients died (4.5%, n=460). More than half (54.3%, n=250) of these deaths were cancer-related.

Other causes of death included:

• Cardiac death—7.0% (n=32)
• PE—3.5% (n=16)
• Bleeding—3.3% (n=15)
• VTE complications—1.3% (n=6)
• Stroke—1.1%  (n=5)
• Other cause—17.8% (n=82)
• Unknown cause—11.7% (n=54).

Additional data from the GARFIELD-VTE registry were presented at ISTH 2017 as posters (PB 460 and PB 1188) and in an oral presentation (ASY 35.4). The next set of data from the registry is slated to be presented at the 2017 ASH Annual Meeting.

GARFIELD-VTE is supported by an unrestricted educational grant from Bayer AG. For further information on the registry, visit http://www.garfieldregistry.org.

Andrew Wei, MBBS, PhD

MADRID—The combination of venetoclax and low-dose cytarabine (VEN+LDAC) appears to be a feasible treatment option for elderly patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

In a phase 1/2 study of such patients, VEN+LDAC was considered well-tolerated, conferring moderate myelosuppression and largely low-grade non-hematologic toxicities.

In addition, the combination produced “rapid and durable” responses, and early death rates were low, according to Andrew H. Wei, MBBS, PhD, of Monash University in Melbourne, Victoria, Australia.

However, nearly three-quarters of patients ultimately discontinued the treatment, many due to disease progression.

Dr Wei presented these results at the 22nd Congress of the European Hematology Association (EHA) as abstract S473. AbbVie and Genentech, the companies developing and marketing venetoclax, provided financial support for this study.

“Expression of pro-survival proteins is an established mechanism of chemoresistance in diverse cancers,” Dr Wei noted. “BCL-2 is 1 of 5 pro-survival molecules which functions to sequester pro-apoptotic molecules and tip the balance in favor of cell survival.”

“Venetoclax is a potent and specific inhibitor of BCL-2 which releases these pro-apoptotic molecules, tipping the balance in favor of cell death. Cytotoxic drugs are well-known to increase the burden of BH3-only proteins, and so it was surmised that the combination of chemotherapy, such as cytarabine, with venetoclax could augment the clinical response.”

Patients

Dr Wei presented data on 61 AML patients treated with VEN+LDAC. He noted that this was a poor-risk population, with nearly half of patients over the age of 75 at baseline.

The patients’ median age was 74 (range, 66-87), and 64% were male. Nearly half of patients had an ECOG performance status of 1 (49%), 30% had a status of 0, and 21% had a status of 2.

Forty-four percent of patients had secondary AML, and 28% had prior treatment with a hypomethylating agent (HMA). Sixty-one percent of patients had intermediate-risk cytogenetics, and 31% had poor-risk cytogenetics.

Treatment

The patients received oral venetoclax at 600 mg daily on days 1 to 28 and subcutaneous cytarabine at 20 mg/m² daily on days 1 to 10 of each 28-day cycle.

In the first cycle, the dose of venetoclax was ramped up gradually—no dose on day 1, 50 mg on day 2, 100 mg on day 3, 200 mg on day 4, 400 mg on day 5, and 600 mg thereafter.

Patients received prophylaxis for tumor lysis syndrome prior to starting cycle 1, and they were hospitalized to enable observation.

The median time on study treatment was 6 months (range, <1 to 19 months). Seventy-two percent of patients discontinued treatment.

Reasons for discontinuation included:

• Progressive disease without death—26%
• Progressive disease with death—10%
• Adverse event (AE) related to progression—10%
• AE not related to progression—8%
• Withdrawn consent—8%
• Other reasons—18%.

Safety

The most common AEs of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 hematologic AEs (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), and anemia (28%).

Grade 3/4 non-hematologic AEs (occurring in at least 10% of patients) included hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Response and survival

The overall response rate was 65%, with 25% of patients achieving a complete response (CR), 38% having a CR with incomplete blood count recovery (CRi), and 2% experiencing a partial response.

Dr Wei noted that VEN+LDAC was active across subgroups.

The CR/CRi rate was 76% among patients with intermediate-risk cytogenetics and 47% among patients with poor-risk cytogenetics.

The CR/CRi rate was 70% among patients older than 75, 52% among patients with secondary AML, 66% among patients with no prior HMA exposure, and 53% in patients with prior HMA exposure.

“Although responses were slightly lower in patients with poor cytogenetic risk, prior HMA exposure, and secondary AML . . ., these responses are far in excess of what we would expect with [LDAC] alone,” Dr Wei said.

“Furthermore, the median time to response was very rapid, and this is extremely important to get patients into remission and avoid the medium-term consequences of active AML.”

The median time to response was 1 month (range, <1 to 9 months).

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

Based on these results, AbbVie has initiated a phase 3 trial comparing VEN+LDAC to LDAC alone in elderly patients with untreated AML who are ineligible for intensive chemotherapy.

Andrew Wei, MBBS, PhD

MADRID—The combination of venetoclax and low-dose cytarabine (VEN+LDAC) appears to be a feasible treatment option for elderly patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

In a phase 1/2 study of such patients, VEN+LDAC was considered well-tolerated, conferring moderate myelosuppression and largely low-grade non-hematologic toxicities.

In addition, the combination produced “rapid and durable” responses, and early death rates were low, according to Andrew H. Wei, MBBS, PhD, of Monash University in Melbourne, Victoria, Australia.

However, nearly three-quarters of patients ultimately discontinued the treatment, many due to disease progression.

Dr Wei presented these results at the 22nd Congress of the European Hematology Association (EHA) as abstract S473. AbbVie and Genentech, the companies developing and marketing venetoclax, provided financial support for this study.

“Expression of pro-survival proteins is an established mechanism of chemoresistance in diverse cancers,” Dr Wei noted. “BCL-2 is 1 of 5 pro-survival molecules which functions to sequester pro-apoptotic molecules and tip the balance in favor of cell survival.”

“Venetoclax is a potent and specific inhibitor of BCL-2 which releases these pro-apoptotic molecules, tipping the balance in favor of cell death. Cytotoxic drugs are well-known to increase the burden of BH3-only proteins, and so it was surmised that the combination of chemotherapy, such as cytarabine, with venetoclax could augment the clinical response.”

Patients

Dr Wei presented data on 61 AML patients treated with VEN+LDAC. He noted that this was a poor-risk population, with nearly half of patients over the age of 75 at baseline.

The patients’ median age was 74 (range, 66-87), and 64% were male. Nearly half of patients had an ECOG performance status of 1 (49%), 30% had a status of 0, and 21% had a status of 2.

Forty-four percent of patients had secondary AML, and 28% had prior treatment with a hypomethylating agent (HMA). Sixty-one percent of patients had intermediate-risk cytogenetics, and 31% had poor-risk cytogenetics.

Treatment

The patients received oral venetoclax at 600 mg daily on days 1 to 28 and subcutaneous cytarabine at 20 mg/m² daily on days 1 to 10 of each 28-day cycle.

In the first cycle, the dose of venetoclax was ramped up gradually—no dose on day 1, 50 mg on day 2, 100 mg on day 3, 200 mg on day 4, 400 mg on day 5, and 600 mg thereafter.

Patients received prophylaxis for tumor lysis syndrome prior to starting cycle 1, and they were hospitalized to enable observation.

The median time on study treatment was 6 months (range, <1 to 19 months). Seventy-two percent of patients discontinued treatment.

Reasons for discontinuation included:

• Progressive disease without death—26%
• Progressive disease with death—10%
• Adverse event (AE) related to progression—10%
• AE not related to progression—8%
• Withdrawn consent—8%
• Other reasons—18%.

Safety

The most common AEs of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 hematologic AEs (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), and anemia (28%).

Grade 3/4 non-hematologic AEs (occurring in at least 10% of patients) included hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Response and survival

The overall response rate was 65%, with 25% of patients achieving a complete response (CR), 38% having a CR with incomplete blood count recovery (CRi), and 2% experiencing a partial response.

Dr Wei noted that VEN+LDAC was active across subgroups.

The CR/CRi rate was 76% among patients with intermediate-risk cytogenetics and 47% among patients with poor-risk cytogenetics.

The CR/CRi rate was 70% among patients older than 75, 52% among patients with secondary AML, 66% among patients with no prior HMA exposure, and 53% in patients with prior HMA exposure.

“Although responses were slightly lower in patients with poor cytogenetic risk, prior HMA exposure, and secondary AML . . ., these responses are far in excess of what we would expect with [LDAC] alone,” Dr Wei said.

“Furthermore, the median time to response was very rapid, and this is extremely important to get patients into remission and avoid the medium-term consequences of active AML.”

The median time to response was 1 month (range, <1 to 9 months).

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

Based on these results, AbbVie has initiated a phase 3 trial comparing VEN+LDAC to LDAC alone in elderly patients with untreated AML who are ineligible for intensive chemotherapy.

Andrew Wei, MBBS, PhD

MADRID—The combination of venetoclax and low-dose cytarabine (VEN+LDAC) appears to be a feasible treatment option for elderly patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

In a phase 1/2 study of such patients, VEN+LDAC was considered well-tolerated, conferring moderate myelosuppression and largely low-grade non-hematologic toxicities.

In addition, the combination produced “rapid and durable” responses, and early death rates were low, according to Andrew H. Wei, MBBS, PhD, of Monash University in Melbourne, Victoria, Australia.

However, nearly three-quarters of patients ultimately discontinued the treatment, many due to disease progression.

Dr Wei presented these results at the 22nd Congress of the European Hematology Association (EHA) as abstract S473. AbbVie and Genentech, the companies developing and marketing venetoclax, provided financial support for this study.

“Expression of pro-survival proteins is an established mechanism of chemoresistance in diverse cancers,” Dr Wei noted. “BCL-2 is 1 of 5 pro-survival molecules which functions to sequester pro-apoptotic molecules and tip the balance in favor of cell survival.”

“Venetoclax is a potent and specific inhibitor of BCL-2 which releases these pro-apoptotic molecules, tipping the balance in favor of cell death. Cytotoxic drugs are well-known to increase the burden of BH3-only proteins, and so it was surmised that the combination of chemotherapy, such as cytarabine, with venetoclax could augment the clinical response.”

Patients

Dr Wei presented data on 61 AML patients treated with VEN+LDAC. He noted that this was a poor-risk population, with nearly half of patients over the age of 75 at baseline.

The patients’ median age was 74 (range, 66-87), and 64% were male. Nearly half of patients had an ECOG performance status of 1 (49%), 30% had a status of 0, and 21% had a status of 2.

Forty-four percent of patients had secondary AML, and 28% had prior treatment with a hypomethylating agent (HMA). Sixty-one percent of patients had intermediate-risk cytogenetics, and 31% had poor-risk cytogenetics.

Treatment

The patients received oral venetoclax at 600 mg daily on days 1 to 28 and subcutaneous cytarabine at 20 mg/m² daily on days 1 to 10 of each 28-day cycle.

In the first cycle, the dose of venetoclax was ramped up gradually—no dose on day 1, 50 mg on day 2, 100 mg on day 3, 200 mg on day 4, 400 mg on day 5, and 600 mg thereafter.

Patients received prophylaxis for tumor lysis syndrome prior to starting cycle 1, and they were hospitalized to enable observation.

The median time on study treatment was 6 months (range, <1 to 19 months). Seventy-two percent of patients discontinued treatment.

Reasons for discontinuation included:

• Progressive disease without death—26%
• Progressive disease with death—10%
• Adverse event (AE) related to progression—10%
• AE not related to progression—8%
• Withdrawn consent—8%
• Other reasons—18%.

Safety

The most common AEs of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 hematologic AEs (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), and anemia (28%).

Grade 3/4 non-hematologic AEs (occurring in at least 10% of patients) included hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Response and survival

The overall response rate was 65%, with 25% of patients achieving a complete response (CR), 38% having a CR with incomplete blood count recovery (CRi), and 2% experiencing a partial response.

Dr Wei noted that VEN+LDAC was active across subgroups.

The CR/CRi rate was 76% among patients with intermediate-risk cytogenetics and 47% among patients with poor-risk cytogenetics.

The CR/CRi rate was 70% among patients older than 75, 52% among patients with secondary AML, 66% among patients with no prior HMA exposure, and 53% in patients with prior HMA exposure.

“Although responses were slightly lower in patients with poor cytogenetic risk, prior HMA exposure, and secondary AML . . ., these responses are far in excess of what we would expect with [LDAC] alone,” Dr Wei said.

“Furthermore, the median time to response was very rapid, and this is extremely important to get patients into remission and avoid the medium-term consequences of active AML.”

The median time to response was 1 month (range, <1 to 9 months).

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

Based on these results, AbbVie has initiated a phase 3 trial comparing VEN+LDAC to LDAC alone in elderly patients with untreated AML who are ineligible for intensive chemotherapy.

NEW ORLEANS – Compared with vancomycin monotherapy, vancomycin combined with cefepime improved some outcomes for patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections, a retrospective study of 109 patients revealed.

A lower likelihood of microbiological failure and fewer bloodstream infections persisting 7 days or more were the notable differences between treatment groups.

National Institute of Allergy and Infectious Diseases (NIAID)

“From what I see here … it seems like they will have a lower duration of bacteremia, which is always great,” Ms. Atwan said. “You want to decrease length of stay in the hospital,” which will cut down on costs and on patients’ risks of getting more infections.

Although the primary outcome was a composite endpoint, “when we looked at them separately, we found the patients in the combination group had more mortality,” Ms. Atwan said at the annual meeting of the American Society for Microbiology. “That surprised me initially. But those patients are sicker and more likely to get dual coverage.”

The investigators confirmed the association between the severity of MRSA bacteremia and combination therapy by looking at Acute Physiology and Chronic Health Evaluation (APACHE II) scores. The median APACHE score was 23 in the combination group, compared with 13.5 in the monotherapy group (P = 0003). Higher APACHE scores were associated with greater odds of meeting the composite failure endpoint (adjusted odds ratio, 1.08) and of developing endocarditis (aOR, 3.6) in multivariate analyses.

More patients in the combination group had pneumonia as the primary source of infection than did patients in the monotherapy group: 54% vs. 29% (P = .016). Further, more of them had skin or soft tissue infections as the primary infection source: 29% vs. 13% (P = .036).

Although the exact mechanism remains unknown, synergy between the two agents could be caused by an increase in penicillin-binding proteins, Ms. Atwan said.

The study is still ongoing; Ms. Atwan hopes additional patients and data will lead to statistically significant differences between the outcomes of combination therapy and vancomycin monotherapy.

“I want to say that combination therapy is something you will always want to go to when you have a sicker patient, but I can’t really tell you that combination therapy is going to cause better outcomes for your patient,” she cautioned. “Hopefully, I can by the end of the study.”

In the meantime, “it looks like vancomycin and beta-lactams could be beneficial for MRSA bacteremia,” she added.

The researchers noted that although vancomycin monotherapy is a mainstay of treatment for MRSA bloodstream infections, emergence of reduced susceptibility and treatment failures warrants other therapeutic strategies.

Ms. Atwan had no relevant financial disclosures.
 

NEW ORLEANS – Compared with vancomycin monotherapy, vancomycin combined with cefepime improved some outcomes for patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections, a retrospective study of 109 patients revealed.

A lower likelihood of microbiological failure and fewer bloodstream infections persisting 7 days or more were the notable differences between treatment groups.

National Institute of Allergy and Infectious Diseases (NIAID)

“From what I see here … it seems like they will have a lower duration of bacteremia, which is always great,” Ms. Atwan said. “You want to decrease length of stay in the hospital,” which will cut down on costs and on patients’ risks of getting more infections.

Although the primary outcome was a composite endpoint, “when we looked at them separately, we found the patients in the combination group had more mortality,” Ms. Atwan said at the annual meeting of the American Society for Microbiology. “That surprised me initially. But those patients are sicker and more likely to get dual coverage.”

The investigators confirmed the association between the severity of MRSA bacteremia and combination therapy by looking at Acute Physiology and Chronic Health Evaluation (APACHE II) scores. The median APACHE score was 23 in the combination group, compared with 13.5 in the monotherapy group (P = 0003). Higher APACHE scores were associated with greater odds of meeting the composite failure endpoint (adjusted odds ratio, 1.08) and of developing endocarditis (aOR, 3.6) in multivariate analyses.

More patients in the combination group had pneumonia as the primary source of infection than did patients in the monotherapy group: 54% vs. 29% (P = .016). Further, more of them had skin or soft tissue infections as the primary infection source: 29% vs. 13% (P = .036).

Although the exact mechanism remains unknown, synergy between the two agents could be caused by an increase in penicillin-binding proteins, Ms. Atwan said.

The study is still ongoing; Ms. Atwan hopes additional patients and data will lead to statistically significant differences between the outcomes of combination therapy and vancomycin monotherapy.

“I want to say that combination therapy is something you will always want to go to when you have a sicker patient, but I can’t really tell you that combination therapy is going to cause better outcomes for your patient,” she cautioned. “Hopefully, I can by the end of the study.”

In the meantime, “it looks like vancomycin and beta-lactams could be beneficial for MRSA bacteremia,” she added.

The researchers noted that although vancomycin monotherapy is a mainstay of treatment for MRSA bloodstream infections, emergence of reduced susceptibility and treatment failures warrants other therapeutic strategies.

Ms. Atwan had no relevant financial disclosures.
 

NEW ORLEANS – Compared with vancomycin monotherapy, vancomycin combined with cefepime improved some outcomes for patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections, a retrospective study of 109 patients revealed.

A lower likelihood of microbiological failure and fewer bloodstream infections persisting 7 days or more were the notable differences between treatment groups.

National Institute of Allergy and Infectious Diseases (NIAID)

“From what I see here … it seems like they will have a lower duration of bacteremia, which is always great,” Ms. Atwan said. “You want to decrease length of stay in the hospital,” which will cut down on costs and on patients’ risks of getting more infections.

Although the primary outcome was a composite endpoint, “when we looked at them separately, we found the patients in the combination group had more mortality,” Ms. Atwan said at the annual meeting of the American Society for Microbiology. “That surprised me initially. But those patients are sicker and more likely to get dual coverage.”

The investigators confirmed the association between the severity of MRSA bacteremia and combination therapy by looking at Acute Physiology and Chronic Health Evaluation (APACHE II) scores. The median APACHE score was 23 in the combination group, compared with 13.5 in the monotherapy group (P = 0003). Higher APACHE scores were associated with greater odds of meeting the composite failure endpoint (adjusted odds ratio, 1.08) and of developing endocarditis (aOR, 3.6) in multivariate analyses.

More patients in the combination group had pneumonia as the primary source of infection than did patients in the monotherapy group: 54% vs. 29% (P = .016). Further, more of them had skin or soft tissue infections as the primary infection source: 29% vs. 13% (P = .036).

Although the exact mechanism remains unknown, synergy between the two agents could be caused by an increase in penicillin-binding proteins, Ms. Atwan said.

The study is still ongoing; Ms. Atwan hopes additional patients and data will lead to statistically significant differences between the outcomes of combination therapy and vancomycin monotherapy.

“I want to say that combination therapy is something you will always want to go to when you have a sicker patient, but I can’t really tell you that combination therapy is going to cause better outcomes for your patient,” she cautioned. “Hopefully, I can by the end of the study.”

In the meantime, “it looks like vancomycin and beta-lactams could be beneficial for MRSA bacteremia,” she added.

The researchers noted that although vancomycin monotherapy is a mainstay of treatment for MRSA bloodstream infections, emergence of reduced susceptibility and treatment failures warrants other therapeutic strategies.

Ms. Atwan had no relevant financial disclosures.
 

Senate Republicans are scrambling to come up with another plan now that at least four member of their caucus have said that they would vote against moving forward with debate on the Better Care Reconciliation Act.

Support for the bill, which included dramatic Medicaid cuts and stripped many coverage provisions of the Affordable Care Act, was lacking after revisions were announced on July 13. At that time, conservative Sen. Ran Paul (R-Ky.) and moderate Susan Collins (R-Maine) voiced their opposition for different ideological reasons. They were joined by Sen. Mike Lee (R-Utah) and Sen. Jerry Moran (R-Kan.), who also declined to support the bill. Senate GOP leadership, with a slim 52-48 majority, could only afford to lose two votes (Vice President Mike Pence would have been the tie-breaking vote).

sndr/istockphoto.com

[email protected]

Senate Republicans are scrambling to come up with another plan now that at least four member of their caucus have said that they would vote against moving forward with debate on the Better Care Reconciliation Act.

Support for the bill, which included dramatic Medicaid cuts and stripped many coverage provisions of the Affordable Care Act, was lacking after revisions were announced on July 13. At that time, conservative Sen. Ran Paul (R-Ky.) and moderate Susan Collins (R-Maine) voiced their opposition for different ideological reasons. They were joined by Sen. Mike Lee (R-Utah) and Sen. Jerry Moran (R-Kan.), who also declined to support the bill. Senate GOP leadership, with a slim 52-48 majority, could only afford to lose two votes (Vice President Mike Pence would have been the tie-breaking vote).

sndr/istockphoto.com

[email protected]

Senate Republicans are scrambling to come up with another plan now that at least four member of their caucus have said that they would vote against moving forward with debate on the Better Care Reconciliation Act.

Support for the bill, which included dramatic Medicaid cuts and stripped many coverage provisions of the Affordable Care Act, was lacking after revisions were announced on July 13. At that time, conservative Sen. Ran Paul (R-Ky.) and moderate Susan Collins (R-Maine) voiced their opposition for different ideological reasons. They were joined by Sen. Mike Lee (R-Utah) and Sen. Jerry Moran (R-Kan.), who also declined to support the bill. Senate GOP leadership, with a slim 52-48 majority, could only afford to lose two votes (Vice President Mike Pence would have been the tie-breaking vote).

sndr/istockphoto.com

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The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).

The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.

The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).

The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.

The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).

The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.

A better understanding of the relationship between psychiatric disorders and epilepsy is needed to help clinicians and researchers find the best treatment options, and to avoid the many misconceptions that currently exist. In a recent critical review, Berg et al address the biases in the literature and the diagnostic errors that may occur because of the difficulty in distinguishing psychogenic nonepileptic seizures from epilepsy.

Berg AT, Altalib HH, Devinsky O. Psychiatric and behavioral comorbidities in epilepsy: A critical reappraisal. Epilepsia. 2017;58:1123-1130.

A better understanding of the relationship between psychiatric disorders and epilepsy is needed to help clinicians and researchers find the best treatment options, and to avoid the many misconceptions that currently exist. In a recent critical review, Berg et al address the biases in the literature and the diagnostic errors that may occur because of the difficulty in distinguishing psychogenic nonepileptic seizures from epilepsy.

Berg AT, Altalib HH, Devinsky O. Psychiatric and behavioral comorbidities in epilepsy: A critical reappraisal. Epilepsia. 2017;58:1123-1130.

A better understanding of the relationship between psychiatric disorders and epilepsy is needed to help clinicians and researchers find the best treatment options, and to avoid the many misconceptions that currently exist. In a recent critical review, Berg et al address the biases in the literature and the diagnostic errors that may occur because of the difficulty in distinguishing psychogenic nonepileptic seizures from epilepsy.

Berg AT, Altalib HH, Devinsky O. Psychiatric and behavioral comorbidities in epilepsy: A critical reappraisal. Epilepsia. 2017;58:1123-1130.