Applications are now open for...

Every Heartbeat Matters Valve Disease Fellowship

Applications for the second award cycle of the Every Heartbeat Matters Valve Fellowship — a joint project of the AATS Graham and Edwards Lifesciences Foundation — are now open. The mission of Every Heartbeat Matters is to impact the global burden of heart valve disease by serving one million people by 2020.

The fellowship’s goal is to enhance the knowledge and skills of practicing cardiothoracic surgeons who are already treating or committed to treating underserved patients worldwide. It provides up to three months of advanced heart valve disease training and education at a host institution.

More information/application
Deadline: February 15, 2016

2016 Graham Surgical Investigator Program

The Graham Surgical Investigator Program supports innovative clinical or translational research for young cardiothoracic surgeons. Topics include, but are not limited to, topics related to outcomes research, as well as robotically assisted surgery, minimally invasive surgery or other applications of new and innovative technologies in cardiothoracic surgery.

Up to four proposals will be funded in 2016.

Thanks to the generosity of Ethicon, Intuitive Surgical, Dr. Mehmet Oz and AATS.

More information/application
Deadline: February 15, 2016

Applications are now open for...

Every Heartbeat Matters Valve Disease Fellowship

Applications for the second award cycle of the Every Heartbeat Matters Valve Fellowship — a joint project of the AATS Graham and Edwards Lifesciences Foundation — are now open. The mission of Every Heartbeat Matters is to impact the global burden of heart valve disease by serving one million people by 2020.

The fellowship’s goal is to enhance the knowledge and skills of practicing cardiothoracic surgeons who are already treating or committed to treating underserved patients worldwide. It provides up to three months of advanced heart valve disease training and education at a host institution.

More information/application
Deadline: February 15, 2016

2016 Graham Surgical Investigator Program

The Graham Surgical Investigator Program supports innovative clinical or translational research for young cardiothoracic surgeons. Topics include, but are not limited to, topics related to outcomes research, as well as robotically assisted surgery, minimally invasive surgery or other applications of new and innovative technologies in cardiothoracic surgery.

Up to four proposals will be funded in 2016.

Thanks to the generosity of Ethicon, Intuitive Surgical, Dr. Mehmet Oz and AATS.

More information/application
Deadline: February 15, 2016

Applications are now open for...

Every Heartbeat Matters Valve Disease Fellowship

Applications for the second award cycle of the Every Heartbeat Matters Valve Fellowship — a joint project of the AATS Graham and Edwards Lifesciences Foundation — are now open. The mission of Every Heartbeat Matters is to impact the global burden of heart valve disease by serving one million people by 2020.

The fellowship’s goal is to enhance the knowledge and skills of practicing cardiothoracic surgeons who are already treating or committed to treating underserved patients worldwide. It provides up to three months of advanced heart valve disease training and education at a host institution.

More information/application
Deadline: February 15, 2016

2016 Graham Surgical Investigator Program

The Graham Surgical Investigator Program supports innovative clinical or translational research for young cardiothoracic surgeons. Topics include, but are not limited to, topics related to outcomes research, as well as robotically assisted surgery, minimally invasive surgery or other applications of new and innovative technologies in cardiothoracic surgery.

Up to four proposals will be funded in 2016.

Thanks to the generosity of Ethicon, Intuitive Surgical, Dr. Mehmet Oz and AATS.

More information/application
Deadline: February 15, 2016

June 24-25, 2016
Renaissance Boston Waterfront Hotel
Boston, MA

Co-Directors
Thoralf M. Sundt, III, MD
Steven Yule, PhD

Program Committee
David J. Bunnell, PA-C, APACVS
David C. Fitzgerald, CCP, AMSECT
Jake Jaquiss, MD
M. Blair Marshall, MD
Shannon Pengel, RN
Kenneth Shann, CCP, LP, AMSECT
Marco Zenati, MD

Improving patient care remains a constant mission for all members of the surgical team. The AATS Surgical Patient Safety Course has been designed to promote a culture of safety and reduce preventable patient harm by engaging, educating, and equipping members of the cardiothoracic surgical team in the multidimensional approach to patient safety.

The course — which features didactic and interactive presentations and focused workshops — will provide attendees with essential patient safety knowledge, skills, and attitudes aimed at improving care in the present and future.

Preliminary Program Now Online

The Patient Safety program includes team training and simulaltion experiences.

Surgical Team Registration
Register three or more members from the same institution and receive one complimentary Healthcare Professional registration. We encourage you to send the entire team to Boston this June for this important course.

Register Your Team Before May 23, 2016 & Save

June 24-25, 2016
Renaissance Boston Waterfront Hotel
Boston, MA

Co-Directors
Thoralf M. Sundt, III, MD
Steven Yule, PhD

Program Committee
David J. Bunnell, PA-C, APACVS
David C. Fitzgerald, CCP, AMSECT
Jake Jaquiss, MD
M. Blair Marshall, MD
Shannon Pengel, RN
Kenneth Shann, CCP, LP, AMSECT
Marco Zenati, MD

Improving patient care remains a constant mission for all members of the surgical team. The AATS Surgical Patient Safety Course has been designed to promote a culture of safety and reduce preventable patient harm by engaging, educating, and equipping members of the cardiothoracic surgical team in the multidimensional approach to patient safety.

The course — which features didactic and interactive presentations and focused workshops — will provide attendees with essential patient safety knowledge, skills, and attitudes aimed at improving care in the present and future.

Preliminary Program Now Online

The Patient Safety program includes team training and simulaltion experiences.

Surgical Team Registration
Register three or more members from the same institution and receive one complimentary Healthcare Professional registration. We encourage you to send the entire team to Boston this June for this important course.

Register Your Team Before May 23, 2016 & Save

June 24-25, 2016
Renaissance Boston Waterfront Hotel
Boston, MA

Co-Directors
Thoralf M. Sundt, III, MD
Steven Yule, PhD

Program Committee
David J. Bunnell, PA-C, APACVS
David C. Fitzgerald, CCP, AMSECT
Jake Jaquiss, MD
M. Blair Marshall, MD
Shannon Pengel, RN
Kenneth Shann, CCP, LP, AMSECT
Marco Zenati, MD

Improving patient care remains a constant mission for all members of the surgical team. The AATS Surgical Patient Safety Course has been designed to promote a culture of safety and reduce preventable patient harm by engaging, educating, and equipping members of the cardiothoracic surgical team in the multidimensional approach to patient safety.

The course — which features didactic and interactive presentations and focused workshops — will provide attendees with essential patient safety knowledge, skills, and attitudes aimed at improving care in the present and future.

Preliminary Program Now Online

The Patient Safety program includes team training and simulaltion experiences.

Surgical Team Registration
Register three or more members from the same institution and receive one complimentary Healthcare Professional registration. We encourage you to send the entire team to Boston this June for this important course.

Register Your Team Before May 23, 2016 & Save

March 19-20, 2016
Hilton Shanghai Hongqiao
Shanghai, China

Program Directors
Haiquan Chen
Ke-Neng Chen
G. Alec Patterson
David J. Sugarbaker

Preliminary Program Now Available

Overview
Lung and esophageal disease remain a global concern as two of the deadliest issues facing patients and thoracic surgeons. The 2016 AATS Focus on Thoracic Surgery: Lung and Esophageal Cancer meeting will concentrate on the complex nature of treating both lung and esophageal disease while also discussing innovative approaches to enhancing patient care.

The two-day program features a mixture of lectures, relevant case studies, panel discussions, and videos. The faculty includes local and internationally recognized experts in lung and esophageal disease ensuring that attendees will receive insights from a broad spectrum of leaders thoracic surgery field.

More Information/Register

March 19-20, 2016
Hilton Shanghai Hongqiao
Shanghai, China

Program Directors
Haiquan Chen
Ke-Neng Chen
G. Alec Patterson
David J. Sugarbaker

Preliminary Program Now Available

Overview
Lung and esophageal disease remain a global concern as two of the deadliest issues facing patients and thoracic surgeons. The 2016 AATS Focus on Thoracic Surgery: Lung and Esophageal Cancer meeting will concentrate on the complex nature of treating both lung and esophageal disease while also discussing innovative approaches to enhancing patient care.

The two-day program features a mixture of lectures, relevant case studies, panel discussions, and videos. The faculty includes local and internationally recognized experts in lung and esophageal disease ensuring that attendees will receive insights from a broad spectrum of leaders thoracic surgery field.

More Information/Register

March 19-20, 2016
Hilton Shanghai Hongqiao
Shanghai, China

Program Directors
Haiquan Chen
Ke-Neng Chen
G. Alec Patterson
David J. Sugarbaker

Preliminary Program Now Available

Overview
Lung and esophageal disease remain a global concern as two of the deadliest issues facing patients and thoracic surgeons. The 2016 AATS Focus on Thoracic Surgery: Lung and Esophageal Cancer meeting will concentrate on the complex nature of treating both lung and esophageal disease while also discussing innovative approaches to enhancing patient care.

The two-day program features a mixture of lectures, relevant case studies, panel discussions, and videos. The faculty includes local and internationally recognized experts in lung and esophageal disease ensuring that attendees will receive insights from a broad spectrum of leaders thoracic surgery field.

More Information/Register

Dr. Lillian M. Beard discusses the challenges of getting reimbursed for providing mental and behavioral health care within her pediatric practice. Addressing her patients’ mental health needs can take three of her regular appointment times. “I am never adequately reimbursed for the time that it really takes,” she says. Having a mental health specialist on site might be one possibility, but is this model feasible? In this video, Dr. Beard, Dr. April Barbour, and Dr. Lorenzo Norris explore ways primary care and psychiatry can work together to provide patients with the best possible care.

Dr. Lillian M. Beard discusses the challenges of getting reimbursed for providing mental and behavioral health care within her pediatric practice. Addressing her patients’ mental health needs can take three of her regular appointment times. “I am never adequately reimbursed for the time that it really takes,” she says. Having a mental health specialist on site might be one possibility, but is this model feasible? In this video, Dr. Beard, Dr. April Barbour, and Dr. Lorenzo Norris explore ways primary care and psychiatry can work together to provide patients with the best possible care.

Dr. Lillian M. Beard discusses the challenges of getting reimbursed for providing mental and behavioral health care within her pediatric practice. Addressing her patients’ mental health needs can take three of her regular appointment times. “I am never adequately reimbursed for the time that it really takes,” she says. Having a mental health specialist on site might be one possibility, but is this model feasible? In this video, Dr. Beard, Dr. April Barbour, and Dr. Lorenzo Norris explore ways primary care and psychiatry can work together to provide patients with the best possible care.

The role of primary care physicians in recognizing patients with behavioral and mental health problems is critical, psychiatrist Dr. David Pickar says. “That is what you do for a living. You find out these things. I want to make sure that the primary care physician [who] may be watching this understands he or she is not just the first line, but he or she has good skills at observing what is going on with the patient.” The primary care physician also has a relationship with the patient, psychiatrist Dr. Lorenzo Norris says. “The patient is more inclined to listen to [the primary care physician] than to just some random specialist.” In this video, Dr. Pickar and Dr. Norris discuss the importance of communicating about shared patients – not through electronic medical records, but through true dialogue.

The role of primary care physicians in recognizing patients with behavioral and mental health problems is critical, psychiatrist Dr. David Pickar says. “That is what you do for a living. You find out these things. I want to make sure that the primary care physician [who] may be watching this understands he or she is not just the first line, but he or she has good skills at observing what is going on with the patient.” The primary care physician also has a relationship with the patient, psychiatrist Dr. Lorenzo Norris says. “The patient is more inclined to listen to [the primary care physician] than to just some random specialist.” In this video, Dr. Pickar and Dr. Norris discuss the importance of communicating about shared patients – not through electronic medical records, but through true dialogue.

The role of primary care physicians in recognizing patients with behavioral and mental health problems is critical, psychiatrist Dr. David Pickar says. “That is what you do for a living. You find out these things. I want to make sure that the primary care physician [who] may be watching this understands he or she is not just the first line, but he or she has good skills at observing what is going on with the patient.” The primary care physician also has a relationship with the patient, psychiatrist Dr. Lorenzo Norris says. “The patient is more inclined to listen to [the primary care physician] than to just some random specialist.” In this video, Dr. Pickar and Dr. Norris discuss the importance of communicating about shared patients – not through electronic medical records, but through true dialogue.

Primary care physicians have the potential to detect “distress” diagnoses and mental or behavioral disorders in most patients who come to the office, noted Dr. Lawrence “Bopper” Deyton, senior associate dean for clinical public health and professor of medicine and health policy at George Washington University.

If one embraces the Acceptable Care Act’s priorities of improving quality of care, reducing cost, and improving patient satisfaction, “Aren’t we at the cusp of a reimbursement system that should reward for that?” he asks.

Kennedy Forum policy director Lauren Alfred says there’s only so much that can be done. “Then at some point, we have to talk about collaborative care ... and where we’re going to bring specialists into the equation.”

In this video, Dr. Deyton and Ms. Alfred discuss how much mental health care primary care physicians should be asked to shoulder – and when such care should be more collaborative.

Primary care physicians have the potential to detect “distress” diagnoses and mental or behavioral disorders in most patients who come to the office, noted Dr. Lawrence “Bopper” Deyton, senior associate dean for clinical public health and professor of medicine and health policy at George Washington University.

If one embraces the Acceptable Care Act’s priorities of improving quality of care, reducing cost, and improving patient satisfaction, “Aren’t we at the cusp of a reimbursement system that should reward for that?” he asks.

Kennedy Forum policy director Lauren Alfred says there’s only so much that can be done. “Then at some point, we have to talk about collaborative care ... and where we’re going to bring specialists into the equation.”

In this video, Dr. Deyton and Ms. Alfred discuss how much mental health care primary care physicians should be asked to shoulder – and when such care should be more collaborative.

Primary care physicians have the potential to detect “distress” diagnoses and mental or behavioral disorders in most patients who come to the office, noted Dr. Lawrence “Bopper” Deyton, senior associate dean for clinical public health and professor of medicine and health policy at George Washington University.

If one embraces the Acceptable Care Act’s priorities of improving quality of care, reducing cost, and improving patient satisfaction, “Aren’t we at the cusp of a reimbursement system that should reward for that?” he asks.

Kennedy Forum policy director Lauren Alfred says there’s only so much that can be done. “Then at some point, we have to talk about collaborative care ... and where we’re going to bring specialists into the equation.”

In this video, Dr. Deyton and Ms. Alfred discuss how much mental health care primary care physicians should be asked to shoulder – and when such care should be more collaborative.

Primary care physicians want a collaborative approach to mental and behavioral health care, according to Dr. April Barbour, director of general internal medicine and the primary care residency program at George Washington University, Washington. “That’s a lot of what we teach and train our residents ... and this allows us to truly treat the whole patient.”

Training models are out there, but the question of whether funding is available to keep these models viable is an issue.

“Every professional is going to look to be compensated for his or her time and input,” explains Dr. Lillian M. Beard, physician director of Children’s Pediatricians and Associates, Silver Spring, Md. “We have to look at mind, body, spirit. It’s the whole thing.”

In this video, Dr. Barbour, Dr. Beard, and psychiatrists Dr. Lorenzo Norris and Dr. David Pickar discuss how to make primary care practices responsive to patients in ways that are both holistic and cost effective.

Primary care physicians want a collaborative approach to mental and behavioral health care, according to Dr. April Barbour, director of general internal medicine and the primary care residency program at George Washington University, Washington. “That’s a lot of what we teach and train our residents ... and this allows us to truly treat the whole patient.”

Training models are out there, but the question of whether funding is available to keep these models viable is an issue.

“Every professional is going to look to be compensated for his or her time and input,” explains Dr. Lillian M. Beard, physician director of Children’s Pediatricians and Associates, Silver Spring, Md. “We have to look at mind, body, spirit. It’s the whole thing.”

In this video, Dr. Barbour, Dr. Beard, and psychiatrists Dr. Lorenzo Norris and Dr. David Pickar discuss how to make primary care practices responsive to patients in ways that are both holistic and cost effective.

Primary care physicians want a collaborative approach to mental and behavioral health care, according to Dr. April Barbour, director of general internal medicine and the primary care residency program at George Washington University, Washington. “That’s a lot of what we teach and train our residents ... and this allows us to truly treat the whole patient.”

Training models are out there, but the question of whether funding is available to keep these models viable is an issue.

“Every professional is going to look to be compensated for his or her time and input,” explains Dr. Lillian M. Beard, physician director of Children’s Pediatricians and Associates, Silver Spring, Md. “We have to look at mind, body, spirit. It’s the whole thing.”

In this video, Dr. Barbour, Dr. Beard, and psychiatrists Dr. Lorenzo Norris and Dr. David Pickar discuss how to make primary care practices responsive to patients in ways that are both holistic and cost effective.

SNOWMASS, COLO. – Don’t be in a rush to refer a patient with drug-refractory, symptomatic atrial fibrillation (AF) for catheter ablation of the arrhythmia, a prominent electrophysiologist advised at the Annual Cardiovascular Conference at Snowmass.

“AF ablation is not salvation – and that’s coming from somebody who does these procedures. One really needs to be very selective in referring patients for this,” said Dr. N.A. Mark Estes III, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

Misconceptions about AF catheter ablation outcomes abound among nonelectrophysiologists. Results have often been overstated, Dr. Estes continued. And there’s a far more attractive alternative treatment option for those AF patients who are overweight or obese: weight loss.

In the Australian LEGACY study, which he considers practice changing, patients with AF who had a body mass index of at least 27 kg/m² who participated in a simple structured weight management program and achieved a sustained loss of at least 10% of their body weight had a 65% reduction in their AF burden as objectively documented by repeated 7-day ambulatory monitoring over 5 years of follow-up. Moreover, 46% of patients who maintained that degree of weight reduction were totally free of AF without use of drugs or ablation procedures (J Am Coll Cardiol. 2015 May 26;65[20]:2159-69).

In a related study, the Australian investigators, led by Dr. Rajeev K. Pathak of the University of Adelaide, showed in the same study population that participation in a tailored exercise program paid added dividends on top of the weight loss. Patients who achieved at least a 2-MET increase in cardiorespiratory fitness had a significantly greater rate of freedom from AF than those who didn’t reach that fitness threshold (J Am Coll Cardiol. Sep 1;66[9]:985-96).

“The data are compelling for improved outcomes, including reduced AF burden, with lifestyle modification in obese patients with AF. This is first-line therapy. You can bet it will be in the guidelines soon. It should be in your practice now,” Dr. Estes declared.

“The starting point is weight reduction, even before sending patients to an electrophysiologist for ablation,” he continued. “And if you’ve got patients on drugs who’ve had ablation in whom there continues to be AF, weight reduction – particularly reaching that 10% threshold – results in a dramatic decline in the burden of AF,” he said.

One of the common misconceptions about catheter ablation for AF is that if the pulmonary vein isolation procedure is successful in eliminating the arrhythmia, then the patient can discontinue oral anticoagulant therapy.

“That rationale, while logical, doesn’t really hold up. In many of the ablation trials, including the AFFIRM trial, if you discontinue anticoagulation in patients in sinus rhythm the stroke rate goes back to the same as in patients with AF,” according to the cardiologist.

In a meta-analysis of prospective studies published through 2007, the single-procedure success rate for radiofrequency ablation in achieving sinus rhythm without the use of antiarrhythmic drugs was 57%, climbing to 71% with multiple ablation procedures. In contrast, antiarrhythmic drugs were substantially less successful, with about a 50% success rate as compared with a 25% placebo response (Circ Arrhythm Electrophysiol. 2009 Aug;2[4]:349-61).

“It’s notable that antiarrhythmic drug development has almost been stopped because the drugs don’t work, with the possible exception of amiodarone, which requires an individualized risk/benefit assessment,” according to Dr. Estes.

There is a major caveat regarding the ablation studies: They’ve mainly enrolled patients who are in their 50s, when AF is far less common than in later decades.

“Whether these results are going to hold up long-term in elderly patients who are hypertensive, diabetic, and may have sleep apnea really remains an unanswered question,” Dr. Estes observed.

Also, significant periprocedural complications occur in roughly 1 in 20 patients undergoing radiofrequency catheter ablation, although the safety data for cryoablation look somewhat better, he continued.

Dr. Estes predicted that the future of catheter ablation of AF hangs on three major ongoing rigorous randomized clinical trials comparing it to drug therapy with hard endpoints including all-cause mortality and cardiovascular hospitalizations. These are CASTLE-AF, with 420 patients; CABANA, with 2,200; and the German EAST study, with roughly 3,000 patients. Results are expected in 2018-2019.

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Don’t be in a rush to refer a patient with drug-refractory, symptomatic atrial fibrillation (AF) for catheter ablation of the arrhythmia, a prominent electrophysiologist advised at the Annual Cardiovascular Conference at Snowmass.

“AF ablation is not salvation – and that’s coming from somebody who does these procedures. One really needs to be very selective in referring patients for this,” said Dr. N.A. Mark Estes III, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

Misconceptions about AF catheter ablation outcomes abound among nonelectrophysiologists. Results have often been overstated, Dr. Estes continued. And there’s a far more attractive alternative treatment option for those AF patients who are overweight or obese: weight loss.

In the Australian LEGACY study, which he considers practice changing, patients with AF who had a body mass index of at least 27 kg/m² who participated in a simple structured weight management program and achieved a sustained loss of at least 10% of their body weight had a 65% reduction in their AF burden as objectively documented by repeated 7-day ambulatory monitoring over 5 years of follow-up. Moreover, 46% of patients who maintained that degree of weight reduction were totally free of AF without use of drugs or ablation procedures (J Am Coll Cardiol. 2015 May 26;65[20]:2159-69).

In a related study, the Australian investigators, led by Dr. Rajeev K. Pathak of the University of Adelaide, showed in the same study population that participation in a tailored exercise program paid added dividends on top of the weight loss. Patients who achieved at least a 2-MET increase in cardiorespiratory fitness had a significantly greater rate of freedom from AF than those who didn’t reach that fitness threshold (J Am Coll Cardiol. Sep 1;66[9]:985-96).

“The data are compelling for improved outcomes, including reduced AF burden, with lifestyle modification in obese patients with AF. This is first-line therapy. You can bet it will be in the guidelines soon. It should be in your practice now,” Dr. Estes declared.

“The starting point is weight reduction, even before sending patients to an electrophysiologist for ablation,” he continued. “And if you’ve got patients on drugs who’ve had ablation in whom there continues to be AF, weight reduction – particularly reaching that 10% threshold – results in a dramatic decline in the burden of AF,” he said.

One of the common misconceptions about catheter ablation for AF is that if the pulmonary vein isolation procedure is successful in eliminating the arrhythmia, then the patient can discontinue oral anticoagulant therapy.

“That rationale, while logical, doesn’t really hold up. In many of the ablation trials, including the AFFIRM trial, if you discontinue anticoagulation in patients in sinus rhythm the stroke rate goes back to the same as in patients with AF,” according to the cardiologist.

In a meta-analysis of prospective studies published through 2007, the single-procedure success rate for radiofrequency ablation in achieving sinus rhythm without the use of antiarrhythmic drugs was 57%, climbing to 71% with multiple ablation procedures. In contrast, antiarrhythmic drugs were substantially less successful, with about a 50% success rate as compared with a 25% placebo response (Circ Arrhythm Electrophysiol. 2009 Aug;2[4]:349-61).

“It’s notable that antiarrhythmic drug development has almost been stopped because the drugs don’t work, with the possible exception of amiodarone, which requires an individualized risk/benefit assessment,” according to Dr. Estes.

There is a major caveat regarding the ablation studies: They’ve mainly enrolled patients who are in their 50s, when AF is far less common than in later decades.

“Whether these results are going to hold up long-term in elderly patients who are hypertensive, diabetic, and may have sleep apnea really remains an unanswered question,” Dr. Estes observed.

Also, significant periprocedural complications occur in roughly 1 in 20 patients undergoing radiofrequency catheter ablation, although the safety data for cryoablation look somewhat better, he continued.

Dr. Estes predicted that the future of catheter ablation of AF hangs on three major ongoing rigorous randomized clinical trials comparing it to drug therapy with hard endpoints including all-cause mortality and cardiovascular hospitalizations. These are CASTLE-AF, with 420 patients; CABANA, with 2,200; and the German EAST study, with roughly 3,000 patients. Results are expected in 2018-2019.

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Don’t be in a rush to refer a patient with drug-refractory, symptomatic atrial fibrillation (AF) for catheter ablation of the arrhythmia, a prominent electrophysiologist advised at the Annual Cardiovascular Conference at Snowmass.

“AF ablation is not salvation – and that’s coming from somebody who does these procedures. One really needs to be very selective in referring patients for this,” said Dr. N.A. Mark Estes III, professor of medicine and director of cardiac arrhythmia services at Tufts University, Boston.

Misconceptions about AF catheter ablation outcomes abound among nonelectrophysiologists. Results have often been overstated, Dr. Estes continued. And there’s a far more attractive alternative treatment option for those AF patients who are overweight or obese: weight loss.

In the Australian LEGACY study, which he considers practice changing, patients with AF who had a body mass index of at least 27 kg/m² who participated in a simple structured weight management program and achieved a sustained loss of at least 10% of their body weight had a 65% reduction in their AF burden as objectively documented by repeated 7-day ambulatory monitoring over 5 years of follow-up. Moreover, 46% of patients who maintained that degree of weight reduction were totally free of AF without use of drugs or ablation procedures (J Am Coll Cardiol. 2015 May 26;65[20]:2159-69).

In a related study, the Australian investigators, led by Dr. Rajeev K. Pathak of the University of Adelaide, showed in the same study population that participation in a tailored exercise program paid added dividends on top of the weight loss. Patients who achieved at least a 2-MET increase in cardiorespiratory fitness had a significantly greater rate of freedom from AF than those who didn’t reach that fitness threshold (J Am Coll Cardiol. Sep 1;66[9]:985-96).

“The data are compelling for improved outcomes, including reduced AF burden, with lifestyle modification in obese patients with AF. This is first-line therapy. You can bet it will be in the guidelines soon. It should be in your practice now,” Dr. Estes declared.

“The starting point is weight reduction, even before sending patients to an electrophysiologist for ablation,” he continued. “And if you’ve got patients on drugs who’ve had ablation in whom there continues to be AF, weight reduction – particularly reaching that 10% threshold – results in a dramatic decline in the burden of AF,” he said.

One of the common misconceptions about catheter ablation for AF is that if the pulmonary vein isolation procedure is successful in eliminating the arrhythmia, then the patient can discontinue oral anticoagulant therapy.

“That rationale, while logical, doesn’t really hold up. In many of the ablation trials, including the AFFIRM trial, if you discontinue anticoagulation in patients in sinus rhythm the stroke rate goes back to the same as in patients with AF,” according to the cardiologist.

In a meta-analysis of prospective studies published through 2007, the single-procedure success rate for radiofrequency ablation in achieving sinus rhythm without the use of antiarrhythmic drugs was 57%, climbing to 71% with multiple ablation procedures. In contrast, antiarrhythmic drugs were substantially less successful, with about a 50% success rate as compared with a 25% placebo response (Circ Arrhythm Electrophysiol. 2009 Aug;2[4]:349-61).

“It’s notable that antiarrhythmic drug development has almost been stopped because the drugs don’t work, with the possible exception of amiodarone, which requires an individualized risk/benefit assessment,” according to Dr. Estes.

There is a major caveat regarding the ablation studies: They’ve mainly enrolled patients who are in their 50s, when AF is far less common than in later decades.

“Whether these results are going to hold up long-term in elderly patients who are hypertensive, diabetic, and may have sleep apnea really remains an unanswered question,” Dr. Estes observed.

Also, significant periprocedural complications occur in roughly 1 in 20 patients undergoing radiofrequency catheter ablation, although the safety data for cryoablation look somewhat better, he continued.

Dr. Estes predicted that the future of catheter ablation of AF hangs on three major ongoing rigorous randomized clinical trials comparing it to drug therapy with hard endpoints including all-cause mortality and cardiovascular hospitalizations. These are CASTLE-AF, with 420 patients; CABANA, with 2,200; and the German EAST study, with roughly 3,000 patients. Results are expected in 2018-2019.

Dr. Estes reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.

bjancin@frontlinemedcom.com

People under the age of 45 with chronic back pain for more than 3 months can be reliably identified as having axial spondyloarthritis (axSpA) if they have one or more of three SpA disease features, researchers report in Arthritis & Rheumatology.

The research team, led by rheumatologist Dr. Atul Deodhar from Oregon Health & Science University in Portland, noted that results of the German MASTER study indicated that among undiagnosed patients with chronic back pain starting before the age of 45 the presence of inflammatory back pain, human leukocyte antigen B27 (HLA-B27), and/or sacroiliitis on imaging was a reliable screening method for axSpA.

However, the authors said, there is limited information on the epidemiology of axSpA, which encompasses ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA), in the United States. Both AS and nr-axSpA typically go undiagnosed for many years, but AS is more easily identified by the presence of sacroiliitis on radiographs.

In order to determine if the German research finding applied to the U.S. population, the researchers conducted the Prevalence of Axial SpA (PROSpA) trial, involving 751 patients from 68 rheumatology centers who were either existing patients in rheumatology practices, new referrals, or were self-referred.

Participants were required to have chronic back pain for 3 or more months beginning at less than 45 years of age and have one or more of three SpA features: 1. positive HLA-B27; 2. current inflammatory back pain; and 3. MRI/x-ray evidence of sacroiliitis, and no prior SpA diagnosis.

Medical history/physical exam, pelvic x-ray, MRI of sacroiliac joints, C-reactive protein, and HLA-B27 were collected and rheumatologists were asked if a clinical diagnosis of axSpA could be made based upon results. 

Results showed that out of a total of 697 patients, 319 (46%) were given a clinical diagnosis of axSpA by the rheumatologist (Arthritis Rheumatol. 2016 Jan 27. doi: 10.1002/art.39612).

Of 744 patients, 348 (47%) fulfilled Assessment of SpondyloArthritis International Society (ASAS) criteria. Of these, 238 were classified as nr-axSpA, and 108 were classified as having AS based on fulfillment of the modified New York criteria. (Two patients had missing data.)

Additionally, 238 (32%) patients were categorized as having nr-axSpA, and 396 patients did not fulfill ASAS criteria or the modified New York criteria for AS.

The specificity and sensitivity of the ASAS criteria are reported at 84% and 83%. About 80% of the patients who received a clinical diagnosis of axSpA also fulfilled the ASAS axSpA criteria. The specificity and sensitivity of the criteria in this study were 79% (95% confidence interval, 75%-83%) and 81% (95% CI, 77%-85%), respectively.

The researchers noted that the majority of patients who received a diagnosis from a rheumatologist fulfilled the imaging arm of the ASAS criteria, whereas those who did not receive a diagnosis fulfilled the clinical arm.

“This observation highlights the need for accurate interpretation of MRI images in clinical practice given the importance of MRI imaging for evaluation of patients for axial SpA,” they wrote.

Overall, the findings emphasized the need to improve the identification and diagnosis of both AS and nr-axSpA among patients already receiving care in rheumatology practices and those newly referred to rheumatologists, the researchers said.

“These patients experience similar burden of disease and can remain undiagnosed, and therefore, untreated, for many years,” they wrote.

Indeed, the data indicated that some of the patients included in the study had symptoms for an average of 14 years, they said.

People under the age of 45 with chronic back pain for more than 3 months can be reliably identified as having axial spondyloarthritis (axSpA) if they have one or more of three SpA disease features, researchers report in Arthritis & Rheumatology.

The research team, led by rheumatologist Dr. Atul Deodhar from Oregon Health & Science University in Portland, noted that results of the German MASTER study indicated that among undiagnosed patients with chronic back pain starting before the age of 45 the presence of inflammatory back pain, human leukocyte antigen B27 (HLA-B27), and/or sacroiliitis on imaging was a reliable screening method for axSpA.

However, the authors said, there is limited information on the epidemiology of axSpA, which encompasses ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA), in the United States. Both AS and nr-axSpA typically go undiagnosed for many years, but AS is more easily identified by the presence of sacroiliitis on radiographs.

In order to determine if the German research finding applied to the U.S. population, the researchers conducted the Prevalence of Axial SpA (PROSpA) trial, involving 751 patients from 68 rheumatology centers who were either existing patients in rheumatology practices, new referrals, or were self-referred.

Participants were required to have chronic back pain for 3 or more months beginning at less than 45 years of age and have one or more of three SpA features: 1. positive HLA-B27; 2. current inflammatory back pain; and 3. MRI/x-ray evidence of sacroiliitis, and no prior SpA diagnosis.

Medical history/physical exam, pelvic x-ray, MRI of sacroiliac joints, C-reactive protein, and HLA-B27 were collected and rheumatologists were asked if a clinical diagnosis of axSpA could be made based upon results. 

Results showed that out of a total of 697 patients, 319 (46%) were given a clinical diagnosis of axSpA by the rheumatologist (Arthritis Rheumatol. 2016 Jan 27. doi: 10.1002/art.39612).

Of 744 patients, 348 (47%) fulfilled Assessment of SpondyloArthritis International Society (ASAS) criteria. Of these, 238 were classified as nr-axSpA, and 108 were classified as having AS based on fulfillment of the modified New York criteria. (Two patients had missing data.)

Additionally, 238 (32%) patients were categorized as having nr-axSpA, and 396 patients did not fulfill ASAS criteria or the modified New York criteria for AS.

The specificity and sensitivity of the ASAS criteria are reported at 84% and 83%. About 80% of the patients who received a clinical diagnosis of axSpA also fulfilled the ASAS axSpA criteria. The specificity and sensitivity of the criteria in this study were 79% (95% confidence interval, 75%-83%) and 81% (95% CI, 77%-85%), respectively.

The researchers noted that the majority of patients who received a diagnosis from a rheumatologist fulfilled the imaging arm of the ASAS criteria, whereas those who did not receive a diagnosis fulfilled the clinical arm.

“This observation highlights the need for accurate interpretation of MRI images in clinical practice given the importance of MRI imaging for evaluation of patients for axial SpA,” they wrote.

Overall, the findings emphasized the need to improve the identification and diagnosis of both AS and nr-axSpA among patients already receiving care in rheumatology practices and those newly referred to rheumatologists, the researchers said.

“These patients experience similar burden of disease and can remain undiagnosed, and therefore, untreated, for many years,” they wrote.

Indeed, the data indicated that some of the patients included in the study had symptoms for an average of 14 years, they said.

People under the age of 45 with chronic back pain for more than 3 months can be reliably identified as having axial spondyloarthritis (axSpA) if they have one or more of three SpA disease features, researchers report in Arthritis & Rheumatology.

The research team, led by rheumatologist Dr. Atul Deodhar from Oregon Health & Science University in Portland, noted that results of the German MASTER study indicated that among undiagnosed patients with chronic back pain starting before the age of 45 the presence of inflammatory back pain, human leukocyte antigen B27 (HLA-B27), and/or sacroiliitis on imaging was a reliable screening method for axSpA.

However, the authors said, there is limited information on the epidemiology of axSpA, which encompasses ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA), in the United States. Both AS and nr-axSpA typically go undiagnosed for many years, but AS is more easily identified by the presence of sacroiliitis on radiographs.

In order to determine if the German research finding applied to the U.S. population, the researchers conducted the Prevalence of Axial SpA (PROSpA) trial, involving 751 patients from 68 rheumatology centers who were either existing patients in rheumatology practices, new referrals, or were self-referred.

Participants were required to have chronic back pain for 3 or more months beginning at less than 45 years of age and have one or more of three SpA features: 1. positive HLA-B27; 2. current inflammatory back pain; and 3. MRI/x-ray evidence of sacroiliitis, and no prior SpA diagnosis.

Medical history/physical exam, pelvic x-ray, MRI of sacroiliac joints, C-reactive protein, and HLA-B27 were collected and rheumatologists were asked if a clinical diagnosis of axSpA could be made based upon results. 

Results showed that out of a total of 697 patients, 319 (46%) were given a clinical diagnosis of axSpA by the rheumatologist (Arthritis Rheumatol. 2016 Jan 27. doi: 10.1002/art.39612).

Of 744 patients, 348 (47%) fulfilled Assessment of SpondyloArthritis International Society (ASAS) criteria. Of these, 238 were classified as nr-axSpA, and 108 were classified as having AS based on fulfillment of the modified New York criteria. (Two patients had missing data.)

Additionally, 238 (32%) patients were categorized as having nr-axSpA, and 396 patients did not fulfill ASAS criteria or the modified New York criteria for AS.

The specificity and sensitivity of the ASAS criteria are reported at 84% and 83%. About 80% of the patients who received a clinical diagnosis of axSpA also fulfilled the ASAS axSpA criteria. The specificity and sensitivity of the criteria in this study were 79% (95% confidence interval, 75%-83%) and 81% (95% CI, 77%-85%), respectively.

The researchers noted that the majority of patients who received a diagnosis from a rheumatologist fulfilled the imaging arm of the ASAS criteria, whereas those who did not receive a diagnosis fulfilled the clinical arm.

“This observation highlights the need for accurate interpretation of MRI images in clinical practice given the importance of MRI imaging for evaluation of patients for axial SpA,” they wrote.

Overall, the findings emphasized the need to improve the identification and diagnosis of both AS and nr-axSpA among patients already receiving care in rheumatology practices and those newly referred to rheumatologists, the researchers said.

“These patients experience similar burden of disease and can remain undiagnosed, and therefore, untreated, for many years,” they wrote.

Indeed, the data indicated that some of the patients included in the study had symptoms for an average of 14 years, they said.

Youn Kim, MD

Photo by Larry Young

SAN FRANCISCO—The PD-1-blocking antibody pembrolizumab can produce “significant objective clinical responses” in patients with relapsed or refractory cutaneous T-cell lymphoma, according to researchers.

The drug elicited partial responses in 33% of patients enrolled in a phase 2 study. Half of the responders had mycosis fungoides (MF), and half had Sézary syndrome (SS).

All responses are ongoing, and a few patients with stable disease remain on treatment, so they may convert to partial responses, according to Youn Kim, MD, of Stanford University School of Medicine in California.

Dr Kim presented this research at the 8th Annual T-cell Lymphoma Forum.

The study was conducted by the Cancer Immunotherapy Trials Network (CITN) and supported by the National Cancer Institute and Merck, the company developing pembrolizumab.

“There’s good rationale for immune checkpoint blockade in [MF and SS],” Dr Kim said. “There’s systemic and local immune impairment in MF and Sézary, and there’s mounting evidence that T-cell immunity is critical for meaningful antitumor response.”

“[T]umor-infiltrating CD8+ T cells [have been] associated with improved survival, and therapies which augment T-cell function are effective in [MF and SS]. PD-1 and PD-L1 are very well expressed in the tissue and blood, [and] there’s good genomic evidence of immune evasion in [MF and SS].”

With all this in mind, Dr Kim and her colleagues conducted their phase 2 trial of pembrolizumab in 24 patients with relapsed or refractory MF/SS. Patients were excluded if they had central nervous system disease, autoimmune disease, immunodeficiency, or had received immunosuppressive therapy within 7 days.

The patients’ median age was 67 (range, 44-85), and most were male (75%). Thirty-eight percent of patients (n=9) had MF, and 62% (n=15) had SS. Twelve percent (n=3) had large-cell transformation.

Most patients had Stage IVA disease (62%, n=15), followed by IIIB (13%, n=3), IIIA (13%, n=3), IIB (8%, n=2), and IB (4%, n=1). The median number of prior systemic therapies was 4 (range, 1-10).

Treatment and response

Patients received pembrolizumab at 2 mg/kg intravenously every 3 weeks and were allowed to continue therapy for up to 2 years. Dr Kim noted that patients could continue treatment even after the initial documentation of progressive disease (PD) due to the possibility of immune-mediated flare reactions.

“So it’s the investigator’s decision to allow treatment beyond the initial PD,” she said. “However, if there’s confirmation of PD, those people will be removed.”

The median follow-up was 21 weeks (range, 7-39). Eight patients responded to treatment (according to global response criteria), all of which were partial responses. Four of the responders had MF, and 4 had SS. Responses occurred across all disease stages except IB.

“The range of prior therapies varied in the responders,” Dr Kim noted. “People think [patients tend to respond to] immunotherapy [if they are only] mildly [pre-]treated, but that was not the case. Heavily treated patients had great responses to pembrolizumab.”

All responses are ongoing, with a median duration of 13+ weeks (range, 3+ to 30+). The median time to response was 11 weeks (range, 8-22).

Dr Kim noted that 1 responder discontinued treatment because of a severe adverse event, but this patient remains in response without having received subsequent treatment.

The median best mSWAT (modified Skin Weighted Assessment Tool) reduction was 16%. Two patients had near-complete responses in the skin, and 2 patients with stable disease in the skin continue to improve.

Eleven of the 15 SS patients had measurable Sézary burden pre-treatment. And 3 of these patients had a greater than 50% reduction in Sézary count after treatment.

Four patients with stable disease are still on treatment. And at 20 weeks, 75% of patients are progression-free, according to Kaplan-Meier estimates.

Adverse events

Drug-related adverse events occurring at least twice included skin eruptions (21%, n=5), anemia (13%, n=3), decrease in white blood cell count (8%, n=2), elevated liver tests (8%, n=2), diarrhea (8%, n=2), fever (8%, n=2), and face edema (8%, n=2).

Grade 3/4 adverse events included skin eruptions (8%, n=2), anemia (8%, n=2), elevated liver tests (4%, n=1), and face edema (4%, n=1). Skin eruptions (of all grades) included exfoliative dermatitis (n=2), immune-mediated skin flare (n=2), and excessive peeling/edema (n=1).

There were no drug-related serious adverse events. The cause of the aforementioned serious adverse event (which prompted the responding patient to discontinue treatment) could not be determined.

There were 4 patients who did not report any adverse events, regardless of attribution.

In closing, Dr Kim said it is important to conduct biomarker correlative studies to understand the tumor escape mechanisms and enrich the response population.

She and her colleagues at CITN are now exploring the use of pembrolizumab in combination therapy. They are considering combining the drug with interferon-gamma, interleukin-12, low-dose total skin radiation, intratumoral ipilimumab, or Toll-like receptor agonists.

Youn Kim, MD

Photo by Larry Young

SAN FRANCISCO—The PD-1-blocking antibody pembrolizumab can produce “significant objective clinical responses” in patients with relapsed or refractory cutaneous T-cell lymphoma, according to researchers.

The drug elicited partial responses in 33% of patients enrolled in a phase 2 study. Half of the responders had mycosis fungoides (MF), and half had Sézary syndrome (SS).

All responses are ongoing, and a few patients with stable disease remain on treatment, so they may convert to partial responses, according to Youn Kim, MD, of Stanford University School of Medicine in California.

Dr Kim presented this research at the 8th Annual T-cell Lymphoma Forum.

The study was conducted by the Cancer Immunotherapy Trials Network (CITN) and supported by the National Cancer Institute and Merck, the company developing pembrolizumab.

“There’s good rationale for immune checkpoint blockade in [MF and SS],” Dr Kim said. “There’s systemic and local immune impairment in MF and Sézary, and there’s mounting evidence that T-cell immunity is critical for meaningful antitumor response.”

“[T]umor-infiltrating CD8+ T cells [have been] associated with improved survival, and therapies which augment T-cell function are effective in [MF and SS]. PD-1 and PD-L1 are very well expressed in the tissue and blood, [and] there’s good genomic evidence of immune evasion in [MF and SS].”

With all this in mind, Dr Kim and her colleagues conducted their phase 2 trial of pembrolizumab in 24 patients with relapsed or refractory MF/SS. Patients were excluded if they had central nervous system disease, autoimmune disease, immunodeficiency, or had received immunosuppressive therapy within 7 days.

The patients’ median age was 67 (range, 44-85), and most were male (75%). Thirty-eight percent of patients (n=9) had MF, and 62% (n=15) had SS. Twelve percent (n=3) had large-cell transformation.

Most patients had Stage IVA disease (62%, n=15), followed by IIIB (13%, n=3), IIIA (13%, n=3), IIB (8%, n=2), and IB (4%, n=1). The median number of prior systemic therapies was 4 (range, 1-10).

Treatment and response

Patients received pembrolizumab at 2 mg/kg intravenously every 3 weeks and were allowed to continue therapy for up to 2 years. Dr Kim noted that patients could continue treatment even after the initial documentation of progressive disease (PD) due to the possibility of immune-mediated flare reactions.

“So it’s the investigator’s decision to allow treatment beyond the initial PD,” she said. “However, if there’s confirmation of PD, those people will be removed.”

The median follow-up was 21 weeks (range, 7-39). Eight patients responded to treatment (according to global response criteria), all of which were partial responses. Four of the responders had MF, and 4 had SS. Responses occurred across all disease stages except IB.

“The range of prior therapies varied in the responders,” Dr Kim noted. “People think [patients tend to respond to] immunotherapy [if they are only] mildly [pre-]treated, but that was not the case. Heavily treated patients had great responses to pembrolizumab.”

All responses are ongoing, with a median duration of 13+ weeks (range, 3+ to 30+). The median time to response was 11 weeks (range, 8-22).

Dr Kim noted that 1 responder discontinued treatment because of a severe adverse event, but this patient remains in response without having received subsequent treatment.

The median best mSWAT (modified Skin Weighted Assessment Tool) reduction was 16%. Two patients had near-complete responses in the skin, and 2 patients with stable disease in the skin continue to improve.

Eleven of the 15 SS patients had measurable Sézary burden pre-treatment. And 3 of these patients had a greater than 50% reduction in Sézary count after treatment.

Four patients with stable disease are still on treatment. And at 20 weeks, 75% of patients are progression-free, according to Kaplan-Meier estimates.

Adverse events

Drug-related adverse events occurring at least twice included skin eruptions (21%, n=5), anemia (13%, n=3), decrease in white blood cell count (8%, n=2), elevated liver tests (8%, n=2), diarrhea (8%, n=2), fever (8%, n=2), and face edema (8%, n=2).

Grade 3/4 adverse events included skin eruptions (8%, n=2), anemia (8%, n=2), elevated liver tests (4%, n=1), and face edema (4%, n=1). Skin eruptions (of all grades) included exfoliative dermatitis (n=2), immune-mediated skin flare (n=2), and excessive peeling/edema (n=1).

There were no drug-related serious adverse events. The cause of the aforementioned serious adverse event (which prompted the responding patient to discontinue treatment) could not be determined.

There were 4 patients who did not report any adverse events, regardless of attribution.

In closing, Dr Kim said it is important to conduct biomarker correlative studies to understand the tumor escape mechanisms and enrich the response population.

She and her colleagues at CITN are now exploring the use of pembrolizumab in combination therapy. They are considering combining the drug with interferon-gamma, interleukin-12, low-dose total skin radiation, intratumoral ipilimumab, or Toll-like receptor agonists.

Youn Kim, MD

Photo by Larry Young

SAN FRANCISCO—The PD-1-blocking antibody pembrolizumab can produce “significant objective clinical responses” in patients with relapsed or refractory cutaneous T-cell lymphoma, according to researchers.

The drug elicited partial responses in 33% of patients enrolled in a phase 2 study. Half of the responders had mycosis fungoides (MF), and half had Sézary syndrome (SS).

All responses are ongoing, and a few patients with stable disease remain on treatment, so they may convert to partial responses, according to Youn Kim, MD, of Stanford University School of Medicine in California.

Dr Kim presented this research at the 8th Annual T-cell Lymphoma Forum.

The study was conducted by the Cancer Immunotherapy Trials Network (CITN) and supported by the National Cancer Institute and Merck, the company developing pembrolizumab.

“There’s good rationale for immune checkpoint blockade in [MF and SS],” Dr Kim said. “There’s systemic and local immune impairment in MF and Sézary, and there’s mounting evidence that T-cell immunity is critical for meaningful antitumor response.”

“[T]umor-infiltrating CD8+ T cells [have been] associated with improved survival, and therapies which augment T-cell function are effective in [MF and SS]. PD-1 and PD-L1 are very well expressed in the tissue and blood, [and] there’s good genomic evidence of immune evasion in [MF and SS].”

With all this in mind, Dr Kim and her colleagues conducted their phase 2 trial of pembrolizumab in 24 patients with relapsed or refractory MF/SS. Patients were excluded if they had central nervous system disease, autoimmune disease, immunodeficiency, or had received immunosuppressive therapy within 7 days.

The patients’ median age was 67 (range, 44-85), and most were male (75%). Thirty-eight percent of patients (n=9) had MF, and 62% (n=15) had SS. Twelve percent (n=3) had large-cell transformation.

Most patients had Stage IVA disease (62%, n=15), followed by IIIB (13%, n=3), IIIA (13%, n=3), IIB (8%, n=2), and IB (4%, n=1). The median number of prior systemic therapies was 4 (range, 1-10).

Treatment and response

Patients received pembrolizumab at 2 mg/kg intravenously every 3 weeks and were allowed to continue therapy for up to 2 years. Dr Kim noted that patients could continue treatment even after the initial documentation of progressive disease (PD) due to the possibility of immune-mediated flare reactions.

“So it’s the investigator’s decision to allow treatment beyond the initial PD,” she said. “However, if there’s confirmation of PD, those people will be removed.”

The median follow-up was 21 weeks (range, 7-39). Eight patients responded to treatment (according to global response criteria), all of which were partial responses. Four of the responders had MF, and 4 had SS. Responses occurred across all disease stages except IB.

“The range of prior therapies varied in the responders,” Dr Kim noted. “People think [patients tend to respond to] immunotherapy [if they are only] mildly [pre-]treated, but that was not the case. Heavily treated patients had great responses to pembrolizumab.”

All responses are ongoing, with a median duration of 13+ weeks (range, 3+ to 30+). The median time to response was 11 weeks (range, 8-22).

Dr Kim noted that 1 responder discontinued treatment because of a severe adverse event, but this patient remains in response without having received subsequent treatment.

The median best mSWAT (modified Skin Weighted Assessment Tool) reduction was 16%. Two patients had near-complete responses in the skin, and 2 patients with stable disease in the skin continue to improve.

Eleven of the 15 SS patients had measurable Sézary burden pre-treatment. And 3 of these patients had a greater than 50% reduction in Sézary count after treatment.

Four patients with stable disease are still on treatment. And at 20 weeks, 75% of patients are progression-free, according to Kaplan-Meier estimates.

Adverse events

Drug-related adverse events occurring at least twice included skin eruptions (21%, n=5), anemia (13%, n=3), decrease in white blood cell count (8%, n=2), elevated liver tests (8%, n=2), diarrhea (8%, n=2), fever (8%, n=2), and face edema (8%, n=2).

Grade 3/4 adverse events included skin eruptions (8%, n=2), anemia (8%, n=2), elevated liver tests (4%, n=1), and face edema (4%, n=1). Skin eruptions (of all grades) included exfoliative dermatitis (n=2), immune-mediated skin flare (n=2), and excessive peeling/edema (n=1).

There were no drug-related serious adverse events. The cause of the aforementioned serious adverse event (which prompted the responding patient to discontinue treatment) could not be determined.

There were 4 patients who did not report any adverse events, regardless of attribution.

In closing, Dr Kim said it is important to conduct biomarker correlative studies to understand the tumor escape mechanisms and enrich the response population.

She and her colleagues at CITN are now exploring the use of pembrolizumab in combination therapy. They are considering combining the drug with interferon-gamma, interleukin-12, low-dose total skin radiation, intratumoral ipilimumab, or Toll-like receptor agonists.