EDINBURGH – Treatment induction with obinutuzumab and ibrutinib followed by a minimal residual disease (MRD)–driven treatment strategy in patients with chronic lymphocytic leukemia (CLL) yields a high long-term complete response rate and prolonged progression-free and overall survival, according to findings from the phase 2 ICLL-07 trial.

The intent-to-treat (ITT) complete response rate at 16 months in 135 patients who were treated with this strategy was 62%, Anne-Sophie Michallet, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Patients in the multicenter, open-label trial conducted by the French Innovative Leukemia Organization (FILO) were previously untreated, medically fit patients with CLL and no 17p deletion. They were enrolled between November 2015 and May 2017 to receive eight 1,000 mg IV doses of obinutuzumab over six 4-week cycles along with oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib at a dose of 420 mg daily for 9 months.

Ten patients (7.7%) achieved complete response with bone marrow MRD less than 0.01% (undetectable) at 9 months and, by study protocol, continued on only the ibrutinib for 6 additional months. The remaining 120 evaluable patients received four 4-week cycles of fludarabine/cyclophosphamide along with the obinutuzumab and ibrutinib for 6 additional months, explained Dr. Michallet of Centre Léon Bérard, Lyon, France.

The ITT rate at 16 months – the primary endpoint of the study – was achieved with no more than four cycles of fludarabine/cyclophosphamide and obinutuzumab, and exceeded the primary objective of demonstrating a 30% or higher rate of complete response with bone marrow MRD less than 0.01% at the month 16 ITT analysis, she said.

“The ... strategy yielded an overall response rate of 100%, a complete response rate, according to iwCLL [criteria], of 73%, a bone marrow MRD–undetectable rate of 79% [in the ITT population],” she said, adding that the primary objective was achieved with a complete response with a peripheral blood and bone marrow MRD–undetectable rate of 62%.

Response assessments at months 9 and 16 involved whole-body computed tomography scans with tumor measurements and bone marrow trephine biopsy for patients in clinical complete response. MRD testing was performed by eight-color flow cytometry in both peripheral blood and bone marrow.

After month 16, response was clinically assessed every 3 months, and peripheral blood MRD was assessed every 6 months until month 40.

“With a median follow-up of 26.3 months, the 2-year progression-free survival and overall survival were, respectively, 97% and 97.5%,” Dr. Michallet said, noting that the longitudinal follow-up of peripheral blood MRD in the entire cohort showed durability of a deep response. The rate of peripheral blood MRD less than 0.01% at 22 months was 77% in the 10 patients who received only ibrutinib after the 9-month assessment, and 93% in those who received fludarabine/cyclophosphamide after the 9-month assessment.

In patients with immunoglobulin heavy gene variable (IGHV) mutations, the rate of peripheral blood MRD less than 0.01% at month 22 was 96%, and in those without IGHV mutations, the rate was 77%, she noted.

The findings demonstrate that the approach has merit in medically fit, treatment-naive patients with CLL and no 17p deletion, she said, explaining that the fixed-duration, MRD-driven strategy used in this study was developed to “avoid or at least reduce chemotherapy exposure” in the first-line treatment of such patients.

Indeed, the approach was associated with “a high [complete response] rate, a high level of undetectable bone marrow MRD, an acceptable safety profile, and a sustained MRD negativity rate at 12 months after the end of the treatment,” she said.

“This highly effective strategy combining a BTK inhibitor and abbreviated immunochemotherapy deserves further investigation with randomized trials,” she concluded.

ICLL-07 FILO was funded by Roche and Janssen. Dr. Michallet reported having no disclosures.

sworcester@mdedge.com

EDINBURGH – Treatment induction with obinutuzumab and ibrutinib followed by a minimal residual disease (MRD)–driven treatment strategy in patients with chronic lymphocytic leukemia (CLL) yields a high long-term complete response rate and prolonged progression-free and overall survival, according to findings from the phase 2 ICLL-07 trial.

The intent-to-treat (ITT) complete response rate at 16 months in 135 patients who were treated with this strategy was 62%, Anne-Sophie Michallet, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Patients in the multicenter, open-label trial conducted by the French Innovative Leukemia Organization (FILO) were previously untreated, medically fit patients with CLL and no 17p deletion. They were enrolled between November 2015 and May 2017 to receive eight 1,000 mg IV doses of obinutuzumab over six 4-week cycles along with oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib at a dose of 420 mg daily for 9 months.

Ten patients (7.7%) achieved complete response with bone marrow MRD less than 0.01% (undetectable) at 9 months and, by study protocol, continued on only the ibrutinib for 6 additional months. The remaining 120 evaluable patients received four 4-week cycles of fludarabine/cyclophosphamide along with the obinutuzumab and ibrutinib for 6 additional months, explained Dr. Michallet of Centre Léon Bérard, Lyon, France.

The ITT rate at 16 months – the primary endpoint of the study – was achieved with no more than four cycles of fludarabine/cyclophosphamide and obinutuzumab, and exceeded the primary objective of demonstrating a 30% or higher rate of complete response with bone marrow MRD less than 0.01% at the month 16 ITT analysis, she said.

“The ... strategy yielded an overall response rate of 100%, a complete response rate, according to iwCLL [criteria], of 73%, a bone marrow MRD–undetectable rate of 79% [in the ITT population],” she said, adding that the primary objective was achieved with a complete response with a peripheral blood and bone marrow MRD–undetectable rate of 62%.

Response assessments at months 9 and 16 involved whole-body computed tomography scans with tumor measurements and bone marrow trephine biopsy for patients in clinical complete response. MRD testing was performed by eight-color flow cytometry in both peripheral blood and bone marrow.

After month 16, response was clinically assessed every 3 months, and peripheral blood MRD was assessed every 6 months until month 40.

“With a median follow-up of 26.3 months, the 2-year progression-free survival and overall survival were, respectively, 97% and 97.5%,” Dr. Michallet said, noting that the longitudinal follow-up of peripheral blood MRD in the entire cohort showed durability of a deep response. The rate of peripheral blood MRD less than 0.01% at 22 months was 77% in the 10 patients who received only ibrutinib after the 9-month assessment, and 93% in those who received fludarabine/cyclophosphamide after the 9-month assessment.

In patients with immunoglobulin heavy gene variable (IGHV) mutations, the rate of peripheral blood MRD less than 0.01% at month 22 was 96%, and in those without IGHV mutations, the rate was 77%, she noted.

The findings demonstrate that the approach has merit in medically fit, treatment-naive patients with CLL and no 17p deletion, she said, explaining that the fixed-duration, MRD-driven strategy used in this study was developed to “avoid or at least reduce chemotherapy exposure” in the first-line treatment of such patients.

Indeed, the approach was associated with “a high [complete response] rate, a high level of undetectable bone marrow MRD, an acceptable safety profile, and a sustained MRD negativity rate at 12 months after the end of the treatment,” she said.

“This highly effective strategy combining a BTK inhibitor and abbreviated immunochemotherapy deserves further investigation with randomized trials,” she concluded.

ICLL-07 FILO was funded by Roche and Janssen. Dr. Michallet reported having no disclosures.

sworcester@mdedge.com

EDINBURGH – Treatment induction with obinutuzumab and ibrutinib followed by a minimal residual disease (MRD)–driven treatment strategy in patients with chronic lymphocytic leukemia (CLL) yields a high long-term complete response rate and prolonged progression-free and overall survival, according to findings from the phase 2 ICLL-07 trial.

The intent-to-treat (ITT) complete response rate at 16 months in 135 patients who were treated with this strategy was 62%, Anne-Sophie Michallet, MD, reported at the International Workshop on Chronic Lymphocytic Leukemia.

Patients in the multicenter, open-label trial conducted by the French Innovative Leukemia Organization (FILO) were previously untreated, medically fit patients with CLL and no 17p deletion. They were enrolled between November 2015 and May 2017 to receive eight 1,000 mg IV doses of obinutuzumab over six 4-week cycles along with oral Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib at a dose of 420 mg daily for 9 months.

Ten patients (7.7%) achieved complete response with bone marrow MRD less than 0.01% (undetectable) at 9 months and, by study protocol, continued on only the ibrutinib for 6 additional months. The remaining 120 evaluable patients received four 4-week cycles of fludarabine/cyclophosphamide along with the obinutuzumab and ibrutinib for 6 additional months, explained Dr. Michallet of Centre Léon Bérard, Lyon, France.

The ITT rate at 16 months – the primary endpoint of the study – was achieved with no more than four cycles of fludarabine/cyclophosphamide and obinutuzumab, and exceeded the primary objective of demonstrating a 30% or higher rate of complete response with bone marrow MRD less than 0.01% at the month 16 ITT analysis, she said.

“The ... strategy yielded an overall response rate of 100%, a complete response rate, according to iwCLL [criteria], of 73%, a bone marrow MRD–undetectable rate of 79% [in the ITT population],” she said, adding that the primary objective was achieved with a complete response with a peripheral blood and bone marrow MRD–undetectable rate of 62%.

Response assessments at months 9 and 16 involved whole-body computed tomography scans with tumor measurements and bone marrow trephine biopsy for patients in clinical complete response. MRD testing was performed by eight-color flow cytometry in both peripheral blood and bone marrow.

After month 16, response was clinically assessed every 3 months, and peripheral blood MRD was assessed every 6 months until month 40.

“With a median follow-up of 26.3 months, the 2-year progression-free survival and overall survival were, respectively, 97% and 97.5%,” Dr. Michallet said, noting that the longitudinal follow-up of peripheral blood MRD in the entire cohort showed durability of a deep response. The rate of peripheral blood MRD less than 0.01% at 22 months was 77% in the 10 patients who received only ibrutinib after the 9-month assessment, and 93% in those who received fludarabine/cyclophosphamide after the 9-month assessment.

In patients with immunoglobulin heavy gene variable (IGHV) mutations, the rate of peripheral blood MRD less than 0.01% at month 22 was 96%, and in those without IGHV mutations, the rate was 77%, she noted.

The findings demonstrate that the approach has merit in medically fit, treatment-naive patients with CLL and no 17p deletion, she said, explaining that the fixed-duration, MRD-driven strategy used in this study was developed to “avoid or at least reduce chemotherapy exposure” in the first-line treatment of such patients.

Indeed, the approach was associated with “a high [complete response] rate, a high level of undetectable bone marrow MRD, an acceptable safety profile, and a sustained MRD negativity rate at 12 months after the end of the treatment,” she said.

“This highly effective strategy combining a BTK inhibitor and abbreviated immunochemotherapy deserves further investigation with randomized trials,” she concluded.

ICLL-07 FILO was funded by Roche and Janssen. Dr. Michallet reported having no disclosures.

sworcester@mdedge.com

Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.

“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”

The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.

An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.

Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.

At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.

Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).

Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.

“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.

“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.

Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.

SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.

Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.

“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”

The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.

An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.

Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.

At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.

Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).

Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.

“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.

“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.

Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.

SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.

Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.

“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”

The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.

An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.

Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.

At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.

Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).

Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.

“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.

“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.

Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.

SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.

Both the Society of Hospital Medicine and Jefferson College of Population Health, of Thomas Jefferson University in Philadelphia, share a goal to educate physicians to be effective leaders and managers in the pursuit of health care quality, safety, and population health, and they have entered into a partnership with this in mind.

Alexis Skoufalos, EdD, associate dean, strategic development, for Jefferson College of Population Health, recently spoke with The Hospitalist to discuss the importance of population health to hospital medicine professionals, the health care landscape as a whole, and the benefits of this new partnership with SHM.
 

Can you explain the importance of population health in the current health care landscape?

Many people confuse population health with public health. While they are related, they are different disciplines. Public health focuses on prevention and health promotion (clean water, vaccines, exercise, using seat belts, and so on), but it stops there.

Population health builds on the foundation of public health and goes a step further, working to connect health and health care delivery. It takes a more holistic approach, looking at what we need to do inside and outside the delivery system to help people to get and stay healthy, as well as take better care of them when they do get sick.

We work to identify and understand the health impact of social and environmental factors, while also looking for ways to make health care delivery safer, better, and more affordable and accessible.

This can get complicated. It involves sorting through lots of information to uncover the best way to meet the needs of a specific group, whether that is a community, a neighborhood, or a patient with a particular condition.

It’s about taking the time to really look at things from different vantage points. You won’t see the same view if you are looking at something through a telescope as you would looking through a microscope. That information can help you to adjust your perspective to identify the best course of action.

In order to be successful in improving population health, providers need to understand how to work with the other stakeholders in the health care ecosystem. Collaboration and coordination are the best ways to optimize the resources available.

It is important for delivery systems to establish good working relationships with community nonprofit and service organizations, faith-based organizations, social service providers, school systems, and federal, state, and local government.

At Jefferson, we thought it was important to create a college and programs that would prepare professionals across the workforce for this new challenge.
 

How did this partnership between SHM and Jefferson College of Population Health come to fruition?

Hospitalists are an important link with a person’s primary care team. The work they do to prepare a person and their family for successful discharge to the community after a hospital stay can make all the difference in a person’s recovery, condition management, and preventing readmission to the hospital.

Because both of our organizations are based in Philadelphia, we have had longstanding connections with SHM leadership. It was only natural for us to talk with SHM about how we can build upon the society’s excellent continuing education offerings and work together to provide members with additional content that can equip them to advance their careers.
 

How did SHM and Jefferson College of Population Health identify the mutually beneficial educational offerings in each institution that are included in this partnership?

Members of our respective leadership teams got together to complete a detailed review of the offerings from each organization. SHM’s Leadership Academy and JCPH’s Population Health Academy are rigorous continuing education programs that can provide physicians with excellent just-in-time information they can put to use right away.

After a careful examination of the curriculum, JCPH determined that SHM members can apply the credits they earn from completing two qualified sessions from the Leadership Academy to satisfy the elective course requirement for a Master’s degree. (Note: This does not apply to the Population Health Intelligence Program, which does not include an elective course.)
 

How will this partnership benefit Jefferson College of Population Health?

Our mission is to prepare health care leaders with the skills and tools they need to be effective in improving population health. Clinicians who work in a hospital setting have a key role to play.

We are also dedicated to making a difference right here in Philadelphia. The more students we have in our programs, the more of an impact we (and they) will have in improving outcomes in our own community.

We need to move the needle and get Philadelphia County out of the basement in terms of health rankings. We have a responsibility to do what we can to make a difference, and we appreciate the partnership with SHM to make it happen.
 

What other components of the partnership are especially noteworthy to highlight?

In addition to what I’ve already discussed, the following are some of the significant benefits that SHM members are entitled to as a result of the partnership with JCPH:

• 15% discount on tuition for any JCPH online graduate degree program.
• Registration discount for JCPH’s Population Health Academy in Philadelphia.
• Special registration rate for Annual Population Health Colloquium.

For more information about this partnership, visit hospitalmedicine.org/jefferson.






 

Both the Society of Hospital Medicine and Jefferson College of Population Health, of Thomas Jefferson University in Philadelphia, share a goal to educate physicians to be effective leaders and managers in the pursuit of health care quality, safety, and population health, and they have entered into a partnership with this in mind.

Alexis Skoufalos, EdD, associate dean, strategic development, for Jefferson College of Population Health, recently spoke with The Hospitalist to discuss the importance of population health to hospital medicine professionals, the health care landscape as a whole, and the benefits of this new partnership with SHM.
 

Can you explain the importance of population health in the current health care landscape?

Many people confuse population health with public health. While they are related, they are different disciplines. Public health focuses on prevention and health promotion (clean water, vaccines, exercise, using seat belts, and so on), but it stops there.

Population health builds on the foundation of public health and goes a step further, working to connect health and health care delivery. It takes a more holistic approach, looking at what we need to do inside and outside the delivery system to help people to get and stay healthy, as well as take better care of them when they do get sick.

We work to identify and understand the health impact of social and environmental factors, while also looking for ways to make health care delivery safer, better, and more affordable and accessible.

This can get complicated. It involves sorting through lots of information to uncover the best way to meet the needs of a specific group, whether that is a community, a neighborhood, or a patient with a particular condition.

It’s about taking the time to really look at things from different vantage points. You won’t see the same view if you are looking at something through a telescope as you would looking through a microscope. That information can help you to adjust your perspective to identify the best course of action.

In order to be successful in improving population health, providers need to understand how to work with the other stakeholders in the health care ecosystem. Collaboration and coordination are the best ways to optimize the resources available.

It is important for delivery systems to establish good working relationships with community nonprofit and service organizations, faith-based organizations, social service providers, school systems, and federal, state, and local government.

At Jefferson, we thought it was important to create a college and programs that would prepare professionals across the workforce for this new challenge.
 

How did this partnership between SHM and Jefferson College of Population Health come to fruition?

Hospitalists are an important link with a person’s primary care team. The work they do to prepare a person and their family for successful discharge to the community after a hospital stay can make all the difference in a person’s recovery, condition management, and preventing readmission to the hospital.

Because both of our organizations are based in Philadelphia, we have had longstanding connections with SHM leadership. It was only natural for us to talk with SHM about how we can build upon the society’s excellent continuing education offerings and work together to provide members with additional content that can equip them to advance their careers.
 

How did SHM and Jefferson College of Population Health identify the mutually beneficial educational offerings in each institution that are included in this partnership?

Members of our respective leadership teams got together to complete a detailed review of the offerings from each organization. SHM’s Leadership Academy and JCPH’s Population Health Academy are rigorous continuing education programs that can provide physicians with excellent just-in-time information they can put to use right away.

After a careful examination of the curriculum, JCPH determined that SHM members can apply the credits they earn from completing two qualified sessions from the Leadership Academy to satisfy the elective course requirement for a Master’s degree. (Note: This does not apply to the Population Health Intelligence Program, which does not include an elective course.)
 

How will this partnership benefit Jefferson College of Population Health?

Our mission is to prepare health care leaders with the skills and tools they need to be effective in improving population health. Clinicians who work in a hospital setting have a key role to play.

We are also dedicated to making a difference right here in Philadelphia. The more students we have in our programs, the more of an impact we (and they) will have in improving outcomes in our own community.

We need to move the needle and get Philadelphia County out of the basement in terms of health rankings. We have a responsibility to do what we can to make a difference, and we appreciate the partnership with SHM to make it happen.
 

What other components of the partnership are especially noteworthy to highlight?

In addition to what I’ve already discussed, the following are some of the significant benefits that SHM members are entitled to as a result of the partnership with JCPH:

• 15% discount on tuition for any JCPH online graduate degree program.
• Registration discount for JCPH’s Population Health Academy in Philadelphia.
• Special registration rate for Annual Population Health Colloquium.

For more information about this partnership, visit hospitalmedicine.org/jefferson.






 

Both the Society of Hospital Medicine and Jefferson College of Population Health, of Thomas Jefferson University in Philadelphia, share a goal to educate physicians to be effective leaders and managers in the pursuit of health care quality, safety, and population health, and they have entered into a partnership with this in mind.

Alexis Skoufalos, EdD, associate dean, strategic development, for Jefferson College of Population Health, recently spoke with The Hospitalist to discuss the importance of population health to hospital medicine professionals, the health care landscape as a whole, and the benefits of this new partnership with SHM.
 

Can you explain the importance of population health in the current health care landscape?

Many people confuse population health with public health. While they are related, they are different disciplines. Public health focuses on prevention and health promotion (clean water, vaccines, exercise, using seat belts, and so on), but it stops there.

Population health builds on the foundation of public health and goes a step further, working to connect health and health care delivery. It takes a more holistic approach, looking at what we need to do inside and outside the delivery system to help people to get and stay healthy, as well as take better care of them when they do get sick.

We work to identify and understand the health impact of social and environmental factors, while also looking for ways to make health care delivery safer, better, and more affordable and accessible.

This can get complicated. It involves sorting through lots of information to uncover the best way to meet the needs of a specific group, whether that is a community, a neighborhood, or a patient with a particular condition.

It’s about taking the time to really look at things from different vantage points. You won’t see the same view if you are looking at something through a telescope as you would looking through a microscope. That information can help you to adjust your perspective to identify the best course of action.

In order to be successful in improving population health, providers need to understand how to work with the other stakeholders in the health care ecosystem. Collaboration and coordination are the best ways to optimize the resources available.

It is important for delivery systems to establish good working relationships with community nonprofit and service organizations, faith-based organizations, social service providers, school systems, and federal, state, and local government.

At Jefferson, we thought it was important to create a college and programs that would prepare professionals across the workforce for this new challenge.
 

How did this partnership between SHM and Jefferson College of Population Health come to fruition?

Hospitalists are an important link with a person’s primary care team. The work they do to prepare a person and their family for successful discharge to the community after a hospital stay can make all the difference in a person’s recovery, condition management, and preventing readmission to the hospital.

Because both of our organizations are based in Philadelphia, we have had longstanding connections with SHM leadership. It was only natural for us to talk with SHM about how we can build upon the society’s excellent continuing education offerings and work together to provide members with additional content that can equip them to advance their careers.
 

How did SHM and Jefferson College of Population Health identify the mutually beneficial educational offerings in each institution that are included in this partnership?

Members of our respective leadership teams got together to complete a detailed review of the offerings from each organization. SHM’s Leadership Academy and JCPH’s Population Health Academy are rigorous continuing education programs that can provide physicians with excellent just-in-time information they can put to use right away.

After a careful examination of the curriculum, JCPH determined that SHM members can apply the credits they earn from completing two qualified sessions from the Leadership Academy to satisfy the elective course requirement for a Master’s degree. (Note: This does not apply to the Population Health Intelligence Program, which does not include an elective course.)
 

How will this partnership benefit Jefferson College of Population Health?

Our mission is to prepare health care leaders with the skills and tools they need to be effective in improving population health. Clinicians who work in a hospital setting have a key role to play.

We are also dedicated to making a difference right here in Philadelphia. The more students we have in our programs, the more of an impact we (and they) will have in improving outcomes in our own community.

We need to move the needle and get Philadelphia County out of the basement in terms of health rankings. We have a responsibility to do what we can to make a difference, and we appreciate the partnership with SHM to make it happen.
 

What other components of the partnership are especially noteworthy to highlight?

In addition to what I’ve already discussed, the following are some of the significant benefits that SHM members are entitled to as a result of the partnership with JCPH:

• 15% discount on tuition for any JCPH online graduate degree program.
• Registration discount for JCPH’s Population Health Academy in Philadelphia.
• Special registration rate for Annual Population Health Colloquium.

For more information about this partnership, visit hospitalmedicine.org/jefferson.






 

BARCELONA – Cancer drug prices are significantly higher in the United States than in Europe, and they don’t correlate with clinical benefit in either region, according to an analysis of drug costs and value-related scores between 2009 and 2018.

Of 63 cancer drugs approved by the Food and Drug Administration between 2009 and 2017 and by the European Medicines Agency as of December 31, 2018, 46 (73%) were approved for solid tumors, and 17 (27%) for hematologic malignancies. Median cancer drug prices in Europe were 52% lower than U.S. prices, Kerstin N. Vokinger, MD, Academic Chair For Health Policy at the Institute For Primary Care, University Hospital Zürich, and colleagues found.

The findings were released via press release at the European Society for Medical Oncology (ESMO) Congress and will be part of a poster discussion session there.

The investigators found no association between monthly treatment cost and the American Society of Clinical Oncology Value Framework (ASCO-VF) or the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores in any country. They also found no association between the price differential in the United States and Europe and either ASCO-VF (P = .599) or ESMO-MBCS (P = .321) scores.

For the analysis, they assessed U.S. average sales prices or, when those weren’t available, wholesale acquisition costs as of Feb. 1, 2019, and compared them with comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland.

ASCO-VF and ESMO-MCBS scores were then assessed based on the highest score from pivotal trials supporting each solid tumor drug.

The median monthly cost for drugs with low-benefit scores on ESMO-MCBS ranged from $4,361-$5,273 in the European countries, compared with $12,436 in the United States, according to the release.

“Drug costs were not associated with clinical benefit score in any of the countries we looked at. For example, some of the more expensive drugs for prostate and lung cancer in Switzerland had lower ESMO-MCBS scores, while cheaper drugs had higher scores,” said Dr. Vokinger, who also is affiliated with the Program on Regulation, Therapeutics, and Law at Harvard Medical School, Boston. “It is important that drug pricing is aligned with clinical value and that our limited resources are spent on innovative medicines that offer improved outcomes.”

Barbara Kiesewetter, MD, of the Medical University of Vienna and a member of the ESMO-MCBS Working Group, said the findings underscore the importance of using the scoring systems in clinical practice to assist in treatment-related decision making.

The ESMO-MCBS, for example, is available online, easy to use, and helps explain “the factors that are used to grade the clinical benefit of medicines.

“It’s very important to have this validated score not only for daily decision making, but to influence reimbursement decisions and reduce treatment disparities,” she said, also noting in the release that “[c]ost is one of the main reasons why patients are denied access to the newer anticancer drugs.”

“By showing which drugs are most likely to be worth the higher cost, we can hopefully improve access to the drugs with greatest value so that patients receive standardized, optimal therapy wherever they live,” she said.

The study was funded by the Swiss Cancer League. The authors reported having no conflicts of interest.

SOURCE: Vokinger KN et al. ESMO 2019, Abstract 1631PD-PR.

BARCELONA – Cancer drug prices are significantly higher in the United States than in Europe, and they don’t correlate with clinical benefit in either region, according to an analysis of drug costs and value-related scores between 2009 and 2018.

Of 63 cancer drugs approved by the Food and Drug Administration between 2009 and 2017 and by the European Medicines Agency as of December 31, 2018, 46 (73%) were approved for solid tumors, and 17 (27%) for hematologic malignancies. Median cancer drug prices in Europe were 52% lower than U.S. prices, Kerstin N. Vokinger, MD, Academic Chair For Health Policy at the Institute For Primary Care, University Hospital Zürich, and colleagues found.

The findings were released via press release at the European Society for Medical Oncology (ESMO) Congress and will be part of a poster discussion session there.

The investigators found no association between monthly treatment cost and the American Society of Clinical Oncology Value Framework (ASCO-VF) or the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores in any country. They also found no association between the price differential in the United States and Europe and either ASCO-VF (P = .599) or ESMO-MBCS (P = .321) scores.

For the analysis, they assessed U.S. average sales prices or, when those weren’t available, wholesale acquisition costs as of Feb. 1, 2019, and compared them with comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland.

ASCO-VF and ESMO-MCBS scores were then assessed based on the highest score from pivotal trials supporting each solid tumor drug.

The median monthly cost for drugs with low-benefit scores on ESMO-MCBS ranged from $4,361-$5,273 in the European countries, compared with $12,436 in the United States, according to the release.

“Drug costs were not associated with clinical benefit score in any of the countries we looked at. For example, some of the more expensive drugs for prostate and lung cancer in Switzerland had lower ESMO-MCBS scores, while cheaper drugs had higher scores,” said Dr. Vokinger, who also is affiliated with the Program on Regulation, Therapeutics, and Law at Harvard Medical School, Boston. “It is important that drug pricing is aligned with clinical value and that our limited resources are spent on innovative medicines that offer improved outcomes.”

Barbara Kiesewetter, MD, of the Medical University of Vienna and a member of the ESMO-MCBS Working Group, said the findings underscore the importance of using the scoring systems in clinical practice to assist in treatment-related decision making.

The ESMO-MCBS, for example, is available online, easy to use, and helps explain “the factors that are used to grade the clinical benefit of medicines.

“It’s very important to have this validated score not only for daily decision making, but to influence reimbursement decisions and reduce treatment disparities,” she said, also noting in the release that “[c]ost is one of the main reasons why patients are denied access to the newer anticancer drugs.”

“By showing which drugs are most likely to be worth the higher cost, we can hopefully improve access to the drugs with greatest value so that patients receive standardized, optimal therapy wherever they live,” she said.

The study was funded by the Swiss Cancer League. The authors reported having no conflicts of interest.

SOURCE: Vokinger KN et al. ESMO 2019, Abstract 1631PD-PR.

BARCELONA – Cancer drug prices are significantly higher in the United States than in Europe, and they don’t correlate with clinical benefit in either region, according to an analysis of drug costs and value-related scores between 2009 and 2018.

Of 63 cancer drugs approved by the Food and Drug Administration between 2009 and 2017 and by the European Medicines Agency as of December 31, 2018, 46 (73%) were approved for solid tumors, and 17 (27%) for hematologic malignancies. Median cancer drug prices in Europe were 52% lower than U.S. prices, Kerstin N. Vokinger, MD, Academic Chair For Health Policy at the Institute For Primary Care, University Hospital Zürich, and colleagues found.

The findings were released via press release at the European Society for Medical Oncology (ESMO) Congress and will be part of a poster discussion session there.

The investigators found no association between monthly treatment cost and the American Society of Clinical Oncology Value Framework (ASCO-VF) or the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores in any country. They also found no association between the price differential in the United States and Europe and either ASCO-VF (P = .599) or ESMO-MBCS (P = .321) scores.

For the analysis, they assessed U.S. average sales prices or, when those weren’t available, wholesale acquisition costs as of Feb. 1, 2019, and compared them with comparable currency-adjusted ex-factory drug costs in England, France, Germany, and Switzerland.

ASCO-VF and ESMO-MCBS scores were then assessed based on the highest score from pivotal trials supporting each solid tumor drug.

The median monthly cost for drugs with low-benefit scores on ESMO-MCBS ranged from $4,361-$5,273 in the European countries, compared with $12,436 in the United States, according to the release.

“Drug costs were not associated with clinical benefit score in any of the countries we looked at. For example, some of the more expensive drugs for prostate and lung cancer in Switzerland had lower ESMO-MCBS scores, while cheaper drugs had higher scores,” said Dr. Vokinger, who also is affiliated with the Program on Regulation, Therapeutics, and Law at Harvard Medical School, Boston. “It is important that drug pricing is aligned with clinical value and that our limited resources are spent on innovative medicines that offer improved outcomes.”

Barbara Kiesewetter, MD, of the Medical University of Vienna and a member of the ESMO-MCBS Working Group, said the findings underscore the importance of using the scoring systems in clinical practice to assist in treatment-related decision making.

The ESMO-MCBS, for example, is available online, easy to use, and helps explain “the factors that are used to grade the clinical benefit of medicines.

“It’s very important to have this validated score not only for daily decision making, but to influence reimbursement decisions and reduce treatment disparities,” she said, also noting in the release that “[c]ost is one of the main reasons why patients are denied access to the newer anticancer drugs.”

“By showing which drugs are most likely to be worth the higher cost, we can hopefully improve access to the drugs with greatest value so that patients receive standardized, optimal therapy wherever they live,” she said.

The study was funded by the Swiss Cancer League. The authors reported having no conflicts of interest.

SOURCE: Vokinger KN et al. ESMO 2019, Abstract 1631PD-PR.

Sex predicts mortality after a breast cancer diagnosis, with male patients about one-fifth more likely than female counterparts to have died by the 5-year mark, finds a cohort study of more than 1.8 million patients. Clinical characteristics and undertreatment explained much, but not all, of this excess mortality.

“Studies have indicated that male patients with breast cancer had worse overall survival than their female counterparts, including those with early-stage disease, although results have been inconsistent,” the investigators note. However, “few studies have systematically investigated the factors associated with mortality in male patients with breast cancer or assessed whether breast cancer prognosis for men is congruent with that for women, accounting for the differences in clinical characteristics and treatment.”

Senior investigator Xiao-Ou Shu, MD, PhD, of the Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tenn., and coinvestigators conducted a nationwide, registry-based cohort study using the National Cancer Database to identify patients receiving a breast cancer diagnosis during 2004-2014. Analyses were based on 16,025 male patients (mean age, 63.3 years) having a median follow-up of 54.0 months and 1,800,708 female patients (mean age, 59.9 years) having a median follow-up of 60.5 months.

Results reported in JAMA Oncology showed that men had higher mortality across all stages (P less than .001 for each). Male patients also had poorer relative overall survival (45.8% vs. 60.4%, P less than .001), 3-year survival (86.4% vs. 91.7%, P less than .001), and 5-year survival (77.6% vs. 86.4%, P less than .001).

Age, clinical factors (tumor size; nodal status; stage, ER, PR, and HER2 statuses; histologic type; grade; lymphovascular invasion; OncotypeDX Breast Recurrence Score; and Charlson/Deyo score), and treatment factors (surgical procedure, chemotherapy, endocrine therapy, radiation therapy, and immunotherapy) collectively explained 63.3% of the excess mortality rate for male patients. They explained fully 66.0% of the excess mortality in the first 3 years after diagnosis, including 30.5% and 13.6% of that among patients with stage I and stage II disease, respectively.

However, even after adjustment for these factors plus race/ethnicity and access to care, men still had significantly higher risks of overall mortality (adjusted hazard ratio, 1.19), 3-year mortality (adjusted hazard ratio, 1.15), and 5-year mortality (adjusted hazard ratio, 1.19).

The database used did not contain information on causes of death or on cancer recurrence or progression events, precluding analyses of disease-free survival.

“Future research should focus on why and how clinical characteristics, as well as biological features, may have different implications for the survival of male and female patients with breast cancer,” Dr. Shu and coinvestigators recommended. “Additional factors, particularly compliance to treatment, biological attributes, and lifestyle factors (e.g., smoking, drinking, and obesity), should be assessed to help in developing treatments tailored for men, which would mitigate this sex-based disparity.”

Dr. Shu disclosed no relevant conflicts of interest. One author was funded by the program of the China Scholarship Council.

SOURCE: Wang F et al. JAMA Oncol. 2019 Sep 19. doi: 10.1001/jamaoncol.2019.2803.

Sex predicts mortality after a breast cancer diagnosis, with male patients about one-fifth more likely than female counterparts to have died by the 5-year mark, finds a cohort study of more than 1.8 million patients. Clinical characteristics and undertreatment explained much, but not all, of this excess mortality.

“Studies have indicated that male patients with breast cancer had worse overall survival than their female counterparts, including those with early-stage disease, although results have been inconsistent,” the investigators note. However, “few studies have systematically investigated the factors associated with mortality in male patients with breast cancer or assessed whether breast cancer prognosis for men is congruent with that for women, accounting for the differences in clinical characteristics and treatment.”

Senior investigator Xiao-Ou Shu, MD, PhD, of the Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tenn., and coinvestigators conducted a nationwide, registry-based cohort study using the National Cancer Database to identify patients receiving a breast cancer diagnosis during 2004-2014. Analyses were based on 16,025 male patients (mean age, 63.3 years) having a median follow-up of 54.0 months and 1,800,708 female patients (mean age, 59.9 years) having a median follow-up of 60.5 months.

Results reported in JAMA Oncology showed that men had higher mortality across all stages (P less than .001 for each). Male patients also had poorer relative overall survival (45.8% vs. 60.4%, P less than .001), 3-year survival (86.4% vs. 91.7%, P less than .001), and 5-year survival (77.6% vs. 86.4%, P less than .001).

Age, clinical factors (tumor size; nodal status; stage, ER, PR, and HER2 statuses; histologic type; grade; lymphovascular invasion; OncotypeDX Breast Recurrence Score; and Charlson/Deyo score), and treatment factors (surgical procedure, chemotherapy, endocrine therapy, radiation therapy, and immunotherapy) collectively explained 63.3% of the excess mortality rate for male patients. They explained fully 66.0% of the excess mortality in the first 3 years after diagnosis, including 30.5% and 13.6% of that among patients with stage I and stage II disease, respectively.

However, even after adjustment for these factors plus race/ethnicity and access to care, men still had significantly higher risks of overall mortality (adjusted hazard ratio, 1.19), 3-year mortality (adjusted hazard ratio, 1.15), and 5-year mortality (adjusted hazard ratio, 1.19).

The database used did not contain information on causes of death or on cancer recurrence or progression events, precluding analyses of disease-free survival.

“Future research should focus on why and how clinical characteristics, as well as biological features, may have different implications for the survival of male and female patients with breast cancer,” Dr. Shu and coinvestigators recommended. “Additional factors, particularly compliance to treatment, biological attributes, and lifestyle factors (e.g., smoking, drinking, and obesity), should be assessed to help in developing treatments tailored for men, which would mitigate this sex-based disparity.”

Dr. Shu disclosed no relevant conflicts of interest. One author was funded by the program of the China Scholarship Council.

SOURCE: Wang F et al. JAMA Oncol. 2019 Sep 19. doi: 10.1001/jamaoncol.2019.2803.

Sex predicts mortality after a breast cancer diagnosis, with male patients about one-fifth more likely than female counterparts to have died by the 5-year mark, finds a cohort study of more than 1.8 million patients. Clinical characteristics and undertreatment explained much, but not all, of this excess mortality.

“Studies have indicated that male patients with breast cancer had worse overall survival than their female counterparts, including those with early-stage disease, although results have been inconsistent,” the investigators note. However, “few studies have systematically investigated the factors associated with mortality in male patients with breast cancer or assessed whether breast cancer prognosis for men is congruent with that for women, accounting for the differences in clinical characteristics and treatment.”

Senior investigator Xiao-Ou Shu, MD, PhD, of the Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tenn., and coinvestigators conducted a nationwide, registry-based cohort study using the National Cancer Database to identify patients receiving a breast cancer diagnosis during 2004-2014. Analyses were based on 16,025 male patients (mean age, 63.3 years) having a median follow-up of 54.0 months and 1,800,708 female patients (mean age, 59.9 years) having a median follow-up of 60.5 months.

Results reported in JAMA Oncology showed that men had higher mortality across all stages (P less than .001 for each). Male patients also had poorer relative overall survival (45.8% vs. 60.4%, P less than .001), 3-year survival (86.4% vs. 91.7%, P less than .001), and 5-year survival (77.6% vs. 86.4%, P less than .001).

Age, clinical factors (tumor size; nodal status; stage, ER, PR, and HER2 statuses; histologic type; grade; lymphovascular invasion; OncotypeDX Breast Recurrence Score; and Charlson/Deyo score), and treatment factors (surgical procedure, chemotherapy, endocrine therapy, radiation therapy, and immunotherapy) collectively explained 63.3% of the excess mortality rate for male patients. They explained fully 66.0% of the excess mortality in the first 3 years after diagnosis, including 30.5% and 13.6% of that among patients with stage I and stage II disease, respectively.

However, even after adjustment for these factors plus race/ethnicity and access to care, men still had significantly higher risks of overall mortality (adjusted hazard ratio, 1.19), 3-year mortality (adjusted hazard ratio, 1.15), and 5-year mortality (adjusted hazard ratio, 1.19).

The database used did not contain information on causes of death or on cancer recurrence or progression events, precluding analyses of disease-free survival.

“Future research should focus on why and how clinical characteristics, as well as biological features, may have different implications for the survival of male and female patients with breast cancer,” Dr. Shu and coinvestigators recommended. “Additional factors, particularly compliance to treatment, biological attributes, and lifestyle factors (e.g., smoking, drinking, and obesity), should be assessed to help in developing treatments tailored for men, which would mitigate this sex-based disparity.”

Dr. Shu disclosed no relevant conflicts of interest. One author was funded by the program of the China Scholarship Council.

SOURCE: Wang F et al. JAMA Oncol. 2019 Sep 19. doi: 10.1001/jamaoncol.2019.2803.

SAN FRANCISCO – Anticoagulation with apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have an acute coronary syndrome, compared with regimens that include vitamin K antagonists, aspirin, or both.

Doug Brunk/MDedge News

The findings come from a prespecified analysis of data from the AUGUSTUS trial presented by Stephan Windecker, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting.

“This study adds very important information [to the notion] that triple therapy in the setting of atrial fibrillation and PCI [percutaneous coronary intervention] is really not the way to go,” Ori Ben-Yehuda, MD, FACC, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center, said during a media briefing.

In the recent multicenter AUGUSTUS trial, Dr. Windecker, of the department of cardiology at Bern University Hospital, Switzerland, and colleagues found that among 4,614 patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, apixaban without aspirin resulted in less bleeding, fewer hospitalizations, and no significant differences in ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both (N Engl J Med. 2019;380:1509-24). For this prespecified analysis, the researchers used a 2×2 factorial design to compare apixaban with VKA and aspirin with placebo in the AUGUSTUS trial participants with ACS treated medically (group 1; 1,097 patients, or 24%), those with ACS treated with PCI (group 2; 1,714 patients, or 37%), and those undergoing elective PCI (group 3; 1,784 patients, or 39%). The outcomes of interest were bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in the study participants. This marks the only trial in the field that included patients with ACS managed medically, Dr. Windecker said.

At baseline, the median age of patients was 71 years, 30% were female, 36% had diabetes, and 45% had heart failure. Patients managed medically were younger (a median age of 70) and more frequently female; 57% presented with heart failure. The groups had identical CHA2DS2VASc scores (4), and very similar HAS-BLED scores (2 in groups 1 and 2, and 3 in group 3).

Apixaban compared with VKA showed lower International Society on Thrombosis and Haemostasis–defined major or clinically relevant nonmajor bleeding among patients in group 1 (HR, 0.44), group 2 (HR, 0.68), and group 3 (HR, 0.82) (P for interaction = .052). Apixaban compared with VKA reduced death or hospitalization among patients in group 1 (HR, 0.71), group 2 (HR 0.88), and group 3 (HR, 0.87) (P for interaction = .345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events among patients in all three treatment groups (P for interaction = .356).

Compared with placebo, aspirin had a higher rate of bleeding among patients in group 1 (HR, 1.49), group 2 (HR, 2.02) and group 3 (HR, 1.91) (P for interaction = .479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization and death and ischemic events.

“The overall results of the AUGUSTUS trial are consistent across the three clinically important subgroups,” Dr. Windecker said. The reasons why patients received medical therapy remain unclear, “because it was at the physician’s discretion as to whether they were treated medically or underwent PCI,” he said. “The proportion very much reflects our clinical practice, where 20%-25% of patients are treated medically. What was surprising for me is that I would have anticipated there would be more elderly patients with comorbidities, but I did anticipate that there would be more female patients (in this subgroup).”

Robert A. Harrington, MD, an interventional cardiologist at Stanford (Calif.) University who served on the Data Safety and Monitoring Board for the trial, noted that the patients with atrial fibrillation represent 7%-10% of all ACS patients, “so it’s a big population,” he said. “What’s been disappointing is that none of the trials have been big enough to uncouple the bleeding vs. ischemic issue. We don’t know the answer for how long do you need the triple therapy versus when you can switch to the double therapy.”

Dr. Windecker said that the optimal duration of short-term aspirin remains unclear in this patient population. “Whether there is a benefit of giving aspirin for 2 weeks or 4 weeks remains unanswered,” he said. “Triple therapy is not the way to go, but we need to fine-tune, and probably individualize, which patients may benefit from a certain duration of aspirin.”

The study results were published online at the time of presentation (Circulation 2019 Sep 26. doi: 10.1161/CIRCULATIONAHA.119.043308.

AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer Inc. Dr. Windecker reported having received institutional research and educational grants to Bern University Hospital from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. His coauthors reported having numerous financial ties to the pharmaceutical and device industries.

dbrunk@mdedge.com

SOURCE: Windecker S. TCT 2019, Late-Breaking Trials 1 session.

SAN FRANCISCO – Anticoagulation with apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have an acute coronary syndrome, compared with regimens that include vitamin K antagonists, aspirin, or both.

Doug Brunk/MDedge News

The findings come from a prespecified analysis of data from the AUGUSTUS trial presented by Stephan Windecker, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting.

“This study adds very important information [to the notion] that triple therapy in the setting of atrial fibrillation and PCI [percutaneous coronary intervention] is really not the way to go,” Ori Ben-Yehuda, MD, FACC, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center, said during a media briefing.

In the recent multicenter AUGUSTUS trial, Dr. Windecker, of the department of cardiology at Bern University Hospital, Switzerland, and colleagues found that among 4,614 patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, apixaban without aspirin resulted in less bleeding, fewer hospitalizations, and no significant differences in ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both (N Engl J Med. 2019;380:1509-24). For this prespecified analysis, the researchers used a 2×2 factorial design to compare apixaban with VKA and aspirin with placebo in the AUGUSTUS trial participants with ACS treated medically (group 1; 1,097 patients, or 24%), those with ACS treated with PCI (group 2; 1,714 patients, or 37%), and those undergoing elective PCI (group 3; 1,784 patients, or 39%). The outcomes of interest were bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in the study participants. This marks the only trial in the field that included patients with ACS managed medically, Dr. Windecker said.

At baseline, the median age of patients was 71 years, 30% were female, 36% had diabetes, and 45% had heart failure. Patients managed medically were younger (a median age of 70) and more frequently female; 57% presented with heart failure. The groups had identical CHA2DS2VASc scores (4), and very similar HAS-BLED scores (2 in groups 1 and 2, and 3 in group 3).

Apixaban compared with VKA showed lower International Society on Thrombosis and Haemostasis–defined major or clinically relevant nonmajor bleeding among patients in group 1 (HR, 0.44), group 2 (HR, 0.68), and group 3 (HR, 0.82) (P for interaction = .052). Apixaban compared with VKA reduced death or hospitalization among patients in group 1 (HR, 0.71), group 2 (HR 0.88), and group 3 (HR, 0.87) (P for interaction = .345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events among patients in all three treatment groups (P for interaction = .356).

Compared with placebo, aspirin had a higher rate of bleeding among patients in group 1 (HR, 1.49), group 2 (HR, 2.02) and group 3 (HR, 1.91) (P for interaction = .479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization and death and ischemic events.

“The overall results of the AUGUSTUS trial are consistent across the three clinically important subgroups,” Dr. Windecker said. The reasons why patients received medical therapy remain unclear, “because it was at the physician’s discretion as to whether they were treated medically or underwent PCI,” he said. “The proportion very much reflects our clinical practice, where 20%-25% of patients are treated medically. What was surprising for me is that I would have anticipated there would be more elderly patients with comorbidities, but I did anticipate that there would be more female patients (in this subgroup).”

Robert A. Harrington, MD, an interventional cardiologist at Stanford (Calif.) University who served on the Data Safety and Monitoring Board for the trial, noted that the patients with atrial fibrillation represent 7%-10% of all ACS patients, “so it’s a big population,” he said. “What’s been disappointing is that none of the trials have been big enough to uncouple the bleeding vs. ischemic issue. We don’t know the answer for how long do you need the triple therapy versus when you can switch to the double therapy.”

Dr. Windecker said that the optimal duration of short-term aspirin remains unclear in this patient population. “Whether there is a benefit of giving aspirin for 2 weeks or 4 weeks remains unanswered,” he said. “Triple therapy is not the way to go, but we need to fine-tune, and probably individualize, which patients may benefit from a certain duration of aspirin.”

The study results were published online at the time of presentation (Circulation 2019 Sep 26. doi: 10.1161/CIRCULATIONAHA.119.043308.

AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer Inc. Dr. Windecker reported having received institutional research and educational grants to Bern University Hospital from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. His coauthors reported having numerous financial ties to the pharmaceutical and device industries.

dbrunk@mdedge.com

SOURCE: Windecker S. TCT 2019, Late-Breaking Trials 1 session.

SAN FRANCISCO – Anticoagulation with apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have an acute coronary syndrome, compared with regimens that include vitamin K antagonists, aspirin, or both.

Doug Brunk/MDedge News

The findings come from a prespecified analysis of data from the AUGUSTUS trial presented by Stephan Windecker, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting.

“This study adds very important information [to the notion] that triple therapy in the setting of atrial fibrillation and PCI [percutaneous coronary intervention] is really not the way to go,” Ori Ben-Yehuda, MD, FACC, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center, said during a media briefing.

In the recent multicenter AUGUSTUS trial, Dr. Windecker, of the department of cardiology at Bern University Hospital, Switzerland, and colleagues found that among 4,614 patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, apixaban without aspirin resulted in less bleeding, fewer hospitalizations, and no significant differences in ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both (N Engl J Med. 2019;380:1509-24). For this prespecified analysis, the researchers used a 2×2 factorial design to compare apixaban with VKA and aspirin with placebo in the AUGUSTUS trial participants with ACS treated medically (group 1; 1,097 patients, or 24%), those with ACS treated with PCI (group 2; 1,714 patients, or 37%), and those undergoing elective PCI (group 3; 1,784 patients, or 39%). The outcomes of interest were bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in the study participants. This marks the only trial in the field that included patients with ACS managed medically, Dr. Windecker said.

At baseline, the median age of patients was 71 years, 30% were female, 36% had diabetes, and 45% had heart failure. Patients managed medically were younger (a median age of 70) and more frequently female; 57% presented with heart failure. The groups had identical CHA2DS2VASc scores (4), and very similar HAS-BLED scores (2 in groups 1 and 2, and 3 in group 3).

Apixaban compared with VKA showed lower International Society on Thrombosis and Haemostasis–defined major or clinically relevant nonmajor bleeding among patients in group 1 (HR, 0.44), group 2 (HR, 0.68), and group 3 (HR, 0.82) (P for interaction = .052). Apixaban compared with VKA reduced death or hospitalization among patients in group 1 (HR, 0.71), group 2 (HR 0.88), and group 3 (HR, 0.87) (P for interaction = .345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events among patients in all three treatment groups (P for interaction = .356).

Compared with placebo, aspirin had a higher rate of bleeding among patients in group 1 (HR, 1.49), group 2 (HR, 2.02) and group 3 (HR, 1.91) (P for interaction = .479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization and death and ischemic events.

“The overall results of the AUGUSTUS trial are consistent across the three clinically important subgroups,” Dr. Windecker said. The reasons why patients received medical therapy remain unclear, “because it was at the physician’s discretion as to whether they were treated medically or underwent PCI,” he said. “The proportion very much reflects our clinical practice, where 20%-25% of patients are treated medically. What was surprising for me is that I would have anticipated there would be more elderly patients with comorbidities, but I did anticipate that there would be more female patients (in this subgroup).”

Robert A. Harrington, MD, an interventional cardiologist at Stanford (Calif.) University who served on the Data Safety and Monitoring Board for the trial, noted that the patients with atrial fibrillation represent 7%-10% of all ACS patients, “so it’s a big population,” he said. “What’s been disappointing is that none of the trials have been big enough to uncouple the bleeding vs. ischemic issue. We don’t know the answer for how long do you need the triple therapy versus when you can switch to the double therapy.”

Dr. Windecker said that the optimal duration of short-term aspirin remains unclear in this patient population. “Whether there is a benefit of giving aspirin for 2 weeks or 4 weeks remains unanswered,” he said. “Triple therapy is not the way to go, but we need to fine-tune, and probably individualize, which patients may benefit from a certain duration of aspirin.”

The study results were published online at the time of presentation (Circulation 2019 Sep 26. doi: 10.1161/CIRCULATIONAHA.119.043308.

AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer Inc. Dr. Windecker reported having received institutional research and educational grants to Bern University Hospital from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. His coauthors reported having numerous financial ties to the pharmaceutical and device industries.

dbrunk@mdedge.com

SOURCE: Windecker S. TCT 2019, Late-Breaking Trials 1 session.

Universal screening for autism spectrum disorder in primary care is feasible, but the current screening tool noticeably underperformed, especially in children of color and in those from lower-income households, new research found.

Guidelines for universal autism spectrum disorder (ASD) screening currently conflict, Whitney Guthrie, PhD, of the Children’s Hospital of Philadelphia, and associates wrote in Pediatrics. The American Academy of Pediatrics recommends universal screening in children aged 18 months and 24 months to expedite earlier identification and diagnosis. However, the U.S. Preventive Services Task Force has concluded that “there is insufficient evidence to recommend universal screening, in part because of limited data on outcomes for children who screen negative and from diverse samples.”

Dr. Guthrie and associates conducted a study of 25,999 children aged 16-26 months who had a well-child visit between January 2011 and July 2015 at a Children’s Hospital of Philadelphia site that had implemented universal electronic screening. Of this group, 43% were white, 37% were black, and the remainder were Asian or of other/multiple races; 92% were non-Hispanic. The median parental income was $59,597, 54% had private insurance and 45.3% had public insurance/Medicaid, and 42% came from an urban primary care site while the rest came from suburban primary care.

Screening rates were good over the study period, with 91% of children undergoing at least one screen with the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F). While 50% were screened more than once, only 48% of children were screened at 18 and 24 months, as per the AAP guideline. Children who were screened multiple times were more likely to be white and non-Hispanic, to be from a suburban site, and to have higher incomes and private insurance.

After the first M-CHAT/F screen, 9.5% of children were positive, a rate comparable with that seen in other large-scale, U.S.-based studies. Of the 2,256 children who tested positive, 41% received a second screen; 782 (95%) of these children tested negative.

After the study period, most children (n = 20,437; 87%) continued receiving care with the Children’s Hospital of Philadelphia system and had diagnostic data available past the age of 4 years. ASD prevalence was 2%, giving the M-CHAT/F a sensitivity of 39%, a specificity of 95%, a positive predictive value of 15%, and a negative predictive value of 99%.

M-CHAT/F sensitivity was higher in older children (49% at 21-26 months vs. 35% at 16-20 months) and with repeated screenings (40% vs. 32%), and positive predictive value was lower in girls (8% vs. 20%). Specificity and positive predictive value were higher in white children (98% and 24%, respectively), compared with black children (92% and 12%, respectively), Asian children (90% and 11%, respectively), and those from other/multiple racial groups (94% and 13%, respectively). Higher-income families also saw increased specificity (97% vs. 92%) and positive predictive value (20% vs. 12%), compared with lower-income families.

While Dr. Guthrie and associates wrote of new methods of screening, such as parental reporting tools supported by picture or video and “direct data-gathering methods that leverage technological advances in computing and machine learning,” Lonnie Zwaigenbaum, MD, MSc, and Jonathon Maguire, MD, MSc, argued in an editorial, also published in Pediatrics, that the M-CHAT/F “remains a strong candidate” for universal ASD screening, despite the notable weaknesses.

“Ultimately, the potential added value of ASD screening must be considered relative to what would occur in its absence,” wrote Dr. Zwaigenbaum of the Women’s and Children’s Health Research Institute at the University of Alberta, Edmonton, and Dr. Maguire of St Michael’s Hospital, Toronto, and the University of Toronto. “Although it is difficult to object to the guidance from the U.S. Preventive Services Task Force to listen carefully to parents’ concerns, we must acknowledge the false dichotomy between screening and surveillance in this context. ... Why not use the best available measurement tools to identify developmental concerns with the highest possible accuracy?”

The study was funded by the Allerton Foundation, Eagles Charitable Foundation, and the National Institute of Mental Health; the study investigators reported that they had no conflicts of interest. Dr. Zwaigenbaum is a member of an independent data monitoring committee for a Roche-funded medication trial and Dr. Maguire reported receiving nonfinancial support from Ddrops for an investigator-initiated study on vitamin D and respiratory tract infections. Dr Zwaigenbaum is supported by the Stollery Children’s Hospital Foundation Chair in Autism Research. Dr Maguire is supported by St. Michael’s Hospital and the Hospital for Sick Children.

lfranki@mdedge.com

SOURCEs: Guthrie W et al. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2018-3963; Zwaigenbaum L, Maguire J. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2019-0925.

Universal screening for autism spectrum disorder in primary care is feasible, but the current screening tool noticeably underperformed, especially in children of color and in those from lower-income households, new research found.

Guidelines for universal autism spectrum disorder (ASD) screening currently conflict, Whitney Guthrie, PhD, of the Children’s Hospital of Philadelphia, and associates wrote in Pediatrics. The American Academy of Pediatrics recommends universal screening in children aged 18 months and 24 months to expedite earlier identification and diagnosis. However, the U.S. Preventive Services Task Force has concluded that “there is insufficient evidence to recommend universal screening, in part because of limited data on outcomes for children who screen negative and from diverse samples.”

Dr. Guthrie and associates conducted a study of 25,999 children aged 16-26 months who had a well-child visit between January 2011 and July 2015 at a Children’s Hospital of Philadelphia site that had implemented universal electronic screening. Of this group, 43% were white, 37% were black, and the remainder were Asian or of other/multiple races; 92% were non-Hispanic. The median parental income was $59,597, 54% had private insurance and 45.3% had public insurance/Medicaid, and 42% came from an urban primary care site while the rest came from suburban primary care.

Screening rates were good over the study period, with 91% of children undergoing at least one screen with the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F). While 50% were screened more than once, only 48% of children were screened at 18 and 24 months, as per the AAP guideline. Children who were screened multiple times were more likely to be white and non-Hispanic, to be from a suburban site, and to have higher incomes and private insurance.

After the first M-CHAT/F screen, 9.5% of children were positive, a rate comparable with that seen in other large-scale, U.S.-based studies. Of the 2,256 children who tested positive, 41% received a second screen; 782 (95%) of these children tested negative.

After the study period, most children (n = 20,437; 87%) continued receiving care with the Children’s Hospital of Philadelphia system and had diagnostic data available past the age of 4 years. ASD prevalence was 2%, giving the M-CHAT/F a sensitivity of 39%, a specificity of 95%, a positive predictive value of 15%, and a negative predictive value of 99%.

M-CHAT/F sensitivity was higher in older children (49% at 21-26 months vs. 35% at 16-20 months) and with repeated screenings (40% vs. 32%), and positive predictive value was lower in girls (8% vs. 20%). Specificity and positive predictive value were higher in white children (98% and 24%, respectively), compared with black children (92% and 12%, respectively), Asian children (90% and 11%, respectively), and those from other/multiple racial groups (94% and 13%, respectively). Higher-income families also saw increased specificity (97% vs. 92%) and positive predictive value (20% vs. 12%), compared with lower-income families.

While Dr. Guthrie and associates wrote of new methods of screening, such as parental reporting tools supported by picture or video and “direct data-gathering methods that leverage technological advances in computing and machine learning,” Lonnie Zwaigenbaum, MD, MSc, and Jonathon Maguire, MD, MSc, argued in an editorial, also published in Pediatrics, that the M-CHAT/F “remains a strong candidate” for universal ASD screening, despite the notable weaknesses.

“Ultimately, the potential added value of ASD screening must be considered relative to what would occur in its absence,” wrote Dr. Zwaigenbaum of the Women’s and Children’s Health Research Institute at the University of Alberta, Edmonton, and Dr. Maguire of St Michael’s Hospital, Toronto, and the University of Toronto. “Although it is difficult to object to the guidance from the U.S. Preventive Services Task Force to listen carefully to parents’ concerns, we must acknowledge the false dichotomy between screening and surveillance in this context. ... Why not use the best available measurement tools to identify developmental concerns with the highest possible accuracy?”

The study was funded by the Allerton Foundation, Eagles Charitable Foundation, and the National Institute of Mental Health; the study investigators reported that they had no conflicts of interest. Dr. Zwaigenbaum is a member of an independent data monitoring committee for a Roche-funded medication trial and Dr. Maguire reported receiving nonfinancial support from Ddrops for an investigator-initiated study on vitamin D and respiratory tract infections. Dr Zwaigenbaum is supported by the Stollery Children’s Hospital Foundation Chair in Autism Research. Dr Maguire is supported by St. Michael’s Hospital and the Hospital for Sick Children.

lfranki@mdedge.com

SOURCEs: Guthrie W et al. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2018-3963; Zwaigenbaum L, Maguire J. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2019-0925.

Universal screening for autism spectrum disorder in primary care is feasible, but the current screening tool noticeably underperformed, especially in children of color and in those from lower-income households, new research found.

Guidelines for universal autism spectrum disorder (ASD) screening currently conflict, Whitney Guthrie, PhD, of the Children’s Hospital of Philadelphia, and associates wrote in Pediatrics. The American Academy of Pediatrics recommends universal screening in children aged 18 months and 24 months to expedite earlier identification and diagnosis. However, the U.S. Preventive Services Task Force has concluded that “there is insufficient evidence to recommend universal screening, in part because of limited data on outcomes for children who screen negative and from diverse samples.”

Dr. Guthrie and associates conducted a study of 25,999 children aged 16-26 months who had a well-child visit between January 2011 and July 2015 at a Children’s Hospital of Philadelphia site that had implemented universal electronic screening. Of this group, 43% were white, 37% were black, and the remainder were Asian or of other/multiple races; 92% were non-Hispanic. The median parental income was $59,597, 54% had private insurance and 45.3% had public insurance/Medicaid, and 42% came from an urban primary care site while the rest came from suburban primary care.

Screening rates were good over the study period, with 91% of children undergoing at least one screen with the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F). While 50% were screened more than once, only 48% of children were screened at 18 and 24 months, as per the AAP guideline. Children who were screened multiple times were more likely to be white and non-Hispanic, to be from a suburban site, and to have higher incomes and private insurance.

After the first M-CHAT/F screen, 9.5% of children were positive, a rate comparable with that seen in other large-scale, U.S.-based studies. Of the 2,256 children who tested positive, 41% received a second screen; 782 (95%) of these children tested negative.

After the study period, most children (n = 20,437; 87%) continued receiving care with the Children’s Hospital of Philadelphia system and had diagnostic data available past the age of 4 years. ASD prevalence was 2%, giving the M-CHAT/F a sensitivity of 39%, a specificity of 95%, a positive predictive value of 15%, and a negative predictive value of 99%.

M-CHAT/F sensitivity was higher in older children (49% at 21-26 months vs. 35% at 16-20 months) and with repeated screenings (40% vs. 32%), and positive predictive value was lower in girls (8% vs. 20%). Specificity and positive predictive value were higher in white children (98% and 24%, respectively), compared with black children (92% and 12%, respectively), Asian children (90% and 11%, respectively), and those from other/multiple racial groups (94% and 13%, respectively). Higher-income families also saw increased specificity (97% vs. 92%) and positive predictive value (20% vs. 12%), compared with lower-income families.

While Dr. Guthrie and associates wrote of new methods of screening, such as parental reporting tools supported by picture or video and “direct data-gathering methods that leverage technological advances in computing and machine learning,” Lonnie Zwaigenbaum, MD, MSc, and Jonathon Maguire, MD, MSc, argued in an editorial, also published in Pediatrics, that the M-CHAT/F “remains a strong candidate” for universal ASD screening, despite the notable weaknesses.

“Ultimately, the potential added value of ASD screening must be considered relative to what would occur in its absence,” wrote Dr. Zwaigenbaum of the Women’s and Children’s Health Research Institute at the University of Alberta, Edmonton, and Dr. Maguire of St Michael’s Hospital, Toronto, and the University of Toronto. “Although it is difficult to object to the guidance from the U.S. Preventive Services Task Force to listen carefully to parents’ concerns, we must acknowledge the false dichotomy between screening and surveillance in this context. ... Why not use the best available measurement tools to identify developmental concerns with the highest possible accuracy?”

The study was funded by the Allerton Foundation, Eagles Charitable Foundation, and the National Institute of Mental Health; the study investigators reported that they had no conflicts of interest. Dr. Zwaigenbaum is a member of an independent data monitoring committee for a Roche-funded medication trial and Dr. Maguire reported receiving nonfinancial support from Ddrops for an investigator-initiated study on vitamin D and respiratory tract infections. Dr Zwaigenbaum is supported by the Stollery Children’s Hospital Foundation Chair in Autism Research. Dr Maguire is supported by St. Michael’s Hospital and the Hospital for Sick Children.

lfranki@mdedge.com

SOURCEs: Guthrie W et al. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2018-3963; Zwaigenbaum L, Maguire J. Pediatrics. 2019 Sep 27. doi: 10.1542/peds.2019-0925.

COPENHAGEN – Exposure to maternal somatic anxiety during pregnancy and toddlerhood increases a child’s risk of hyperactivity symptoms in adolescence, Blanca Bolea, MD, said at the annual congress of the European College of Neuropsychopharmacology.

In contrast, the children of mothers who were anxious were not at increased risk for subsequent inattention symptoms in an analysis of 8,725 mothers and their children participating in the Avon Longitudinal Study of Parents and Children, a prospective epidemiologic cohort study ongoing in southwest England since 1991, said Dr. Bolea, a psychiatrist at the University of Toronto.

These findings have practical implications for clinical care: “If we know that women who are anxious in the perinatal period put their children at risk for hyperactivity later on, then we can tackle their anxiety in pregnancy or toddlerhood. And that’s easy to do: You can do group [cognitive-behavioral therapy]; you can give medications, so there are things you can do to reduce that risk. That’s relevant, because we don’t know much about how to reduce levels of ADHD. We know it has a genetic component, but we can’t touch that. You cannot change your genes, so far. But environmental things, we can change. So if we can identify the mothers who are more anxious during pregnancy and toddlerhood and give them resources to reduce their anxiety, then we can potentially reduce hyperactivity later on,” she explained in an interview.

In the Avon study, maternal anxiety was serially assessed from early pregnancy up until a child’s 5th birthday.

“We looked for maternal symptoms similar to panic disorder: shortness of breath, dizziness, sweating, things like that. These are symptoms that any clinician can identify by asking the mothers, so it’s not hard to identify the mothers who could be at risk,” according to the psychiatrist.

Children in the Avon study were assessed for symptoms of inattention at age 8.5 years using the Sky Search, Sky Search Dual Test, and Opposite Worlds subtests of the Tests of Everyday Attention for Children. Hyperactivity symptoms were assessed at age 16 years via the Strengths and Difficulties Questionnaire.

In an analysis adjusted for potentially confounding sociodemographic factors, adolescents whose mothers were rated by investigators as having moderate or high somatic anxiety during pregnancy and the toddlerhood years were at 2.1-fold increased risk of hyperactivity symptoms compared to those whose mothers had low or no anxiety, but increased maternal anxiety wasn’t associated with scores on any of the three tests of inattention.

Dr. Bolea cautioned that, while these Avon study findings document an association between early maternal anxiety and subsequent adolescent hyperactivity, that doesn’t prove causality. The findings are consistent, however, with the fetal origins hypothesis put forth by the late British epidemiologist David J. Barker, MD, PhD, which postulates that stressful fetal circumstances have profound effects later in life.

“What we’re thinking here is, if the mother is anxious during pregnancy, that may change how the fetal brain develops, and it makes kids hyperactive later on,” she said.

The hypothesis has been borne out in animal studies: Stress a pregnant rat, and her offspring will display hyperactivity.

Dr. Bolea reported having no financial conflicts regarding her study. The Avon Longitudinal Study of Parents and Children is funded by the Medical Research Council and the Wellcome Trust.

bjancin@mdedge.com

COPENHAGEN – Exposure to maternal somatic anxiety during pregnancy and toddlerhood increases a child’s risk of hyperactivity symptoms in adolescence, Blanca Bolea, MD, said at the annual congress of the European College of Neuropsychopharmacology.

In contrast, the children of mothers who were anxious were not at increased risk for subsequent inattention symptoms in an analysis of 8,725 mothers and their children participating in the Avon Longitudinal Study of Parents and Children, a prospective epidemiologic cohort study ongoing in southwest England since 1991, said Dr. Bolea, a psychiatrist at the University of Toronto.

These findings have practical implications for clinical care: “If we know that women who are anxious in the perinatal period put their children at risk for hyperactivity later on, then we can tackle their anxiety in pregnancy or toddlerhood. And that’s easy to do: You can do group [cognitive-behavioral therapy]; you can give medications, so there are things you can do to reduce that risk. That’s relevant, because we don’t know much about how to reduce levels of ADHD. We know it has a genetic component, but we can’t touch that. You cannot change your genes, so far. But environmental things, we can change. So if we can identify the mothers who are more anxious during pregnancy and toddlerhood and give them resources to reduce their anxiety, then we can potentially reduce hyperactivity later on,” she explained in an interview.

In the Avon study, maternal anxiety was serially assessed from early pregnancy up until a child’s 5th birthday.

“We looked for maternal symptoms similar to panic disorder: shortness of breath, dizziness, sweating, things like that. These are symptoms that any clinician can identify by asking the mothers, so it’s not hard to identify the mothers who could be at risk,” according to the psychiatrist.

Children in the Avon study were assessed for symptoms of inattention at age 8.5 years using the Sky Search, Sky Search Dual Test, and Opposite Worlds subtests of the Tests of Everyday Attention for Children. Hyperactivity symptoms were assessed at age 16 years via the Strengths and Difficulties Questionnaire.

In an analysis adjusted for potentially confounding sociodemographic factors, adolescents whose mothers were rated by investigators as having moderate or high somatic anxiety during pregnancy and the toddlerhood years were at 2.1-fold increased risk of hyperactivity symptoms compared to those whose mothers had low or no anxiety, but increased maternal anxiety wasn’t associated with scores on any of the three tests of inattention.

Dr. Bolea cautioned that, while these Avon study findings document an association between early maternal anxiety and subsequent adolescent hyperactivity, that doesn’t prove causality. The findings are consistent, however, with the fetal origins hypothesis put forth by the late British epidemiologist David J. Barker, MD, PhD, which postulates that stressful fetal circumstances have profound effects later in life.

“What we’re thinking here is, if the mother is anxious during pregnancy, that may change how the fetal brain develops, and it makes kids hyperactive later on,” she said.

The hypothesis has been borne out in animal studies: Stress a pregnant rat, and her offspring will display hyperactivity.

Dr. Bolea reported having no financial conflicts regarding her study. The Avon Longitudinal Study of Parents and Children is funded by the Medical Research Council and the Wellcome Trust.

bjancin@mdedge.com

COPENHAGEN – Exposure to maternal somatic anxiety during pregnancy and toddlerhood increases a child’s risk of hyperactivity symptoms in adolescence, Blanca Bolea, MD, said at the annual congress of the European College of Neuropsychopharmacology.

In contrast, the children of mothers who were anxious were not at increased risk for subsequent inattention symptoms in an analysis of 8,725 mothers and their children participating in the Avon Longitudinal Study of Parents and Children, a prospective epidemiologic cohort study ongoing in southwest England since 1991, said Dr. Bolea, a psychiatrist at the University of Toronto.

These findings have practical implications for clinical care: “If we know that women who are anxious in the perinatal period put their children at risk for hyperactivity later on, then we can tackle their anxiety in pregnancy or toddlerhood. And that’s easy to do: You can do group [cognitive-behavioral therapy]; you can give medications, so there are things you can do to reduce that risk. That’s relevant, because we don’t know much about how to reduce levels of ADHD. We know it has a genetic component, but we can’t touch that. You cannot change your genes, so far. But environmental things, we can change. So if we can identify the mothers who are more anxious during pregnancy and toddlerhood and give them resources to reduce their anxiety, then we can potentially reduce hyperactivity later on,” she explained in an interview.

In the Avon study, maternal anxiety was serially assessed from early pregnancy up until a child’s 5th birthday.

“We looked for maternal symptoms similar to panic disorder: shortness of breath, dizziness, sweating, things like that. These are symptoms that any clinician can identify by asking the mothers, so it’s not hard to identify the mothers who could be at risk,” according to the psychiatrist.

Children in the Avon study were assessed for symptoms of inattention at age 8.5 years using the Sky Search, Sky Search Dual Test, and Opposite Worlds subtests of the Tests of Everyday Attention for Children. Hyperactivity symptoms were assessed at age 16 years via the Strengths and Difficulties Questionnaire.

In an analysis adjusted for potentially confounding sociodemographic factors, adolescents whose mothers were rated by investigators as having moderate or high somatic anxiety during pregnancy and the toddlerhood years were at 2.1-fold increased risk of hyperactivity symptoms compared to those whose mothers had low or no anxiety, but increased maternal anxiety wasn’t associated with scores on any of the three tests of inattention.

Dr. Bolea cautioned that, while these Avon study findings document an association between early maternal anxiety and subsequent adolescent hyperactivity, that doesn’t prove causality. The findings are consistent, however, with the fetal origins hypothesis put forth by the late British epidemiologist David J. Barker, MD, PhD, which postulates that stressful fetal circumstances have profound effects later in life.

“What we’re thinking here is, if the mother is anxious during pregnancy, that may change how the fetal brain develops, and it makes kids hyperactive later on,” she said.

The hypothesis has been borne out in animal studies: Stress a pregnant rat, and her offspring will display hyperactivity.

Dr. Bolea reported having no financial conflicts regarding her study. The Avon Longitudinal Study of Parents and Children is funded by the Medical Research Council and the Wellcome Trust.

bjancin@mdedge.com

The Food and Drug Administration has approved daratumumab in combination with certain therapies for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant.

Olivier Le Moal/Getty Images

The approval specifies combination of this CD38-directed antibody with bortezomib (Velcade), thalidomide, and dexamethasone (VTd), according to an announcement from Janssen.

The approval is based on results from the CASSIOPEIA study. The first part of the study randomized 1,085 patients (median age, 58 years) and showed that, compared with VTd alone, the daratumumab-VTd combination had significantly better postconsolidation stringent complete response (29% vs. 20%; odds ratio, 1.60; 95% confidence interval, 1.21-2.12; P = .001) and a 53% reduction in risk of disease progression or death (hazard ratio, 0.47; 95% CI, 0.33-0.67; P = .0001).

The most frequent adverse reactions with 5% greater frequency in the daratumumab-VTd group were infusion reactions (including anaphylaxis), nausea, pyrexia, upper respiratory tract infection, and bronchitis. Full prescribing information, including contraindications and warnings, can be found on the Janssen website.

Daratumumab was initially approved in 2015, and in June 2019, it received approval, in combination with lenalidomide and dexamethasone, for treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

cpalmer@mdedge.com

The Food and Drug Administration has approved daratumumab in combination with certain therapies for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant.

Olivier Le Moal/Getty Images

The approval specifies combination of this CD38-directed antibody with bortezomib (Velcade), thalidomide, and dexamethasone (VTd), according to an announcement from Janssen.

The approval is based on results from the CASSIOPEIA study. The first part of the study randomized 1,085 patients (median age, 58 years) and showed that, compared with VTd alone, the daratumumab-VTd combination had significantly better postconsolidation stringent complete response (29% vs. 20%; odds ratio, 1.60; 95% confidence interval, 1.21-2.12; P = .001) and a 53% reduction in risk of disease progression or death (hazard ratio, 0.47; 95% CI, 0.33-0.67; P = .0001).

The most frequent adverse reactions with 5% greater frequency in the daratumumab-VTd group were infusion reactions (including anaphylaxis), nausea, pyrexia, upper respiratory tract infection, and bronchitis. Full prescribing information, including contraindications and warnings, can be found on the Janssen website.

Daratumumab was initially approved in 2015, and in June 2019, it received approval, in combination with lenalidomide and dexamethasone, for treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

cpalmer@mdedge.com

The Food and Drug Administration has approved daratumumab in combination with certain therapies for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant.

Olivier Le Moal/Getty Images

The approval specifies combination of this CD38-directed antibody with bortezomib (Velcade), thalidomide, and dexamethasone (VTd), according to an announcement from Janssen.

The approval is based on results from the CASSIOPEIA study. The first part of the study randomized 1,085 patients (median age, 58 years) and showed that, compared with VTd alone, the daratumumab-VTd combination had significantly better postconsolidation stringent complete response (29% vs. 20%; odds ratio, 1.60; 95% confidence interval, 1.21-2.12; P = .001) and a 53% reduction in risk of disease progression or death (hazard ratio, 0.47; 95% CI, 0.33-0.67; P = .0001).

The most frequent adverse reactions with 5% greater frequency in the daratumumab-VTd group were infusion reactions (including anaphylaxis), nausea, pyrexia, upper respiratory tract infection, and bronchitis. Full prescribing information, including contraindications and warnings, can be found on the Janssen website.

Daratumumab was initially approved in 2015, and in June 2019, it received approval, in combination with lenalidomide and dexamethasone, for treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

cpalmer@mdedge.com

BOSTON – Subcutaneous daratumumab in combination with standard care is comparable to intravenous daratumumab plus standard care in patients with newly diagnosed or relapsed/refractory multiple myeloma, according to a speaker at the International Myeloma Workshop.

Jennifer Smith/MDedge News

Overall response rates (ORRs) observed with subcutaneous daratumumab–based combinations in the phase 2 PLEIADES trial were similar to ORRs observed with intravenous daratumumab–based combinations in three other trials – GRIFFIN, ALCYONE, and POLLUX.

Ajai Chari, MD, of the Icahn School of Medicine at Mount Sinai, New York, presented these findings at the workshop, which is held by the International Myeloma Society.

In the PLEIADES trial, researchers tested subcutaneous daratumumab (D) in combination with:

• Bortezomib, lenalidomide, and dexamethasone (VRd) in transplant-eligible patients with newly diagnosed multiple myeloma
• Bortezomib, melphalan, and prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma
• Lenalidomide and dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma who had received at least one prior line of therapy.

There were 67 patients in the D-VRd arm, and they had a median age of 59 years (range, 33-76 years). There were 67 patients in the D-VMP arm, and they had a median age of 75 years (range, 66-86 years). There were 65 patients in the D-Rd arm, they had a median age of 69 years (range, 33-82 years), and they had received a median of one (range, one to five) prior therapies.

Dr. Chari noted that baseline characteristics in this study were “pretty comparable” to characteristics in the studies of intravenous daratumumab. He also pointed out that the median administration time for subcutaneous daratumumab was 5 minutes in this study, which is “substantially” shorter than the typical administration time for intravenous daratumumab.

The median number of treatment cycles was 4 (range, 1-4) in the D-VRd arm, 8 (range, 1-10) in the D-VMP arm, and 12 (range, 1-15) in the D-Rd arm. The median duration of treatment was 2.6 months, 10.6 months, and 11.1 months, respectively.

The proportion of patients who discontinued treatment was 3% in the D-VRd arm, 10.4% in the D-VMP arm, and 20% in the D-Rd arm.

Response

Dr. Chari said response rates in the three arms of PLEAIDES were similar to response rates in corresponding groups from the studies of intravenous daratumumab–based combinations.

After four induction cycles, subcutaneous D-VRd produced an ORR of 97% in PLEAIDES, and intravenous D-VRd produced an ORR of 98% in the GRIFFIN trial (IMW 2019. Abstract OAB-087).

Subcutaneous D-VMP produced an ORR of 89.6% at a median follow-up of 11 months. In the ALCYONE trial, intravenous D-VMP produced an ORR of 90.9% at a median follow-up of 16.5 months (N Engl J Med. 2018; 378:518-28).

Subcutaneous D-Rd produced an ORR of 93.8% at a median follow-up of 11.2 months. In the POLLUX trial, intravenous D-Rd produced an ORR of 92.9% at a median follow-up of 13.5 months (N Engl J Med. 2016; 375:1319-31).

Safety

All patients in PLEIADES had treatment-related adverse events (TEAEs). The rate of serious TEAEs was 28.4% in the D-VRd arm, 38.8% in the D-VMP arm, and 47.7% in the D-Rd arm. The rate of grade 3/4 TEAEs was 56.7%, 68.7%, and 83.1%, respectively. There was one fatal TEAE in the D-VRd arm, two fatal TEAEs in the D-VMP arm, and two in the D-Rd arm.

Infusion-related reactions occurred in 7.5% of all patients (15/199). Most infusion-related reactions were grade 1/2. One patient had a grade 3 reaction, and there were no grade 4 reactions. The median time to onset was 3.3 hours.

“Daratumumab in combination with standard of care, when given subcutaneously, demonstrated comparable clinical activity and safety and corresponded to daratumumab intravenous–containing regimens,” Dr. Chari said. “These results support the use of flat-dose 1,800 mg [subcutaneous daratumumab] in combination with standard treatment regimens.”

The PLEIADES trial was sponsored by Janssen Research & Development. Dr. Chari reported relationships with Janssen and several other companies.

jensmith@mdedge.com

SOURCE: Chari A et al. IMW 2019, Abstract OAB-022.

BOSTON – Subcutaneous daratumumab in combination with standard care is comparable to intravenous daratumumab plus standard care in patients with newly diagnosed or relapsed/refractory multiple myeloma, according to a speaker at the International Myeloma Workshop.

Jennifer Smith/MDedge News

Overall response rates (ORRs) observed with subcutaneous daratumumab–based combinations in the phase 2 PLEIADES trial were similar to ORRs observed with intravenous daratumumab–based combinations in three other trials – GRIFFIN, ALCYONE, and POLLUX.

Ajai Chari, MD, of the Icahn School of Medicine at Mount Sinai, New York, presented these findings at the workshop, which is held by the International Myeloma Society.

In the PLEIADES trial, researchers tested subcutaneous daratumumab (D) in combination with:

• Bortezomib, lenalidomide, and dexamethasone (VRd) in transplant-eligible patients with newly diagnosed multiple myeloma
• Bortezomib, melphalan, and prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma
• Lenalidomide and dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma who had received at least one prior line of therapy.

There were 67 patients in the D-VRd arm, and they had a median age of 59 years (range, 33-76 years). There were 67 patients in the D-VMP arm, and they had a median age of 75 years (range, 66-86 years). There were 65 patients in the D-Rd arm, they had a median age of 69 years (range, 33-82 years), and they had received a median of one (range, one to five) prior therapies.

Dr. Chari noted that baseline characteristics in this study were “pretty comparable” to characteristics in the studies of intravenous daratumumab. He also pointed out that the median administration time for subcutaneous daratumumab was 5 minutes in this study, which is “substantially” shorter than the typical administration time for intravenous daratumumab.

The median number of treatment cycles was 4 (range, 1-4) in the D-VRd arm, 8 (range, 1-10) in the D-VMP arm, and 12 (range, 1-15) in the D-Rd arm. The median duration of treatment was 2.6 months, 10.6 months, and 11.1 months, respectively.

The proportion of patients who discontinued treatment was 3% in the D-VRd arm, 10.4% in the D-VMP arm, and 20% in the D-Rd arm.

Response

Dr. Chari said response rates in the three arms of PLEAIDES were similar to response rates in corresponding groups from the studies of intravenous daratumumab–based combinations.

After four induction cycles, subcutaneous D-VRd produced an ORR of 97% in PLEAIDES, and intravenous D-VRd produced an ORR of 98% in the GRIFFIN trial (IMW 2019. Abstract OAB-087).

Subcutaneous D-VMP produced an ORR of 89.6% at a median follow-up of 11 months. In the ALCYONE trial, intravenous D-VMP produced an ORR of 90.9% at a median follow-up of 16.5 months (N Engl J Med. 2018; 378:518-28).

Subcutaneous D-Rd produced an ORR of 93.8% at a median follow-up of 11.2 months. In the POLLUX trial, intravenous D-Rd produced an ORR of 92.9% at a median follow-up of 13.5 months (N Engl J Med. 2016; 375:1319-31).

Safety

All patients in PLEIADES had treatment-related adverse events (TEAEs). The rate of serious TEAEs was 28.4% in the D-VRd arm, 38.8% in the D-VMP arm, and 47.7% in the D-Rd arm. The rate of grade 3/4 TEAEs was 56.7%, 68.7%, and 83.1%, respectively. There was one fatal TEAE in the D-VRd arm, two fatal TEAEs in the D-VMP arm, and two in the D-Rd arm.

Infusion-related reactions occurred in 7.5% of all patients (15/199). Most infusion-related reactions were grade 1/2. One patient had a grade 3 reaction, and there were no grade 4 reactions. The median time to onset was 3.3 hours.

“Daratumumab in combination with standard of care, when given subcutaneously, demonstrated comparable clinical activity and safety and corresponded to daratumumab intravenous–containing regimens,” Dr. Chari said. “These results support the use of flat-dose 1,800 mg [subcutaneous daratumumab] in combination with standard treatment regimens.”

The PLEIADES trial was sponsored by Janssen Research & Development. Dr. Chari reported relationships with Janssen and several other companies.

jensmith@mdedge.com

SOURCE: Chari A et al. IMW 2019, Abstract OAB-022.

BOSTON – Subcutaneous daratumumab in combination with standard care is comparable to intravenous daratumumab plus standard care in patients with newly diagnosed or relapsed/refractory multiple myeloma, according to a speaker at the International Myeloma Workshop.

Jennifer Smith/MDedge News

Overall response rates (ORRs) observed with subcutaneous daratumumab–based combinations in the phase 2 PLEIADES trial were similar to ORRs observed with intravenous daratumumab–based combinations in three other trials – GRIFFIN, ALCYONE, and POLLUX.

Ajai Chari, MD, of the Icahn School of Medicine at Mount Sinai, New York, presented these findings at the workshop, which is held by the International Myeloma Society.

In the PLEIADES trial, researchers tested subcutaneous daratumumab (D) in combination with:

• Bortezomib, lenalidomide, and dexamethasone (VRd) in transplant-eligible patients with newly diagnosed multiple myeloma
• Bortezomib, melphalan, and prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma
• Lenalidomide and dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma who had received at least one prior line of therapy.

There were 67 patients in the D-VRd arm, and they had a median age of 59 years (range, 33-76 years). There were 67 patients in the D-VMP arm, and they had a median age of 75 years (range, 66-86 years). There were 65 patients in the D-Rd arm, they had a median age of 69 years (range, 33-82 years), and they had received a median of one (range, one to five) prior therapies.

Dr. Chari noted that baseline characteristics in this study were “pretty comparable” to characteristics in the studies of intravenous daratumumab. He also pointed out that the median administration time for subcutaneous daratumumab was 5 minutes in this study, which is “substantially” shorter than the typical administration time for intravenous daratumumab.

The median number of treatment cycles was 4 (range, 1-4) in the D-VRd arm, 8 (range, 1-10) in the D-VMP arm, and 12 (range, 1-15) in the D-Rd arm. The median duration of treatment was 2.6 months, 10.6 months, and 11.1 months, respectively.

The proportion of patients who discontinued treatment was 3% in the D-VRd arm, 10.4% in the D-VMP arm, and 20% in the D-Rd arm.

Response

Dr. Chari said response rates in the three arms of PLEAIDES were similar to response rates in corresponding groups from the studies of intravenous daratumumab–based combinations.

After four induction cycles, subcutaneous D-VRd produced an ORR of 97% in PLEAIDES, and intravenous D-VRd produced an ORR of 98% in the GRIFFIN trial (IMW 2019. Abstract OAB-087).

Subcutaneous D-VMP produced an ORR of 89.6% at a median follow-up of 11 months. In the ALCYONE trial, intravenous D-VMP produced an ORR of 90.9% at a median follow-up of 16.5 months (N Engl J Med. 2018; 378:518-28).

Subcutaneous D-Rd produced an ORR of 93.8% at a median follow-up of 11.2 months. In the POLLUX trial, intravenous D-Rd produced an ORR of 92.9% at a median follow-up of 13.5 months (N Engl J Med. 2016; 375:1319-31).

Safety

All patients in PLEIADES had treatment-related adverse events (TEAEs). The rate of serious TEAEs was 28.4% in the D-VRd arm, 38.8% in the D-VMP arm, and 47.7% in the D-Rd arm. The rate of grade 3/4 TEAEs was 56.7%, 68.7%, and 83.1%, respectively. There was one fatal TEAE in the D-VRd arm, two fatal TEAEs in the D-VMP arm, and two in the D-Rd arm.

Infusion-related reactions occurred in 7.5% of all patients (15/199). Most infusion-related reactions were grade 1/2. One patient had a grade 3 reaction, and there were no grade 4 reactions. The median time to onset was 3.3 hours.

“Daratumumab in combination with standard of care, when given subcutaneously, demonstrated comparable clinical activity and safety and corresponded to daratumumab intravenous–containing regimens,” Dr. Chari said. “These results support the use of flat-dose 1,800 mg [subcutaneous daratumumab] in combination with standard treatment regimens.”

The PLEIADES trial was sponsored by Janssen Research & Development. Dr. Chari reported relationships with Janssen and several other companies.

jensmith@mdedge.com

SOURCE: Chari A et al. IMW 2019, Abstract OAB-022.