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Dupilumab efficacy extends to chronic rhinosinusitis/nasal polyposis
PARIS – Severe asthma patients with chronic rhinosinusitis (CRS), nasal polyposis (NP), or both derive more protection from severe exacerbations with the monoclonal antibody dupilumab than do those who do not have these comorbidities, according to a post hoc analysis of a phase 3 trial presented at the annual congress of the European Respiratory Society.
“Dupilumab reduced rates of severe exacerbations and improved FEV1 [forced expiratory volume in 1 second] in patients in asthma patients with or without CRS/NP. In those with CRS/NP, dupilumab reduced symptoms associated with these comorbidities,” reported Ian Pavord, MBBS, statutory chair in respiratory medicine at University of Oxford (England).
The data were drawn from the phase 3 Liberty Asthma Quest trial, which was published earlier this year in the New England Journal of Medicine (2018;378:2486-96). In that study, both the 200-mg and 300-mg dose of dupilumab (Dupixent) administered every 2 weeks was associated with about a 50% reduction in the annualized rate of severe exacerbations relative to placebo (P less than .001 for both doses).
In this new post hoc analysis, response in the 382 patients who entered the study with a history of CRS/NP was compared with the 1,520 without CRS/NP. In the CRS/NP patients, the reductions relative to placebo in the rates of severe exacerbations, defined as 3 or more days of systemic glucocorticoids or visit to an emergency department leading to treatment with systemic glucocorticoids, were 63% and 61% for the 200-mg and 300-mg doses of dupilumab, respectively (both P less than .001).
In the non-CRS/NP arms, the reductions relative to placebo were 42% and 40%, respectively (both P less than .001). The greater relative reductions in the CRS/NP patients were achieved even though they were older (mean age approximately 52 vs. 47 years for non-CRS/NP patients), had a significantly greater number of exacerbations in the past year (P = .027), and had higher baseline fractional exhaled nitric oxide and eosinophil levels (both P less than .001), Dr. Pavord reported.
“The greater asthma severity in the CRS/NP patients in this trial is consistent with that reported previously by others,” Dr. Pavord said.
Although the greater asthma severity may have provided a larger margin for benefit, Dr. Pavord also reported that there were improvements in CRS/NP-specific symptoms as measured with the 22-item Sino-Nasal Outcome Test (SNOT-22). By week 12, the total score reduction in SNOT-22 was approximately 15 points (P less than .05) from baseline for both the 200-mg and 300-mg dupilumab doses. This was significantly greater (P less than .05) relative to modest SNOT-22 reductions in the placebo arms (P less than .05). After 52 weeks, the reduction In SNOT-22 scores were sustained, providing an even greater statistical advantage over placebo (P less than .001).
In addition to greater protection against severe exacerbations and CRS/NP-specific symptoms, dupilumab may offer specific improvements on CRS/NP pathology, according to Dr. Pavord. Although imaging was not part of this study, he noted in particular that previous studies with dupilumab as well as other biologics have shown shrinkage of nasal polyps with treatment.
Dupilumab was similarly well tolerated in those with and without CRS/NP. The most common adverse event was injection site reactions in both groups, Dr. Pavord said.
Calling CRS and NP “important comorbidities” in severe asthma patients, Dr. Pavord said that this analysis should be reassuring for those who with CRS/NP who are being considered for dupilumab. Already approved for treatment of atopic dermatitis, dupilumab, which binds to interleukin-4 (IL-4) and IL-13 receptors, is currently under review for the treatment of moderate to severe asthma.
Dr. Pavord has financial relationships with Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Knapp, Merck Sharpe, Novartis, Knapp Teva, RespiVert, and Schering-Plough.
PARIS – Severe asthma patients with chronic rhinosinusitis (CRS), nasal polyposis (NP), or both derive more protection from severe exacerbations with the monoclonal antibody dupilumab than do those who do not have these comorbidities, according to a post hoc analysis of a phase 3 trial presented at the annual congress of the European Respiratory Society.
“Dupilumab reduced rates of severe exacerbations and improved FEV1 [forced expiratory volume in 1 second] in patients in asthma patients with or without CRS/NP. In those with CRS/NP, dupilumab reduced symptoms associated with these comorbidities,” reported Ian Pavord, MBBS, statutory chair in respiratory medicine at University of Oxford (England).
The data were drawn from the phase 3 Liberty Asthma Quest trial, which was published earlier this year in the New England Journal of Medicine (2018;378:2486-96). In that study, both the 200-mg and 300-mg dose of dupilumab (Dupixent) administered every 2 weeks was associated with about a 50% reduction in the annualized rate of severe exacerbations relative to placebo (P less than .001 for both doses).
In this new post hoc analysis, response in the 382 patients who entered the study with a history of CRS/NP was compared with the 1,520 without CRS/NP. In the CRS/NP patients, the reductions relative to placebo in the rates of severe exacerbations, defined as 3 or more days of systemic glucocorticoids or visit to an emergency department leading to treatment with systemic glucocorticoids, were 63% and 61% for the 200-mg and 300-mg doses of dupilumab, respectively (both P less than .001).
In the non-CRS/NP arms, the reductions relative to placebo were 42% and 40%, respectively (both P less than .001). The greater relative reductions in the CRS/NP patients were achieved even though they were older (mean age approximately 52 vs. 47 years for non-CRS/NP patients), had a significantly greater number of exacerbations in the past year (P = .027), and had higher baseline fractional exhaled nitric oxide and eosinophil levels (both P less than .001), Dr. Pavord reported.
“The greater asthma severity in the CRS/NP patients in this trial is consistent with that reported previously by others,” Dr. Pavord said.
Although the greater asthma severity may have provided a larger margin for benefit, Dr. Pavord also reported that there were improvements in CRS/NP-specific symptoms as measured with the 22-item Sino-Nasal Outcome Test (SNOT-22). By week 12, the total score reduction in SNOT-22 was approximately 15 points (P less than .05) from baseline for both the 200-mg and 300-mg dupilumab doses. This was significantly greater (P less than .05) relative to modest SNOT-22 reductions in the placebo arms (P less than .05). After 52 weeks, the reduction In SNOT-22 scores were sustained, providing an even greater statistical advantage over placebo (P less than .001).
In addition to greater protection against severe exacerbations and CRS/NP-specific symptoms, dupilumab may offer specific improvements on CRS/NP pathology, according to Dr. Pavord. Although imaging was not part of this study, he noted in particular that previous studies with dupilumab as well as other biologics have shown shrinkage of nasal polyps with treatment.
Dupilumab was similarly well tolerated in those with and without CRS/NP. The most common adverse event was injection site reactions in both groups, Dr. Pavord said.
Calling CRS and NP “important comorbidities” in severe asthma patients, Dr. Pavord said that this analysis should be reassuring for those who with CRS/NP who are being considered for dupilumab. Already approved for treatment of atopic dermatitis, dupilumab, which binds to interleukin-4 (IL-4) and IL-13 receptors, is currently under review for the treatment of moderate to severe asthma.
Dr. Pavord has financial relationships with Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Knapp, Merck Sharpe, Novartis, Knapp Teva, RespiVert, and Schering-Plough.
PARIS – Severe asthma patients with chronic rhinosinusitis (CRS), nasal polyposis (NP), or both derive more protection from severe exacerbations with the monoclonal antibody dupilumab than do those who do not have these comorbidities, according to a post hoc analysis of a phase 3 trial presented at the annual congress of the European Respiratory Society.
“Dupilumab reduced rates of severe exacerbations and improved FEV1 [forced expiratory volume in 1 second] in patients in asthma patients with or without CRS/NP. In those with CRS/NP, dupilumab reduced symptoms associated with these comorbidities,” reported Ian Pavord, MBBS, statutory chair in respiratory medicine at University of Oxford (England).
The data were drawn from the phase 3 Liberty Asthma Quest trial, which was published earlier this year in the New England Journal of Medicine (2018;378:2486-96). In that study, both the 200-mg and 300-mg dose of dupilumab (Dupixent) administered every 2 weeks was associated with about a 50% reduction in the annualized rate of severe exacerbations relative to placebo (P less than .001 for both doses).
In this new post hoc analysis, response in the 382 patients who entered the study with a history of CRS/NP was compared with the 1,520 without CRS/NP. In the CRS/NP patients, the reductions relative to placebo in the rates of severe exacerbations, defined as 3 or more days of systemic glucocorticoids or visit to an emergency department leading to treatment with systemic glucocorticoids, were 63% and 61% for the 200-mg and 300-mg doses of dupilumab, respectively (both P less than .001).
In the non-CRS/NP arms, the reductions relative to placebo were 42% and 40%, respectively (both P less than .001). The greater relative reductions in the CRS/NP patients were achieved even though they were older (mean age approximately 52 vs. 47 years for non-CRS/NP patients), had a significantly greater number of exacerbations in the past year (P = .027), and had higher baseline fractional exhaled nitric oxide and eosinophil levels (both P less than .001), Dr. Pavord reported.
“The greater asthma severity in the CRS/NP patients in this trial is consistent with that reported previously by others,” Dr. Pavord said.
Although the greater asthma severity may have provided a larger margin for benefit, Dr. Pavord also reported that there were improvements in CRS/NP-specific symptoms as measured with the 22-item Sino-Nasal Outcome Test (SNOT-22). By week 12, the total score reduction in SNOT-22 was approximately 15 points (P less than .05) from baseline for both the 200-mg and 300-mg dupilumab doses. This was significantly greater (P less than .05) relative to modest SNOT-22 reductions in the placebo arms (P less than .05). After 52 weeks, the reduction In SNOT-22 scores were sustained, providing an even greater statistical advantage over placebo (P less than .001).
In addition to greater protection against severe exacerbations and CRS/NP-specific symptoms, dupilumab may offer specific improvements on CRS/NP pathology, according to Dr. Pavord. Although imaging was not part of this study, he noted in particular that previous studies with dupilumab as well as other biologics have shown shrinkage of nasal polyps with treatment.
Dupilumab was similarly well tolerated in those with and without CRS/NP. The most common adverse event was injection site reactions in both groups, Dr. Pavord said.
Calling CRS and NP “important comorbidities” in severe asthma patients, Dr. Pavord said that this analysis should be reassuring for those who with CRS/NP who are being considered for dupilumab. Already approved for treatment of atopic dermatitis, dupilumab, which binds to interleukin-4 (IL-4) and IL-13 receptors, is currently under review for the treatment of moderate to severe asthma.
Dr. Pavord has financial relationships with Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Knapp, Merck Sharpe, Novartis, Knapp Teva, RespiVert, and Schering-Plough.
REPORTING FROM THE ERS CONGRESS 2018
Key clinical point: In asthma patients with chronic rhinosinusitis and/or nasal polyposis (CRS/NP), dupilumab reduces exacerbations.
Major finding: At 52 weeks, severe exacerbations were reduced 61% in CRS/NP patients and 40% in non-CRS/NP patients (both P less than .001).
Study details: Post hoc analysis of phase 3 trial.
Disclosures: Dr. Pavord has financial relationships with Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Knapp, Merck Sharpe, Novartis, Knapp Teva, RespiVert, and Schering-Plough.
Updated IPF guideline refines diagnostic criteria with HRCT
A recently updated guideline for idiopathic pulmonary fibrosis (IPF) provides refined diagnostic criteria in an effort to improve clinical application and diagnostic accuracy.
Of note, the guideline recommends that high-resolution CT (HRCT) patterns be used to dictate management course. The guideline also calls for detailed medical history, serological testing to exclude connective tissue disease, and multidisciplinary discussion. Serum biomarkers are recommended against as a means of distinguishing between IPF and other interstitial lung diseases (ILDs).
“Diagnosing IPF is challenging because these symptoms are nonspecific: They occur with all other interstitial lung diseases and with other respiratory problems,” Ganesh Raghu, MD, chair of the guideline committee and professor of medicine and director of the Center for Interstitial Lung Disease at the University of Washington, Seattle, said in a written statement. “Because drugs may slow the progression of IPF, an early and accurate diagnosis is essential for prompt and appropriate treatment for this fatal disease.”
The 2018 guideline represents a second collaborative effort from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. The guideline committee consisted of 29 clinicians, scientists, and a patient with IPF. They evaluated all IPF-related evidence and rated the quality of findings with the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. The first IPF guideline was published 7 years ago; the intervening time has revealed some clinical limitations that the 2018 guideline aims to fix.
“The 2011 guideline provided the first evidence-based, formal criteria for diagnosis of IPF and allowed patients with a well-defined diagnosis of IPF to participate in numerous clinical studies and randomized controlled trials that enhanced our understanding of the disease,” Dr. Raghu said. “However, it became clear that there were significant challenges in ascertaining the diagnosis per the 2011 criteria, and abundant evidence accumulated since then allowed the committee to refine the diagnostic criteria now.”
“This [updated] guideline is intended to help clinicians make an accurate diagnosis of IPF,” the authors wrote in the American Journal of Respiratory and Critical Care Medicine, “and to empower them to implement recommended courses of action in the context of individual patient values and preferences, particularly decisions regarding which diagnostic interventions to pursue.”
While the 2011 guideline did not distinguish between patients with different HRCT patterns, the 2018 guideline emphasizes the use of HRCT. It is now recommended that patients undergo HRCT to determine the pattern of usual interstitial pneumonia (UIP). Broadly, patients exhibit the UIP pattern or one of three possible non-UIP patterns (probable UIP, indeterminate UIP, or an alternative diagnosis). Recommendations are specific for UIP and non-UIP.
Patients with probable UIP, indeterminate UIP, or an alternative diagnosis should undergo bronchoalveolar lavage (BAL) and surgical lung biopsy (SLB). Transbronchial lung biopsy (TBBx) and lung cryobiopsy recommendations were not described in these patients because of a lack of evidence. However, patients with UIP should not undergo BAL, SLB, TBBx, or cryobiopsy.
For all patients, the 2018 guideline recommends that medical histories include environmental exposure and medication use, and that serological testing is performed to exclude connective tissue disease. Multidisciplinary discussion is conditionally recommended for diagnostic decision making, particularly when a patient has probable UIP, indeterminate UIP, or an alternative diagnosis.
Finally, the guideline recommends against the use of serum biomarkers as a means of distinguishing between IPF and other ILDs because of weak data on this point. “For the time being, the guideline panel dismissed serum biomarker measurement as an approach to distinguishing IPF from other ILDs because of the high false-positive and false-negative result rates,” the panel wrote.
“Our hope is that this new guideline will bridge the gap between the experienced IPF experts and general pulmonologists in making a prompt and accurate diagnosis of IPF for the individual unfortunately confronted with the disease,” Dr. Raghu said. “This will allow patients to make well-informed decisions about treatment options and participation in clinical trials.”
Looking to the future, the panel described an “urgent need to refine and validate diagnostic approaches to ILD. These needs can be roughly categorized as investigations into the roles of clinical observations, HRCT, bronchoscopy, histopathology, and biomarkers.” The authors also emphasized “the need to refine prognostic approaches, identify risk factors for the development of IPF, and determine the impact and approach to the diagnosis of comorbid illness in the patient with IPF.”
The authors reported funding from Bellerophon, Gilead, Roche, Sanofi, and others.
SOURCE: Raghu G et al. Am J Respir Crit Care Med. 2018 Sep 1. doi: 10.1164/rccm.201807-1255ST.
A recently updated guideline for idiopathic pulmonary fibrosis (IPF) provides refined diagnostic criteria in an effort to improve clinical application and diagnostic accuracy.
Of note, the guideline recommends that high-resolution CT (HRCT) patterns be used to dictate management course. The guideline also calls for detailed medical history, serological testing to exclude connective tissue disease, and multidisciplinary discussion. Serum biomarkers are recommended against as a means of distinguishing between IPF and other interstitial lung diseases (ILDs).
“Diagnosing IPF is challenging because these symptoms are nonspecific: They occur with all other interstitial lung diseases and with other respiratory problems,” Ganesh Raghu, MD, chair of the guideline committee and professor of medicine and director of the Center for Interstitial Lung Disease at the University of Washington, Seattle, said in a written statement. “Because drugs may slow the progression of IPF, an early and accurate diagnosis is essential for prompt and appropriate treatment for this fatal disease.”
The 2018 guideline represents a second collaborative effort from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. The guideline committee consisted of 29 clinicians, scientists, and a patient with IPF. They evaluated all IPF-related evidence and rated the quality of findings with the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. The first IPF guideline was published 7 years ago; the intervening time has revealed some clinical limitations that the 2018 guideline aims to fix.
“The 2011 guideline provided the first evidence-based, formal criteria for diagnosis of IPF and allowed patients with a well-defined diagnosis of IPF to participate in numerous clinical studies and randomized controlled trials that enhanced our understanding of the disease,” Dr. Raghu said. “However, it became clear that there were significant challenges in ascertaining the diagnosis per the 2011 criteria, and abundant evidence accumulated since then allowed the committee to refine the diagnostic criteria now.”
“This [updated] guideline is intended to help clinicians make an accurate diagnosis of IPF,” the authors wrote in the American Journal of Respiratory and Critical Care Medicine, “and to empower them to implement recommended courses of action in the context of individual patient values and preferences, particularly decisions regarding which diagnostic interventions to pursue.”
While the 2011 guideline did not distinguish between patients with different HRCT patterns, the 2018 guideline emphasizes the use of HRCT. It is now recommended that patients undergo HRCT to determine the pattern of usual interstitial pneumonia (UIP). Broadly, patients exhibit the UIP pattern or one of three possible non-UIP patterns (probable UIP, indeterminate UIP, or an alternative diagnosis). Recommendations are specific for UIP and non-UIP.
Patients with probable UIP, indeterminate UIP, or an alternative diagnosis should undergo bronchoalveolar lavage (BAL) and surgical lung biopsy (SLB). Transbronchial lung biopsy (TBBx) and lung cryobiopsy recommendations were not described in these patients because of a lack of evidence. However, patients with UIP should not undergo BAL, SLB, TBBx, or cryobiopsy.
For all patients, the 2018 guideline recommends that medical histories include environmental exposure and medication use, and that serological testing is performed to exclude connective tissue disease. Multidisciplinary discussion is conditionally recommended for diagnostic decision making, particularly when a patient has probable UIP, indeterminate UIP, or an alternative diagnosis.
Finally, the guideline recommends against the use of serum biomarkers as a means of distinguishing between IPF and other ILDs because of weak data on this point. “For the time being, the guideline panel dismissed serum biomarker measurement as an approach to distinguishing IPF from other ILDs because of the high false-positive and false-negative result rates,” the panel wrote.
“Our hope is that this new guideline will bridge the gap between the experienced IPF experts and general pulmonologists in making a prompt and accurate diagnosis of IPF for the individual unfortunately confronted with the disease,” Dr. Raghu said. “This will allow patients to make well-informed decisions about treatment options and participation in clinical trials.”
Looking to the future, the panel described an “urgent need to refine and validate diagnostic approaches to ILD. These needs can be roughly categorized as investigations into the roles of clinical observations, HRCT, bronchoscopy, histopathology, and biomarkers.” The authors also emphasized “the need to refine prognostic approaches, identify risk factors for the development of IPF, and determine the impact and approach to the diagnosis of comorbid illness in the patient with IPF.”
The authors reported funding from Bellerophon, Gilead, Roche, Sanofi, and others.
SOURCE: Raghu G et al. Am J Respir Crit Care Med. 2018 Sep 1. doi: 10.1164/rccm.201807-1255ST.
A recently updated guideline for idiopathic pulmonary fibrosis (IPF) provides refined diagnostic criteria in an effort to improve clinical application and diagnostic accuracy.
Of note, the guideline recommends that high-resolution CT (HRCT) patterns be used to dictate management course. The guideline also calls for detailed medical history, serological testing to exclude connective tissue disease, and multidisciplinary discussion. Serum biomarkers are recommended against as a means of distinguishing between IPF and other interstitial lung diseases (ILDs).
“Diagnosing IPF is challenging because these symptoms are nonspecific: They occur with all other interstitial lung diseases and with other respiratory problems,” Ganesh Raghu, MD, chair of the guideline committee and professor of medicine and director of the Center for Interstitial Lung Disease at the University of Washington, Seattle, said in a written statement. “Because drugs may slow the progression of IPF, an early and accurate diagnosis is essential for prompt and appropriate treatment for this fatal disease.”
The 2018 guideline represents a second collaborative effort from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. The guideline committee consisted of 29 clinicians, scientists, and a patient with IPF. They evaluated all IPF-related evidence and rated the quality of findings with the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. The first IPF guideline was published 7 years ago; the intervening time has revealed some clinical limitations that the 2018 guideline aims to fix.
“The 2011 guideline provided the first evidence-based, formal criteria for diagnosis of IPF and allowed patients with a well-defined diagnosis of IPF to participate in numerous clinical studies and randomized controlled trials that enhanced our understanding of the disease,” Dr. Raghu said. “However, it became clear that there were significant challenges in ascertaining the diagnosis per the 2011 criteria, and abundant evidence accumulated since then allowed the committee to refine the diagnostic criteria now.”
“This [updated] guideline is intended to help clinicians make an accurate diagnosis of IPF,” the authors wrote in the American Journal of Respiratory and Critical Care Medicine, “and to empower them to implement recommended courses of action in the context of individual patient values and preferences, particularly decisions regarding which diagnostic interventions to pursue.”
While the 2011 guideline did not distinguish between patients with different HRCT patterns, the 2018 guideline emphasizes the use of HRCT. It is now recommended that patients undergo HRCT to determine the pattern of usual interstitial pneumonia (UIP). Broadly, patients exhibit the UIP pattern or one of three possible non-UIP patterns (probable UIP, indeterminate UIP, or an alternative diagnosis). Recommendations are specific for UIP and non-UIP.
Patients with probable UIP, indeterminate UIP, or an alternative diagnosis should undergo bronchoalveolar lavage (BAL) and surgical lung biopsy (SLB). Transbronchial lung biopsy (TBBx) and lung cryobiopsy recommendations were not described in these patients because of a lack of evidence. However, patients with UIP should not undergo BAL, SLB, TBBx, or cryobiopsy.
For all patients, the 2018 guideline recommends that medical histories include environmental exposure and medication use, and that serological testing is performed to exclude connective tissue disease. Multidisciplinary discussion is conditionally recommended for diagnostic decision making, particularly when a patient has probable UIP, indeterminate UIP, or an alternative diagnosis.
Finally, the guideline recommends against the use of serum biomarkers as a means of distinguishing between IPF and other ILDs because of weak data on this point. “For the time being, the guideline panel dismissed serum biomarker measurement as an approach to distinguishing IPF from other ILDs because of the high false-positive and false-negative result rates,” the panel wrote.
“Our hope is that this new guideline will bridge the gap between the experienced IPF experts and general pulmonologists in making a prompt and accurate diagnosis of IPF for the individual unfortunately confronted with the disease,” Dr. Raghu said. “This will allow patients to make well-informed decisions about treatment options and participation in clinical trials.”
Looking to the future, the panel described an “urgent need to refine and validate diagnostic approaches to ILD. These needs can be roughly categorized as investigations into the roles of clinical observations, HRCT, bronchoscopy, histopathology, and biomarkers.” The authors also emphasized “the need to refine prognostic approaches, identify risk factors for the development of IPF, and determine the impact and approach to the diagnosis of comorbid illness in the patient with IPF.”
The authors reported funding from Bellerophon, Gilead, Roche, Sanofi, and others.
SOURCE: Raghu G et al. Am J Respir Crit Care Med. 2018 Sep 1. doi: 10.1164/rccm.201807-1255ST.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
VA Releases Spanish Version of Health Benefits Application
Nearly 1.5 million veterans and more than 500,000 already enrolled in the VA health care system identify as being Hispanic or Latino. “Our veteran population is made up of an increasingly diverse group of people,” said VA Secretary Robert Wilkie. “It’s our duty to expand the ways we communicate with all veterans, so they’re properly informed about the benefits they’ve earned.”
To that end, the VA has released a Spanish version of the application for health benefits, “to simplify and improve the health care enrollment process.” The new language version follows on the VA Advisory Committee on Minority Veterans’ recommendation.
The form is available at VA medical facilities and online at https://www.va.gov/vaforms/medical/pdf/10-10EZ_Spanish.pdf.
Nearly 1.5 million veterans and more than 500,000 already enrolled in the VA health care system identify as being Hispanic or Latino. “Our veteran population is made up of an increasingly diverse group of people,” said VA Secretary Robert Wilkie. “It’s our duty to expand the ways we communicate with all veterans, so they’re properly informed about the benefits they’ve earned.”
To that end, the VA has released a Spanish version of the application for health benefits, “to simplify and improve the health care enrollment process.” The new language version follows on the VA Advisory Committee on Minority Veterans’ recommendation.
The form is available at VA medical facilities and online at https://www.va.gov/vaforms/medical/pdf/10-10EZ_Spanish.pdf.
Nearly 1.5 million veterans and more than 500,000 already enrolled in the VA health care system identify as being Hispanic or Latino. “Our veteran population is made up of an increasingly diverse group of people,” said VA Secretary Robert Wilkie. “It’s our duty to expand the ways we communicate with all veterans, so they’re properly informed about the benefits they’ve earned.”
To that end, the VA has released a Spanish version of the application for health benefits, “to simplify and improve the health care enrollment process.” The new language version follows on the VA Advisory Committee on Minority Veterans’ recommendation.
The form is available at VA medical facilities and online at https://www.va.gov/vaforms/medical/pdf/10-10EZ_Spanish.pdf.
Be wary of watchful waiting in follicular lymphoma
A substantial proportion of patients with follicular lymphoma managed with watchful waiting develop organ dysfunction or transformation that may negatively impact survival outcomes, results of a retrospective study suggest.
About one-quarter of patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.
Organ dysfunction and transformation were associated with significantly worse overall survival that could not be predicted based on baseline characteristics, the study authors reported in Clinical Lymphoma, Myeloma & Leukemia.
The study confirmed certain benefits of watchful waiting, including a low risk of progression and an “excellent” rate of overall survival, the investigators said.
However, the substantial rate of organ dysfunction and transformation in a subset of patients is “clinically meaningful for informed decision making,” reported Gwynivere A. Davies, MD, of the University of Calgary (Alta.), and her coauthors.
“While consenting patients to initial [watchful waiting], patients need to be informed about the risk for these adverse events, as well as receiving education and the need for close monitoring regarding symptoms that may indicate serious progression events,” Dr. Davies and her coauthors wrote.
Alternatively, rituximab chemotherapy, with or without rituximab maintenance, might be warranted for watchful waiting patients with clear disease progression before organ dysfunction or transformation events, despite not meeting high-tumor burden therapy indications.
The retrospective study included data from the Alberta Lymphoma Database on patients with grade 1-3a follicular lymphoma aged 18-70 years who were diagnosed between 1994 and 2011. Investigators identified 238 patients initially managed with watchful waiting, with a median age of 54.1 years at diagnosis. More than 80% were advanced stage.
Only 71% of these patients progressed, with a median time to progression of about 30 months and a 10-year survival rate from diagnosis of 81.2%, investigators said. However, 58 patients (24.4%) had organ dysfunction or transformation at the time of progression.
Those adverse outcomes significantly affected overall survival. The 10-year overall survival was 65.4% for patients with transformation at progression versus 83.2% for those without (P = .0017). Likewise, 10-year overall survival was 71.5% and 82.7%, respectively, for those with organ dysfunction at progression and those without (P = .028).
Investigators also looked at a comparison group of 236 follicular lymphoma patients managed with immediate rituximab chemotherapy. They found survival outcomes in that group were similar to those in the subgroup of 56 watchful waiting patients who received primarily rituximab-containing regimens at the time of organ dysfunction or transformation.
Taken together, the findings suggest management changes may be warranted for follicular lymphoma patients managed according to a watchful waiting strategy, the investigators wrote. “Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events.”
Dr. Davies reported having no financial disclosures. Study coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
SOURCE: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
A substantial proportion of patients with follicular lymphoma managed with watchful waiting develop organ dysfunction or transformation that may negatively impact survival outcomes, results of a retrospective study suggest.
About one-quarter of patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.
Organ dysfunction and transformation were associated with significantly worse overall survival that could not be predicted based on baseline characteristics, the study authors reported in Clinical Lymphoma, Myeloma & Leukemia.
The study confirmed certain benefits of watchful waiting, including a low risk of progression and an “excellent” rate of overall survival, the investigators said.
However, the substantial rate of organ dysfunction and transformation in a subset of patients is “clinically meaningful for informed decision making,” reported Gwynivere A. Davies, MD, of the University of Calgary (Alta.), and her coauthors.
“While consenting patients to initial [watchful waiting], patients need to be informed about the risk for these adverse events, as well as receiving education and the need for close monitoring regarding symptoms that may indicate serious progression events,” Dr. Davies and her coauthors wrote.
Alternatively, rituximab chemotherapy, with or without rituximab maintenance, might be warranted for watchful waiting patients with clear disease progression before organ dysfunction or transformation events, despite not meeting high-tumor burden therapy indications.
The retrospective study included data from the Alberta Lymphoma Database on patients with grade 1-3a follicular lymphoma aged 18-70 years who were diagnosed between 1994 and 2011. Investigators identified 238 patients initially managed with watchful waiting, with a median age of 54.1 years at diagnosis. More than 80% were advanced stage.
Only 71% of these patients progressed, with a median time to progression of about 30 months and a 10-year survival rate from diagnosis of 81.2%, investigators said. However, 58 patients (24.4%) had organ dysfunction or transformation at the time of progression.
Those adverse outcomes significantly affected overall survival. The 10-year overall survival was 65.4% for patients with transformation at progression versus 83.2% for those without (P = .0017). Likewise, 10-year overall survival was 71.5% and 82.7%, respectively, for those with organ dysfunction at progression and those without (P = .028).
Investigators also looked at a comparison group of 236 follicular lymphoma patients managed with immediate rituximab chemotherapy. They found survival outcomes in that group were similar to those in the subgroup of 56 watchful waiting patients who received primarily rituximab-containing regimens at the time of organ dysfunction or transformation.
Taken together, the findings suggest management changes may be warranted for follicular lymphoma patients managed according to a watchful waiting strategy, the investigators wrote. “Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events.”
Dr. Davies reported having no financial disclosures. Study coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
SOURCE: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
A substantial proportion of patients with follicular lymphoma managed with watchful waiting develop organ dysfunction or transformation that may negatively impact survival outcomes, results of a retrospective study suggest.
About one-quarter of patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.
Organ dysfunction and transformation were associated with significantly worse overall survival that could not be predicted based on baseline characteristics, the study authors reported in Clinical Lymphoma, Myeloma & Leukemia.
The study confirmed certain benefits of watchful waiting, including a low risk of progression and an “excellent” rate of overall survival, the investigators said.
However, the substantial rate of organ dysfunction and transformation in a subset of patients is “clinically meaningful for informed decision making,” reported Gwynivere A. Davies, MD, of the University of Calgary (Alta.), and her coauthors.
“While consenting patients to initial [watchful waiting], patients need to be informed about the risk for these adverse events, as well as receiving education and the need for close monitoring regarding symptoms that may indicate serious progression events,” Dr. Davies and her coauthors wrote.
Alternatively, rituximab chemotherapy, with or without rituximab maintenance, might be warranted for watchful waiting patients with clear disease progression before organ dysfunction or transformation events, despite not meeting high-tumor burden therapy indications.
The retrospective study included data from the Alberta Lymphoma Database on patients with grade 1-3a follicular lymphoma aged 18-70 years who were diagnosed between 1994 and 2011. Investigators identified 238 patients initially managed with watchful waiting, with a median age of 54.1 years at diagnosis. More than 80% were advanced stage.
Only 71% of these patients progressed, with a median time to progression of about 30 months and a 10-year survival rate from diagnosis of 81.2%, investigators said. However, 58 patients (24.4%) had organ dysfunction or transformation at the time of progression.
Those adverse outcomes significantly affected overall survival. The 10-year overall survival was 65.4% for patients with transformation at progression versus 83.2% for those without (P = .0017). Likewise, 10-year overall survival was 71.5% and 82.7%, respectively, for those with organ dysfunction at progression and those without (P = .028).
Investigators also looked at a comparison group of 236 follicular lymphoma patients managed with immediate rituximab chemotherapy. They found survival outcomes in that group were similar to those in the subgroup of 56 watchful waiting patients who received primarily rituximab-containing regimens at the time of organ dysfunction or transformation.
Taken together, the findings suggest management changes may be warranted for follicular lymphoma patients managed according to a watchful waiting strategy, the investigators wrote. “Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events.”
Dr. Davies reported having no financial disclosures. Study coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
SOURCE: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Key clinical point:
Major finding: A total of 58 patients (24.4%) had organ dysfunction or transformation at the time of progression and had worse survival outcomes, compared with patients who did not experience those events.
Study details: A retrospective study including data on 238 patients with grade 1-3a follicular lymphoma aged 18-70 years who were managed with watchful waiting.
Disclosures: Study authors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.
Source: Davies GA et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 28. doi: 10.1016/j.clml.2018.08.015.
Pruritus linked to wide variety of cancers
A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.
Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.
The results by race help address a gap in the literature, according to Shawn G. Kwatra, MD, of Johns Hopkins University, Baltimore, and his coinvestigators.
“Little is known about the association between pruritus and malignancy among different ethnic groups,” Dr. Kwatra and his coauthors wrote in the Journal of the American Academy of Dermatology.
The study shows a stronger association with more types of malignancies than has been reported previously, according to the investigators.
“The main difference is that prior studies focused on diagnosis of malignancy after the onset of pruritus, while our study includes malignancies diagnosed on or after pruritus onset,” they wrote.
Retrospective data for the study, which came from the Johns Hopkins Health System, included 16,925 patients aged 18 years or older who presented with itching or pruritus between April 4, 2013 and Dec. 31, 2017.
Of those 16,925 patients, 2,903 were also diagnosed with a concomitant malignancy during that time period. Compared with patients with no itching diagnosis during that time period, the pruritus patients more likely to have a concomitant malignancy, with an OR of 5.76 (95% confidence interval, 5.53-6.00), Dr. Kwatra and his colleagues found.
Malignancies most strongly associated with pruritus included those of the skin, liver, gallbladder and biliary tract, and hematopoietic system.
Among hematologic malignancies, pruritus was most strongly linked to myeloid leukemia and primary cutaneous lymphoma, while among skin cancers, squamous cell carcinoma was most strongly linked.
Whites had higher odds of any malignancy versus blacks, according to investigators, with ORs of 6.12 (95% CI, 5.81-6.46) and 5.61 (95% CI, 5.21-6.04), respectively.
Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.
The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.
The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.
Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.
Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.
The results by race help address a gap in the literature, according to Shawn G. Kwatra, MD, of Johns Hopkins University, Baltimore, and his coinvestigators.
“Little is known about the association between pruritus and malignancy among different ethnic groups,” Dr. Kwatra and his coauthors wrote in the Journal of the American Academy of Dermatology.
The study shows a stronger association with more types of malignancies than has been reported previously, according to the investigators.
“The main difference is that prior studies focused on diagnosis of malignancy after the onset of pruritus, while our study includes malignancies diagnosed on or after pruritus onset,” they wrote.
Retrospective data for the study, which came from the Johns Hopkins Health System, included 16,925 patients aged 18 years or older who presented with itching or pruritus between April 4, 2013 and Dec. 31, 2017.
Of those 16,925 patients, 2,903 were also diagnosed with a concomitant malignancy during that time period. Compared with patients with no itching diagnosis during that time period, the pruritus patients more likely to have a concomitant malignancy, with an OR of 5.76 (95% confidence interval, 5.53-6.00), Dr. Kwatra and his colleagues found.
Malignancies most strongly associated with pruritus included those of the skin, liver, gallbladder and biliary tract, and hematopoietic system.
Among hematologic malignancies, pruritus was most strongly linked to myeloid leukemia and primary cutaneous lymphoma, while among skin cancers, squamous cell carcinoma was most strongly linked.
Whites had higher odds of any malignancy versus blacks, according to investigators, with ORs of 6.12 (95% CI, 5.81-6.46) and 5.61 (95% CI, 5.21-6.04), respectively.
Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.
The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.
The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.
Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
A wide variety of hematologic, dermatologic, and solid organ malignancies are associated with pruritus, a large, single-center, retrospective study suggests.
Blacks with pruritus had a higher odds ratio of hematologic malignancies, among others, while whites had higher likelihood of liver, gastrointestinal, respiratory and gynecologic cancers, results of the study show.
The results by race help address a gap in the literature, according to Shawn G. Kwatra, MD, of Johns Hopkins University, Baltimore, and his coinvestigators.
“Little is known about the association between pruritus and malignancy among different ethnic groups,” Dr. Kwatra and his coauthors wrote in the Journal of the American Academy of Dermatology.
The study shows a stronger association with more types of malignancies than has been reported previously, according to the investigators.
“The main difference is that prior studies focused on diagnosis of malignancy after the onset of pruritus, while our study includes malignancies diagnosed on or after pruritus onset,” they wrote.
Retrospective data for the study, which came from the Johns Hopkins Health System, included 16,925 patients aged 18 years or older who presented with itching or pruritus between April 4, 2013 and Dec. 31, 2017.
Of those 16,925 patients, 2,903 were also diagnosed with a concomitant malignancy during that time period. Compared with patients with no itching diagnosis during that time period, the pruritus patients more likely to have a concomitant malignancy, with an OR of 5.76 (95% confidence interval, 5.53-6.00), Dr. Kwatra and his colleagues found.
Malignancies most strongly associated with pruritus included those of the skin, liver, gallbladder and biliary tract, and hematopoietic system.
Among hematologic malignancies, pruritus was most strongly linked to myeloid leukemia and primary cutaneous lymphoma, while among skin cancers, squamous cell carcinoma was most strongly linked.
Whites had higher odds of any malignancy versus blacks, according to investigators, with ORs of 6.12 (95% CI, 5.81-6.46) and 5.61 (95% CI, 5.21-6.04), respectively.
Blacks with pruritus had higher ORs for hematologic and soft tissue malignancies including those of the muscle, fat, and peripheral nerve, investigators said, while whites had higher ORs for skin and liver malignancies.
The investigators also looked at the prevalence of skin eruptions in patients with pruritus and malignancy. “Eruption is variable by malignancy type and points to differing underlying mechanisms of pruritus,” they reported.
The highest rates of skin eruption were in patients with myeloid leukemia at 66%, followed by bone cancers at 58%, lymphocytic leukemia at 57%, multiple myeloma at 53%, and bronchus at 53%. The lowest rates of skin eruption were in patients with gallbladder and biliary tract, colon, pancreas, and liver malignancies.
Dr. Kwatra reported that he is an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
SOURCE: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point:
Major finding: Blacks with pruritus had higher odds ratios for hematologic and soft tissue malignancies, while whites had higher ORs for skin and liver malignancies.
Study details: A retrospective study of 16,925 adults with itching or pruritus seen at a tertiary care center.
Disclosures: Dr. Kwatra reported serving as an advisory board member for Menlo Therapeutics and Trevi Therapeutics.
Source: Kwatra SG et al. J Am Acad Dermatol. 2018 Sep 11. doi: 10.1016/j.jaad.2018.08.044.
Opioid Use Disorder Numbers Among Pregnant Women Are on the Rise
The number of women with opioid use disorder (OUD) at labor and delivery more than quadrupled between 1999 and 2014, according to a first-ever multistate analysis of trends by the CDC.
Researchers found that the national prevalence rate of OUD rose from 1.5 per 1,000 delivery hospitalizations in 1999 to 6.5 in 2014. On average, the national prevalence rate grew by 0.39 cases per 1,000 each year.
The increases were significant and seen in all of the 28 states with at least 3 years of data available for analysis. The average increases were lowest in California and Hawaii and highest in Maine, New Mexico, Vermont, and West Virginia.
Opioid use disorder during pregnancy has been associated with a range of negative health outcomes, including maternal death, preterm birth, stillbirth, and neonatal abstinence syndrome (NAS).
The CDC’s recommended strategies include:
- Implementing universal substance use screening at the first prenatal visit;
- Ensuring pregnant women with OUD have access to medication-assisted therapy and related addiction services; and
- Ensuring that mothers with OUD receive adequate patient-centered postpartum care, including mental health and substance use treatment, relapse-prevention programs, and family planning services
The CDC also is supporting state-based perinatal quality cooperatives, networks of teams working to better identify women with OUD during pregnancy and to standardize care for mothers and NAS-affected infants.
The number of women with opioid use disorder (OUD) at labor and delivery more than quadrupled between 1999 and 2014, according to a first-ever multistate analysis of trends by the CDC.
Researchers found that the national prevalence rate of OUD rose from 1.5 per 1,000 delivery hospitalizations in 1999 to 6.5 in 2014. On average, the national prevalence rate grew by 0.39 cases per 1,000 each year.
The increases were significant and seen in all of the 28 states with at least 3 years of data available for analysis. The average increases were lowest in California and Hawaii and highest in Maine, New Mexico, Vermont, and West Virginia.
Opioid use disorder during pregnancy has been associated with a range of negative health outcomes, including maternal death, preterm birth, stillbirth, and neonatal abstinence syndrome (NAS).
The CDC’s recommended strategies include:
- Implementing universal substance use screening at the first prenatal visit;
- Ensuring pregnant women with OUD have access to medication-assisted therapy and related addiction services; and
- Ensuring that mothers with OUD receive adequate patient-centered postpartum care, including mental health and substance use treatment, relapse-prevention programs, and family planning services
The CDC also is supporting state-based perinatal quality cooperatives, networks of teams working to better identify women with OUD during pregnancy and to standardize care for mothers and NAS-affected infants.
The number of women with opioid use disorder (OUD) at labor and delivery more than quadrupled between 1999 and 2014, according to a first-ever multistate analysis of trends by the CDC.
Researchers found that the national prevalence rate of OUD rose from 1.5 per 1,000 delivery hospitalizations in 1999 to 6.5 in 2014. On average, the national prevalence rate grew by 0.39 cases per 1,000 each year.
The increases were significant and seen in all of the 28 states with at least 3 years of data available for analysis. The average increases were lowest in California and Hawaii and highest in Maine, New Mexico, Vermont, and West Virginia.
Opioid use disorder during pregnancy has been associated with a range of negative health outcomes, including maternal death, preterm birth, stillbirth, and neonatal abstinence syndrome (NAS).
The CDC’s recommended strategies include:
- Implementing universal substance use screening at the first prenatal visit;
- Ensuring pregnant women with OUD have access to medication-assisted therapy and related addiction services; and
- Ensuring that mothers with OUD receive adequate patient-centered postpartum care, including mental health and substance use treatment, relapse-prevention programs, and family planning services
The CDC also is supporting state-based perinatal quality cooperatives, networks of teams working to better identify women with OUD during pregnancy and to standardize care for mothers and NAS-affected infants.
Venetoclax label now includes MRD data
The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.
The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.
The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.
The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).
Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.
The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.
The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.
The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.
The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.
The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.
The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).
Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.
The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.
The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.
The Food and Drug Administration has expanded the label for venetoclax tablets (Venclexta) to include data on minimal residual disease.
The drug’s prescribing information will now include details on minimal residual disease (MRD) negativity in previously treated patients with chronic lymphocytic leukemia (CLL) who received venetoclax in combination with rituximab in the phase 3 MURANO trial.
The combination of venetoclax and rituximab was approved by the FDA in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma, with or without 17p deletion, who received at least one prior therapy.
The MURANO trial (NCT02005471), which supported the FDA approval, included 389 patients with relapsed or refractory CLL. They were randomized to receive venetoclax plus rituximab or bendamustine plus rituximab (N Engl J Med. 2018; 378:1107-20).
Researchers evaluated MRD in patients who achieved a partial response or better. MRD was assessed using allele-specific oligonucleotide polymerase chain reaction; the definition of MRD negativity was less than one CLL cell per 10,000 lymphocytes.
The researchers assessed MRD in the peripheral blood after about 9 months on therapy (3 months after the last dose of rituximab). At that time, 53% (103/194) of patients in the venetoclax-rituximab arm were MRD negative, as were 12% (23/195) of patients in the bendamustine-rituximab arm.
The researchers also assessed MRD in the peripheral blood of patients with a complete response or complete response with incomplete marrow recovery. MRD negativity was achieved by 3% (6/194) of these patients in the venetoclax-rituximab arm and 2% (3/195) in the bendamustine-rituximab arm.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie outside of the United States.
Review protocols, follow reprocessing guidelines to cut device-related HAIs
ATLANTA – Ongoing vigilance regarding the role of and transmission of antimicrobial-resistant pathogen is needed, according to Isaac Benowitz, MD, of the Centers for Disease Control and Prevention’s Division of Healthcare Quality Promotion (DHQP).
A review of records from the DHQP, which investigates and responds to infections and related adverse events in health care settings upon invitation, showed that in 2017 environmental pathogens were most often the triggers for these investigations, said Dr. Benowitz, a medical epidemiologist.
He reviewed internal records for consultations with state and local health departments involving medical devices and collected data on health care setting, pathogen, investigation findings including possible exposure or transmission, and public health actions.
Of 285 consultations, 48 involved a specific medical device or general medical device reprocessing, he said, noting that most of those 48 were in an acute care hospital (63%) or clinic (19%).
“The most frequent pathogens noted in these consultations were nontuberculous mycobacteria at 21%, Candida species ... at 10%, and Burkholderia species ... at 8%,” he said, noting that a wide variety of devices were implicated.
In the inpatient setting these devices included ventilators, dialysis machines, breast pumps, central lines, and respiratory therapy equipment. In the outpatient setting they included glucometers and opthalmic equipment.
“In many settings we saw issues with endoscopes, including duodenoscopes, but also bronchoscopes,” he added.
Actions taken as part of the investigations included medical device recalls, improved infection control and reprocessing procedures, and patient notification, education, guidance, testing, and treatment.
In some cases there was disciplinary action or oversight for health care professionals, he added.
Investigations identified medical devices contaminated in manufacturing, incorrect reprocessing of endoscopes or ventilators, and inappropriate medical device use or reuse, he said.
A number of lessons can be learned from these and other investigations, he added.
“First, devices can be reservoirs and transmission vectors for health care–associated infections. Second, health care facilities, health care facility staff, and public health partners should take opportunities to review protocols and the practices within those protocol,” he said. “These are opportunities to strengthen infection control practices even in the absence of documented transmission.”
In fact, in most of the investigations he discussed, transmission was rarely confirmed to be associated with a medical device. This was largely because of a lack of “epidemiological rigor,” but associations between health care–associated infections and medical devices “are still quite meaningful and often actionable,” he said.
Dr. Benowitz stressed the importance of engaging public health partners to discuss findings and actions, explaining that “what may look like a single-facility issue may have a very different perspective when you realize that there’s a similar issue at another facility elsewhere.”
“For all devices, it’s important to ensure adherence to the device reprocessing guidelines, “ he added, noting that these include a combination of facility protocols, manufacturer instructions for use, and guidance from organizations like the Food and Drug Administration and the CDC.
Dr. Benowitz reported having no disclosures.
sworcester@mdedge.com
SOURCE: Benowitz I et al. ICEID 2018, Oral Abstract Presentation E2.
ATLANTA – Ongoing vigilance regarding the role of and transmission of antimicrobial-resistant pathogen is needed, according to Isaac Benowitz, MD, of the Centers for Disease Control and Prevention’s Division of Healthcare Quality Promotion (DHQP).
A review of records from the DHQP, which investigates and responds to infections and related adverse events in health care settings upon invitation, showed that in 2017 environmental pathogens were most often the triggers for these investigations, said Dr. Benowitz, a medical epidemiologist.
He reviewed internal records for consultations with state and local health departments involving medical devices and collected data on health care setting, pathogen, investigation findings including possible exposure or transmission, and public health actions.
Of 285 consultations, 48 involved a specific medical device or general medical device reprocessing, he said, noting that most of those 48 were in an acute care hospital (63%) or clinic (19%).
“The most frequent pathogens noted in these consultations were nontuberculous mycobacteria at 21%, Candida species ... at 10%, and Burkholderia species ... at 8%,” he said, noting that a wide variety of devices were implicated.
In the inpatient setting these devices included ventilators, dialysis machines, breast pumps, central lines, and respiratory therapy equipment. In the outpatient setting they included glucometers and opthalmic equipment.
“In many settings we saw issues with endoscopes, including duodenoscopes, but also bronchoscopes,” he added.
Actions taken as part of the investigations included medical device recalls, improved infection control and reprocessing procedures, and patient notification, education, guidance, testing, and treatment.
In some cases there was disciplinary action or oversight for health care professionals, he added.
Investigations identified medical devices contaminated in manufacturing, incorrect reprocessing of endoscopes or ventilators, and inappropriate medical device use or reuse, he said.
A number of lessons can be learned from these and other investigations, he added.
“First, devices can be reservoirs and transmission vectors for health care–associated infections. Second, health care facilities, health care facility staff, and public health partners should take opportunities to review protocols and the practices within those protocol,” he said. “These are opportunities to strengthen infection control practices even in the absence of documented transmission.”
In fact, in most of the investigations he discussed, transmission was rarely confirmed to be associated with a medical device. This was largely because of a lack of “epidemiological rigor,” but associations between health care–associated infections and medical devices “are still quite meaningful and often actionable,” he said.
Dr. Benowitz stressed the importance of engaging public health partners to discuss findings and actions, explaining that “what may look like a single-facility issue may have a very different perspective when you realize that there’s a similar issue at another facility elsewhere.”
“For all devices, it’s important to ensure adherence to the device reprocessing guidelines, “ he added, noting that these include a combination of facility protocols, manufacturer instructions for use, and guidance from organizations like the Food and Drug Administration and the CDC.
Dr. Benowitz reported having no disclosures.
sworcester@mdedge.com
SOURCE: Benowitz I et al. ICEID 2018, Oral Abstract Presentation E2.
ATLANTA – Ongoing vigilance regarding the role of and transmission of antimicrobial-resistant pathogen is needed, according to Isaac Benowitz, MD, of the Centers for Disease Control and Prevention’s Division of Healthcare Quality Promotion (DHQP).
A review of records from the DHQP, which investigates and responds to infections and related adverse events in health care settings upon invitation, showed that in 2017 environmental pathogens were most often the triggers for these investigations, said Dr. Benowitz, a medical epidemiologist.
He reviewed internal records for consultations with state and local health departments involving medical devices and collected data on health care setting, pathogen, investigation findings including possible exposure or transmission, and public health actions.
Of 285 consultations, 48 involved a specific medical device or general medical device reprocessing, he said, noting that most of those 48 were in an acute care hospital (63%) or clinic (19%).
“The most frequent pathogens noted in these consultations were nontuberculous mycobacteria at 21%, Candida species ... at 10%, and Burkholderia species ... at 8%,” he said, noting that a wide variety of devices were implicated.
In the inpatient setting these devices included ventilators, dialysis machines, breast pumps, central lines, and respiratory therapy equipment. In the outpatient setting they included glucometers and opthalmic equipment.
“In many settings we saw issues with endoscopes, including duodenoscopes, but also bronchoscopes,” he added.
Actions taken as part of the investigations included medical device recalls, improved infection control and reprocessing procedures, and patient notification, education, guidance, testing, and treatment.
In some cases there was disciplinary action or oversight for health care professionals, he added.
Investigations identified medical devices contaminated in manufacturing, incorrect reprocessing of endoscopes or ventilators, and inappropriate medical device use or reuse, he said.
A number of lessons can be learned from these and other investigations, he added.
“First, devices can be reservoirs and transmission vectors for health care–associated infections. Second, health care facilities, health care facility staff, and public health partners should take opportunities to review protocols and the practices within those protocol,” he said. “These are opportunities to strengthen infection control practices even in the absence of documented transmission.”
In fact, in most of the investigations he discussed, transmission was rarely confirmed to be associated with a medical device. This was largely because of a lack of “epidemiological rigor,” but associations between health care–associated infections and medical devices “are still quite meaningful and often actionable,” he said.
Dr. Benowitz stressed the importance of engaging public health partners to discuss findings and actions, explaining that “what may look like a single-facility issue may have a very different perspective when you realize that there’s a similar issue at another facility elsewhere.”
“For all devices, it’s important to ensure adherence to the device reprocessing guidelines, “ he added, noting that these include a combination of facility protocols, manufacturer instructions for use, and guidance from organizations like the Food and Drug Administration and the CDC.
Dr. Benowitz reported having no disclosures.
sworcester@mdedge.com
SOURCE: Benowitz I et al. ICEID 2018, Oral Abstract Presentation E2.
REPORTING FROM ICEID 2018
Key clinical point: Medical devices can be reservoirs and transmission vectors for health care–associated infections.
Major finding: Of 285 consultations, 48 involved medical devices or device reprocessing.
Study details: A review of records from 285 consultations
Disclosures: Dr. Benowitz reported having no disclosures
Source: Benowitz I et al. ICEID 2018, Oral Abstract Presentation E2.
New IHS Website Addresses Opioid Crisis
The opioid crisis has taken a toll everywhere, but American Indians and Alaska Natives have been hardest hit. That group had the highest drug overdose death rates in 2015, and the largest percentage increase— > 500%—in the number of deaths between 1999 and 2015 compared with that of other racial and ethnic groups.
In February 2018, the IHS released the revised agency policy on chronic pain management. It also has now launched a website (www.ihs.gov/opioids) as another step in addressing the problem.
The website discusses the crisis response, funding opportunities, best practices, and proper pain management. It includes Community Opioid Action Plans, which inform the public about how indigenous planning using traditional practices and holistic, culturally appropriate approaches can help.
The website also provides resources for tribes, such as links to the Office of Tribal Affairs and Policy, the point of contact for tribal governments, tribal organizations and federal agencies on behavioral health issues that affect tribal communities; the Office of Indian Alcohol and Substance Abuse; and SAMHSA Tribal Training and Technical Assistance.
The opioid crisis has taken a toll everywhere, but American Indians and Alaska Natives have been hardest hit. That group had the highest drug overdose death rates in 2015, and the largest percentage increase— > 500%—in the number of deaths between 1999 and 2015 compared with that of other racial and ethnic groups.
In February 2018, the IHS released the revised agency policy on chronic pain management. It also has now launched a website (www.ihs.gov/opioids) as another step in addressing the problem.
The website discusses the crisis response, funding opportunities, best practices, and proper pain management. It includes Community Opioid Action Plans, which inform the public about how indigenous planning using traditional practices and holistic, culturally appropriate approaches can help.
The website also provides resources for tribes, such as links to the Office of Tribal Affairs and Policy, the point of contact for tribal governments, tribal organizations and federal agencies on behavioral health issues that affect tribal communities; the Office of Indian Alcohol and Substance Abuse; and SAMHSA Tribal Training and Technical Assistance.
The opioid crisis has taken a toll everywhere, but American Indians and Alaska Natives have been hardest hit. That group had the highest drug overdose death rates in 2015, and the largest percentage increase— > 500%—in the number of deaths between 1999 and 2015 compared with that of other racial and ethnic groups.
In February 2018, the IHS released the revised agency policy on chronic pain management. It also has now launched a website (www.ihs.gov/opioids) as another step in addressing the problem.
The website discusses the crisis response, funding opportunities, best practices, and proper pain management. It includes Community Opioid Action Plans, which inform the public about how indigenous planning using traditional practices and holistic, culturally appropriate approaches can help.
The website also provides resources for tribes, such as links to the Office of Tribal Affairs and Policy, the point of contact for tribal governments, tribal organizations and federal agencies on behavioral health issues that affect tribal communities; the Office of Indian Alcohol and Substance Abuse; and SAMHSA Tribal Training and Technical Assistance.
TP53 mutation plus complex karyotype equals poor prognosis
The presence of both TP53 gene mutation and complex karyotype may signal a dismal prognosis in patients with mantle cell lymphoma (MCL), according to results of a study.
All patients who had TP53 mutations and complex karyotype died within 1.2 years of diagnosis, while almost all patients with neither predictor were still alive at 2 years, according to study data reported in the journal Clinical Lymphoma, Myeloma & Leukemia.
By combining the markers, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment regimen, reported the study’s corresponding author Vít Procházka, MD, PhD, of the department of hemato-oncology faculty of medicine and dentistry at Palacký University, Olomouc, Czech Republic, and his coauthors.
“Our findings support a need to perform both tests, molecular cytogenetics, and next-generation sequencing simultaneously before initiation of treatment for MCL,” Dr. Procházka and his coauthors wrote.
In current clinical practice, TP53 mutational status and molecular cytogenetics are not routinely assessed prior to treatment initiation, they noted in their report.
The study, believed to be the first to evaluate the combined prognostic role of TP53 mutation and complex karyotype in an MCL cohort, included 74 consecutive adult patients newly diagnosed with MCL during 2000-2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or complex karyotype, was under observation without therapy.
Complex karyotype was found in 13 patients for whom fixed cells were available to perform cytogenetic analysis, the authors reported, while TP53 mutations were seen in 15 patients who were evaluated for that marker.
Altogether, 48 patients (64.9%) had biological material available to perform both analyses. Of those, 4 patients were found to have both TP53 mutation and complex karyotype, 12 had one of those two markers, and 32 had neither.
While patients with both markers all died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker; those differences were significant between groups (P less than .001), according to investigators.
Progression-free survival analyses showed similar results, with significant differences between the three groups, investigators reported.
Multivariate analysis showed that both TP53 mutation and complex karyotype were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index (MIPI).
While larger studies are needed to confirm the results, investigators suggested that novel treatment approaches might be warranted for patients in the highest-risk subgroup.
“The patients harboring the negative prognostic markers [TP53 mutation] and [complex karyotype] might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” they said.
The study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.
SOURCE: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.
The presence of both TP53 gene mutation and complex karyotype may signal a dismal prognosis in patients with mantle cell lymphoma (MCL), according to results of a study.
All patients who had TP53 mutations and complex karyotype died within 1.2 years of diagnosis, while almost all patients with neither predictor were still alive at 2 years, according to study data reported in the journal Clinical Lymphoma, Myeloma & Leukemia.
By combining the markers, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment regimen, reported the study’s corresponding author Vít Procházka, MD, PhD, of the department of hemato-oncology faculty of medicine and dentistry at Palacký University, Olomouc, Czech Republic, and his coauthors.
“Our findings support a need to perform both tests, molecular cytogenetics, and next-generation sequencing simultaneously before initiation of treatment for MCL,” Dr. Procházka and his coauthors wrote.
In current clinical practice, TP53 mutational status and molecular cytogenetics are not routinely assessed prior to treatment initiation, they noted in their report.
The study, believed to be the first to evaluate the combined prognostic role of TP53 mutation and complex karyotype in an MCL cohort, included 74 consecutive adult patients newly diagnosed with MCL during 2000-2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or complex karyotype, was under observation without therapy.
Complex karyotype was found in 13 patients for whom fixed cells were available to perform cytogenetic analysis, the authors reported, while TP53 mutations were seen in 15 patients who were evaluated for that marker.
Altogether, 48 patients (64.9%) had biological material available to perform both analyses. Of those, 4 patients were found to have both TP53 mutation and complex karyotype, 12 had one of those two markers, and 32 had neither.
While patients with both markers all died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker; those differences were significant between groups (P less than .001), according to investigators.
Progression-free survival analyses showed similar results, with significant differences between the three groups, investigators reported.
Multivariate analysis showed that both TP53 mutation and complex karyotype were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index (MIPI).
While larger studies are needed to confirm the results, investigators suggested that novel treatment approaches might be warranted for patients in the highest-risk subgroup.
“The patients harboring the negative prognostic markers [TP53 mutation] and [complex karyotype] might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” they said.
The study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.
SOURCE: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.
The presence of both TP53 gene mutation and complex karyotype may signal a dismal prognosis in patients with mantle cell lymphoma (MCL), according to results of a study.
All patients who had TP53 mutations and complex karyotype died within 1.2 years of diagnosis, while almost all patients with neither predictor were still alive at 2 years, according to study data reported in the journal Clinical Lymphoma, Myeloma & Leukemia.
By combining the markers, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment regimen, reported the study’s corresponding author Vít Procházka, MD, PhD, of the department of hemato-oncology faculty of medicine and dentistry at Palacký University, Olomouc, Czech Republic, and his coauthors.
“Our findings support a need to perform both tests, molecular cytogenetics, and next-generation sequencing simultaneously before initiation of treatment for MCL,” Dr. Procházka and his coauthors wrote.
In current clinical practice, TP53 mutational status and molecular cytogenetics are not routinely assessed prior to treatment initiation, they noted in their report.
The study, believed to be the first to evaluate the combined prognostic role of TP53 mutation and complex karyotype in an MCL cohort, included 74 consecutive adult patients newly diagnosed with MCL during 2000-2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or complex karyotype, was under observation without therapy.
Complex karyotype was found in 13 patients for whom fixed cells were available to perform cytogenetic analysis, the authors reported, while TP53 mutations were seen in 15 patients who were evaluated for that marker.
Altogether, 48 patients (64.9%) had biological material available to perform both analyses. Of those, 4 patients were found to have both TP53 mutation and complex karyotype, 12 had one of those two markers, and 32 had neither.
While patients with both markers all died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker; those differences were significant between groups (P less than .001), according to investigators.
Progression-free survival analyses showed similar results, with significant differences between the three groups, investigators reported.
Multivariate analysis showed that both TP53 mutation and complex karyotype were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index (MIPI).
While larger studies are needed to confirm the results, investigators suggested that novel treatment approaches might be warranted for patients in the highest-risk subgroup.
“The patients harboring the negative prognostic markers [TP53 mutation] and [complex karyotype] might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” they said.
The study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.
SOURCE: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Key clinical point:
Major finding: Patients with both markers all died within 1.2 years, while 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P less than .001).
Study details: A study of 74 consecutive adult patients newly diagnosed with MCL during 2000-2014.
Disclosures: The study was supported by grants from the Czech Ministry of Health and Palacký University, Olomouc, Czech Republic. Study authors reported having no conflicts of interest.
Source: Obr A et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 23. doi: 10.1016/j.clml.2018.07.282.