The Food and Drug Administration has added a new warning for an increased risk of death in patients with heart disease who have used clarithromycin (Biaxin), on the basis of results of a 10-year follow-up from the CLARICOR trial.

The CLARICOR trial followed 4,372 randomized patients for at least 2 years after undergoing 14 days of treatment with daily doses of 500 mg clarithromycin. Among these patients, researchers observed an unexpected increase in deaths in patients with coronary heart disease. (The Feb. 22 FDA statement announcing the alert did not provide data from CLARICOR.) As of yet, there is no clear explanation of how clarithromycin would lead to more deaths, compared with a placebo, the agency said.

[email protected]

The Food and Drug Administration has added a new warning for an increased risk of death in patients with heart disease who have used clarithromycin (Biaxin), on the basis of results of a 10-year follow-up from the CLARICOR trial.

The CLARICOR trial followed 4,372 randomized patients for at least 2 years after undergoing 14 days of treatment with daily doses of 500 mg clarithromycin. Among these patients, researchers observed an unexpected increase in deaths in patients with coronary heart disease. (The Feb. 22 FDA statement announcing the alert did not provide data from CLARICOR.) As of yet, there is no clear explanation of how clarithromycin would lead to more deaths, compared with a placebo, the agency said.

[email protected]

The Food and Drug Administration has added a new warning for an increased risk of death in patients with heart disease who have used clarithromycin (Biaxin), on the basis of results of a 10-year follow-up from the CLARICOR trial.

The CLARICOR trial followed 4,372 randomized patients for at least 2 years after undergoing 14 days of treatment with daily doses of 500 mg clarithromycin. Among these patients, researchers observed an unexpected increase in deaths in patients with coronary heart disease. (The Feb. 22 FDA statement announcing the alert did not provide data from CLARICOR.) As of yet, there is no clear explanation of how clarithromycin would lead to more deaths, compared with a placebo, the agency said.

[email protected]

Peter A. LeWitt, MD

Dr. LeWitt is the Director of the Parkinson Disease and Movement Disorder Program at Henry Ford Hospital, West Bloomfield, Michigan.

For most neurology subspecialties, the past quarter-century was only the latest chapter of a productive history extending through the mid-19th century, but for movement disorders, these years were formative. Before then, movement disorder specialists were few in number, and their medical literature was far more scanty than it is now, with multiple journals and texts now devoted to this topic. Twenty-five years ago, the international society devoted to Parkinson disease and other movement disorders was only a recent arrival. Fortunately, two charismatic and brilliant leaders—the American neurologist Stanley Fahn, MD, and the British neurologist C. David Marsden, MBBS—came forward to inspire a generation of trainees with their broad interests in bridging clinical neurology, experimental neuroscience, and patient advocacy. Today, the impact of these pioneers is still felt by a growing community of movement disorder clinicians and researchers who have transformed movement disorders from an earlier realm of descriptive neurology into a vibrant field exploring disease mechanisms and therapeutics, as well as an expanding array of clinical insights.

When Neurology Reviews was founded in 1993, the majority of significant developments in movement disorders concerned Parkinson’s disease. Strategies to improve upon dopaminergic therapy were being tested in clinical trials, along with ventures into pallidotomy as a neurosurgical treatment. Animal models of parkinsonism and neurochemical analysis of brain and putative biomarkers provided scientific guidance for trials of disease modification. Another milestone from the 1990s was discovery of the first gene leading to autosomal-dominant parkinsonism. This rare mutation in the structural protein alpha-synuclein had a much broader impact on Parkinson’s disease research in that it provided important information about the sporadic disorder’s final common pathway of pathogenesis. Today, alpha-synuclein is the focus of therapeutic intervention utilizing immunologic therapies to halt disease progression. Over the past quarter-century, more than two dozen additional gene mutations associated with parkinsonism have been discovered. These mutations provide additional insight into disease mechanisms. Beyond the science and clinical insights that have propelled advances in understanding Parkinson’s disease and its related disorders, the growth of the patient advocacy and caregiver movement has also been remarkable in expanding what is needed to improve daily life with this disorder.

Since 1993, other movement disorders have also profited from the tremendous growth of molecular neuroscience and its applications. Novel neuroimaging techniques like functional MRI, computation of neural pathways, and scanning using PET and SPECT have helped work out the brain mechanisms of several disorders. Genetic probing of familial disorders like dystonia and myoclonus have helped to unravel the neurochemistry of what has gone wrong to cause certain movement disorders. In turn, transgenic animal models using these human genetic mutations have allowed exploration of what might be done to fix the problems. These developments could have huge implications for making progress in the therapies of the future, since the most common categories of movement disorders—dystonia, myoclonus, ataxia, tremor, restless legs syndrome, Tourette syndrome, choreic disorders, and paroxysmal movement disorders—all can have hereditary patterns. Genetic testing can be valuable for choosing at-risk individuals for participation in trials of disease-modifying drugs for Huntington’s disease, for example, and this strategy may be the way of the future for other late-life emergent disorders. In the past decade, several gene therapy studies have been carried out in patients with Parkinson’s disease. The promise of this approach and the recent gene editing and RNA interference approaches, all part of the molecular biology revolution of the past 25 years, may further change the landscape of movement disorder therapeutics ahead.

Today, movement disorder specialists routinely use therapeutic approaches that were in their infancy in 1993. Botulinum toxin selective denervation has had a major impact by improving quality of life for patients affected with a wide range of movement disorders: dystonic necks, hands, and feet; involuntary facial movements and voice aberrations; tics; spasticity; and drooling. Deep brain stimulation is a routine option for many patients with tremor, Parkinson’s disease, and dystonia. Developments in this field have refined the choice of targets for stimulation and the possibility of treating other disorders with these techniques, like Tourette syndrome. A nonsurgical approach to abolishing tremor, MRI-guided focused ultrasound, recently was approved. In the background of these advances is the increasing knowledge of movement disorders that practitioners have to offer many patients with disorders that in the past were merely neurologic curiosities. Through clinical trial research and serendipity (the major treatment options for essential tremor arose this way), there is an expanding search for repurposing older medications and harnessing new biotechnology to target the mechanisms leading to various movement disorders.

It is impressive how much the neurologic discipline of movement disorders has changed in response to the new era of electronic communications and other technologies. In the past quarter-century, medical students, residents, and practicing neurologists have had instant access to a curriculum that includes resources such as video-recorded movement disorders. Clinical trials are being revolutionized by electronic technologies that record information in ways that improve upon human ratings. A patient with Parkinson’s disease, essential tremor, or restless legs syndrome can now have symptoms monitored remotely by wearable devices that offer a real-world view on how a new therapy is performing. But perhaps the greatest revolution in the recent past has been increasing confidence that progressive disabilities caused by movement disorders might be halted by emerging insights into disease mechanisms. There has been tremendous growth of interest among the basic neuroscience community in human diseases affecting motor control. More than half of research presentations at recent international Parkinson’s disease and movement disorder conferences reflect this trend. These efforts support an optimistic view that, over the next quarter-century, the most challenging movement disorder problems of today will experience as much progress as in the past 25 years.

Peter A. LeWitt, MD

Dr. LeWitt is the Director of the Parkinson Disease and Movement Disorder Program at Henry Ford Hospital, West Bloomfield, Michigan.

For most neurology subspecialties, the past quarter-century was only the latest chapter of a productive history extending through the mid-19th century, but for movement disorders, these years were formative. Before then, movement disorder specialists were few in number, and their medical literature was far more scanty than it is now, with multiple journals and texts now devoted to this topic. Twenty-five years ago, the international society devoted to Parkinson disease and other movement disorders was only a recent arrival. Fortunately, two charismatic and brilliant leaders—the American neurologist Stanley Fahn, MD, and the British neurologist C. David Marsden, MBBS—came forward to inspire a generation of trainees with their broad interests in bridging clinical neurology, experimental neuroscience, and patient advocacy. Today, the impact of these pioneers is still felt by a growing community of movement disorder clinicians and researchers who have transformed movement disorders from an earlier realm of descriptive neurology into a vibrant field exploring disease mechanisms and therapeutics, as well as an expanding array of clinical insights.

When Neurology Reviews was founded in 1993, the majority of significant developments in movement disorders concerned Parkinson’s disease. Strategies to improve upon dopaminergic therapy were being tested in clinical trials, along with ventures into pallidotomy as a neurosurgical treatment. Animal models of parkinsonism and neurochemical analysis of brain and putative biomarkers provided scientific guidance for trials of disease modification. Another milestone from the 1990s was discovery of the first gene leading to autosomal-dominant parkinsonism. This rare mutation in the structural protein alpha-synuclein had a much broader impact on Parkinson’s disease research in that it provided important information about the sporadic disorder’s final common pathway of pathogenesis. Today, alpha-synuclein is the focus of therapeutic intervention utilizing immunologic therapies to halt disease progression. Over the past quarter-century, more than two dozen additional gene mutations associated with parkinsonism have been discovered. These mutations provide additional insight into disease mechanisms. Beyond the science and clinical insights that have propelled advances in understanding Parkinson’s disease and its related disorders, the growth of the patient advocacy and caregiver movement has also been remarkable in expanding what is needed to improve daily life with this disorder.

Since 1993, other movement disorders have also profited from the tremendous growth of molecular neuroscience and its applications. Novel neuroimaging techniques like functional MRI, computation of neural pathways, and scanning using PET and SPECT have helped work out the brain mechanisms of several disorders. Genetic probing of familial disorders like dystonia and myoclonus have helped to unravel the neurochemistry of what has gone wrong to cause certain movement disorders. In turn, transgenic animal models using these human genetic mutations have allowed exploration of what might be done to fix the problems. These developments could have huge implications for making progress in the therapies of the future, since the most common categories of movement disorders—dystonia, myoclonus, ataxia, tremor, restless legs syndrome, Tourette syndrome, choreic disorders, and paroxysmal movement disorders—all can have hereditary patterns. Genetic testing can be valuable for choosing at-risk individuals for participation in trials of disease-modifying drugs for Huntington’s disease, for example, and this strategy may be the way of the future for other late-life emergent disorders. In the past decade, several gene therapy studies have been carried out in patients with Parkinson’s disease. The promise of this approach and the recent gene editing and RNA interference approaches, all part of the molecular biology revolution of the past 25 years, may further change the landscape of movement disorder therapeutics ahead.

Today, movement disorder specialists routinely use therapeutic approaches that were in their infancy in 1993. Botulinum toxin selective denervation has had a major impact by improving quality of life for patients affected with a wide range of movement disorders: dystonic necks, hands, and feet; involuntary facial movements and voice aberrations; tics; spasticity; and drooling. Deep brain stimulation is a routine option for many patients with tremor, Parkinson’s disease, and dystonia. Developments in this field have refined the choice of targets for stimulation and the possibility of treating other disorders with these techniques, like Tourette syndrome. A nonsurgical approach to abolishing tremor, MRI-guided focused ultrasound, recently was approved. In the background of these advances is the increasing knowledge of movement disorders that practitioners have to offer many patients with disorders that in the past were merely neurologic curiosities. Through clinical trial research and serendipity (the major treatment options for essential tremor arose this way), there is an expanding search for repurposing older medications and harnessing new biotechnology to target the mechanisms leading to various movement disorders.

It is impressive how much the neurologic discipline of movement disorders has changed in response to the new era of electronic communications and other technologies. In the past quarter-century, medical students, residents, and practicing neurologists have had instant access to a curriculum that includes resources such as video-recorded movement disorders. Clinical trials are being revolutionized by electronic technologies that record information in ways that improve upon human ratings. A patient with Parkinson’s disease, essential tremor, or restless legs syndrome can now have symptoms monitored remotely by wearable devices that offer a real-world view on how a new therapy is performing. But perhaps the greatest revolution in the recent past has been increasing confidence that progressive disabilities caused by movement disorders might be halted by emerging insights into disease mechanisms. There has been tremendous growth of interest among the basic neuroscience community in human diseases affecting motor control. More than half of research presentations at recent international Parkinson’s disease and movement disorder conferences reflect this trend. These efforts support an optimistic view that, over the next quarter-century, the most challenging movement disorder problems of today will experience as much progress as in the past 25 years.

Peter A. LeWitt, MD

Dr. LeWitt is the Director of the Parkinson Disease and Movement Disorder Program at Henry Ford Hospital, West Bloomfield, Michigan.

For most neurology subspecialties, the past quarter-century was only the latest chapter of a productive history extending through the mid-19th century, but for movement disorders, these years were formative. Before then, movement disorder specialists were few in number, and their medical literature was far more scanty than it is now, with multiple journals and texts now devoted to this topic. Twenty-five years ago, the international society devoted to Parkinson disease and other movement disorders was only a recent arrival. Fortunately, two charismatic and brilliant leaders—the American neurologist Stanley Fahn, MD, and the British neurologist C. David Marsden, MBBS—came forward to inspire a generation of trainees with their broad interests in bridging clinical neurology, experimental neuroscience, and patient advocacy. Today, the impact of these pioneers is still felt by a growing community of movement disorder clinicians and researchers who have transformed movement disorders from an earlier realm of descriptive neurology into a vibrant field exploring disease mechanisms and therapeutics, as well as an expanding array of clinical insights.

When Neurology Reviews was founded in 1993, the majority of significant developments in movement disorders concerned Parkinson’s disease. Strategies to improve upon dopaminergic therapy were being tested in clinical trials, along with ventures into pallidotomy as a neurosurgical treatment. Animal models of parkinsonism and neurochemical analysis of brain and putative biomarkers provided scientific guidance for trials of disease modification. Another milestone from the 1990s was discovery of the first gene leading to autosomal-dominant parkinsonism. This rare mutation in the structural protein alpha-synuclein had a much broader impact on Parkinson’s disease research in that it provided important information about the sporadic disorder’s final common pathway of pathogenesis. Today, alpha-synuclein is the focus of therapeutic intervention utilizing immunologic therapies to halt disease progression. Over the past quarter-century, more than two dozen additional gene mutations associated with parkinsonism have been discovered. These mutations provide additional insight into disease mechanisms. Beyond the science and clinical insights that have propelled advances in understanding Parkinson’s disease and its related disorders, the growth of the patient advocacy and caregiver movement has also been remarkable in expanding what is needed to improve daily life with this disorder.

Since 1993, other movement disorders have also profited from the tremendous growth of molecular neuroscience and its applications. Novel neuroimaging techniques like functional MRI, computation of neural pathways, and scanning using PET and SPECT have helped work out the brain mechanisms of several disorders. Genetic probing of familial disorders like dystonia and myoclonus have helped to unravel the neurochemistry of what has gone wrong to cause certain movement disorders. In turn, transgenic animal models using these human genetic mutations have allowed exploration of what might be done to fix the problems. These developments could have huge implications for making progress in the therapies of the future, since the most common categories of movement disorders—dystonia, myoclonus, ataxia, tremor, restless legs syndrome, Tourette syndrome, choreic disorders, and paroxysmal movement disorders—all can have hereditary patterns. Genetic testing can be valuable for choosing at-risk individuals for participation in trials of disease-modifying drugs for Huntington’s disease, for example, and this strategy may be the way of the future for other late-life emergent disorders. In the past decade, several gene therapy studies have been carried out in patients with Parkinson’s disease. The promise of this approach and the recent gene editing and RNA interference approaches, all part of the molecular biology revolution of the past 25 years, may further change the landscape of movement disorder therapeutics ahead.

Today, movement disorder specialists routinely use therapeutic approaches that were in their infancy in 1993. Botulinum toxin selective denervation has had a major impact by improving quality of life for patients affected with a wide range of movement disorders: dystonic necks, hands, and feet; involuntary facial movements and voice aberrations; tics; spasticity; and drooling. Deep brain stimulation is a routine option for many patients with tremor, Parkinson’s disease, and dystonia. Developments in this field have refined the choice of targets for stimulation and the possibility of treating other disorders with these techniques, like Tourette syndrome. A nonsurgical approach to abolishing tremor, MRI-guided focused ultrasound, recently was approved. In the background of these advances is the increasing knowledge of movement disorders that practitioners have to offer many patients with disorders that in the past were merely neurologic curiosities. Through clinical trial research and serendipity (the major treatment options for essential tremor arose this way), there is an expanding search for repurposing older medications and harnessing new biotechnology to target the mechanisms leading to various movement disorders.

It is impressive how much the neurologic discipline of movement disorders has changed in response to the new era of electronic communications and other technologies. In the past quarter-century, medical students, residents, and practicing neurologists have had instant access to a curriculum that includes resources such as video-recorded movement disorders. Clinical trials are being revolutionized by electronic technologies that record information in ways that improve upon human ratings. A patient with Parkinson’s disease, essential tremor, or restless legs syndrome can now have symptoms monitored remotely by wearable devices that offer a real-world view on how a new therapy is performing. But perhaps the greatest revolution in the recent past has been increasing confidence that progressive disabilities caused by movement disorders might be halted by emerging insights into disease mechanisms. There has been tremendous growth of interest among the basic neuroscience community in human diseases affecting motor control. More than half of research presentations at recent international Parkinson’s disease and movement disorder conferences reflect this trend. These efforts support an optimistic view that, over the next quarter-century, the most challenging movement disorder problems of today will experience as much progress as in the past 25 years.

Background: Previous research on the use of PFO closure to prevent recurrent stroke has yielded mixed results.

Study design: Gore REDUCE, CLOSE, and RESPECT were all multicenter, randomized, open-label superiority trials, with blinded adjudication of endpoint events. RESPECT data reflected an exploratory analysis of an extended follow up period.

Setting: Gore REDUCE was a multinational study conducted at 63 sites in Europe and North America, from 2008-2015. CLOSE was conducted at 34 sites in France and Germany, from 2007 to 2016. RESPECT was conducted at 69 sites in the United States and Canada, from 2003 to 2011.

Synopsis: Three trials reexamined the impact of PFO closure with standard antiplatelet treatment, with a total of 2,307 patients between the ages of 16 and 60 years. CLOSE included only patients with a PFO and an associated atrial septal aneurysm or a large interatrial shunt. Gore REDUCE and RESPECT were both industry funded. All three trials found a statistically significant reduction in risk of recurrent ischemic stroke associated with PFO closure and antiplatelet therapy compared to antiplatelet therapy alone (CLOSE HR 0.03 [95% CI 0-0.26; P less than .001], RESPECT HR 0.55 [95% CI 0.31-0.999; P = .046], Gore REDUCE HR 0.23 [95% CI 0.09-0.62; P = .002]). Gore REDUCE and CLOSE identified increased rates of postprocedural atrial fibrillation or flutter (6.6% vs. 0.4% [P less than .001], 4.6% vs. 0.9% [P = .02], respectively). Serious adverse events related to the procedure or device ranged from 3.9-5.9%.

Bottom line: PFO closure combined with antiplatelet therapy in patients aged 60 years or younger, particularly in those with significant right-to-left shunts and atrial septal aneurysms, reduced the risk of recurrent ischemic stroke compared to antiplatelet therapy alone.

Citation: Mas JL. Derumeaux B. Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-21.

Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022-32.

Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033-42.

Background: Previous research on the use of PFO closure to prevent recurrent stroke has yielded mixed results.

Study design: Gore REDUCE, CLOSE, and RESPECT were all multicenter, randomized, open-label superiority trials, with blinded adjudication of endpoint events. RESPECT data reflected an exploratory analysis of an extended follow up period.

Setting: Gore REDUCE was a multinational study conducted at 63 sites in Europe and North America, from 2008-2015. CLOSE was conducted at 34 sites in France and Germany, from 2007 to 2016. RESPECT was conducted at 69 sites in the United States and Canada, from 2003 to 2011.

Synopsis: Three trials reexamined the impact of PFO closure with standard antiplatelet treatment, with a total of 2,307 patients between the ages of 16 and 60 years. CLOSE included only patients with a PFO and an associated atrial septal aneurysm or a large interatrial shunt. Gore REDUCE and RESPECT were both industry funded. All three trials found a statistically significant reduction in risk of recurrent ischemic stroke associated with PFO closure and antiplatelet therapy compared to antiplatelet therapy alone (CLOSE HR 0.03 [95% CI 0-0.26; P less than .001], RESPECT HR 0.55 [95% CI 0.31-0.999; P = .046], Gore REDUCE HR 0.23 [95% CI 0.09-0.62; P = .002]). Gore REDUCE and CLOSE identified increased rates of postprocedural atrial fibrillation or flutter (6.6% vs. 0.4% [P less than .001], 4.6% vs. 0.9% [P = .02], respectively). Serious adverse events related to the procedure or device ranged from 3.9-5.9%.

Bottom line: PFO closure combined with antiplatelet therapy in patients aged 60 years or younger, particularly in those with significant right-to-left shunts and atrial septal aneurysms, reduced the risk of recurrent ischemic stroke compared to antiplatelet therapy alone.

Citation: Mas JL. Derumeaux B. Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-21.

Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022-32.

Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033-42.

Background: Previous research on the use of PFO closure to prevent recurrent stroke has yielded mixed results.

Study design: Gore REDUCE, CLOSE, and RESPECT were all multicenter, randomized, open-label superiority trials, with blinded adjudication of endpoint events. RESPECT data reflected an exploratory analysis of an extended follow up period.

Setting: Gore REDUCE was a multinational study conducted at 63 sites in Europe and North America, from 2008-2015. CLOSE was conducted at 34 sites in France and Germany, from 2007 to 2016. RESPECT was conducted at 69 sites in the United States and Canada, from 2003 to 2011.

Synopsis: Three trials reexamined the impact of PFO closure with standard antiplatelet treatment, with a total of 2,307 patients between the ages of 16 and 60 years. CLOSE included only patients with a PFO and an associated atrial septal aneurysm or a large interatrial shunt. Gore REDUCE and RESPECT were both industry funded. All three trials found a statistically significant reduction in risk of recurrent ischemic stroke associated with PFO closure and antiplatelet therapy compared to antiplatelet therapy alone (CLOSE HR 0.03 [95% CI 0-0.26; P less than .001], RESPECT HR 0.55 [95% CI 0.31-0.999; P = .046], Gore REDUCE HR 0.23 [95% CI 0.09-0.62; P = .002]). Gore REDUCE and CLOSE identified increased rates of postprocedural atrial fibrillation or flutter (6.6% vs. 0.4% [P less than .001], 4.6% vs. 0.9% [P = .02], respectively). Serious adverse events related to the procedure or device ranged from 3.9-5.9%.

Bottom line: PFO closure combined with antiplatelet therapy in patients aged 60 years or younger, particularly in those with significant right-to-left shunts and atrial septal aneurysms, reduced the risk of recurrent ischemic stroke compared to antiplatelet therapy alone.

Citation: Mas JL. Derumeaux B. Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-21.

Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022-32.

Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033-42.

Baseline cancer-specific stress predicts poorer psychological function during chronic lymphocytic leukemia treatment, according to a prospective study of 152 patients.

“These findings suggest that integration of psychological intervention for patients who have high cancer-specific stress at baseline might be appropriate for this population,” wrote investigators led by Neha G. Goyal, PhD, a research fellow at Wake Forest University, Winston-Salem, N.C.

The subjects all had relapsed/refractory chronic lymphocytic leukemia (CLL). They filled out mental and physical function questionnaires at baseline, then at months 1, 2, and 5 during a nonrandomized phase 2 trial of ibrutinib (Imbruvica). The findings were published in the Annals of Behavioral Medicine.

Cancer-specific stress – essentially traumatic stress associated with cancer diagnosis, recurrence, and treatment – was assessed by the Impact of Event Scale, a common cancer research tool in which patients rate the intensity of intrusive thoughts and avoidant thoughts and behaviors. A score of 8 – out of a range of 0-64 – was the cut point used to separate patients with low versus high stress; higher scores mean worse symptoms.

“At treatment initiation, cancer-specific stress was associated with higher levels of cognitive-affective depressive symptoms, negative mood, fatigue interference, and sleep problems, and lower mental health quality of life. While patients with higher cancer-specific stress at baseline improved more rapidly on these outcomes ... higher cancer-specific stress at baseline was still associated with poorer psychological outcomes, but not physical outcomes, at 5 months,” the investigators said (Ann Behav Med. 2018 Feb 9. doi: 10.1093/abm/kax004).

For instance, high-stress patients started the trial with mean scores of about 4.5 on the 42-point cognitive-affective subscale of the Beck Depression Inventory; scores improved to about 2.5 after 5 months of treatment. Low-stress patients, however, started and ended the study with scores of about 1.5.

Cancer-specific stress has been associated with poorer outcomes in previous cancer studies, but its impact on CLL hasn’t been clear until now. It might be a particularly bad problem in CLL, because the disease is incurable and patients go through multiple relapses and treatment cycles.

“There has been a call to screen cancer patients to determine those who may be at risk for poor outcomes, and assessment of cancer-specific stress may have clinical utility as an individual difference predictor of psychological responses,” the team noted.

The mean age in the study was 64.1 years; 71% of the subjects were men. The majority were educated beyond high school, and almost all reported significant, supportive relationships. Patients had a median of three prior therapies, but one patients had been through 16.

Dr. Goyal reported having no financial disclosures. One author disclosed ties to Pharmacyclics and Janssen, marketers of ibrutinib. The work was supported by the National Cancer Institute and Pharmacyclics, among others.
 

[email protected]

Baseline cancer-specific stress predicts poorer psychological function during chronic lymphocytic leukemia treatment, according to a prospective study of 152 patients.

“These findings suggest that integration of psychological intervention for patients who have high cancer-specific stress at baseline might be appropriate for this population,” wrote investigators led by Neha G. Goyal, PhD, a research fellow at Wake Forest University, Winston-Salem, N.C.

The subjects all had relapsed/refractory chronic lymphocytic leukemia (CLL). They filled out mental and physical function questionnaires at baseline, then at months 1, 2, and 5 during a nonrandomized phase 2 trial of ibrutinib (Imbruvica). The findings were published in the Annals of Behavioral Medicine.

Cancer-specific stress – essentially traumatic stress associated with cancer diagnosis, recurrence, and treatment – was assessed by the Impact of Event Scale, a common cancer research tool in which patients rate the intensity of intrusive thoughts and avoidant thoughts and behaviors. A score of 8 – out of a range of 0-64 – was the cut point used to separate patients with low versus high stress; higher scores mean worse symptoms.

“At treatment initiation, cancer-specific stress was associated with higher levels of cognitive-affective depressive symptoms, negative mood, fatigue interference, and sleep problems, and lower mental health quality of life. While patients with higher cancer-specific stress at baseline improved more rapidly on these outcomes ... higher cancer-specific stress at baseline was still associated with poorer psychological outcomes, but not physical outcomes, at 5 months,” the investigators said (Ann Behav Med. 2018 Feb 9. doi: 10.1093/abm/kax004).

For instance, high-stress patients started the trial with mean scores of about 4.5 on the 42-point cognitive-affective subscale of the Beck Depression Inventory; scores improved to about 2.5 after 5 months of treatment. Low-stress patients, however, started and ended the study with scores of about 1.5.

Cancer-specific stress has been associated with poorer outcomes in previous cancer studies, but its impact on CLL hasn’t been clear until now. It might be a particularly bad problem in CLL, because the disease is incurable and patients go through multiple relapses and treatment cycles.

“There has been a call to screen cancer patients to determine those who may be at risk for poor outcomes, and assessment of cancer-specific stress may have clinical utility as an individual difference predictor of psychological responses,” the team noted.

The mean age in the study was 64.1 years; 71% of the subjects were men. The majority were educated beyond high school, and almost all reported significant, supportive relationships. Patients had a median of three prior therapies, but one patients had been through 16.

Dr. Goyal reported having no financial disclosures. One author disclosed ties to Pharmacyclics and Janssen, marketers of ibrutinib. The work was supported by the National Cancer Institute and Pharmacyclics, among others.
 

[email protected]

Baseline cancer-specific stress predicts poorer psychological function during chronic lymphocytic leukemia treatment, according to a prospective study of 152 patients.

“These findings suggest that integration of psychological intervention for patients who have high cancer-specific stress at baseline might be appropriate for this population,” wrote investigators led by Neha G. Goyal, PhD, a research fellow at Wake Forest University, Winston-Salem, N.C.

The subjects all had relapsed/refractory chronic lymphocytic leukemia (CLL). They filled out mental and physical function questionnaires at baseline, then at months 1, 2, and 5 during a nonrandomized phase 2 trial of ibrutinib (Imbruvica). The findings were published in the Annals of Behavioral Medicine.

Cancer-specific stress – essentially traumatic stress associated with cancer diagnosis, recurrence, and treatment – was assessed by the Impact of Event Scale, a common cancer research tool in which patients rate the intensity of intrusive thoughts and avoidant thoughts and behaviors. A score of 8 – out of a range of 0-64 – was the cut point used to separate patients with low versus high stress; higher scores mean worse symptoms.

“At treatment initiation, cancer-specific stress was associated with higher levels of cognitive-affective depressive symptoms, negative mood, fatigue interference, and sleep problems, and lower mental health quality of life. While patients with higher cancer-specific stress at baseline improved more rapidly on these outcomes ... higher cancer-specific stress at baseline was still associated with poorer psychological outcomes, but not physical outcomes, at 5 months,” the investigators said (Ann Behav Med. 2018 Feb 9. doi: 10.1093/abm/kax004).

For instance, high-stress patients started the trial with mean scores of about 4.5 on the 42-point cognitive-affective subscale of the Beck Depression Inventory; scores improved to about 2.5 after 5 months of treatment. Low-stress patients, however, started and ended the study with scores of about 1.5.

Cancer-specific stress has been associated with poorer outcomes in previous cancer studies, but its impact on CLL hasn’t been clear until now. It might be a particularly bad problem in CLL, because the disease is incurable and patients go through multiple relapses and treatment cycles.

“There has been a call to screen cancer patients to determine those who may be at risk for poor outcomes, and assessment of cancer-specific stress may have clinical utility as an individual difference predictor of psychological responses,” the team noted.

The mean age in the study was 64.1 years; 71% of the subjects were men. The majority were educated beyond high school, and almost all reported significant, supportive relationships. Patients had a median of three prior therapies, but one patients had been through 16.

Dr. Goyal reported having no financial disclosures. One author disclosed ties to Pharmacyclics and Janssen, marketers of ibrutinib. The work was supported by the National Cancer Institute and Pharmacyclics, among others.
 

[email protected]

SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.

“This revolution in atopic dermatitis, or eczema, stems from our increased knowledge of the disease. We understand ... the immune molecules that are involved in the disease, and we are going after them. And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.

In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.

[email protected]

SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.

“This revolution in atopic dermatitis, or eczema, stems from our increased knowledge of the disease. We understand ... the immune molecules that are involved in the disease, and we are going after them. And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.

In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.

[email protected]

SAN DIEGO – A long dry spell in the development of new atopic dermatitis (AD) medications came to an end in 2016 with the approval of a topical treatment, and last year brought the first biologic for AD to the market. With more targets and potential treatments being studied, “it’s the decade of eczema,” according to a leading researcher.

“This revolution in atopic dermatitis, or eczema, stems from our increased knowledge of the disease. We understand ... the immune molecules that are involved in the disease, and we are going after them. And I think we’ll have many more approvals in the next few years,” said Emma Guttman, MD, PhD, said in a video interview at the annual meeting of the American Academy of Dermatology, where she was presenting a talk on the translational revolution in atopic dermatitis.

In the interview, she also discussed research showing that children with AD don’t have the same distribution of lesions as adults, and a study of young children, which found that during an early stage of the disease, when compared with adults, they showed much higher increases in Th17 similar to that seen in psoriasis. It will be interesting to see if “some drugs that work for psoriasis may work in children,” said Dr. Guttman, professor of dermatology and director of the laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Guttman disclosed research support, consulting, or lecture fees from Regeneron, Sanofi, Pfizer, and other companies developing AD treatments.

[email protected]

TAMPA – The distinct features of substance use disorders (SUDs) in women argue for gender-specific treatment, according to a comprehensive update presented at the annual meeting of the American College of Psychiatrists.

“There is a shorter time between landmarks of SUD progression, and these landmarks are reached at lower doses of alcohol consumed less frequently,” reported Shelly F. Greenfield, MD, chief academic officer at McLean Hospital in Boston.

Tadas_Zvinklys/Thinkstock

TAMPA – The distinct features of substance use disorders (SUDs) in women argue for gender-specific treatment, according to a comprehensive update presented at the annual meeting of the American College of Psychiatrists.

“There is a shorter time between landmarks of SUD progression, and these landmarks are reached at lower doses of alcohol consumed less frequently,” reported Shelly F. Greenfield, MD, chief academic officer at McLean Hospital in Boston.

Tadas_Zvinklys/Thinkstock

TAMPA – The distinct features of substance use disorders (SUDs) in women argue for gender-specific treatment, according to a comprehensive update presented at the annual meeting of the American College of Psychiatrists.

“There is a shorter time between landmarks of SUD progression, and these landmarks are reached at lower doses of alcohol consumed less frequently,” reported Shelly F. Greenfield, MD, chief academic officer at McLean Hospital in Boston.

Tadas_Zvinklys/Thinkstock

SAN DIEGO – U.S. annual melanoma incidence rates steadily climbed in recent years, bucking the trend of flat or dropping rates for most other U.S. cancers.

“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.

The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.

Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.

During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.

A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.

[email protected]

SAN DIEGO – U.S. annual melanoma incidence rates steadily climbed in recent years, bucking the trend of flat or dropping rates for most other U.S. cancers.

“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.

The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.

Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.

During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.

A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.

[email protected]

SAN DIEGO – U.S. annual melanoma incidence rates steadily climbed in recent years, bucking the trend of flat or dropping rates for most other U.S. cancers.

“Nobody’s quite sure why the [melanoma] rates are still rising so dramatically,” Darrell S. Rigel, MD, said in a video interview during the annual meeting of the American Academy of Dermatology. The increase remains even after adjustment of incidence rates for the increasing mean age of U.S. adults.

The American Cancer Society reported that the estimated annual incidence rate for invasive melanoma will be 91,270 cases for 2018, following what the society called a rapid rise in the rate for the past 30 years. Add to that the estimate of more than 87,000 U.S. cases of in situ melanoma for an overall annual U.S. rate of 178,560, Dr. Rigel said.

Melanoma has a latency of 5-20 years, “so what we’re seeing right now are the effects of what happened 5, 10, or 20 years ago,” said Dr. Rigel, a dermatologist at New York University.

During a talk at the meeting, Dr. Rigel said that based on current incident levels he projected a lifetime U.S. incidence rate of invasive melanoma of one case for every 40 adults by the end of this decade, and a lifetime incidence rate for either invasive or in situ melanoma of one case for every 20 adults by 2020.

A positive trend is that for the first time, the number of melanoma deaths has started to fall, with an estimated 9,320 deaths from melanoma in 2018 according to American Cancer Society statistics, down from a peak of 10,130 melanoma deaths in 2016, Dr. Rigel said.

[email protected]

Is 100 really greater than 50 when it comes to sunscreen? A new hepatitis B vaccine gets the nod, a new JAK inhibitor takes aim at atopic dermatitis, and why house cleaning does women’s lungs no favors.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Is 100 really greater than 50 when it comes to sunscreen? A new hepatitis B vaccine gets the nod, a new JAK inhibitor takes aim at atopic dermatitis, and why house cleaning does women’s lungs no favors.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Is 100 really greater than 50 when it comes to sunscreen? A new hepatitis B vaccine gets the nod, a new JAK inhibitor takes aim at atopic dermatitis, and why house cleaning does women’s lungs no favors.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Keren Osman, MD

SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.

Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.

The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.

The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.

Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.

Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.

“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.

She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.

Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).

The patients had a median of 174 days since diagnosis (range, 98-393).

All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.

Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.

Treatment

Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.

They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.

Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.

Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.

Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.

Safety

“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”

One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.

One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.

Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.

Efficacy

At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).

At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.

“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”

At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.

So the 1-year progression-free survival rate was 86% (13/15).

“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”

*Information in the abstract differs from the presentation.

Keren Osman, MD

SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.

Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.

The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.

The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.

Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.

Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.

“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.

She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.

Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).

The patients had a median of 174 days since diagnosis (range, 98-393).

All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.

Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.

Treatment

Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.

They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.

Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.

Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.

Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.

Safety

“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”

One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.

One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.

Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.

Efficacy

At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).

At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.

“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”

At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.

So the 1-year progression-free survival rate was 86% (13/15).

“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”

*Information in the abstract differs from the presentation.

Keren Osman, MD

SALT LAKE CITY—A novel transplant regimen is “safe and feasible” for patients with multiple myeloma (MM), according to a presentation at the 2018 BMT Tandem Meetings.

Researchers conducted a phase 1 trial investigating the addition of elotuzumab and autologous peripheral blood mononuclear cell (PBMC) reconstitution to standard autologous hematopoietic stem cell transplant (ASCT) and lenalidomide maintenance in MM patients.

The regimen was considered well tolerated, as most adverse events (AEs) were grade 1 or 2.

The complete response (CR) rate was 40% at both 90 days and 1 year after ASCT.

Keren Osman, MD, of Mount Sinai Health System in New York, New York, reported these results as abstract 26.* This is an investigator-sponsored study, conducted in collaboration with Bristol Myers Squibb, the company marketing elotuzumab.

Dr Osman noted that elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7. The drug directly activates natural killer (NK) cells through the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on MM cells and facilitates interaction with NK cells to mediate the killing of MM cells through antibody-dependent cellular cytotoxicity.

“The hypothesis behind this phase 1 study was that . . ., in the peri-transplant period, if we add elotuzumab, we will succeed in promoting NK-mediated elimination of residual multiple myeloma cells as well as promote transition from innate to adaptive immune responses against multiple myeloma-associated antigens,” Dr Osman said.

She and her colleagues tested this hypothesis in 15 MM patients. They had a median age of 59 (range, 49-70), and 60% of them were male.

Forty percent of patients had stage I disease, 27% had stage II, and 20% had stage III. All patients had an ECOG status of 0 (47%) or 1 (53%).

The patients had a median of 174 days since diagnosis (range, 98-393).

All patients had received 1 to 2 prior lines of therapy. They all had bortezomib as part of their induction therapy, and 67% of them had received lenalidomide.

Seventy-three percent of patients had any cytogenetic abnormality, and 47% had high-risk cytogenetics.

Treatment

Patients underwent leukopheresis for PBMC collection, followed by standard peripheral blood stem cell mobilization and harvest.

They received standard melphalan conditioning on day -1 and autologous stem cell rescue on day 0. Autologous PBMCs were reinfused on day 3 after stem cell infusion.

Elotuzumab was given at 20 mg/kg intravenously on day 4. The drug was given every 28 days up to cycle 12.

Lenalidomide maintenance was given at 10 mg orally on days 1 to 21 of every 28-day cycle, starting with cycle 4 of elotuzumab (90 days post-ASCT). Maintenance could continue beyond cycle 12 at the investigators’ discretion.

Thirteen patients completed a year of treatment. One patient withdrew from the study due to early progression. The other patient withdrew due to personal choice and had a very good partial response (VGPR) at withdrawal.

Safety

“The majority of the adverse events, including infusion reactions attributable to elotuzumab, were grade 2 or lower,” Dr Osman noted. “And there were no AEs related to PBMC administration.”

One patient had a delay in hematopoietic reconstitution, which resulted in hospitalization exceeding 21 days.

One patient had grade 3 hypertension, which was attributed to elotuzumab and resolved with supportive care.

Eight patients had grade 3 lymphopenia, which was associated with elotuzumab, during the maintenance phase. Patients received prophylactic antibiotics, and there were no opportunistic infections.

Efficacy

At screening (after induction but before ASCT), 13 patients (87%) had a VGPR, and 2 (13%) had a partial response (PR).

At 90 days post-ASCT, 2 patients (13%) had a stringent CR, and 4 (27%) had a CR. Six patients (40%) had a VGPR, and 2 (13%) had a PR. One patient (7%) had progressed.

“In this very high-risk PR/VGPR population, stem cell transplant with elotuzumab and PBMC infusion resulted in a CR rate of 40%—with 13% of patients achieving stringent CR—by day 90,” Dr Osman noted. “And maintenance elotuzumab plus lenalidomide promoted further conversion to 33% stringent CR by 1 year.”

At 1 year, 5 patients (33%) had a stringent CR, and 1 (7%) had a CR. Six patients (40%) had a VGPR, and 1 (7%) had a PR. Two patients (13%) had progressed.

So the 1-year progression-free survival rate was 86% (13/15).

“In conclusion, we see that elotuzumab and PBMC administration with standard autologous stem cell transplant and lenalidomide maintenance for consolidation therapy in multiple myeloma is certainly both safe and feasible,” Dr Osman said. “We’re planning a phase 2 study.”

*Information in the abstract differs from the presentation.

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)