NEW ORLEANS—A single bout of treadmill walking might affect cognitive processing to a greater degree than stationary cycling, particularly among those with multiple sclerosis (MS) who demonstrate low aerobic fitness, according to a report presented at the 31st Annual Meeting of the Consortium of MS Centers. "This [finding] highlights the importance of targeting those with low aerobic fitness in treadmill walking exercise training interventions for improving cognition in persons with MS, as improving aerobic fitness may be beneficial for reducing MS-related cognitive-motor interference," said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey, and colleagues.

The mechanisms by which treadmill walking improves cognition in patients with MS are not well understood. Researchers have hypothesized that treadmill walking is essentially a complex cognitive task that requires more attentional resources than other modalities of aerobic exercise (eg, cycle ergometry), and that repeated exposure trains the person in cognitive-motor processing. If this hypothesis is true, then patients with MS should demonstrate worse cognitive performance during treadmill walking than during cycle ergometry, as more attentional resources would presumably be devoted to walking on a treadmill than to cycling on a stationary bicycle. Furthermore, it is unknown whether better aerobic fitness attenuates such cognitive-motor interference in patients with MS.  

Dr. Sandroff and colleagues conducted a pilot study to examine cognitive performance before and during acute bouts of treadmill walking, stationary cycling, and seated quiet rest in 12 fully ambulatory patients with MS with high or low aerobic fitness using a within-subjects, repeated-measures design.  

Participants underwent a baseline incremental exercise test to exhaustion for measurement of aerobic fitness (ie, VO_2peak). Participants further completed three experimental conditions that consisted of 20 minutes of moderate- to vigorous-intensity treadmill walking exercise, moderate- to vigorous-intensity cycle ergometer exercise, and seated quiet rest in a randomized, counterbalanced order. Participants underwent the three-second Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive performance prior to and during each condition.  

Overall, decreases in PASAT performance during treadmill walking were not larger than those during cycle ergometry, relative to quiet rest. However, decreases in PASAT performance were larger for those with lower aerobic fitness during treadmill walking than during cycle ergometry, compared with quiet rest.

NEW ORLEANS—A single bout of treadmill walking might affect cognitive processing to a greater degree than stationary cycling, particularly among those with multiple sclerosis (MS) who demonstrate low aerobic fitness, according to a report presented at the 31st Annual Meeting of the Consortium of MS Centers. "This [finding] highlights the importance of targeting those with low aerobic fitness in treadmill walking exercise training interventions for improving cognition in persons with MS, as improving aerobic fitness may be beneficial for reducing MS-related cognitive-motor interference," said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey, and colleagues.

The mechanisms by which treadmill walking improves cognition in patients with MS are not well understood. Researchers have hypothesized that treadmill walking is essentially a complex cognitive task that requires more attentional resources than other modalities of aerobic exercise (eg, cycle ergometry), and that repeated exposure trains the person in cognitive-motor processing. If this hypothesis is true, then patients with MS should demonstrate worse cognitive performance during treadmill walking than during cycle ergometry, as more attentional resources would presumably be devoted to walking on a treadmill than to cycling on a stationary bicycle. Furthermore, it is unknown whether better aerobic fitness attenuates such cognitive-motor interference in patients with MS.  

Dr. Sandroff and colleagues conducted a pilot study to examine cognitive performance before and during acute bouts of treadmill walking, stationary cycling, and seated quiet rest in 12 fully ambulatory patients with MS with high or low aerobic fitness using a within-subjects, repeated-measures design.  

Participants underwent a baseline incremental exercise test to exhaustion for measurement of aerobic fitness (ie, VO_2peak). Participants further completed three experimental conditions that consisted of 20 minutes of moderate- to vigorous-intensity treadmill walking exercise, moderate- to vigorous-intensity cycle ergometer exercise, and seated quiet rest in a randomized, counterbalanced order. Participants underwent the three-second Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive performance prior to and during each condition.  

Overall, decreases in PASAT performance during treadmill walking were not larger than those during cycle ergometry, relative to quiet rest. However, decreases in PASAT performance were larger for those with lower aerobic fitness during treadmill walking than during cycle ergometry, compared with quiet rest.

NEW ORLEANS—A single bout of treadmill walking might affect cognitive processing to a greater degree than stationary cycling, particularly among those with multiple sclerosis (MS) who demonstrate low aerobic fitness, according to a report presented at the 31st Annual Meeting of the Consortium of MS Centers. "This [finding] highlights the importance of targeting those with low aerobic fitness in treadmill walking exercise training interventions for improving cognition in persons with MS, as improving aerobic fitness may be beneficial for reducing MS-related cognitive-motor interference," said Brian M. Sandroff, PhD, of the Kessler Foundation in West Orange, New Jersey, and colleagues.

The mechanisms by which treadmill walking improves cognition in patients with MS are not well understood. Researchers have hypothesized that treadmill walking is essentially a complex cognitive task that requires more attentional resources than other modalities of aerobic exercise (eg, cycle ergometry), and that repeated exposure trains the person in cognitive-motor processing. If this hypothesis is true, then patients with MS should demonstrate worse cognitive performance during treadmill walking than during cycle ergometry, as more attentional resources would presumably be devoted to walking on a treadmill than to cycling on a stationary bicycle. Furthermore, it is unknown whether better aerobic fitness attenuates such cognitive-motor interference in patients with MS.  

Dr. Sandroff and colleagues conducted a pilot study to examine cognitive performance before and during acute bouts of treadmill walking, stationary cycling, and seated quiet rest in 12 fully ambulatory patients with MS with high or low aerobic fitness using a within-subjects, repeated-measures design.  

Participants underwent a baseline incremental exercise test to exhaustion for measurement of aerobic fitness (ie, VO_2peak). Participants further completed three experimental conditions that consisted of 20 minutes of moderate- to vigorous-intensity treadmill walking exercise, moderate- to vigorous-intensity cycle ergometer exercise, and seated quiet rest in a randomized, counterbalanced order. Participants underwent the three-second Paced Auditory Serial Addition Test (PASAT) as a measure of cognitive performance prior to and during each condition.  

Overall, decreases in PASAT performance during treadmill walking were not larger than those during cycle ergometry, relative to quiet rest. However, decreases in PASAT performance were larger for those with lower aerobic fitness during treadmill walking than during cycle ergometry, compared with quiet rest.

A fever-monitoring patch was well tolerated in hospitalized patients undergoing stem cell transplant or intensive chemotherapy for leukemia, and alerted physicians to the presence of a fever much earlier than did standard temperature-taking procedures, according to findings from a study abstract that was published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The patch can transmit data via Bluetooth to an iPad or smartphone, and it attempts to bring temperature recording in line with other vital signs. “It’s the only vital sign that’s not continuously monitored outside of the ICU,” said John Gannon, CEO of Blue Spark, which markets the TempTraq underarm patch used in the study.

The units are constructed with thin batteries that can be “printed” on to any surface. “Being disposable makes it a very usable work flow device,” said Mr. Gannon.

The researchers tested the TempTraq in 10 patients who had been admitted for stem cell transplant or high dose chemotherapy for leukemia.

In addition to wearing the patch, patients had their temperature measured in standard fashion every 4 hours. The researchers defined a temperature rise as a spike above 100.4° F. The device measured body temperature every 10 minutes (14,342 temperature measurements).

Standard of care measurement identified 23 temperature rise episodes, 21 of which were recorded by the TempTraq patch. The device caught temperature spikes much sooner than did standard of care measures – a median of 140.1 minutes earlier (range, 30-180 minutes).

All 10 patients continued to wear the patch throughout the hospital stay, with 9 of 10 reporting that the patch was comfortable and didn’t produce any skin irritation. Eight patients indicated interest in using the patch again, and 8 said they were completely satisfied with the patch.

The next step is to determine if the patch could be used successfully in an outpatient stem cell transplant setting.

The device could also be integrated directly with hospital central monitoring systems using Blue Spark’s TempTraq Connect, which is a HIPAA-compliant service supported by the Google Healthcare Cloud Platform, though this was not tested in the current study.

The TempTraq could be used to monitor patients for the onset of sepsis and allow faster interventions, according to Mr. Gannon. Also, patients who are susceptible to infections could be sent home with a TempTraq monitor, which would send signals to a central monitoring station.

A fever-monitoring patch was well tolerated in hospitalized patients undergoing stem cell transplant or intensive chemotherapy for leukemia, and alerted physicians to the presence of a fever much earlier than did standard temperature-taking procedures, according to findings from a study abstract that was published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The patch can transmit data via Bluetooth to an iPad or smartphone, and it attempts to bring temperature recording in line with other vital signs. “It’s the only vital sign that’s not continuously monitored outside of the ICU,” said John Gannon, CEO of Blue Spark, which markets the TempTraq underarm patch used in the study.

The units are constructed with thin batteries that can be “printed” on to any surface. “Being disposable makes it a very usable work flow device,” said Mr. Gannon.

The researchers tested the TempTraq in 10 patients who had been admitted for stem cell transplant or high dose chemotherapy for leukemia.

In addition to wearing the patch, patients had their temperature measured in standard fashion every 4 hours. The researchers defined a temperature rise as a spike above 100.4° F. The device measured body temperature every 10 minutes (14,342 temperature measurements).

Standard of care measurement identified 23 temperature rise episodes, 21 of which were recorded by the TempTraq patch. The device caught temperature spikes much sooner than did standard of care measures – a median of 140.1 minutes earlier (range, 30-180 minutes).

All 10 patients continued to wear the patch throughout the hospital stay, with 9 of 10 reporting that the patch was comfortable and didn’t produce any skin irritation. Eight patients indicated interest in using the patch again, and 8 said they were completely satisfied with the patch.

The next step is to determine if the patch could be used successfully in an outpatient stem cell transplant setting.

The device could also be integrated directly with hospital central monitoring systems using Blue Spark’s TempTraq Connect, which is a HIPAA-compliant service supported by the Google Healthcare Cloud Platform, though this was not tested in the current study.

The TempTraq could be used to monitor patients for the onset of sepsis and allow faster interventions, according to Mr. Gannon. Also, patients who are susceptible to infections could be sent home with a TempTraq monitor, which would send signals to a central monitoring station.

A fever-monitoring patch was well tolerated in hospitalized patients undergoing stem cell transplant or intensive chemotherapy for leukemia, and alerted physicians to the presence of a fever much earlier than did standard temperature-taking procedures, according to findings from a study abstract that was published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The patch can transmit data via Bluetooth to an iPad or smartphone, and it attempts to bring temperature recording in line with other vital signs. “It’s the only vital sign that’s not continuously monitored outside of the ICU,” said John Gannon, CEO of Blue Spark, which markets the TempTraq underarm patch used in the study.

The units are constructed with thin batteries that can be “printed” on to any surface. “Being disposable makes it a very usable work flow device,” said Mr. Gannon.

The researchers tested the TempTraq in 10 patients who had been admitted for stem cell transplant or high dose chemotherapy for leukemia.

In addition to wearing the patch, patients had their temperature measured in standard fashion every 4 hours. The researchers defined a temperature rise as a spike above 100.4° F. The device measured body temperature every 10 minutes (14,342 temperature measurements).

Standard of care measurement identified 23 temperature rise episodes, 21 of which were recorded by the TempTraq patch. The device caught temperature spikes much sooner than did standard of care measures – a median of 140.1 minutes earlier (range, 30-180 minutes).

All 10 patients continued to wear the patch throughout the hospital stay, with 9 of 10 reporting that the patch was comfortable and didn’t produce any skin irritation. Eight patients indicated interest in using the patch again, and 8 said they were completely satisfied with the patch.

The next step is to determine if the patch could be used successfully in an outpatient stem cell transplant setting.

The device could also be integrated directly with hospital central monitoring systems using Blue Spark’s TempTraq Connect, which is a HIPAA-compliant service supported by the Google Healthcare Cloud Platform, though this was not tested in the current study.

The TempTraq could be used to monitor patients for the onset of sepsis and allow faster interventions, according to Mr. Gannon. Also, patients who are susceptible to infections could be sent home with a TempTraq monitor, which would send signals to a central monitoring station.

A Retrospective Chart Review

Ms. Vollmer and colleagues conducted a retrospective study to compare the discontinuation rates and efficacy of fingolimod and dimethyl fumarate to those of natalizumab. In a retrospective chart review, they identified patients with multiple sclerosis (MS) who presented to the Rocky Mountain MS Center in Aurora, Colorado. Eligible participants initiated drug therapy between January 2010 and October 2013. Patients who initiated natalizumab had to be negative for the John Cunningham virus (JCV) at baseline. Ms. Vollmer and colleagues retrospectively collected clinician-recorded data.

The study’s primary outcome was discontinuation at 24 months. Secondary outcomes included reasons for discontinuation, relapse activity, MRI activity, and a composite disease activity measure that comprised clinical relapse, contrast enhancement, and new T2 lesions on follow-up MRI. Ms. Vollmer and colleagues identified 1,302 patients who initiated insurance paperwork for natalizumab. To reduce the size of this sample, they randomly selected 800 patients, of whom 270 met the inclusion criteria. In all, 440 participants initiated paperwork for fingolimod, of whom 271 met the inclusion criteria. For dimethyl fumarate, the researchers found 592 participants who initiated the paperwork, and 342 met the inclusion criteria.

Patients receiving natalizumab were significantly younger (mean age, 39.8) than patients receiving fingolimod (42.5) or dimethyl fumarate (45.8). Furthermore, patients treated with natalizumab were more likely to be female (77.8%) than patients treated with fingolimod (72.0%) or dimethyl fumarate (69.6%). Patients receiving natalizumab also were more likely to have contrast enhancement on baseline MRI (31.2%) than were participants receiving fingolimod (24.6%) or dimethyl fumarate (14.6%). Mean disease duration was approximately 12 years for all groups.

Discontinuation and Disease Activity

The rate of discontinuation was similar for natalizumab (33.3%) and fingolimod (34.3%), but the researchers observed a significant difference between natalizumab and dimethyl fumarate (47.1%). Disease activity and adverse events were the most common reasons for discontinuation of fingolimod and dimethyl fumarate, and JCV positivity was the most common reason for discontinuation of natalizumab. Of the seven participants who discontinued natalizumab because of disease activity, five had neutralizing antibodies. Of the 20 patients who discontinued natalizumab because of adverse events, nine had rashes during infusion, eight of whom tested positive for neutralizing antibodies.

Ms. Vollmer and colleagues found no significant difference between natalizumab and fingolimod in the rate of patients with a clinical relapse (5.6% and 8.9%, respectively), but they observed a significant difference between dimethyl fumarate (12.9%) and natalizumab for this outcome. Contrast enhancement was less common among patients receiving natalizumab (6.6%), compared with fingolimod (13.1%), but there was no significant difference between natalizumab and dimethyl fumarate (10.0%).

The rate of new T2 lesions was lower with natalizumab (21.4%), compared with fingolimod (35.0%) and dimethyl fumarate (31.5%). Similarly, the composite disease activity measure was less common with natalizumab (20.7%), compared with fingolimod (34.7%) and dimethyl fumarate (33.6%). Data adjustments indicated that discontinuation was equally likely among patients receiving fingolimod and those receiving natalizumab. Patients receiving dimethyl fumarate, however, were approximately twice as likely to discontinue treatment, compared with patients receiving natalizumab.

Furthermore, patients receiving fingolimod were approximately twice as likely to discontinue treatment because of adverse events, compared with patients receiving natalizumab. Patients treated with dimethyl fumarate were approximately four times as likely to discontinue because of adverse events, compared with patients treated with natalizumab. In addition, patients were approximately twice as likely to have disease activity on fingolimod or dimethyl fumarate, compared with natalizumab.

—Erik Greb

Suggested Reading

Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. Neurology. 2016;86(8):771-778.

A Retrospective Chart Review

Ms. Vollmer and colleagues conducted a retrospective study to compare the discontinuation rates and efficacy of fingolimod and dimethyl fumarate to those of natalizumab. In a retrospective chart review, they identified patients with multiple sclerosis (MS) who presented to the Rocky Mountain MS Center in Aurora, Colorado. Eligible participants initiated drug therapy between January 2010 and October 2013. Patients who initiated natalizumab had to be negative for the John Cunningham virus (JCV) at baseline. Ms. Vollmer and colleagues retrospectively collected clinician-recorded data.

The study’s primary outcome was discontinuation at 24 months. Secondary outcomes included reasons for discontinuation, relapse activity, MRI activity, and a composite disease activity measure that comprised clinical relapse, contrast enhancement, and new T2 lesions on follow-up MRI. Ms. Vollmer and colleagues identified 1,302 patients who initiated insurance paperwork for natalizumab. To reduce the size of this sample, they randomly selected 800 patients, of whom 270 met the inclusion criteria. In all, 440 participants initiated paperwork for fingolimod, of whom 271 met the inclusion criteria. For dimethyl fumarate, the researchers found 592 participants who initiated the paperwork, and 342 met the inclusion criteria.

Patients receiving natalizumab were significantly younger (mean age, 39.8) than patients receiving fingolimod (42.5) or dimethyl fumarate (45.8). Furthermore, patients treated with natalizumab were more likely to be female (77.8%) than patients treated with fingolimod (72.0%) or dimethyl fumarate (69.6%). Patients receiving natalizumab also were more likely to have contrast enhancement on baseline MRI (31.2%) than were participants receiving fingolimod (24.6%) or dimethyl fumarate (14.6%). Mean disease duration was approximately 12 years for all groups.

Discontinuation and Disease Activity

The rate of discontinuation was similar for natalizumab (33.3%) and fingolimod (34.3%), but the researchers observed a significant difference between natalizumab and dimethyl fumarate (47.1%). Disease activity and adverse events were the most common reasons for discontinuation of fingolimod and dimethyl fumarate, and JCV positivity was the most common reason for discontinuation of natalizumab. Of the seven participants who discontinued natalizumab because of disease activity, five had neutralizing antibodies. Of the 20 patients who discontinued natalizumab because of adverse events, nine had rashes during infusion, eight of whom tested positive for neutralizing antibodies.

Ms. Vollmer and colleagues found no significant difference between natalizumab and fingolimod in the rate of patients with a clinical relapse (5.6% and 8.9%, respectively), but they observed a significant difference between dimethyl fumarate (12.9%) and natalizumab for this outcome. Contrast enhancement was less common among patients receiving natalizumab (6.6%), compared with fingolimod (13.1%), but there was no significant difference between natalizumab and dimethyl fumarate (10.0%).

The rate of new T2 lesions was lower with natalizumab (21.4%), compared with fingolimod (35.0%) and dimethyl fumarate (31.5%). Similarly, the composite disease activity measure was less common with natalizumab (20.7%), compared with fingolimod (34.7%) and dimethyl fumarate (33.6%). Data adjustments indicated that discontinuation was equally likely among patients receiving fingolimod and those receiving natalizumab. Patients receiving dimethyl fumarate, however, were approximately twice as likely to discontinue treatment, compared with patients receiving natalizumab.

Furthermore, patients receiving fingolimod were approximately twice as likely to discontinue treatment because of adverse events, compared with patients receiving natalizumab. Patients treated with dimethyl fumarate were approximately four times as likely to discontinue because of adverse events, compared with patients treated with natalizumab. In addition, patients were approximately twice as likely to have disease activity on fingolimod or dimethyl fumarate, compared with natalizumab.

—Erik Greb

Suggested Reading

Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. Neurology. 2016;86(8):771-778.

A Retrospective Chart Review

Ms. Vollmer and colleagues conducted a retrospective study to compare the discontinuation rates and efficacy of fingolimod and dimethyl fumarate to those of natalizumab. In a retrospective chart review, they identified patients with multiple sclerosis (MS) who presented to the Rocky Mountain MS Center in Aurora, Colorado. Eligible participants initiated drug therapy between January 2010 and October 2013. Patients who initiated natalizumab had to be negative for the John Cunningham virus (JCV) at baseline. Ms. Vollmer and colleagues retrospectively collected clinician-recorded data.

The study’s primary outcome was discontinuation at 24 months. Secondary outcomes included reasons for discontinuation, relapse activity, MRI activity, and a composite disease activity measure that comprised clinical relapse, contrast enhancement, and new T2 lesions on follow-up MRI. Ms. Vollmer and colleagues identified 1,302 patients who initiated insurance paperwork for natalizumab. To reduce the size of this sample, they randomly selected 800 patients, of whom 270 met the inclusion criteria. In all, 440 participants initiated paperwork for fingolimod, of whom 271 met the inclusion criteria. For dimethyl fumarate, the researchers found 592 participants who initiated the paperwork, and 342 met the inclusion criteria.

Patients receiving natalizumab were significantly younger (mean age, 39.8) than patients receiving fingolimod (42.5) or dimethyl fumarate (45.8). Furthermore, patients treated with natalizumab were more likely to be female (77.8%) than patients treated with fingolimod (72.0%) or dimethyl fumarate (69.6%). Patients receiving natalizumab also were more likely to have contrast enhancement on baseline MRI (31.2%) than were participants receiving fingolimod (24.6%) or dimethyl fumarate (14.6%). Mean disease duration was approximately 12 years for all groups.

Discontinuation and Disease Activity

The rate of discontinuation was similar for natalizumab (33.3%) and fingolimod (34.3%), but the researchers observed a significant difference between natalizumab and dimethyl fumarate (47.1%). Disease activity and adverse events were the most common reasons for discontinuation of fingolimod and dimethyl fumarate, and JCV positivity was the most common reason for discontinuation of natalizumab. Of the seven participants who discontinued natalizumab because of disease activity, five had neutralizing antibodies. Of the 20 patients who discontinued natalizumab because of adverse events, nine had rashes during infusion, eight of whom tested positive for neutralizing antibodies.

Ms. Vollmer and colleagues found no significant difference between natalizumab and fingolimod in the rate of patients with a clinical relapse (5.6% and 8.9%, respectively), but they observed a significant difference between dimethyl fumarate (12.9%) and natalizumab for this outcome. Contrast enhancement was less common among patients receiving natalizumab (6.6%), compared with fingolimod (13.1%), but there was no significant difference between natalizumab and dimethyl fumarate (10.0%).

The rate of new T2 lesions was lower with natalizumab (21.4%), compared with fingolimod (35.0%) and dimethyl fumarate (31.5%). Similarly, the composite disease activity measure was less common with natalizumab (20.7%), compared with fingolimod (34.7%) and dimethyl fumarate (33.6%). Data adjustments indicated that discontinuation was equally likely among patients receiving fingolimod and those receiving natalizumab. Patients receiving dimethyl fumarate, however, were approximately twice as likely to discontinue treatment, compared with patients receiving natalizumab.

Furthermore, patients receiving fingolimod were approximately twice as likely to discontinue treatment because of adverse events, compared with patients receiving natalizumab. Patients treated with dimethyl fumarate were approximately four times as likely to discontinue because of adverse events, compared with patients treated with natalizumab. In addition, patients were approximately twice as likely to have disease activity on fingolimod or dimethyl fumarate, compared with natalizumab.

—Erik Greb

Suggested Reading

Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study. Neurology. 2016;86(8):771-778.

Eye tracking is a noninvasive technique that may help to assess two key physiologic signs of concussion, intracranial pressure (ICP) and ocular motility dysfunction, according to a study published online ahead of print June 2 in the Journal of Neurosurgery. This technique does not require a trained examiner, pupil dilation, imaging studies, or an invasive procedure such as lumbar or ventricular puncture, the authors noted.

“With these data, we are presenting a new application for eye-tracking technology, as well as a new mechanism for assessment of elevated ICP that is noninvasive, automatable, and could potentially be performed and analyzed remotely,” said Uzma Samadani, MD, PhD, Associate Professor of Neurosurgery at the University of Minnesota in Minneapolis, and colleagues.

The boundaries of normal and elevated intracranial pressure vary between patients, said the authors. People with elevated intracranial pressure can develop abnormalities in global cerebral functioning. Elevated ICP can also affect the function of cranial nerves, which may contribute to ocular dysmotility. Dr. Samadani and colleagues assessed the impact of elevated ICP on eye-tracking sessions performed while patients watched a short film clip.

Eligible participants ranged in age from 18 to 70, were admitted to the Bellevue Hospital neurosurgical intensive care unit in New York City with vision correctable to within 20/500 bilaterally, and had denied a history of ocular dysmotility. In addition, these patients were conscious and able to communicate and to provide an ophthalmologic, medical, and neurologic history, as well as medications, drugs, and alcohol consumed within 24 hours prior to eye tracking.

Awake patients who required placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video. The investigators recorded pupil position at 500 Hz and calculated metrics associated with each eye individually and both eyes together. In addition, the researchers performed linear regression with generalized estimating equations to test the association of eye-tracking metrics with changes in ICP.

The investigators performed eye tracking at ICP levels ranging from –3 mm Hg to 30 mm Hg in 23 patients (12 women, mean age 46.8) on 55 occasions. Eye-tracking measures correlating with cranial nerve function decreased linearly with increasing ICP.

Researchers also found that measures for cranial nerve VI were the most prominently affected. The area under the curve for eye-tracking metrics to discriminate between an ICP <12 mm Hg and one of ≥12 mm Hg was 0.798. To discriminate between an ICP <15 mm Hg and one of ≥15 mm Hg, the area under the curve was 0.833. Finally, to discriminate between an ICP <20 mm Hg and ≥20 mm Hg, the area under the curve was 0.889.

Overall, increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching the short film. The “technology has clinical applications for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome,” said Dr. Samadani and colleagues.

The major limitation of this study was the lack of continuous data in patients with higher ICP recordings, the authors said. Few patients with elevated ICP could open their eyes long enough to undergo eye tracking.

—Erica Tricarico

Suggested Reading

Kolecki R, Dammavalam V, Zahid A, et al. Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip. J Neurosurg. 2017 Jun 2 [Epub ahead of print].

Eye tracking is a noninvasive technique that may help to assess two key physiologic signs of concussion, intracranial pressure (ICP) and ocular motility dysfunction, according to a study published online ahead of print June 2 in the Journal of Neurosurgery. This technique does not require a trained examiner, pupil dilation, imaging studies, or an invasive procedure such as lumbar or ventricular puncture, the authors noted.

“With these data, we are presenting a new application for eye-tracking technology, as well as a new mechanism for assessment of elevated ICP that is noninvasive, automatable, and could potentially be performed and analyzed remotely,” said Uzma Samadani, MD, PhD, Associate Professor of Neurosurgery at the University of Minnesota in Minneapolis, and colleagues.

The boundaries of normal and elevated intracranial pressure vary between patients, said the authors. People with elevated intracranial pressure can develop abnormalities in global cerebral functioning. Elevated ICP can also affect the function of cranial nerves, which may contribute to ocular dysmotility. Dr. Samadani and colleagues assessed the impact of elevated ICP on eye-tracking sessions performed while patients watched a short film clip.

Eligible participants ranged in age from 18 to 70, were admitted to the Bellevue Hospital neurosurgical intensive care unit in New York City with vision correctable to within 20/500 bilaterally, and had denied a history of ocular dysmotility. In addition, these patients were conscious and able to communicate and to provide an ophthalmologic, medical, and neurologic history, as well as medications, drugs, and alcohol consumed within 24 hours prior to eye tracking.

Awake patients who required placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video. The investigators recorded pupil position at 500 Hz and calculated metrics associated with each eye individually and both eyes together. In addition, the researchers performed linear regression with generalized estimating equations to test the association of eye-tracking metrics with changes in ICP.

The investigators performed eye tracking at ICP levels ranging from –3 mm Hg to 30 mm Hg in 23 patients (12 women, mean age 46.8) on 55 occasions. Eye-tracking measures correlating with cranial nerve function decreased linearly with increasing ICP.

Researchers also found that measures for cranial nerve VI were the most prominently affected. The area under the curve for eye-tracking metrics to discriminate between an ICP <12 mm Hg and one of ≥12 mm Hg was 0.798. To discriminate between an ICP <15 mm Hg and one of ≥15 mm Hg, the area under the curve was 0.833. Finally, to discriminate between an ICP <20 mm Hg and ≥20 mm Hg, the area under the curve was 0.889.

Overall, increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching the short film. The “technology has clinical applications for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome,” said Dr. Samadani and colleagues.

The major limitation of this study was the lack of continuous data in patients with higher ICP recordings, the authors said. Few patients with elevated ICP could open their eyes long enough to undergo eye tracking.

—Erica Tricarico

Suggested Reading

Kolecki R, Dammavalam V, Zahid A, et al. Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip. J Neurosurg. 2017 Jun 2 [Epub ahead of print].

Eye tracking is a noninvasive technique that may help to assess two key physiologic signs of concussion, intracranial pressure (ICP) and ocular motility dysfunction, according to a study published online ahead of print June 2 in the Journal of Neurosurgery. This technique does not require a trained examiner, pupil dilation, imaging studies, or an invasive procedure such as lumbar or ventricular puncture, the authors noted.

“With these data, we are presenting a new application for eye-tracking technology, as well as a new mechanism for assessment of elevated ICP that is noninvasive, automatable, and could potentially be performed and analyzed remotely,” said Uzma Samadani, MD, PhD, Associate Professor of Neurosurgery at the University of Minnesota in Minneapolis, and colleagues.

The boundaries of normal and elevated intracranial pressure vary between patients, said the authors. People with elevated intracranial pressure can develop abnormalities in global cerebral functioning. Elevated ICP can also affect the function of cranial nerves, which may contribute to ocular dysmotility. Dr. Samadani and colleagues assessed the impact of elevated ICP on eye-tracking sessions performed while patients watched a short film clip.

Eligible participants ranged in age from 18 to 70, were admitted to the Bellevue Hospital neurosurgical intensive care unit in New York City with vision correctable to within 20/500 bilaterally, and had denied a history of ocular dysmotility. In addition, these patients were conscious and able to communicate and to provide an ophthalmologic, medical, and neurologic history, as well as medications, drugs, and alcohol consumed within 24 hours prior to eye tracking.

Awake patients who required placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video. The investigators recorded pupil position at 500 Hz and calculated metrics associated with each eye individually and both eyes together. In addition, the researchers performed linear regression with generalized estimating equations to test the association of eye-tracking metrics with changes in ICP.

The investigators performed eye tracking at ICP levels ranging from –3 mm Hg to 30 mm Hg in 23 patients (12 women, mean age 46.8) on 55 occasions. Eye-tracking measures correlating with cranial nerve function decreased linearly with increasing ICP.

Researchers also found that measures for cranial nerve VI were the most prominently affected. The area under the curve for eye-tracking metrics to discriminate between an ICP <12 mm Hg and one of ≥12 mm Hg was 0.798. To discriminate between an ICP <15 mm Hg and one of ≥15 mm Hg, the area under the curve was 0.833. Finally, to discriminate between an ICP <20 mm Hg and ≥20 mm Hg, the area under the curve was 0.889.

Overall, increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching the short film. The “technology has clinical applications for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome,” said Dr. Samadani and colleagues.

The major limitation of this study was the lack of continuous data in patients with higher ICP recordings, the authors said. Few patients with elevated ICP could open their eyes long enough to undergo eye tracking.

—Erica Tricarico

Suggested Reading

Kolecki R, Dammavalam V, Zahid A, et al. Elevated intracranial pressure and reversible eye-tracking changes detected while viewing a film clip. J Neurosurg. 2017 Jun 2 [Epub ahead of print].

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

CHICAGO – A therapeutic target and possibly a treatment for acute myeloid leukemia and myelodysplastic syndrome may lie in the immortalized B cells of a patient whose acute myeloid leukemia was cured after allogeneic stem cell transplantation.

A B cell clone isolated from this patient makes a hypermutated immunoglobulin G1 antibody that binds leukemic blasts of all World Health Organization 2008 AML and myelodysplastic syndrome (MDS) types, based on cells obtained from 60 AML or MDS patients, but does not target healthy cells and lymphoid tissue, Mette D. Hazenberg, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

Mary Jo M. Dales

[email protected]

On Twitter @maryjodales

CHICAGO – A therapeutic target and possibly a treatment for acute myeloid leukemia and myelodysplastic syndrome may lie in the immortalized B cells of a patient whose acute myeloid leukemia was cured after allogeneic stem cell transplantation.

A B cell clone isolated from this patient makes a hypermutated immunoglobulin G1 antibody that binds leukemic blasts of all World Health Organization 2008 AML and myelodysplastic syndrome (MDS) types, based on cells obtained from 60 AML or MDS patients, but does not target healthy cells and lymphoid tissue, Mette D. Hazenberg, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

Mary Jo M. Dales

[email protected]

On Twitter @maryjodales

CHICAGO – A therapeutic target and possibly a treatment for acute myeloid leukemia and myelodysplastic syndrome may lie in the immortalized B cells of a patient whose acute myeloid leukemia was cured after allogeneic stem cell transplantation.

A B cell clone isolated from this patient makes a hypermutated immunoglobulin G1 antibody that binds leukemic blasts of all World Health Organization 2008 AML and myelodysplastic syndrome (MDS) types, based on cells obtained from 60 AML or MDS patients, but does not target healthy cells and lymphoid tissue, Mette D. Hazenberg, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

Mary Jo M. Dales

[email protected]

On Twitter @maryjodales

FROM AN ACIP MEETING

New draft recommendations on influenza vaccines for children and pregnant women were unanimously passed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.

The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”

Steve Mann/Thinkstock

[email protected]

On Twitter @eaztweets

FROM AN ACIP MEETING

New draft recommendations on influenza vaccines for children and pregnant women were unanimously passed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.

The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”

Steve Mann/Thinkstock

[email protected]

On Twitter @eaztweets

FROM AN ACIP MEETING

New draft recommendations on influenza vaccines for children and pregnant women were unanimously passed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.

The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”

Steve Mann/Thinkstock

[email protected]

On Twitter @eaztweets

LAS VEGAS – A novel lipid formulation of ibuprofen given at 1,200 mg/day proved noninferior to high-dose standard ibuprofen at 2,400 mg/day for management of episodic knee pain flares in a phase III randomized trial, and it accomplished this with significantly fewer gastrointestinal side effects, Sita M.A. Bierma-Zeinstra, MD, reported.

Episodic flares of knee pain are a disabling feature of knee osteoarthritis that can occur at all stages of the disease, including prior to clinical diagnosis. There is a need for a fast-acting analgesic designed for short-term use with minimal side effects to provide pain relief during these flares. This was the motivation for developing Flarin, a lipid formulation soft-gel capsule of ibuprofen that is effective at less-than-standard doses of the conventional NSAID, she explained at the World Congress on Osteoarthritis.

[email protected]

LAS VEGAS – A novel lipid formulation of ibuprofen given at 1,200 mg/day proved noninferior to high-dose standard ibuprofen at 2,400 mg/day for management of episodic knee pain flares in a phase III randomized trial, and it accomplished this with significantly fewer gastrointestinal side effects, Sita M.A. Bierma-Zeinstra, MD, reported.

Episodic flares of knee pain are a disabling feature of knee osteoarthritis that can occur at all stages of the disease, including prior to clinical diagnosis. There is a need for a fast-acting analgesic designed for short-term use with minimal side effects to provide pain relief during these flares. This was the motivation for developing Flarin, a lipid formulation soft-gel capsule of ibuprofen that is effective at less-than-standard doses of the conventional NSAID, she explained at the World Congress on Osteoarthritis.

[email protected]

LAS VEGAS – A novel lipid formulation of ibuprofen given at 1,200 mg/day proved noninferior to high-dose standard ibuprofen at 2,400 mg/day for management of episodic knee pain flares in a phase III randomized trial, and it accomplished this with significantly fewer gastrointestinal side effects, Sita M.A. Bierma-Zeinstra, MD, reported.

Episodic flares of knee pain are a disabling feature of knee osteoarthritis that can occur at all stages of the disease, including prior to clinical diagnosis. There is a need for a fast-acting analgesic designed for short-term use with minimal side effects to provide pain relief during these flares. This was the motivation for developing Flarin, a lipid formulation soft-gel capsule of ibuprofen that is effective at less-than-standard doses of the conventional NSAID, she explained at the World Congress on Osteoarthritis.

[email protected]

MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.

The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.

Courtesy of EULAR

Courtesy of EULAR

Courtesy of EULAR

• Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
• An alternative treatment target for PsA may be low or minimal disease activity.
• Measure disease activity by clinical signs and symptoms and by acute phase reactants.
• Once a treatment target is reached it should be maintained.

The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.

Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.

[email protected]

On Twitter @mitchelzoler

MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.

The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.

Courtesy of EULAR

Courtesy of EULAR

Courtesy of EULAR

• Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
• An alternative treatment target for PsA may be low or minimal disease activity.
• Measure disease activity by clinical signs and symptoms and by acute phase reactants.
• Once a treatment target is reached it should be maintained.

The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.

Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.

[email protected]

On Twitter @mitchelzoler

MADRID – The newly revised recommendations from an unaffiliated, international expert panel on a treat-to-target approach for axial spondyloarthritis and psoriatic arthritis has one conspicuous feature that the prior recommendations lacked: evidence.

The first treat-to-target recommendations for spondyloarthritis (SpA) and psoriatic arthritis (PsA) from 2013 were based entirely on expert opinion (Ann Rheum Dis. 2014 Jan;73[1]:6-16), but in the new update 4 of the 11 recommendations now have an evidence base as well as a fifth recommendation for the part that pertains to PsA, Désirée van der Heijde, MD, said at the European Congress of Rheumatology.

Courtesy of EULAR

Courtesy of EULAR

Courtesy of EULAR

• Define clinical remission or minimal disease as the absence of clinical and laboratory evidence of significant disease activity.
• An alternative treatment target for PsA may be low or minimal disease activity.
• Measure disease activity by clinical signs and symptoms and by acute phase reactants.
• Once a treatment target is reached it should be maintained.

The task force also outlined “an extensive research agenda” where evidence is needed, specifying close to 50 individual research topics. Among them Dr. van der Heijde particularly called out the role of the Health Assessment Questionnaire (HAQ), validation of PsA target outcomes, and better parsing of the differences using remission or low disease activity as the treatment target.

Dr. van der Heijde, Dr. Dougados, and Dr. Braun are all consultants for several drug companies.

[email protected]

On Twitter @mitchelzoler

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.” 

Mantle cell lymphoma

LUGANO, SWITZERLAND—A chemotherapy-free combination regimen has demonstrated “favorable” safety and efficacy in patients with advanced chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), according to researchers.

They found that treatment with ublituximab, umbralisib, and ibrutinib produced responses in patients with CLL/SLL, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL).

Many of these patients are still receiving the combination, some of them beyond 1 year, said Lorretta Nastoupil, MD, of MD Anderson Cancer Center in Houston, Texas.

She presented results with the treatment at the 14th International Conference on Malignant Lymphoma (ICML).

The research was sponsored by TG Therapeutics, the company developing ublituximab (TG-1101) and umbralisib (TGR-1202).

Patients and treatment

Dr Nastoupil presented data on 38 patients—20 with CLL/SLL, and 18 with NHL. Three of the CLL/SLL patients were treatment-naïve. The rest had relapsed/refractory disease.

All NHL patients had relapsed/refractory disease—6 with DLBCL, 6 with FL, 4 with MCL, and 2 with MZL.

For the entire cohort, the median age was 65 (range, 32-85), and most patients (n=29) were male. They had received a median of 3 prior treatment regimens (range, 0-6).

In this trial, the patients received:

• Ublituximab at 900 mg
• Ibrutinib at 420 mg (CLL/SLL) or 560 mg (NHL)
• Umbralisib at 400 mg, 600 mg, or 800 mg.

Eighty-one percent of patients have been on study for more than 6 months. The median time on study is 11.1 months (range, 0.4 to 30+ months).

Safety

There was 1 dose-limiting toxicity in the CLL cohort (umbralisib at 400 mg)—reactivated varicella zoster. And 2 patients discontinued treatment due to an adverse event (AE)—1 due to sepsis and 1 due to pneumonia.

Neutropenia (18%) and pneumonia (11%) were the only grade 3/4 AEs that occurred in more than 10% of patients. Other grade 3/4 AEs included thrombocytopenia (8%), diarrhea (3%), dizziness (3%), pyrexia (3%), rash (3%), anemia (3%), dyspnea (3%), and stomatitis (3%).

The most common AEs of any grade were diarrhea (47%), fatigue (47%), dizziness (37%), insomnia (34%), nausea (34%), neutropenia (32%), cough (32%), and infusion-related reactions (32%).

Efficacy

Thirty-six patients were evaluable for efficacy—19 with CLL/SLL and 17 with NHL patients. Two patients discontinued treatment before the first efficacy assessment—1 due to pneumonia and 1 at investigator discretion.

For the entire cohort, the overall response rate (ORR) was 83%.

In the CLL/SLL cohort, the ORR was 100% (19/19), and the complete response (CR) rate was 32% (n=6). However, 4 of the 6 CRs are pending bone marrow confirmation.

Dr Nastoupil noted that 8 of the CLL patients had a 17p and/or 11q deletion, and 3 had previously received treatment with a BTK and/or PI3Kδ inhibitor.

One patient who was refractory to both idelalisib and ibrutinib achieved a CR with the triplet regimen, and this response has been ongoing for more than 1.5 years.

Among patients with NHL, the ORR was 100% in patients with MZL (2/2) and MCL (4/4). The ORR was 80% (4/5) in FL patients, and 17% (1/6) in DLBCL patients.

The CR rate was 50% in patients with MZL (1/2) and MCL (2/4) and 20% in patients with FL (1/5).

Dr Nastoupil pointed out that the FL patients were heavily pretreated. Two of them had received an autologous stem cell transplant, 1 was refractory to prior ibrutinib treatment, and 1 had received 5 prior lines of rituximab-based therapy.

She also noted that the DLBCL patients had a median of 4 prior therapies, and 4 of these patients had non-GCB DLBCL, including the only patient who responded to the triplet.

“[T]he combination of ublituximab, umbralisib, and ibrutinib in advanced CLL and NHL demonstrated a favorable toxicity profile as well as favorable efficacy,” Dr Nastoupil said in closing.

“[This] suggests umbralisib may be safely combined with other targeted agents to overcome mechanisms of resistance.”