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Cognitive impairment in HSCT recipients
New research suggests the risk of cognitive impairment after hematopoietic stem cell transplant (HSCT) is greatest among recipients of myeloablative allogeneic (allo) HSCTs.
Compared to healthy controls, patients who received myeloablative allo-HSCT had a significantly higher risk of global cognitive deficit at a few time points after transplant.
There was a trend toward increased global cognitive deficit in recipients of allo-HSCT who had reduced-intensity conditioning (RIC), but there was no increased risk of global cognitive deficit in recipients of autologous (auto) HSCT.
Researchers reported these findings in the Journal of Clinical Oncology.
“With this research from our longitudinal prospective assessment, we are able to deduce that a significant population of allogeneic [HSCT] survivors will experience cognitive impairment that can and will impact different aspects of their lives moving forward,” said study author Noha Sharafeldin, MD, PhD, of the University of Alabama at Birmingham.
“And it’s critical that we as clinicians develop interventions for these patients. This research is just the beginning of our figuring out how we can best care for [HSCT] survivors and enable them to live healthy lives.”
This study included 477 patients who underwent HSCT between 2004 and 2014. There were 236 auto-HSCTs, 128 RIC allo-HSCTs, and 113 myeloablative allo-HSCTs.
Patients underwent standardized neuropsychological testing before HSCT as well as at 6 months, 1 year, 2 years, and 3 years after transplant.
There were 429 patients who completed pre-HSCT testing (89.9%), 341 (81.6%) who underwent testing at 6 months after HSCT, 308 (81.5%) at 1 year, 247 (80.7%) at 2 years, and 227 (81.4%) at 3 years.
Testing was conducted on 8 cognitive domains—executive function, verbal fluency and speed, processing speed, working memory, visual and auditory memory, and fine motor dexterity.
The researchers conducted this testing in 99 healthy control subjects as well.
Before and after HSCT
Prior to HSCT, there were no significant differences in the cognitive domains tested between auto-HSCT recipients and controls or between RIC allo-HSCT recipients and controls.
Recipients of myeloablative allo-HSCT had significantly lower pre-HSCT scores for processing speed (P=0.001), as compared to controls.
After HSCT, there were no significant differences in overall scores between auto-HSCT recipients and controls or between RIC allo-HSCT recipients and controls.
However, recipients of myeloablative allo-HSCT had significantly lower scores than controls for executive function, verbal speed, processing speed, auditory memory, and fine motor dexterity (P≤0.003 for all).
Outcomes over time
For auto-HSCT recipients, there was a significant improvement from pre-HSCT to 6 months post-HSCT in verbal fluency (P<0.001). Meanwhile, there was a significant decrease in verbal processing and fine motor dexterity (P<0.001 for both).
At 3 years, auto-HSCT recipients had a significant increase in verbal fluency (P<0.001) but a significant decrease in visual memory (P=0.001) and fine motor dexterity (P<0.001).
For RIC allo-HSCT recipients, there was a significant decrease from pre-HSCT to 3 years post-HSCT in executive functioning (P=0.003), verbal fluency (P<0.001), and working memory (P<0.001). There were no significant differences between pre-HSCT and 6-month scores.
For patients who received myeloablative allo-HSCT, the only significant difference from pre-HSCT to 6 months or 3 years was a decrease in fine motor dexterity (P<0.001 for both time points).
Global cognitive deficit
There was no significant difference in the prevalence of global cognitive deficit between auto-HSCT recipients and controls before HSCT (22.5% vs 17.2%; P=0.28) or at any time point after—6 months (26.1% vs 16.5%; P=0.07), 1 year (21.4% vs 19.5%; P=0.73), 2 years (21.1% vs 16.4%; P=0.43), and 3 years (18.7% vs 8.7%, P=0.11).
There was no significant difference in the prevalence of global cognitive deficit between RIC allo-HSCT recipients and controls before HSCT (17.2% for both; P=1.0), at 6 months (22.0% vs 16.5%; P=0.35), 1 year (24.1% vs 19.5%; P=0.46), or 2 years (30.6% vs 16.4%; P=0.05) after HSCT.
However, the prevalence was significantly higher for RIC allo-HSCT recipients 3 years after HSCT (35.4% vs 8.7%; P=0.0012).
There was no significant difference in the prevalence of global cognitive deficit between myeloablative allo-HSCT recipients and controls before HSCT (22.3% vs 17.2%; P=0.37) or at 1 year after (28.4% vs 19.5%; P=0.20).
However, the prevalence was significantly higher for myeloablative allo-HSCT recipients at 6 months (31.1% vs 16.5%; P=0.03), 2 years (34.6% vs 16.4%; P=0.02), and 3 years after HSCT (36.0% vs 8.7%; P=0.0015).
“From this data, it’s clear that we have to make strides in supporting allogeneic [HSCT] recipients in their recovery to ensure that we are educating patients and their families on signs of cognitive impairment,” Dr Sharafeldin said. “This data will help us identify patients at highest risk of cognitive impairment and inform the development of interventions that facilitate a patient’s recovery and return to normal life.”
New research suggests the risk of cognitive impairment after hematopoietic stem cell transplant (HSCT) is greatest among recipients of myeloablative allogeneic (allo) HSCTs.
Compared to healthy controls, patients who received myeloablative allo-HSCT had a significantly higher risk of global cognitive deficit at a few time points after transplant.
There was a trend toward increased global cognitive deficit in recipients of allo-HSCT who had reduced-intensity conditioning (RIC), but there was no increased risk of global cognitive deficit in recipients of autologous (auto) HSCT.
Researchers reported these findings in the Journal of Clinical Oncology.
“With this research from our longitudinal prospective assessment, we are able to deduce that a significant population of allogeneic [HSCT] survivors will experience cognitive impairment that can and will impact different aspects of their lives moving forward,” said study author Noha Sharafeldin, MD, PhD, of the University of Alabama at Birmingham.
“And it’s critical that we as clinicians develop interventions for these patients. This research is just the beginning of our figuring out how we can best care for [HSCT] survivors and enable them to live healthy lives.”
This study included 477 patients who underwent HSCT between 2004 and 2014. There were 236 auto-HSCTs, 128 RIC allo-HSCTs, and 113 myeloablative allo-HSCTs.
Patients underwent standardized neuropsychological testing before HSCT as well as at 6 months, 1 year, 2 years, and 3 years after transplant.
There were 429 patients who completed pre-HSCT testing (89.9%), 341 (81.6%) who underwent testing at 6 months after HSCT, 308 (81.5%) at 1 year, 247 (80.7%) at 2 years, and 227 (81.4%) at 3 years.
Testing was conducted on 8 cognitive domains—executive function, verbal fluency and speed, processing speed, working memory, visual and auditory memory, and fine motor dexterity.
The researchers conducted this testing in 99 healthy control subjects as well.
Before and after HSCT
Prior to HSCT, there were no significant differences in the cognitive domains tested between auto-HSCT recipients and controls or between RIC allo-HSCT recipients and controls.
Recipients of myeloablative allo-HSCT had significantly lower pre-HSCT scores for processing speed (P=0.001), as compared to controls.
After HSCT, there were no significant differences in overall scores between auto-HSCT recipients and controls or between RIC allo-HSCT recipients and controls.
However, recipients of myeloablative allo-HSCT had significantly lower scores than controls for executive function, verbal speed, processing speed, auditory memory, and fine motor dexterity (P≤0.003 for all).
Outcomes over time
For auto-HSCT recipients, there was a significant improvement from pre-HSCT to 6 months post-HSCT in verbal fluency (P<0.001). Meanwhile, there was a significant decrease in verbal processing and fine motor dexterity (P<0.001 for both).
At 3 years, auto-HSCT recipients had a significant increase in verbal fluency (P<0.001) but a significant decrease in visual memory (P=0.001) and fine motor dexterity (P<0.001).
For RIC allo-HSCT recipients, there was a significant decrease from pre-HSCT to 3 years post-HSCT in executive functioning (P=0.003), verbal fluency (P<0.001), and working memory (P<0.001). There were no significant differences between pre-HSCT and 6-month scores.
For patients who received myeloablative allo-HSCT, the only significant difference from pre-HSCT to 6 months or 3 years was a decrease in fine motor dexterity (P<0.001 for both time points).
Global cognitive deficit
There was no significant difference in the prevalence of global cognitive deficit between auto-HSCT recipients and controls before HSCT (22.5% vs 17.2%; P=0.28) or at any time point after—6 months (26.1% vs 16.5%; P=0.07), 1 year (21.4% vs 19.5%; P=0.73), 2 years (21.1% vs 16.4%; P=0.43), and 3 years (18.7% vs 8.7%, P=0.11).
There was no significant difference in the prevalence of global cognitive deficit between RIC allo-HSCT recipients and controls before HSCT (17.2% for both; P=1.0), at 6 months (22.0% vs 16.5%; P=0.35), 1 year (24.1% vs 19.5%; P=0.46), or 2 years (30.6% vs 16.4%; P=0.05) after HSCT.
However, the prevalence was significantly higher for RIC allo-HSCT recipients 3 years after HSCT (35.4% vs 8.7%; P=0.0012).
There was no significant difference in the prevalence of global cognitive deficit between myeloablative allo-HSCT recipients and controls before HSCT (22.3% vs 17.2%; P=0.37) or at 1 year after (28.4% vs 19.5%; P=0.20).
However, the prevalence was significantly higher for myeloablative allo-HSCT recipients at 6 months (31.1% vs 16.5%; P=0.03), 2 years (34.6% vs 16.4%; P=0.02), and 3 years after HSCT (36.0% vs 8.7%; P=0.0015).
“From this data, it’s clear that we have to make strides in supporting allogeneic [HSCT] recipients in their recovery to ensure that we are educating patients and their families on signs of cognitive impairment,” Dr Sharafeldin said. “This data will help us identify patients at highest risk of cognitive impairment and inform the development of interventions that facilitate a patient’s recovery and return to normal life.”
New research suggests the risk of cognitive impairment after hematopoietic stem cell transplant (HSCT) is greatest among recipients of myeloablative allogeneic (allo) HSCTs.
Compared to healthy controls, patients who received myeloablative allo-HSCT had a significantly higher risk of global cognitive deficit at a few time points after transplant.
There was a trend toward increased global cognitive deficit in recipients of allo-HSCT who had reduced-intensity conditioning (RIC), but there was no increased risk of global cognitive deficit in recipients of autologous (auto) HSCT.
Researchers reported these findings in the Journal of Clinical Oncology.
“With this research from our longitudinal prospective assessment, we are able to deduce that a significant population of allogeneic [HSCT] survivors will experience cognitive impairment that can and will impact different aspects of their lives moving forward,” said study author Noha Sharafeldin, MD, PhD, of the University of Alabama at Birmingham.
“And it’s critical that we as clinicians develop interventions for these patients. This research is just the beginning of our figuring out how we can best care for [HSCT] survivors and enable them to live healthy lives.”
This study included 477 patients who underwent HSCT between 2004 and 2014. There were 236 auto-HSCTs, 128 RIC allo-HSCTs, and 113 myeloablative allo-HSCTs.
Patients underwent standardized neuropsychological testing before HSCT as well as at 6 months, 1 year, 2 years, and 3 years after transplant.
There were 429 patients who completed pre-HSCT testing (89.9%), 341 (81.6%) who underwent testing at 6 months after HSCT, 308 (81.5%) at 1 year, 247 (80.7%) at 2 years, and 227 (81.4%) at 3 years.
Testing was conducted on 8 cognitive domains—executive function, verbal fluency and speed, processing speed, working memory, visual and auditory memory, and fine motor dexterity.
The researchers conducted this testing in 99 healthy control subjects as well.
Before and after HSCT
Prior to HSCT, there were no significant differences in the cognitive domains tested between auto-HSCT recipients and controls or between RIC allo-HSCT recipients and controls.
Recipients of myeloablative allo-HSCT had significantly lower pre-HSCT scores for processing speed (P=0.001), as compared to controls.
After HSCT, there were no significant differences in overall scores between auto-HSCT recipients and controls or between RIC allo-HSCT recipients and controls.
However, recipients of myeloablative allo-HSCT had significantly lower scores than controls for executive function, verbal speed, processing speed, auditory memory, and fine motor dexterity (P≤0.003 for all).
Outcomes over time
For auto-HSCT recipients, there was a significant improvement from pre-HSCT to 6 months post-HSCT in verbal fluency (P<0.001). Meanwhile, there was a significant decrease in verbal processing and fine motor dexterity (P<0.001 for both).
At 3 years, auto-HSCT recipients had a significant increase in verbal fluency (P<0.001) but a significant decrease in visual memory (P=0.001) and fine motor dexterity (P<0.001).
For RIC allo-HSCT recipients, there was a significant decrease from pre-HSCT to 3 years post-HSCT in executive functioning (P=0.003), verbal fluency (P<0.001), and working memory (P<0.001). There were no significant differences between pre-HSCT and 6-month scores.
For patients who received myeloablative allo-HSCT, the only significant difference from pre-HSCT to 6 months or 3 years was a decrease in fine motor dexterity (P<0.001 for both time points).
Global cognitive deficit
There was no significant difference in the prevalence of global cognitive deficit between auto-HSCT recipients and controls before HSCT (22.5% vs 17.2%; P=0.28) or at any time point after—6 months (26.1% vs 16.5%; P=0.07), 1 year (21.4% vs 19.5%; P=0.73), 2 years (21.1% vs 16.4%; P=0.43), and 3 years (18.7% vs 8.7%, P=0.11).
There was no significant difference in the prevalence of global cognitive deficit between RIC allo-HSCT recipients and controls before HSCT (17.2% for both; P=1.0), at 6 months (22.0% vs 16.5%; P=0.35), 1 year (24.1% vs 19.5%; P=0.46), or 2 years (30.6% vs 16.4%; P=0.05) after HSCT.
However, the prevalence was significantly higher for RIC allo-HSCT recipients 3 years after HSCT (35.4% vs 8.7%; P=0.0012).
There was no significant difference in the prevalence of global cognitive deficit between myeloablative allo-HSCT recipients and controls before HSCT (22.3% vs 17.2%; P=0.37) or at 1 year after (28.4% vs 19.5%; P=0.20).
However, the prevalence was significantly higher for myeloablative allo-HSCT recipients at 6 months (31.1% vs 16.5%; P=0.03), 2 years (34.6% vs 16.4%; P=0.02), and 3 years after HSCT (36.0% vs 8.7%; P=0.0015).
“From this data, it’s clear that we have to make strides in supporting allogeneic [HSCT] recipients in their recovery to ensure that we are educating patients and their families on signs of cognitive impairment,” Dr Sharafeldin said. “This data will help us identify patients at highest risk of cognitive impairment and inform the development of interventions that facilitate a patient’s recovery and return to normal life.”
AYA cancer patients lost to follow-up
ORLANDO—Many adolescent and young adult (AYA) cancer survivors don’t continue with follow-up care, according to a new study.
Researchers analyzed nearly 2400 AYAs diagnosed with cancer between 2000 and 2015 and found that 37% of these patients had no follow-up visits since 2015.
The proportion of patients with follow-up visits in 2016 did not vary according to cancer type or insurance status, but it did vary according to patients’ time since last cancer treatment.
These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 29).
“Many adolescents and young adults are unaware of what their long-term risks are after they have finished their cancer treatment,” said study investigator Lynda M. Beaupin, MD, of the Roswell Park Cancer Institute in Buffalo, New York.
“Doctors and other healthcare providers need to be more diligent in letting these patients know about future potential side effects and health risks that could occur based on certain aspects of their cancer treatment.”
In a previous study, Dr Beaupin and her colleagues conducted a focus group discussion with 27 AYAs, ages 18 to 39, to query them about the major barriers that prevented them from seeking follow-up care.
Among the factors mentioned were poor communication with their oncologists, ongoing problems in adjusting to life as a cancer survivor, and loss of health insurance.
As a follow-up to that focus group session, the investigators looked at a larger group of AYAs who were treated at Roswell Park Comprehensive Cancer Center.
The team analyzed data from the cancer center’s tumor registry, which included information on a patient’s current age, age at cancer diagnosis, gender, date of diagnosis, date of most recent doctor visit, and type of cancer.
The investigators also looked at patient-provided information on follow-up doctor appointments and insurance status for 2 cohorts of AYA cancer survivors. Patients in cohort A were diagnosed with cancer between 2010 and 2014, and patients in cohort B were diagnosed between 2005 and 2009.
The most common types of cancer were leukemia/lymphoma, melanoma, germ cell tumors, and thyroid and breast cancers.
Findings
There were 2367 patients, ages 18 to 39, who were diagnosed with cancer between 2000 and 2015.
Thirty-seven percent of these patients did not have a follow-up visit since 2015.
There was no difference in follow-up contact according to cancer type or insurance status. However, length of time since patients’ final cancer treatment was a factor in not scheduling a follow-up appointment.
Regardless of insurance status, 33% of cohort A (diagnosed 2010-2014) and 48% of cohort B (diagnosed 2005-2009) did not have a follow-up visit in 2016.
Among insured patients, 33% of those in cohort A and 47% of those in cohort B did not have a visit in 2016. Among uninsured patients, the percentages were 39% and 46%, respectively.
Next steps
The investigators hope to conduct future studies looking at other factors that may affect AYAs’ willingness to seek follow-up care, such as employment status, distance to a cancer center, whether they are getting tested or treated at a facility other than a cancer center, and how AYAs perceive their current quality of life.
“These patients have the potential to live a normal lifespan, and we need to educate them to become their own advocates so they may receive follow-up care on a regular basis,” Dr Beaupin said.
“We hope they continue to receive that follow-up at an established cancer center that has the facilities to assess cardiac health and provide rehabilitation if needed. There are now established survivorship programs nationwide that can provide follow-up care for those who have completed treatment.”
This study was supported by the National Cancer Institute.
ORLANDO—Many adolescent and young adult (AYA) cancer survivors don’t continue with follow-up care, according to a new study.
Researchers analyzed nearly 2400 AYAs diagnosed with cancer between 2000 and 2015 and found that 37% of these patients had no follow-up visits since 2015.
The proportion of patients with follow-up visits in 2016 did not vary according to cancer type or insurance status, but it did vary according to patients’ time since last cancer treatment.
These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 29).
“Many adolescents and young adults are unaware of what their long-term risks are after they have finished their cancer treatment,” said study investigator Lynda M. Beaupin, MD, of the Roswell Park Cancer Institute in Buffalo, New York.
“Doctors and other healthcare providers need to be more diligent in letting these patients know about future potential side effects and health risks that could occur based on certain aspects of their cancer treatment.”
In a previous study, Dr Beaupin and her colleagues conducted a focus group discussion with 27 AYAs, ages 18 to 39, to query them about the major barriers that prevented them from seeking follow-up care.
Among the factors mentioned were poor communication with their oncologists, ongoing problems in adjusting to life as a cancer survivor, and loss of health insurance.
As a follow-up to that focus group session, the investigators looked at a larger group of AYAs who were treated at Roswell Park Comprehensive Cancer Center.
The team analyzed data from the cancer center’s tumor registry, which included information on a patient’s current age, age at cancer diagnosis, gender, date of diagnosis, date of most recent doctor visit, and type of cancer.
The investigators also looked at patient-provided information on follow-up doctor appointments and insurance status for 2 cohorts of AYA cancer survivors. Patients in cohort A were diagnosed with cancer between 2010 and 2014, and patients in cohort B were diagnosed between 2005 and 2009.
The most common types of cancer were leukemia/lymphoma, melanoma, germ cell tumors, and thyroid and breast cancers.
Findings
There were 2367 patients, ages 18 to 39, who were diagnosed with cancer between 2000 and 2015.
Thirty-seven percent of these patients did not have a follow-up visit since 2015.
There was no difference in follow-up contact according to cancer type or insurance status. However, length of time since patients’ final cancer treatment was a factor in not scheduling a follow-up appointment.
Regardless of insurance status, 33% of cohort A (diagnosed 2010-2014) and 48% of cohort B (diagnosed 2005-2009) did not have a follow-up visit in 2016.
Among insured patients, 33% of those in cohort A and 47% of those in cohort B did not have a visit in 2016. Among uninsured patients, the percentages were 39% and 46%, respectively.
Next steps
The investigators hope to conduct future studies looking at other factors that may affect AYAs’ willingness to seek follow-up care, such as employment status, distance to a cancer center, whether they are getting tested or treated at a facility other than a cancer center, and how AYAs perceive their current quality of life.
“These patients have the potential to live a normal lifespan, and we need to educate them to become their own advocates so they may receive follow-up care on a regular basis,” Dr Beaupin said.
“We hope they continue to receive that follow-up at an established cancer center that has the facilities to assess cardiac health and provide rehabilitation if needed. There are now established survivorship programs nationwide that can provide follow-up care for those who have completed treatment.”
This study was supported by the National Cancer Institute.
ORLANDO—Many adolescent and young adult (AYA) cancer survivors don’t continue with follow-up care, according to a new study.
Researchers analyzed nearly 2400 AYAs diagnosed with cancer between 2000 and 2015 and found that 37% of these patients had no follow-up visits since 2015.
The proportion of patients with follow-up visits in 2016 did not vary according to cancer type or insurance status, but it did vary according to patients’ time since last cancer treatment.
These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 29).
“Many adolescents and young adults are unaware of what their long-term risks are after they have finished their cancer treatment,” said study investigator Lynda M. Beaupin, MD, of the Roswell Park Cancer Institute in Buffalo, New York.
“Doctors and other healthcare providers need to be more diligent in letting these patients know about future potential side effects and health risks that could occur based on certain aspects of their cancer treatment.”
In a previous study, Dr Beaupin and her colleagues conducted a focus group discussion with 27 AYAs, ages 18 to 39, to query them about the major barriers that prevented them from seeking follow-up care.
Among the factors mentioned were poor communication with their oncologists, ongoing problems in adjusting to life as a cancer survivor, and loss of health insurance.
As a follow-up to that focus group session, the investigators looked at a larger group of AYAs who were treated at Roswell Park Comprehensive Cancer Center.
The team analyzed data from the cancer center’s tumor registry, which included information on a patient’s current age, age at cancer diagnosis, gender, date of diagnosis, date of most recent doctor visit, and type of cancer.
The investigators also looked at patient-provided information on follow-up doctor appointments and insurance status for 2 cohorts of AYA cancer survivors. Patients in cohort A were diagnosed with cancer between 2010 and 2014, and patients in cohort B were diagnosed between 2005 and 2009.
The most common types of cancer were leukemia/lymphoma, melanoma, germ cell tumors, and thyroid and breast cancers.
Findings
There were 2367 patients, ages 18 to 39, who were diagnosed with cancer between 2000 and 2015.
Thirty-seven percent of these patients did not have a follow-up visit since 2015.
There was no difference in follow-up contact according to cancer type or insurance status. However, length of time since patients’ final cancer treatment was a factor in not scheduling a follow-up appointment.
Regardless of insurance status, 33% of cohort A (diagnosed 2010-2014) and 48% of cohort B (diagnosed 2005-2009) did not have a follow-up visit in 2016.
Among insured patients, 33% of those in cohort A and 47% of those in cohort B did not have a visit in 2016. Among uninsured patients, the percentages were 39% and 46%, respectively.
Next steps
The investigators hope to conduct future studies looking at other factors that may affect AYAs’ willingness to seek follow-up care, such as employment status, distance to a cancer center, whether they are getting tested or treated at a facility other than a cancer center, and how AYAs perceive their current quality of life.
“These patients have the potential to live a normal lifespan, and we need to educate them to become their own advocates so they may receive follow-up care on a regular basis,” Dr Beaupin said.
“We hope they continue to receive that follow-up at an established cancer center that has the facilities to assess cardiac health and provide rehabilitation if needed. There are now established survivorship programs nationwide that can provide follow-up care for those who have completed treatment.”
This study was supported by the National Cancer Institute.
Intervention helps kids stay active after cancer treatment
ORLANDO—Results of a pilot study suggest a web-based, reward-driven intervention can motivate adolescent cancer survivors to stay physically active.
Time spent performing moderate-to-vigorous physical activity (MVPA) increased by an average of 5 minutes a week for subjects who were randomized to the intervention.
For control subjects, MVPA decreased by an average of 24 minutes a week.
These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 102).
“Compared to the general population, childhood cancer survivors have an increased risk for obesity and metabolic syndrome, conditions that can lead to heart disease, stroke, and diabetes, so it is really important that they are physically active,” said study investigator Carrie R. Howell, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“By intervening in this young age group, we hope to help kids develop healthy exercise habits for life.”
Dr Howell and her colleagues studied cancer survivors, ages 11 to 15, who were no longer receiving cancer treatment and were physically active less than 60 minutes a day.
The subjects were randomized to the intervention or to a control group. Controls received a wearable activity monitor and an educational handout with information about the importance of physical activity and examples of activities.
The intervention group received the handout and activity monitor but also had access to an interactive website. On at least a weekly basis, subjects would connect their monitor to a computer and log their activity through the website. Upon achieving certain thresholds of activity, they received rewards, such as T-shirts and gift cards by mail.
At the beginning and end of the study, participants visited St. Jude for an assessment of their physical fitness (strength, flexibility, and endurance) and neurocognitive measures (attention and memory), as well as health-related quality of life (assessed using the Pediatric Quality of Life Inventory questionnaire).
Results
Seventy-eight cancer survivors completed the 24-week study, 53 of them in the intervention group and 25 in the control group.
MVPA increased by an average of 4.7 minutes per week in the intervention group and decreased by an average of 24.3 minutes per week in the control group.
“In this age group, it is common to see a decrease in physical activity over time, even among healthy kids,” Dr Howell said. “Therefore, we are encouraged that our intervention was successful at maintaining physical activity levels, but a longer program may be needed to create lasting exercise habits.”
In addition to increases in MVPA, the intervention group had the following improvements in fitness:
- Increase in hand grip strength from an average of 19.9 kg to 21.0 kg
- Increase in number of push-ups from an average of 15 to 18
- Increase in number of sit-ups from an average of 11 to 14.
Furthermore, subjects in the intervention group saw their verbal fluency z-score increase by an average of 0.13 points and their general cognition z-score increase by an average of 0.23 points.
Their quality of life scores increased as well. Both overall quality of life and physical-function-related quality of life scores increased from an average of 74.2 to 78.0.
Control subjects had no significant changes in fitness, neurocognitive measures, or quality of life.
This study was supported by the National Cancer Institute, the American Lebanese Syrian Associated Charities, and HopeLab.
Based on the results of this study, the investigators have designed a larger trial (ALTE1631) to test a web-based physical activity intervention. They hope to enroll 384 survivors of childhood acute lymphoblastic leukemia at institutions across the US. The intervention will last a year, with follow-up at 18 months.
Further down the line, the investigators plan to explore the relationship between physical activity and cognition.
ORLANDO—Results of a pilot study suggest a web-based, reward-driven intervention can motivate adolescent cancer survivors to stay physically active.
Time spent performing moderate-to-vigorous physical activity (MVPA) increased by an average of 5 minutes a week for subjects who were randomized to the intervention.
For control subjects, MVPA decreased by an average of 24 minutes a week.
These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 102).
“Compared to the general population, childhood cancer survivors have an increased risk for obesity and metabolic syndrome, conditions that can lead to heart disease, stroke, and diabetes, so it is really important that they are physically active,” said study investigator Carrie R. Howell, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“By intervening in this young age group, we hope to help kids develop healthy exercise habits for life.”
Dr Howell and her colleagues studied cancer survivors, ages 11 to 15, who were no longer receiving cancer treatment and were physically active less than 60 minutes a day.
The subjects were randomized to the intervention or to a control group. Controls received a wearable activity monitor and an educational handout with information about the importance of physical activity and examples of activities.
The intervention group received the handout and activity monitor but also had access to an interactive website. On at least a weekly basis, subjects would connect their monitor to a computer and log their activity through the website. Upon achieving certain thresholds of activity, they received rewards, such as T-shirts and gift cards by mail.
At the beginning and end of the study, participants visited St. Jude for an assessment of their physical fitness (strength, flexibility, and endurance) and neurocognitive measures (attention and memory), as well as health-related quality of life (assessed using the Pediatric Quality of Life Inventory questionnaire).
Results
Seventy-eight cancer survivors completed the 24-week study, 53 of them in the intervention group and 25 in the control group.
MVPA increased by an average of 4.7 minutes per week in the intervention group and decreased by an average of 24.3 minutes per week in the control group.
“In this age group, it is common to see a decrease in physical activity over time, even among healthy kids,” Dr Howell said. “Therefore, we are encouraged that our intervention was successful at maintaining physical activity levels, but a longer program may be needed to create lasting exercise habits.”
In addition to increases in MVPA, the intervention group had the following improvements in fitness:
- Increase in hand grip strength from an average of 19.9 kg to 21.0 kg
- Increase in number of push-ups from an average of 15 to 18
- Increase in number of sit-ups from an average of 11 to 14.
Furthermore, subjects in the intervention group saw their verbal fluency z-score increase by an average of 0.13 points and their general cognition z-score increase by an average of 0.23 points.
Their quality of life scores increased as well. Both overall quality of life and physical-function-related quality of life scores increased from an average of 74.2 to 78.0.
Control subjects had no significant changes in fitness, neurocognitive measures, or quality of life.
This study was supported by the National Cancer Institute, the American Lebanese Syrian Associated Charities, and HopeLab.
Based on the results of this study, the investigators have designed a larger trial (ALTE1631) to test a web-based physical activity intervention. They hope to enroll 384 survivors of childhood acute lymphoblastic leukemia at institutions across the US. The intervention will last a year, with follow-up at 18 months.
Further down the line, the investigators plan to explore the relationship between physical activity and cognition.
ORLANDO—Results of a pilot study suggest a web-based, reward-driven intervention can motivate adolescent cancer survivors to stay physically active.
Time spent performing moderate-to-vigorous physical activity (MVPA) increased by an average of 5 minutes a week for subjects who were randomized to the intervention.
For control subjects, MVPA decreased by an average of 24 minutes a week.
These findings were presented at the 2018 Cancer Survivorship Symposium (abstract 102).
“Compared to the general population, childhood cancer survivors have an increased risk for obesity and metabolic syndrome, conditions that can lead to heart disease, stroke, and diabetes, so it is really important that they are physically active,” said study investigator Carrie R. Howell, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“By intervening in this young age group, we hope to help kids develop healthy exercise habits for life.”
Dr Howell and her colleagues studied cancer survivors, ages 11 to 15, who were no longer receiving cancer treatment and were physically active less than 60 minutes a day.
The subjects were randomized to the intervention or to a control group. Controls received a wearable activity monitor and an educational handout with information about the importance of physical activity and examples of activities.
The intervention group received the handout and activity monitor but also had access to an interactive website. On at least a weekly basis, subjects would connect their monitor to a computer and log their activity through the website. Upon achieving certain thresholds of activity, they received rewards, such as T-shirts and gift cards by mail.
At the beginning and end of the study, participants visited St. Jude for an assessment of their physical fitness (strength, flexibility, and endurance) and neurocognitive measures (attention and memory), as well as health-related quality of life (assessed using the Pediatric Quality of Life Inventory questionnaire).
Results
Seventy-eight cancer survivors completed the 24-week study, 53 of them in the intervention group and 25 in the control group.
MVPA increased by an average of 4.7 minutes per week in the intervention group and decreased by an average of 24.3 minutes per week in the control group.
“In this age group, it is common to see a decrease in physical activity over time, even among healthy kids,” Dr Howell said. “Therefore, we are encouraged that our intervention was successful at maintaining physical activity levels, but a longer program may be needed to create lasting exercise habits.”
In addition to increases in MVPA, the intervention group had the following improvements in fitness:
- Increase in hand grip strength from an average of 19.9 kg to 21.0 kg
- Increase in number of push-ups from an average of 15 to 18
- Increase in number of sit-ups from an average of 11 to 14.
Furthermore, subjects in the intervention group saw their verbal fluency z-score increase by an average of 0.13 points and their general cognition z-score increase by an average of 0.23 points.
Their quality of life scores increased as well. Both overall quality of life and physical-function-related quality of life scores increased from an average of 74.2 to 78.0.
Control subjects had no significant changes in fitness, neurocognitive measures, or quality of life.
This study was supported by the National Cancer Institute, the American Lebanese Syrian Associated Charities, and HopeLab.
Based on the results of this study, the investigators have designed a larger trial (ALTE1631) to test a web-based physical activity intervention. They hope to enroll 384 survivors of childhood acute lymphoblastic leukemia at institutions across the US. The intervention will last a year, with follow-up at 18 months.
Further down the line, the investigators plan to explore the relationship between physical activity and cognition.
Study reveals lack of sexual aids for cancer survivors
ORLANDO—A new study suggests many US cancer centers do not have therapeutic aids for patients who experience sexual dysfunction after cancer treatment.
Of 25 cancer centers polled, 80% said they had no sexual aids available on site for men, and 64% said they had no such aids for women.
Sharon Bober, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues presented this research at the 2018 Cancer Survivorship Symposium (abstract 134*).
“[P]roviding sexual aids is one step toward treating sexual health like any other aspect of survivorship care,” Dr Bober said.
“It should be no different than providing wigs and head coverings to women who have lost their hair due to chemotherapy. It’s important to give patients the message that regaining sexual health is a perfectly valid and life-affirming aspect of regaining overall quality of life.”
Dr Bober and her colleagues conducted this study to determine the availability of sexual aids at 25 National Cancer Institute-designated cancer centers.
The researchers called these centers posing as a spouse, adult child, or sibling of a patient. The team made separate calls to ask about sexual aids for women and those for men.
Women’s sexual aids
Twenty-four percent of cancer centers (n=6) said they had sexual aids for women, 64% (n=16) did not, and 12% of centers were unreachable (n=3).
The most common aids were personal lubrication, vaginal moisturizer, and vaginal dilators—all of which were available at 5 centers.
Three centers had vibrators, 2 had books/pamphlets, 2 had pelvic floor exercisers, and 2 had product lists.
Men’s sexual aids
Twelve percent of cancer centers (n=3) said they had sexual aids for men, 80% (n=20) did not, and 8% (n=2) were unreachable.
Two centers said they had personal lubrication available for men, 2 had penile support rings, 1 had vacuum erection devices, and 1 had books/pamphlets.
Next steps
Now, Dr Bober and her colleagues hope to query the other 44 National Cancer Institute-designated cancer centers to see what products they are selling and perhaps conduct patient surveys to find out what types of resources are most useful for cancer survivors.
“What we really need to do is go to the centers that are successfully providing sexual health products and find out how they promote and provide resources to their patients,” Dr Bober said.
“We can’t keep the conversation at the 10,000-foot level. We need to talk concretely about how to partner with providers to make sexual health resources, including sexual health aids, available so cancer survivors can get the help that they need.”
*Information presented differs from the abstract.
ORLANDO—A new study suggests many US cancer centers do not have therapeutic aids for patients who experience sexual dysfunction after cancer treatment.
Of 25 cancer centers polled, 80% said they had no sexual aids available on site for men, and 64% said they had no such aids for women.
Sharon Bober, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues presented this research at the 2018 Cancer Survivorship Symposium (abstract 134*).
“[P]roviding sexual aids is one step toward treating sexual health like any other aspect of survivorship care,” Dr Bober said.
“It should be no different than providing wigs and head coverings to women who have lost their hair due to chemotherapy. It’s important to give patients the message that regaining sexual health is a perfectly valid and life-affirming aspect of regaining overall quality of life.”
Dr Bober and her colleagues conducted this study to determine the availability of sexual aids at 25 National Cancer Institute-designated cancer centers.
The researchers called these centers posing as a spouse, adult child, or sibling of a patient. The team made separate calls to ask about sexual aids for women and those for men.
Women’s sexual aids
Twenty-four percent of cancer centers (n=6) said they had sexual aids for women, 64% (n=16) did not, and 12% of centers were unreachable (n=3).
The most common aids were personal lubrication, vaginal moisturizer, and vaginal dilators—all of which were available at 5 centers.
Three centers had vibrators, 2 had books/pamphlets, 2 had pelvic floor exercisers, and 2 had product lists.
Men’s sexual aids
Twelve percent of cancer centers (n=3) said they had sexual aids for men, 80% (n=20) did not, and 8% (n=2) were unreachable.
Two centers said they had personal lubrication available for men, 2 had penile support rings, 1 had vacuum erection devices, and 1 had books/pamphlets.
Next steps
Now, Dr Bober and her colleagues hope to query the other 44 National Cancer Institute-designated cancer centers to see what products they are selling and perhaps conduct patient surveys to find out what types of resources are most useful for cancer survivors.
“What we really need to do is go to the centers that are successfully providing sexual health products and find out how they promote and provide resources to their patients,” Dr Bober said.
“We can’t keep the conversation at the 10,000-foot level. We need to talk concretely about how to partner with providers to make sexual health resources, including sexual health aids, available so cancer survivors can get the help that they need.”
*Information presented differs from the abstract.
ORLANDO—A new study suggests many US cancer centers do not have therapeutic aids for patients who experience sexual dysfunction after cancer treatment.
Of 25 cancer centers polled, 80% said they had no sexual aids available on site for men, and 64% said they had no such aids for women.
Sharon Bober, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues presented this research at the 2018 Cancer Survivorship Symposium (abstract 134*).
“[P]roviding sexual aids is one step toward treating sexual health like any other aspect of survivorship care,” Dr Bober said.
“It should be no different than providing wigs and head coverings to women who have lost their hair due to chemotherapy. It’s important to give patients the message that regaining sexual health is a perfectly valid and life-affirming aspect of regaining overall quality of life.”
Dr Bober and her colleagues conducted this study to determine the availability of sexual aids at 25 National Cancer Institute-designated cancer centers.
The researchers called these centers posing as a spouse, adult child, or sibling of a patient. The team made separate calls to ask about sexual aids for women and those for men.
Women’s sexual aids
Twenty-four percent of cancer centers (n=6) said they had sexual aids for women, 64% (n=16) did not, and 12% of centers were unreachable (n=3).
The most common aids were personal lubrication, vaginal moisturizer, and vaginal dilators—all of which were available at 5 centers.
Three centers had vibrators, 2 had books/pamphlets, 2 had pelvic floor exercisers, and 2 had product lists.
Men’s sexual aids
Twelve percent of cancer centers (n=3) said they had sexual aids for men, 80% (n=20) did not, and 8% (n=2) were unreachable.
Two centers said they had personal lubrication available for men, 2 had penile support rings, 1 had vacuum erection devices, and 1 had books/pamphlets.
Next steps
Now, Dr Bober and her colleagues hope to query the other 44 National Cancer Institute-designated cancer centers to see what products they are selling and perhaps conduct patient surveys to find out what types of resources are most useful for cancer survivors.
“What we really need to do is go to the centers that are successfully providing sexual health products and find out how they promote and provide resources to their patients,” Dr Bober said.
“We can’t keep the conversation at the 10,000-foot level. We need to talk concretely about how to partner with providers to make sexual health resources, including sexual health aids, available so cancer survivors can get the help that they need.”
*Information presented differs from the abstract.
FDA grants ivosidenib NDA priority review
The US Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for ivosidenib, a targeted inhibitor of mutant IDH1.
With this NDA, Agios Pharmaceuticals, Inc., is seeking approval for ivosidenib (formerly AG-120) to treat patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation.
The FDA expects to make a decision on the NDA by August 21, 2018.
The agency aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
Phase 1 data
The priority review for the ivosidenib NDA is based on results from AG120-C-001, a phase 1 trial of patients with advanced hematologic malignancies and an IDH1 mutation. Data from this study were presented at the 2017 ASH Annual Meeting (abstract 725).
This ongoing trial includes a dose-escalation phase and 4 expansion arms. Ivosidenib doses ranged from 200 mg to 1200 mg in the dose-escalation phase. Patients in the dose-expansion arms received a 500 mg daily dose of the drug.
Arm 1 includes IDH1-mutant-positive AML patients who relapsed after bone marrow transplant, were in second or later relapse, were refractory to initial induction or re-induction treatment, or who relapsed within a year of initial treatment, excluding patients with favorable-risk status.
Arms 2, 3 and 4 were not included in the primary efficacy analysis.
The primary analysis set consists of 125 relapsed/refractory AML patients—92 from arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for arm 1 and received ivosidenib at 500 mg once daily.
The median age of these patients was 67 (range, 18-87), and the median number of prior regimens they received was 2 (range, 1-6).
The primary endpoint for these patients is the rate of complete response (CR) and CR with partial hematologic recovery (CRh), which was 30.4%. The CR rate was 21.6% (27/125), and the CRh rate was 8.8% (11/125).
The overall response rate was 41.6% (52/125). The median duration of response was 6.5 months for all patients, 9.3 months for those who achieved a CR, and 8.2 months for those who had a CR/CRh.
At the time of the data cut-off, the median overall survival was 8.8 months. The median overall survival was not reached for patients who achieved a CR/CRh, was 9.3 months for non-CR/CRh responders, and was 3.9 months for non-responders.
There were a few adverse events of interest. Eight percent of patients reported grade 3 or higher leukocytosis, which was managed with hydroxyurea, and none of the cases were fatal.
Eight percent of patients reported grade 3 QT prolongation. Ivosidenib was reduced in 1 patient and held in 5 patients (for any grade of QT prolongation). There were no grade 4 or 5 cases of QT prolongation.
Finally, 9.6% of patients reported IDH-differentiation syndrome, which was managed with corticosteroids and diuretics. None of the cases were grade 4 or 5.
Companion diagnostic
Abbott has submitted a premarket approval application to the FDA for an IDH1 assay to be used on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection.
In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for the development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay is intended to serve as a companion diagnostic for ivosidenib.
The US Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for ivosidenib, a targeted inhibitor of mutant IDH1.
With this NDA, Agios Pharmaceuticals, Inc., is seeking approval for ivosidenib (formerly AG-120) to treat patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation.
The FDA expects to make a decision on the NDA by August 21, 2018.
The agency aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
Phase 1 data
The priority review for the ivosidenib NDA is based on results from AG120-C-001, a phase 1 trial of patients with advanced hematologic malignancies and an IDH1 mutation. Data from this study were presented at the 2017 ASH Annual Meeting (abstract 725).
This ongoing trial includes a dose-escalation phase and 4 expansion arms. Ivosidenib doses ranged from 200 mg to 1200 mg in the dose-escalation phase. Patients in the dose-expansion arms received a 500 mg daily dose of the drug.
Arm 1 includes IDH1-mutant-positive AML patients who relapsed after bone marrow transplant, were in second or later relapse, were refractory to initial induction or re-induction treatment, or who relapsed within a year of initial treatment, excluding patients with favorable-risk status.
Arms 2, 3 and 4 were not included in the primary efficacy analysis.
The primary analysis set consists of 125 relapsed/refractory AML patients—92 from arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for arm 1 and received ivosidenib at 500 mg once daily.
The median age of these patients was 67 (range, 18-87), and the median number of prior regimens they received was 2 (range, 1-6).
The primary endpoint for these patients is the rate of complete response (CR) and CR with partial hematologic recovery (CRh), which was 30.4%. The CR rate was 21.6% (27/125), and the CRh rate was 8.8% (11/125).
The overall response rate was 41.6% (52/125). The median duration of response was 6.5 months for all patients, 9.3 months for those who achieved a CR, and 8.2 months for those who had a CR/CRh.
At the time of the data cut-off, the median overall survival was 8.8 months. The median overall survival was not reached for patients who achieved a CR/CRh, was 9.3 months for non-CR/CRh responders, and was 3.9 months for non-responders.
There were a few adverse events of interest. Eight percent of patients reported grade 3 or higher leukocytosis, which was managed with hydroxyurea, and none of the cases were fatal.
Eight percent of patients reported grade 3 QT prolongation. Ivosidenib was reduced in 1 patient and held in 5 patients (for any grade of QT prolongation). There were no grade 4 or 5 cases of QT prolongation.
Finally, 9.6% of patients reported IDH-differentiation syndrome, which was managed with corticosteroids and diuretics. None of the cases were grade 4 or 5.
Companion diagnostic
Abbott has submitted a premarket approval application to the FDA for an IDH1 assay to be used on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection.
In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for the development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay is intended to serve as a companion diagnostic for ivosidenib.
The US Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for ivosidenib, a targeted inhibitor of mutant IDH1.
With this NDA, Agios Pharmaceuticals, Inc., is seeking approval for ivosidenib (formerly AG-120) to treat patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation.
The FDA expects to make a decision on the NDA by August 21, 2018.
The agency aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
Phase 1 data
The priority review for the ivosidenib NDA is based on results from AG120-C-001, a phase 1 trial of patients with advanced hematologic malignancies and an IDH1 mutation. Data from this study were presented at the 2017 ASH Annual Meeting (abstract 725).
This ongoing trial includes a dose-escalation phase and 4 expansion arms. Ivosidenib doses ranged from 200 mg to 1200 mg in the dose-escalation phase. Patients in the dose-expansion arms received a 500 mg daily dose of the drug.
Arm 1 includes IDH1-mutant-positive AML patients who relapsed after bone marrow transplant, were in second or later relapse, were refractory to initial induction or re-induction treatment, or who relapsed within a year of initial treatment, excluding patients with favorable-risk status.
Arms 2, 3 and 4 were not included in the primary efficacy analysis.
The primary analysis set consists of 125 relapsed/refractory AML patients—92 from arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for arm 1 and received ivosidenib at 500 mg once daily.
The median age of these patients was 67 (range, 18-87), and the median number of prior regimens they received was 2 (range, 1-6).
The primary endpoint for these patients is the rate of complete response (CR) and CR with partial hematologic recovery (CRh), which was 30.4%. The CR rate was 21.6% (27/125), and the CRh rate was 8.8% (11/125).
The overall response rate was 41.6% (52/125). The median duration of response was 6.5 months for all patients, 9.3 months for those who achieved a CR, and 8.2 months for those who had a CR/CRh.
At the time of the data cut-off, the median overall survival was 8.8 months. The median overall survival was not reached for patients who achieved a CR/CRh, was 9.3 months for non-CR/CRh responders, and was 3.9 months for non-responders.
There were a few adverse events of interest. Eight percent of patients reported grade 3 or higher leukocytosis, which was managed with hydroxyurea, and none of the cases were fatal.
Eight percent of patients reported grade 3 QT prolongation. Ivosidenib was reduced in 1 patient and held in 5 patients (for any grade of QT prolongation). There were no grade 4 or 5 cases of QT prolongation.
Finally, 9.6% of patients reported IDH-differentiation syndrome, which was managed with corticosteroids and diuretics. None of the cases were grade 4 or 5.
Companion diagnostic
Abbott has submitted a premarket approval application to the FDA for an IDH1 assay to be used on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection.
In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for the development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay is intended to serve as a companion diagnostic for ivosidenib.
NK-cell therapy in resistant MDS, AML
Results of a phase 1/2 trial suggest treatment with haploidentical natural killer (NK) cells can be effective against relapsed/refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
NK-cell therapy elicited responses in 6 of the 16 patients studied and provided a bridge to transplant for 5 patients.
Three responders were still alive at more than 3 years of follow-up.
There were 4 grade 3 adverse events (AEs) and 2 grade 5 AEs considered possibly or probably related to NK-cell therapy.
Investigators reported these results in Clinical Cancer Research.
The trial enrolled 16 patients. Eight had MDS/AML, 3 had de novo AML, and 5 had high-risk MDS, including refractory anemia with excess blasts (RAEB) type 1 progressing toward type 2, RAEB-2, and chronic myelomonocytic leukemia type 2.
The patients’ median age was 64 (range, 40-70), and they had received a median of 3 prior therapies (range, 1-6). Six patients had received an allogeneic hematopoietic stem cell transplant (HSCT).
For this study, all patients received fludarabine, cyclophosphamide, and total lymphoid irradiation prior to receiving haploidentical NK cells.
The median follow-up was 8 months for all patients and 28 months for responders.
Efficacy
Six patients responded to treatment. One patient with de novo AML had a complete response (CR). Two high-risk MDS patients had a marrow CR (mCR), as did 2 MDS/AML patients. One MDS/AML patient had a partial response (PR).
Two patients had stable disease (SD)—1 with MDS and 1 with MDS/AML. One patient with de novo AML had a morphologic leukemia-free state after NK-cell therapy.
Five patients proceeded to HSCT—3 in mCR, 1 in PR, and 1 with SD.
Three patients were still alive at last follow-up—1 with MDS who achieved an mCR and went on to HSCT, 1 with MDS/AML who achieved an mCR and went on to HSCT, and 1 with MDS/AML who achieved an mCR and went on to receive chemotherapy and donor lymphocyte infusion.
One survivor has more than 5 years of follow-up (the MDS patient), and the other 2 have more than 3 years of follow-up.
“Our study shows that patients with MDS, AML, and MDS/AML can be treated with NK cell-based immunotherapy and that the therapy can be highly efficacious,” said study author Hans-Gustaf Ljunggren, MD, PhD, of Karolinska Institutet in Stockholm, Sweden.
Safety
The most common AEs of any grade considered possibly or probably related to NK-cell therapy were chills (n=13) and nausea (n=4).
Two patients had cytokine release syndrome (CRS) likely associated with hemophagocytic lymphohistiocytosis (HLH).
Each of the following potentially related AEs were reported once: headache, vomiting, encephalitis infection, sinus tachycardia, bone pain, pain in extremity, and maculopapular rash.
There were 4 grade 3 AEs—CRS/HLH (n=1), chills (n=1), and nausea (n=2)—but no grade 4 AEs.
There were 2 grade 5 AEs—CRS/HLH and encephalitis infection. These occurred in a single patient who died with HLH, human herpes virus-6 encephalitis, and AML relapse.
Two investigators involved in this study serve on the scientific advisory board of Fate Therapeutics. Dr Ljunggren serves on the scientific advisory board of CellProtect, Nordic Pharmaceuticals, and HOPE Bio-Sciences. He is also on the board of directors of Vycellix and is a collaborator with Fate Therapeutics.
Results of a phase 1/2 trial suggest treatment with haploidentical natural killer (NK) cells can be effective against relapsed/refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
NK-cell therapy elicited responses in 6 of the 16 patients studied and provided a bridge to transplant for 5 patients.
Three responders were still alive at more than 3 years of follow-up.
There were 4 grade 3 adverse events (AEs) and 2 grade 5 AEs considered possibly or probably related to NK-cell therapy.
Investigators reported these results in Clinical Cancer Research.
The trial enrolled 16 patients. Eight had MDS/AML, 3 had de novo AML, and 5 had high-risk MDS, including refractory anemia with excess blasts (RAEB) type 1 progressing toward type 2, RAEB-2, and chronic myelomonocytic leukemia type 2.
The patients’ median age was 64 (range, 40-70), and they had received a median of 3 prior therapies (range, 1-6). Six patients had received an allogeneic hematopoietic stem cell transplant (HSCT).
For this study, all patients received fludarabine, cyclophosphamide, and total lymphoid irradiation prior to receiving haploidentical NK cells.
The median follow-up was 8 months for all patients and 28 months for responders.
Efficacy
Six patients responded to treatment. One patient with de novo AML had a complete response (CR). Two high-risk MDS patients had a marrow CR (mCR), as did 2 MDS/AML patients. One MDS/AML patient had a partial response (PR).
Two patients had stable disease (SD)—1 with MDS and 1 with MDS/AML. One patient with de novo AML had a morphologic leukemia-free state after NK-cell therapy.
Five patients proceeded to HSCT—3 in mCR, 1 in PR, and 1 with SD.
Three patients were still alive at last follow-up—1 with MDS who achieved an mCR and went on to HSCT, 1 with MDS/AML who achieved an mCR and went on to HSCT, and 1 with MDS/AML who achieved an mCR and went on to receive chemotherapy and donor lymphocyte infusion.
One survivor has more than 5 years of follow-up (the MDS patient), and the other 2 have more than 3 years of follow-up.
“Our study shows that patients with MDS, AML, and MDS/AML can be treated with NK cell-based immunotherapy and that the therapy can be highly efficacious,” said study author Hans-Gustaf Ljunggren, MD, PhD, of Karolinska Institutet in Stockholm, Sweden.
Safety
The most common AEs of any grade considered possibly or probably related to NK-cell therapy were chills (n=13) and nausea (n=4).
Two patients had cytokine release syndrome (CRS) likely associated with hemophagocytic lymphohistiocytosis (HLH).
Each of the following potentially related AEs were reported once: headache, vomiting, encephalitis infection, sinus tachycardia, bone pain, pain in extremity, and maculopapular rash.
There were 4 grade 3 AEs—CRS/HLH (n=1), chills (n=1), and nausea (n=2)—but no grade 4 AEs.
There were 2 grade 5 AEs—CRS/HLH and encephalitis infection. These occurred in a single patient who died with HLH, human herpes virus-6 encephalitis, and AML relapse.
Two investigators involved in this study serve on the scientific advisory board of Fate Therapeutics. Dr Ljunggren serves on the scientific advisory board of CellProtect, Nordic Pharmaceuticals, and HOPE Bio-Sciences. He is also on the board of directors of Vycellix and is a collaborator with Fate Therapeutics.
Results of a phase 1/2 trial suggest treatment with haploidentical natural killer (NK) cells can be effective against relapsed/refractory myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
NK-cell therapy elicited responses in 6 of the 16 patients studied and provided a bridge to transplant for 5 patients.
Three responders were still alive at more than 3 years of follow-up.
There were 4 grade 3 adverse events (AEs) and 2 grade 5 AEs considered possibly or probably related to NK-cell therapy.
Investigators reported these results in Clinical Cancer Research.
The trial enrolled 16 patients. Eight had MDS/AML, 3 had de novo AML, and 5 had high-risk MDS, including refractory anemia with excess blasts (RAEB) type 1 progressing toward type 2, RAEB-2, and chronic myelomonocytic leukemia type 2.
The patients’ median age was 64 (range, 40-70), and they had received a median of 3 prior therapies (range, 1-6). Six patients had received an allogeneic hematopoietic stem cell transplant (HSCT).
For this study, all patients received fludarabine, cyclophosphamide, and total lymphoid irradiation prior to receiving haploidentical NK cells.
The median follow-up was 8 months for all patients and 28 months for responders.
Efficacy
Six patients responded to treatment. One patient with de novo AML had a complete response (CR). Two high-risk MDS patients had a marrow CR (mCR), as did 2 MDS/AML patients. One MDS/AML patient had a partial response (PR).
Two patients had stable disease (SD)—1 with MDS and 1 with MDS/AML. One patient with de novo AML had a morphologic leukemia-free state after NK-cell therapy.
Five patients proceeded to HSCT—3 in mCR, 1 in PR, and 1 with SD.
Three patients were still alive at last follow-up—1 with MDS who achieved an mCR and went on to HSCT, 1 with MDS/AML who achieved an mCR and went on to HSCT, and 1 with MDS/AML who achieved an mCR and went on to receive chemotherapy and donor lymphocyte infusion.
One survivor has more than 5 years of follow-up (the MDS patient), and the other 2 have more than 3 years of follow-up.
“Our study shows that patients with MDS, AML, and MDS/AML can be treated with NK cell-based immunotherapy and that the therapy can be highly efficacious,” said study author Hans-Gustaf Ljunggren, MD, PhD, of Karolinska Institutet in Stockholm, Sweden.
Safety
The most common AEs of any grade considered possibly or probably related to NK-cell therapy were chills (n=13) and nausea (n=4).
Two patients had cytokine release syndrome (CRS) likely associated with hemophagocytic lymphohistiocytosis (HLH).
Each of the following potentially related AEs were reported once: headache, vomiting, encephalitis infection, sinus tachycardia, bone pain, pain in extremity, and maculopapular rash.
There were 4 grade 3 AEs—CRS/HLH (n=1), chills (n=1), and nausea (n=2)—but no grade 4 AEs.
There were 2 grade 5 AEs—CRS/HLH and encephalitis infection. These occurred in a single patient who died with HLH, human herpes virus-6 encephalitis, and AML relapse.
Two investigators involved in this study serve on the scientific advisory board of Fate Therapeutics. Dr Ljunggren serves on the scientific advisory board of CellProtect, Nordic Pharmaceuticals, and HOPE Bio-Sciences. He is also on the board of directors of Vycellix and is a collaborator with Fate Therapeutics.
Team creates device to study hemostasis
Researchers have engineered a miniature model system for studying hemostasis.
They believe the device could serve as a drug discovery platform and potential diagnostic tool.
The team has already used the device to assess the effects of an antiplatelet agent and analyze blood from hemophilia A patients.
The researchers described this work in Nature Communications.
The team noted that hemostasis encompasses the interactions of platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces.
“Current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what’s going with the patient’s blood clotting system,” said study author Wilbur Lam, MD, PhD, of Georgia Institute of Technology and Emory University in Atlanta, Georgia.
With this in mind, Dr Lam and his colleagues developed their device.
They believe it is the first system to reproduce all aspects of blood vessel injury seen in the microvasculature—blood loss due to trauma, clot formation by whole blood, and repair of the blood vessel lining. However, it does not reproduce aspects of larger blood vessels.
The researchers’ device has 3 layers. The top “vascular” layer consists of human endothelial cells cultured in a microchannel. The middle valve layer consists of a polydimethylsiloxane membrane, and the bottom is a “valve actuator” layer.
To assess hemostatic response, the researchers create a “wound” in this system. They exert both positive and negative pressure to create an opening about 130 micrometers across. Donated human blood can flow through this opening for testing.
The researchers said they used this system to demonstrate the importance of von Willebrand factor and endothelial phosphatidylserine in hemostasis.
The team used the device to test the antiplatelet agent eptifibatide as well. They found the drug leads to decreased clot contraction and a lower density of platelets within the hemostatic plug.
Finally, the researchers analyzed blood from hemophilia A patients and found that it “confers unstable hemostatic plug formation and altered fibrin architecture.”
Researchers have engineered a miniature model system for studying hemostasis.
They believe the device could serve as a drug discovery platform and potential diagnostic tool.
The team has already used the device to assess the effects of an antiplatelet agent and analyze blood from hemophilia A patients.
The researchers described this work in Nature Communications.
The team noted that hemostasis encompasses the interactions of platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces.
“Current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what’s going with the patient’s blood clotting system,” said study author Wilbur Lam, MD, PhD, of Georgia Institute of Technology and Emory University in Atlanta, Georgia.
With this in mind, Dr Lam and his colleagues developed their device.
They believe it is the first system to reproduce all aspects of blood vessel injury seen in the microvasculature—blood loss due to trauma, clot formation by whole blood, and repair of the blood vessel lining. However, it does not reproduce aspects of larger blood vessels.
The researchers’ device has 3 layers. The top “vascular” layer consists of human endothelial cells cultured in a microchannel. The middle valve layer consists of a polydimethylsiloxane membrane, and the bottom is a “valve actuator” layer.
To assess hemostatic response, the researchers create a “wound” in this system. They exert both positive and negative pressure to create an opening about 130 micrometers across. Donated human blood can flow through this opening for testing.
The researchers said they used this system to demonstrate the importance of von Willebrand factor and endothelial phosphatidylserine in hemostasis.
The team used the device to test the antiplatelet agent eptifibatide as well. They found the drug leads to decreased clot contraction and a lower density of platelets within the hemostatic plug.
Finally, the researchers analyzed blood from hemophilia A patients and found that it “confers unstable hemostatic plug formation and altered fibrin architecture.”
Researchers have engineered a miniature model system for studying hemostasis.
They believe the device could serve as a drug discovery platform and potential diagnostic tool.
The team has already used the device to assess the effects of an antiplatelet agent and analyze blood from hemophilia A patients.
The researchers described this work in Nature Communications.
The team noted that hemostasis encompasses the interactions of platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces.
“Current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what’s going with the patient’s blood clotting system,” said study author Wilbur Lam, MD, PhD, of Georgia Institute of Technology and Emory University in Atlanta, Georgia.
With this in mind, Dr Lam and his colleagues developed their device.
They believe it is the first system to reproduce all aspects of blood vessel injury seen in the microvasculature—blood loss due to trauma, clot formation by whole blood, and repair of the blood vessel lining. However, it does not reproduce aspects of larger blood vessels.
The researchers’ device has 3 layers. The top “vascular” layer consists of human endothelial cells cultured in a microchannel. The middle valve layer consists of a polydimethylsiloxane membrane, and the bottom is a “valve actuator” layer.
To assess hemostatic response, the researchers create a “wound” in this system. They exert both positive and negative pressure to create an opening about 130 micrometers across. Donated human blood can flow through this opening for testing.
The researchers said they used this system to demonstrate the importance of von Willebrand factor and endothelial phosphatidylserine in hemostasis.
The team used the device to test the antiplatelet agent eptifibatide as well. They found the drug leads to decreased clot contraction and a lower density of platelets within the hemostatic plug.
Finally, the researchers analyzed blood from hemophilia A patients and found that it “confers unstable hemostatic plug formation and altered fibrin architecture.”
Drug receives orphan designation for MM
The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).
PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.
PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).
Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.
In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.
Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.
This research was presented at the 2017 ASH Annual Meeting (abstract 1797).
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).
PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.
PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).
Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.
In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.
Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.
This research was presented at the 2017 ASH Annual Meeting (abstract 1797).
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan designation to PT-112 as a treatment for multiple myeloma (MM).
PT-112 is a small-molecule conjugate of pyrophosphate and platinum that promotes apoptosis with damage-associated molecular patterns, leading to downstream T-cell recruitment in the tumor microenvironment.
PT-112 is currently under investigation in a phase 1/2 study of patients with relapsed or refractory MM (NCT03288480).
Phosplatin Therapeutics LLC, the company developing PT-112, has enrolled the first cohort of patients in this trial.
In preclinical experiments, PT-112 demonstrated synergy with lenalidomide and bortezomib in RPMI-8226 cells and dexamethasone-resistant MM1R cells.
Single-agent PT-112 produced responses in mice with established MM. Researchers said PT-112 had “pronounced” activity against bortezomib-refractory Vk12598 tumors, which significantly improved overall survival in the mice.
This research was presented at the 2017 ASH Annual Meeting (abstract 1797).
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
ASCO, NCCN release guidelines on checkpoint inhibitors
Two cancer organizations have released guidelines for managing the side effects of immune checkpoint inhibitors.
The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network® (NCCN) developed these guidelines because patients who receive immune checkpoint inhibitors experience unique side effects that can be severe, irreversible, and life-threatening.
Given that checkpoint inhibitors have entered the clinic fairly recently, clinicians may need guidance in recognizing and treating these side effects.
“With rapidly increasing use of immune checkpoint inhibitors, it is imperative that clinicians are knowledgeable about their unique toxicity profiles,” said ASCO Chief Executive Officer Clifford A. Hudis, MD.
“These new guidelines from ASCO and NCCN will help our community continue to provide the highest quality of care to all patients as they incorporate these agents into routine care.”
To the develop their guidelines, ASCO and NCCN convened multidisciplinary panels with representation from hematology, oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, emergency medicine, and nursing, as well as patient advocacy experts.
The clinical recommendations are based on a systematic review of the literature and an informal consensus process. The recommendations pertain only to checkpoint inhibitors currently approved in the US—pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, and durvalumab.
Key recommendations from the guidelines include:
- In general, checkpoint inhibitors can be continued with close monitoring if patients experience grade 1 toxicities, with the exception of some neurologic, cardiac, and hematologic toxicities.
- For grade 2 toxicities, checkpoint inhibitors should be held until symptoms and/or lab values revert to grade 1 levels or lower. Corticosteroids may be offered.
- For grade 3 toxicities, patients should receive high-dose corticosteroids for at least 6 weeks. Extreme caution is recommended when restarting immunotherapy after grade 3 toxicity, if it is restarted at all.
- In general, grade 4 toxicities necessitate stopping checkpoint inhibitor therapy permanently.
Consult the guidelines for specific recommendations.
ASCO’s guidelines, “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline,” have been published in the Journal of Clinical Oncology.
NCCN’s guidelines, “Management of Immunotherapy-Related Toxicities (Immune Checkpoint Inhibitor-Related Toxicities),” are available on the NCCN website.
Two cancer organizations have released guidelines for managing the side effects of immune checkpoint inhibitors.
The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network® (NCCN) developed these guidelines because patients who receive immune checkpoint inhibitors experience unique side effects that can be severe, irreversible, and life-threatening.
Given that checkpoint inhibitors have entered the clinic fairly recently, clinicians may need guidance in recognizing and treating these side effects.
“With rapidly increasing use of immune checkpoint inhibitors, it is imperative that clinicians are knowledgeable about their unique toxicity profiles,” said ASCO Chief Executive Officer Clifford A. Hudis, MD.
“These new guidelines from ASCO and NCCN will help our community continue to provide the highest quality of care to all patients as they incorporate these agents into routine care.”
To the develop their guidelines, ASCO and NCCN convened multidisciplinary panels with representation from hematology, oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, emergency medicine, and nursing, as well as patient advocacy experts.
The clinical recommendations are based on a systematic review of the literature and an informal consensus process. The recommendations pertain only to checkpoint inhibitors currently approved in the US—pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, and durvalumab.
Key recommendations from the guidelines include:
- In general, checkpoint inhibitors can be continued with close monitoring if patients experience grade 1 toxicities, with the exception of some neurologic, cardiac, and hematologic toxicities.
- For grade 2 toxicities, checkpoint inhibitors should be held until symptoms and/or lab values revert to grade 1 levels or lower. Corticosteroids may be offered.
- For grade 3 toxicities, patients should receive high-dose corticosteroids for at least 6 weeks. Extreme caution is recommended when restarting immunotherapy after grade 3 toxicity, if it is restarted at all.
- In general, grade 4 toxicities necessitate stopping checkpoint inhibitor therapy permanently.
Consult the guidelines for specific recommendations.
ASCO’s guidelines, “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline,” have been published in the Journal of Clinical Oncology.
NCCN’s guidelines, “Management of Immunotherapy-Related Toxicities (Immune Checkpoint Inhibitor-Related Toxicities),” are available on the NCCN website.
Two cancer organizations have released guidelines for managing the side effects of immune checkpoint inhibitors.
The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network® (NCCN) developed these guidelines because patients who receive immune checkpoint inhibitors experience unique side effects that can be severe, irreversible, and life-threatening.
Given that checkpoint inhibitors have entered the clinic fairly recently, clinicians may need guidance in recognizing and treating these side effects.
“With rapidly increasing use of immune checkpoint inhibitors, it is imperative that clinicians are knowledgeable about their unique toxicity profiles,” said ASCO Chief Executive Officer Clifford A. Hudis, MD.
“These new guidelines from ASCO and NCCN will help our community continue to provide the highest quality of care to all patients as they incorporate these agents into routine care.”
To the develop their guidelines, ASCO and NCCN convened multidisciplinary panels with representation from hematology, oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, emergency medicine, and nursing, as well as patient advocacy experts.
The clinical recommendations are based on a systematic review of the literature and an informal consensus process. The recommendations pertain only to checkpoint inhibitors currently approved in the US—pembrolizumab, nivolumab, atezolizumab, avelumab, ipilimumab, and durvalumab.
Key recommendations from the guidelines include:
- In general, checkpoint inhibitors can be continued with close monitoring if patients experience grade 1 toxicities, with the exception of some neurologic, cardiac, and hematologic toxicities.
- For grade 2 toxicities, checkpoint inhibitors should be held until symptoms and/or lab values revert to grade 1 levels or lower. Corticosteroids may be offered.
- For grade 3 toxicities, patients should receive high-dose corticosteroids for at least 6 weeks. Extreme caution is recommended when restarting immunotherapy after grade 3 toxicity, if it is restarted at all.
- In general, grade 4 toxicities necessitate stopping checkpoint inhibitor therapy permanently.
Consult the guidelines for specific recommendations.
ASCO’s guidelines, “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline,” have been published in the Journal of Clinical Oncology.
NCCN’s guidelines, “Management of Immunotherapy-Related Toxicities (Immune Checkpoint Inhibitor-Related Toxicities),” are available on the NCCN website.
Product seems effective for ITI in severe hemophilia A
Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.
Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.
Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.
In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.
No adverse events were reported in this study.
Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.
The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.
The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.
First-timer results
Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.
Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.
The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.
Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.
The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.
All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.
Rescue results
Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).
Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.
Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.
There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.
Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.
In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.
“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.
“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”
Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).
Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.
Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.
Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.
In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.
No adverse events were reported in this study.
Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.
The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.
The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.
First-timer results
Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.
Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.
The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.
Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.
The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.
All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.
Rescue results
Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).
Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.
Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.
There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.
Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.
In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.
“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.
“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”
Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).
Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.
Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.
Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.
In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.
No adverse events were reported in this study.
Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.
The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.
The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.
First-timer results
Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.
Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.
The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.
Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.
The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.
All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.
Rescue results
Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).
Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.
Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.
There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.
Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.
In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.
“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.
“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”
Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).