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Momelotinib hits the mark for deadly bone marrow cancer
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
“The current state for the treatment of myelofibrosis relies on JAK2,” said Ruben Mesa, MD, of the Mays Cancer Center at the UT Health San Antonio MD Anderson Cancer Center.
“Momelotinib is a JAK1 and JAK2 inhibitor.” However, in the early days of studying momelotinib,“it became clear that there was also potentially an improvement in anemia,” which may be related to the additional inhibition of ACVR1, he explained.
Data suggest that the ability to curb anemia in anemic myelofibrosis patients prolongs their lives for up to 8 years, Dr. Mesa added.
Previous studies, notably the phase 3 SIMPLIFY study, showed that momelotinib was associated with comparable effects on spleen volume, transfusion, and total symptom scores from baseline that were similar to ruxolitinib.
In the current study, known as MOMENTUM, a daily dose of momelotinib was compared to danazol for treatment of symptomatic and anemic myelofibrosis (MF) patients who had previously received standard JAK-inhibitor therapy.
In the study, the researchers randomized 130 patients to momelotinib and 65 to danazol. After 24 weeks, those in the danazol group were allowed to cross over to momelotinib. The primary endpoint of the study was total symptom score (TSS) response after 24 weeks. Secondary endpoints included transfusion independence and splenic response at 24 weeks. The median age of the patients in the momelotinib group was 71 years, 60.8% were male, and 82% were white. The baseline demographics were not significantly different in the danazol group.
Overall, 24.6% of momelotinib patients responded with improved total symptom scores at 24 weeks vs. 9.2% of the danazol group. Spleen response also was significantly higher in the momelotinib group; 40% of patients showed a 25% reduction and 23% showed a 35% reduction, compared with 6.2% and 3.1%, respectively, of patients in the danazol group. Transfusion independence at week 24 also was higher for momelotinib patients, compared with danazol patients (31% vs. 20%, respectively, P = 0064).
Adverse events of grade 3 or higher occurred in 53.8% of momelotinib patients and 64.6% of danazol patients, and serious adverse events occurred in 34.6% and 40.0%, respectively. Nearly all patients had anemia, but only 27.7% and 26.2% of the momelotinib and danazol groups, respectively, had thrombocytopenia of grade 3 or higher. The most common nonhematologic adverse events were diarrhea, nausea, and increased blood creatinine. A total of 27.7% of the patients in the momelotinib group discontinued treatment; 16 of whom did so because of an adverse event.
Also, at 24 weeks, patients in the momelotinib group showed a trend towards increased overall survival, compared with danazol (HR, 0.506, P = 0.719).
With momelotinib, there is a consistent thrombocytopenic profile across subgroups, the data on which were presented separately at ASCO (poster 7061), Dr. Mesa added.
“We feel that these findings support the future use of momelotinib as an effective treatment in MF patients, especially those with anemia,” he concluded.
Cytopenia data are exciting
The key finding in the current study is that “momelotinib leads to important endpoints including significant improvement in symptoms and spleen reduction,” said Dr. Gabriela Hobbs of Harvard Medical School, Boston, who served as the discussant for the study.
“I think a novel finding of momelotinib that is definitely exciting from the treatment perspective is that momelotinib can also lead to improvement in cytopenias,” she said. “We often have to decide between treating the symptoms of the spleen at the expense of blood counts,” in MF patients, she noted.
The study was sponsored by Sierra Oncology. Dr. Mesa disclosed relationships with companies including Constellation Pharmaceutical, La Jolla Pharma, and study sponsor Sierra Oncology, as well as funding from AbbVie, Celgene, Constellation Pharmaceuticals, CTI, Genentech, Incyte, Mays Cancer Center, NCI, Promedior, and Samus. Dr. Hobbs had no financial conflicts to disclose.
This article was updated 06/14/2022.
FROM ASCO 2022
Anticipation key to tackling perioperative anemia
MANCHESTER, ENGLAND –
Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.
It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.
It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.”
The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.
It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.
Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.
Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.
The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.
As an example, she said there are already some excellent guidelines out there, but they are not widely read.
One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.
But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.
The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”
The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.
For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.
However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.
The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.
To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.
More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”
No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND –
Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.
It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.
It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.”
The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.
It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.
Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.
Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.
The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.
As an example, she said there are already some excellent guidelines out there, but they are not widely read.
One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.
But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.
The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”
The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.
For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.
However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.
The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.
To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.
More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”
No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND –
Anemia management may include dietary changes, iron supplementation, blood transfusion, perioperative physiological optimization, delay or review of the surgical plan, medication reviews, and greater intraoperative care.
It is quite clear that patients have a better experience if management covers the whole pathway, said lead author of the guidelines, Scarlett McNally, MD, PhD, East Sussex Healthcare NHS Trust, Eastbourne, England.
It’s much better for the patient “if every individual member of staff knows what’s supposed to happen, not just for their bit, but the whole way along,” she said. “Otherwise things go wrong, and people don’t anticipate things early enough.”
The new guidelines, to be published in full later this year by the Centre for Perioperative Care, cover emergency and elective surgery for all ages.
It follows the 2021 publication of a guideline for perioperative diabetes management, and a previous document that covered frailty.
Dr. McNally was presenting the new guidelines on perioperative anemia at the British Society for Haematology 62nd Annual Scientific Meeting.
Although perioperative anemia is a “big issue” in clinical management, “some health care professionals know a lot about one area,” but tend to work in “silos,” Dr. McNally said.
The result is clinicians believe that all other areas are “complex” and opaque, and they “don’t make the simple decisions” that could have a big impact on patient care.
As an example, she said there are already some excellent guidelines out there, but they are not widely read.
One example of a comprehensive guideline, Dr. McNally said, is that issued by the British Society of Gastroenterology. This guideline notes that in cases where a man or a postmenopausal woman has anemia of unknown cause, about 30% of those cases end up having a gastrointestinal cause, and so gastroenterologists are happy to have those patients referred to them.
But Dr. McNally said that she personally, as an orthopedic surgeon, wouldn’t have known what to do with such a patient, and may have referred that person back to primary care to be investigated.
The new guidelines contain algorithms to help staff plan care. Without those, she said, “a lot is resting on the preassessment nurses, but they are having to think about everything else.”
The guidance suggests proactive measures to identify and manage anemia. These include testing for anemia while assessing renal function ahead of a CT scan, or asking patients about their nutrition.
For low-risk patients, it may be enough to give general advice about a good diet and exercise to try to get them through the operation.
However, patients who are high risk (defined as likely to lose > 500 mL or > 10% of blood volume during surgery) need to be identified as such early on, so that early measures can be put in place, as well as a senior review of their care plan.
The guidelines also recommend that operating room staff consider tranexamic acid and other bloodless minimization strategies, and that senior staff give clinical input in cases of functional iron deficiency, a marker of ill health.
To maximize postoperative outcomes, it is suggested that staff work with prehabilitation services and mobilize patients, as symptoms allow.
More importantly, they emphasize the need for shared decision-making about potential surgery, ensuring that the patients understand “Benefits, Risks, Alternatives, and what if we do Nothing (BRAN).”
No funding was declared. One study author declared relationships with the National Institute for Health Research and Pfizer.
A version of this article first appeared on Medscape.com.
Rapper sings about living with sickle cell disease
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
MANCHESTER, ENGLAND – A London-based rapper known for his gospel-inspired music has now given a voice to patients with sickle cell disease. He is using one of his music videos to raise awareness and educate health care professionals about living with the condition.
One important aim of the video, he says, is to help educate health care professionals, some of whom have not come across this condition, he explained at a session during the annual meeting of the British Society for Haematology, held recently in Manchester, England.
“It’s kind of frustrating to feel like your safe space, when you’re in front of doctors and nurses and paramedics who are supposed to know what it is and react with treatment, [and they] don’t know what it is,” Mr. Gaspar said.
He recalled an occasion in which he was experiencing a crisis, and his wife called for an ambulance. The paramedics arrived and his wife asked them for “gas and air and morphine, and they were, like, no, we don’t want to give that to him.” She tried to explain that he has sickle cell disease, but the paramedics had not heard of the condition and were suspicious that the request for morphine was a sign of drug addiction.
Mr. Gaspar expressed his frustration over “constantly having to prove that you have something serious enough to need the treatment you are asking for.”
At the meeting, Mr. Gaspar was talking on the stage with hematologist Dr. Stephen Hibbs from Barts Health NHS Trust, London.
Mr. Gaspar explained that it took years before he eventually reached “a point where I understood that it’s something that affects me and affects many other people, and I didn’t want to hide it any more.”
Sickle cell disease, which occurs primarily in people of Afro-Caribbean background, is a taboo subject in his community, Mr. Gaspar elaborated in an interview.
The condition has been associated with a great deal of stigma, with young sufferers traditionally seen as “demonically possessed,” he commented.
“So there was always a shameful aspect around it when it came to African families speaking about it, especially back in Africa.”
But after his parents came to the United Kingdom, he was able to “do his research and understand that it’s just genetics.”
This knowledge, Mr. Gaspar said, “takes away the spiritual aspect” and allows people to “have the conversation about sickle cell with potential partners” and ask them to find out their genotype, which in turn helps to “break down the barriers and the stigma.”
Mr. Gaspar emphasizes that there is much more work still to do.
In the video, he appeals to the Black community to make blood donations.
He said that something that “haunts” him is that currently, only 1% of Black people in the United Kingdom give blood, “so I really want the song to move my community to take a step forward and make that difference.”
He has been in contact with NHS Blood and Transplant, which provides blood and transplantation service to the National Health Service. They “really liked” the song, Mr. Gaspar said, and helped him get access to a hospital ward in University College Hospital, London, for the video.
“I really wanted to make a video that made people uncomfortable when watching it,” he said. It shows him hospitalized for pain and breathlessness and recalling having to use a Zimmer frame at the age of 25.
“This is a side of sickle cell that normally people don’t know,” he said.
Since releasing the song and the video, Mr. Gaspar says he has been contacted by many fellow patients. They have told him that he is now their “voice”; when they are asked how the condition affects them, “they can show someone the Hidden Pain video and say: This is how it feels.”
Clinicians have also approached him, asking if they can show his video to illustrate to patients and their families how having the condition may affect their lives.
Preventable deaths
At the meeting, Dr. Hibbs highlighted the 2021 report No One’s Listening, which was issued by the Sickle Cell Society following an inquiry into avoidable deaths and failures of care for sickle cell patients.
The inquiry, published by an All-Party Parliamentary group, found “serious care failings” in acute services and evidence of attitudes underpinned by racism. There was evidence of substandard care for sickle cell patients who were admitted to general wards or to hospital accident and emergency departments, as well as low awareness of the condition among health care professionals.
The report noted that the care failings have led to patient deaths, some which could have been prevented, and that there have been many “near misses.”
Many patients with sickle cell disease said they are “not being listened to” or are not being understood, especially during that vulnerable period when they are “in a crisis.”
Mr. Gaspar said that the report, and also the deaths, really struck a chord with him and many in his community. “We felt like that was us. ... We’ve all been in that same position where we’ve been misunderstood and not heard by nurses, doctors, or paramedics.”
He emphasized the need for awareness of the condition and the need for timely treatment. Just 3 weeks ago, Mr. Gaspar attended the funeral of one of his friends who is in the Hidden Pain video, a fellow sickle cell disease patient, who died at 30 years of age.
Ignorance about the condition ‘all too common’
The lack of awareness about sickle cell disease, even among health care professionals, is “all too common,” says Dr. Subarna Chakravorty, consultant pediatric hematologist, King’s College Hospital, London.
Even in London, where there is a large Black community and the teaching hospitals have world-class expertise, patients with sickle cell disease are “still facing a lot of problems with knowledge” among health care professionals, she said in an interview.
“Often people are having to speak for their own condition; which is fine, except that sometimes they are not believed,” she commented.
“On the one hand, you rely on the patient to provide information about their disease, and then when you receive it, you don’t do anything about it. So [they’re] between a rock and a hard place.”
Why are sickle cell patients treated in this way?
For Dr. Chakravorty, there is “a lot to be said about racism and disparities” in treating patients “as morphine-seekers, opiate addicts, even in children.”
“So we really need to improve the knowledge and perceptions among nonspecialist staff,” she said, “and even among specialists.”
Mr. Gaspar aims to help with this effort and hopes that his song and video will be useful to health care professionals. Sickle cell disease “needs to be spoken about,” and more doctors and nurses need to “know what it is,” he said.
He said it is a relief to encounter health care professionals who are knowledgeable about his condition. There have been times when he has been “having a crisis at home, calling the ambulance, and the paramedic comes and says: ‘Mr. Gaspar, you have sickle cell...we believe that you usually have gas and air and morphine, is that correct?’”
“That gives me a sense of peace, to know that I don’t have to fight my case or convince someone I have sickle cell, and I need to start treatment. They already know.”
No relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
FDA approves first drug for rare inherited anemia
The new drug, mitapivat (Pyrukynd, Agios), was approved on the basis of clinical trials that showed that it significantly improved hemolysis and anemia in patients with PK deficiency.
PK deficiency is rare. In clinical practice, its frequency is approximately 3-9 cases per 1 million people, the FDA noted. However, PK deficiency likely is misdiagnosed or undiagnosed, making it difficult to determine its frequency in the general population
PK deficiency is an inherited disorder that causes premature red blood cell destruction, leading to anemia, the agency explained in its announcement. Symptoms of PK deficiency range in severity and include fatigue, unusually pale skin, jaundice, shortness of breath, and a fast heart rate. Patients can also develop an enlarged spleen, can have too much iron in their blood from repeated blood transfusions, and can develop gallstones.
“Pyrukynd is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, MD, pediatric hematologist and director of hematology clinical research at Boston Children’s Hospital.
She was an investigator in the clinical trials that led to the approval. In a statement from the manufacturer, she added that “partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”
Clinical data
Clinical data that formed the basis of the approval came from two trials, one of which was a randomized, placebo-controlled trial, and the other a single-arm study, the FDA noted. In these studies, patients received up to 50 mg of mitapivat orally twice daily after an initial dose titration period
The randomized trial involved 80 adults with PK deficiency who were not having regular blood transfusions. They were allocated to receive either mitapivat or placebo and were followed for an average of 24 weeks. The primary endpoint was the number of patients who achieved a hemoglobin response (defined as a 1.5 g/dL or greater increase in hemoglobin concentration that was sustained at two or more scheduled assessments). At the end of the study, 40% of participants who received mitapivat had a hemoglobin response, compared with no participants who received placebo.
The single-arm study involved 27 adults with PK deficiency who were receiving regular blood transfusions. They took mitapivat for an average of 40 weeks. In this study, the primary endpoint was the reduction in transfusion burden, defined as at least a 33% reduction in the number of red blood cell units transfused during the last 24 weeks of treatment, compared with the historical transfusion burden on the individual participant (standardized to 24 weeks). The results show that 33% of participants who received mitapivat met this reduction in transfusion burden; 22% of participants did not require any transfusions over the last 24 weeks of treatment.
The most common side effects reported were decreases in estrone and estradiol in men, increased urate level, back pain, and joint stiffness. The effects of estrone and estradiol could not be reliably assessed in women because of normal changes in these hormone levels during the menstrual cycle and use of hormonal contraception.
The FDA warns of drug interactions that could necessitate dose adjustments, and also that abruptly stopping mitapivat could worsen premature red blood cell destruction.
The agency noted that this application received orphan drug designation, fast track designation, and priority review.
Agios is offering access programs aimed at reducing or eliminating patient out-of-pocket costs. Further details are on the myAgios patient support services program.
The company also noted that mitapivat is awaiting approval in the European Union. A decision is expected before the end of 2022.
A version of this article first appeared on Medscape.com.
The new drug, mitapivat (Pyrukynd, Agios), was approved on the basis of clinical trials that showed that it significantly improved hemolysis and anemia in patients with PK deficiency.
PK deficiency is rare. In clinical practice, its frequency is approximately 3-9 cases per 1 million people, the FDA noted. However, PK deficiency likely is misdiagnosed or undiagnosed, making it difficult to determine its frequency in the general population
PK deficiency is an inherited disorder that causes premature red blood cell destruction, leading to anemia, the agency explained in its announcement. Symptoms of PK deficiency range in severity and include fatigue, unusually pale skin, jaundice, shortness of breath, and a fast heart rate. Patients can also develop an enlarged spleen, can have too much iron in their blood from repeated blood transfusions, and can develop gallstones.
“Pyrukynd is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, MD, pediatric hematologist and director of hematology clinical research at Boston Children’s Hospital.
She was an investigator in the clinical trials that led to the approval. In a statement from the manufacturer, she added that “partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”
Clinical data
Clinical data that formed the basis of the approval came from two trials, one of which was a randomized, placebo-controlled trial, and the other a single-arm study, the FDA noted. In these studies, patients received up to 50 mg of mitapivat orally twice daily after an initial dose titration period
The randomized trial involved 80 adults with PK deficiency who were not having regular blood transfusions. They were allocated to receive either mitapivat or placebo and were followed for an average of 24 weeks. The primary endpoint was the number of patients who achieved a hemoglobin response (defined as a 1.5 g/dL or greater increase in hemoglobin concentration that was sustained at two or more scheduled assessments). At the end of the study, 40% of participants who received mitapivat had a hemoglobin response, compared with no participants who received placebo.
The single-arm study involved 27 adults with PK deficiency who were receiving regular blood transfusions. They took mitapivat for an average of 40 weeks. In this study, the primary endpoint was the reduction in transfusion burden, defined as at least a 33% reduction in the number of red blood cell units transfused during the last 24 weeks of treatment, compared with the historical transfusion burden on the individual participant (standardized to 24 weeks). The results show that 33% of participants who received mitapivat met this reduction in transfusion burden; 22% of participants did not require any transfusions over the last 24 weeks of treatment.
The most common side effects reported were decreases in estrone and estradiol in men, increased urate level, back pain, and joint stiffness. The effects of estrone and estradiol could not be reliably assessed in women because of normal changes in these hormone levels during the menstrual cycle and use of hormonal contraception.
The FDA warns of drug interactions that could necessitate dose adjustments, and also that abruptly stopping mitapivat could worsen premature red blood cell destruction.
The agency noted that this application received orphan drug designation, fast track designation, and priority review.
Agios is offering access programs aimed at reducing or eliminating patient out-of-pocket costs. Further details are on the myAgios patient support services program.
The company also noted that mitapivat is awaiting approval in the European Union. A decision is expected before the end of 2022.
A version of this article first appeared on Medscape.com.
The new drug, mitapivat (Pyrukynd, Agios), was approved on the basis of clinical trials that showed that it significantly improved hemolysis and anemia in patients with PK deficiency.
PK deficiency is rare. In clinical practice, its frequency is approximately 3-9 cases per 1 million people, the FDA noted. However, PK deficiency likely is misdiagnosed or undiagnosed, making it difficult to determine its frequency in the general population
PK deficiency is an inherited disorder that causes premature red blood cell destruction, leading to anemia, the agency explained in its announcement. Symptoms of PK deficiency range in severity and include fatigue, unusually pale skin, jaundice, shortness of breath, and a fast heart rate. Patients can also develop an enlarged spleen, can have too much iron in their blood from repeated blood transfusions, and can develop gallstones.
“Pyrukynd is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, MD, pediatric hematologist and director of hematology clinical research at Boston Children’s Hospital.
She was an investigator in the clinical trials that led to the approval. In a statement from the manufacturer, she added that “partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”
Clinical data
Clinical data that formed the basis of the approval came from two trials, one of which was a randomized, placebo-controlled trial, and the other a single-arm study, the FDA noted. In these studies, patients received up to 50 mg of mitapivat orally twice daily after an initial dose titration period
The randomized trial involved 80 adults with PK deficiency who were not having regular blood transfusions. They were allocated to receive either mitapivat or placebo and were followed for an average of 24 weeks. The primary endpoint was the number of patients who achieved a hemoglobin response (defined as a 1.5 g/dL or greater increase in hemoglobin concentration that was sustained at two or more scheduled assessments). At the end of the study, 40% of participants who received mitapivat had a hemoglobin response, compared with no participants who received placebo.
The single-arm study involved 27 adults with PK deficiency who were receiving regular blood transfusions. They took mitapivat for an average of 40 weeks. In this study, the primary endpoint was the reduction in transfusion burden, defined as at least a 33% reduction in the number of red blood cell units transfused during the last 24 weeks of treatment, compared with the historical transfusion burden on the individual participant (standardized to 24 weeks). The results show that 33% of participants who received mitapivat met this reduction in transfusion burden; 22% of participants did not require any transfusions over the last 24 weeks of treatment.
The most common side effects reported were decreases in estrone and estradiol in men, increased urate level, back pain, and joint stiffness. The effects of estrone and estradiol could not be reliably assessed in women because of normal changes in these hormone levels during the menstrual cycle and use of hormonal contraception.
The FDA warns of drug interactions that could necessitate dose adjustments, and also that abruptly stopping mitapivat could worsen premature red blood cell destruction.
The agency noted that this application received orphan drug designation, fast track designation, and priority review.
Agios is offering access programs aimed at reducing or eliminating patient out-of-pocket costs. Further details are on the myAgios patient support services program.
The company also noted that mitapivat is awaiting approval in the European Union. A decision is expected before the end of 2022.
A version of this article first appeared on Medscape.com.
FDA approves first-ever drug for cold agglutinin disease
A new drug has become the first and only treatment for people with cold agglutinin disease (CAD) that is approved by the U.S. Food and Drug Administration.
CAD is a rare autoimmune hemolytic anemia, affecting about 5,000 people in the United States. It is caused by antibodies binding to the surface of red blood cells, which starts a process that causes the body’s immune system to mistakenly attack healthy red blood cells and cause their rupture (hemolysis). This can lead to severe anemia, which is often treated by blood transfusions.
“For people living with cold agglutinin disease, it is as if their body’s immune system is waging a war on itself. The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD. For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients,” commented Catherine Broome, MD, associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center, in a company press release.
Dr. Broome was the principal investigator in the CARDINAL study, which was the basis for the new approval. In this pivotal study, patients treated with sutimlimab had an improvement in anemia as measured by hemoglobin (Hgb) and bilirubin levels, she commented in the company statement.
The CARDINAL study was a 26-week open-label, single-arm phase 3 study conducted in 24 patients with CAD who had recent history of blood transfusion.
The primary efficacy endpoint was a composite defined as the proportion of patients who achieved normalization of Hgb level greater than or equal to 12 g/dL or demonstrated an increase from baseline in Hgb level greater than or equal to 2 g/dL at the treatment assessment time point (mean value from weeks 23, 25, and 26) and no blood transfusion from weeks 5 through 26.
More than half of the patients (13 of 24, 54%) met the composite primary endpoint criteria, with 17 of 24 (71%) patients remaining transfusion-free after week 5. Most patients (22 of 24, 92%) did not use other CAD-related treatments.
For the secondary measures on disease process, patients enrolled in the trial experienced a mean increase in Hgb level of 2.29 g/dL at week 3 and 3.18 g/dL at the 26-week treatment assessment time points (increasing from the mean baseline level of 8.6 g/dL). In addition, there was a mean reduction in bilirubin levels (n = 14) of -2.23 mg/dL from a mean baseline level of 3.23 mg/dL.
The most common adverse reactions occurring in 10% or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema. Serious adverse reactions were reported in 3 of 24 (13%) patients, and these included streptococcal sepsis and staphylococcal wound infection (n = 1), arthralgia (n = 1), and respiratory tract infection (n = 1).
None of the adverse reactions led to discontinuation of the drug, the company noted. Dosage interruptions due to an adverse reaction occurred in 4 of 24 (17%) patients who received the drug.
The recommended dose is based on body weight (6,500 mg for people 39-75 kg and 7,500 mg for people greater than 75 kg). The drug is administered intravenously weekly for the first 2 weeks with administration every 2 weeks thereafter.
Full prescribing information is available here.
The product is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells. Enjaymo does not inhibit the lectin and alternative pathways, the company noted.
In the U.S., Enjaymo received FDA breakthrough therapy and orphan drug designation, as well as priority review. The product is awaiting approval in Europe and Japan.
Sanofi says the product is expected to be available in the United States in the coming weeks, with a list price, or wholesale acquisition cost, of $1,800 per vial. Actual costs to patients are generally anticipated to be lower, as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs. The company offers support for eligible patients on 1-833-223-2428.
A version of this article first appeared on Medscape.com.
A new drug has become the first and only treatment for people with cold agglutinin disease (CAD) that is approved by the U.S. Food and Drug Administration.
CAD is a rare autoimmune hemolytic anemia, affecting about 5,000 people in the United States. It is caused by antibodies binding to the surface of red blood cells, which starts a process that causes the body’s immune system to mistakenly attack healthy red blood cells and cause their rupture (hemolysis). This can lead to severe anemia, which is often treated by blood transfusions.
“For people living with cold agglutinin disease, it is as if their body’s immune system is waging a war on itself. The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD. For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients,” commented Catherine Broome, MD, associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center, in a company press release.
Dr. Broome was the principal investigator in the CARDINAL study, which was the basis for the new approval. In this pivotal study, patients treated with sutimlimab had an improvement in anemia as measured by hemoglobin (Hgb) and bilirubin levels, she commented in the company statement.
The CARDINAL study was a 26-week open-label, single-arm phase 3 study conducted in 24 patients with CAD who had recent history of blood transfusion.
The primary efficacy endpoint was a composite defined as the proportion of patients who achieved normalization of Hgb level greater than or equal to 12 g/dL or demonstrated an increase from baseline in Hgb level greater than or equal to 2 g/dL at the treatment assessment time point (mean value from weeks 23, 25, and 26) and no blood transfusion from weeks 5 through 26.
More than half of the patients (13 of 24, 54%) met the composite primary endpoint criteria, with 17 of 24 (71%) patients remaining transfusion-free after week 5. Most patients (22 of 24, 92%) did not use other CAD-related treatments.
For the secondary measures on disease process, patients enrolled in the trial experienced a mean increase in Hgb level of 2.29 g/dL at week 3 and 3.18 g/dL at the 26-week treatment assessment time points (increasing from the mean baseline level of 8.6 g/dL). In addition, there was a mean reduction in bilirubin levels (n = 14) of -2.23 mg/dL from a mean baseline level of 3.23 mg/dL.
The most common adverse reactions occurring in 10% or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema. Serious adverse reactions were reported in 3 of 24 (13%) patients, and these included streptococcal sepsis and staphylococcal wound infection (n = 1), arthralgia (n = 1), and respiratory tract infection (n = 1).
None of the adverse reactions led to discontinuation of the drug, the company noted. Dosage interruptions due to an adverse reaction occurred in 4 of 24 (17%) patients who received the drug.
The recommended dose is based on body weight (6,500 mg for people 39-75 kg and 7,500 mg for people greater than 75 kg). The drug is administered intravenously weekly for the first 2 weeks with administration every 2 weeks thereafter.
Full prescribing information is available here.
The product is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells. Enjaymo does not inhibit the lectin and alternative pathways, the company noted.
In the U.S., Enjaymo received FDA breakthrough therapy and orphan drug designation, as well as priority review. The product is awaiting approval in Europe and Japan.
Sanofi says the product is expected to be available in the United States in the coming weeks, with a list price, or wholesale acquisition cost, of $1,800 per vial. Actual costs to patients are generally anticipated to be lower, as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs. The company offers support for eligible patients on 1-833-223-2428.
A version of this article first appeared on Medscape.com.
A new drug has become the first and only treatment for people with cold agglutinin disease (CAD) that is approved by the U.S. Food and Drug Administration.
CAD is a rare autoimmune hemolytic anemia, affecting about 5,000 people in the United States. It is caused by antibodies binding to the surface of red blood cells, which starts a process that causes the body’s immune system to mistakenly attack healthy red blood cells and cause their rupture (hemolysis). This can lead to severe anemia, which is often treated by blood transfusions.
“For people living with cold agglutinin disease, it is as if their body’s immune system is waging a war on itself. The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD. For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients,” commented Catherine Broome, MD, associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center, in a company press release.
Dr. Broome was the principal investigator in the CARDINAL study, which was the basis for the new approval. In this pivotal study, patients treated with sutimlimab had an improvement in anemia as measured by hemoglobin (Hgb) and bilirubin levels, she commented in the company statement.
The CARDINAL study was a 26-week open-label, single-arm phase 3 study conducted in 24 patients with CAD who had recent history of blood transfusion.
The primary efficacy endpoint was a composite defined as the proportion of patients who achieved normalization of Hgb level greater than or equal to 12 g/dL or demonstrated an increase from baseline in Hgb level greater than or equal to 2 g/dL at the treatment assessment time point (mean value from weeks 23, 25, and 26) and no blood transfusion from weeks 5 through 26.
More than half of the patients (13 of 24, 54%) met the composite primary endpoint criteria, with 17 of 24 (71%) patients remaining transfusion-free after week 5. Most patients (22 of 24, 92%) did not use other CAD-related treatments.
For the secondary measures on disease process, patients enrolled in the trial experienced a mean increase in Hgb level of 2.29 g/dL at week 3 and 3.18 g/dL at the 26-week treatment assessment time points (increasing from the mean baseline level of 8.6 g/dL). In addition, there was a mean reduction in bilirubin levels (n = 14) of -2.23 mg/dL from a mean baseline level of 3.23 mg/dL.
The most common adverse reactions occurring in 10% or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema. Serious adverse reactions were reported in 3 of 24 (13%) patients, and these included streptococcal sepsis and staphylococcal wound infection (n = 1), arthralgia (n = 1), and respiratory tract infection (n = 1).
None of the adverse reactions led to discontinuation of the drug, the company noted. Dosage interruptions due to an adverse reaction occurred in 4 of 24 (17%) patients who received the drug.
The recommended dose is based on body weight (6,500 mg for people 39-75 kg and 7,500 mg for people greater than 75 kg). The drug is administered intravenously weekly for the first 2 weeks with administration every 2 weeks thereafter.
Full prescribing information is available here.
The product is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells. Enjaymo does not inhibit the lectin and alternative pathways, the company noted.
In the U.S., Enjaymo received FDA breakthrough therapy and orphan drug designation, as well as priority review. The product is awaiting approval in Europe and Japan.
Sanofi says the product is expected to be available in the United States in the coming weeks, with a list price, or wholesale acquisition cost, of $1,800 per vial. Actual costs to patients are generally anticipated to be lower, as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs. The company offers support for eligible patients on 1-833-223-2428.
A version of this article first appeared on Medscape.com.
Voxelotor for sickle cell anemia now down to 4-year-olds
The indication had previously been for patients 12 years old and up, the FDA said in an announcement.
Voxelotor (Oxbryta) was originally approved for sickle cell disease in November 2019 and was described as the first drug that directly inhibits sickle hemoglobin polymerization, the root cause of the disease. It binds and stabilizes hemoglobin to prevent red blood cells from sickling and being destroyed.
Approval for the new indication of use in children down to age 4 was based on data from a phase 2 trial that involved 45 children aged 4-11 years; the results show that 36% had an increase in hemoglobin greater than 1 g/dL by week 24, the FDA said.
“Complications of [sickle cell disease] that can cause irreversible organ damage are known to begin in the first few years of life, which is why earlier intervention is critical,” commented Ted Love, MD, president and CEO of Global Blood Therapeutics, the manufacturer, in a press release.
The company is studying voxelotor in children as young as 9 months old.
The agent was granted an accelerated approval by the FDA, so continued approval depends on additional data to confirm that increases in hemoglobin have clinical benefit.
With the new approvals, voxelotor is now available in 500-mg tablets and the 300-mg tablets for oral suspension. Dosing for ages 12 years and up is 1,500 mg once daily. Dosing for children 4 to up to 12 years old is weight based.
The most common side effects are headache, vomiting, diarrhea, abdominal pain, nausea, rash, and fever.
A version of this article first appeared on Medscape.com.
The indication had previously been for patients 12 years old and up, the FDA said in an announcement.
Voxelotor (Oxbryta) was originally approved for sickle cell disease in November 2019 and was described as the first drug that directly inhibits sickle hemoglobin polymerization, the root cause of the disease. It binds and stabilizes hemoglobin to prevent red blood cells from sickling and being destroyed.
Approval for the new indication of use in children down to age 4 was based on data from a phase 2 trial that involved 45 children aged 4-11 years; the results show that 36% had an increase in hemoglobin greater than 1 g/dL by week 24, the FDA said.
“Complications of [sickle cell disease] that can cause irreversible organ damage are known to begin in the first few years of life, which is why earlier intervention is critical,” commented Ted Love, MD, president and CEO of Global Blood Therapeutics, the manufacturer, in a press release.
The company is studying voxelotor in children as young as 9 months old.
The agent was granted an accelerated approval by the FDA, so continued approval depends on additional data to confirm that increases in hemoglobin have clinical benefit.
With the new approvals, voxelotor is now available in 500-mg tablets and the 300-mg tablets for oral suspension. Dosing for ages 12 years and up is 1,500 mg once daily. Dosing for children 4 to up to 12 years old is weight based.
The most common side effects are headache, vomiting, diarrhea, abdominal pain, nausea, rash, and fever.
A version of this article first appeared on Medscape.com.
The indication had previously been for patients 12 years old and up, the FDA said in an announcement.
Voxelotor (Oxbryta) was originally approved for sickle cell disease in November 2019 and was described as the first drug that directly inhibits sickle hemoglobin polymerization, the root cause of the disease. It binds and stabilizes hemoglobin to prevent red blood cells from sickling and being destroyed.
Approval for the new indication of use in children down to age 4 was based on data from a phase 2 trial that involved 45 children aged 4-11 years; the results show that 36% had an increase in hemoglobin greater than 1 g/dL by week 24, the FDA said.
“Complications of [sickle cell disease] that can cause irreversible organ damage are known to begin in the first few years of life, which is why earlier intervention is critical,” commented Ted Love, MD, president and CEO of Global Blood Therapeutics, the manufacturer, in a press release.
The company is studying voxelotor in children as young as 9 months old.
The agent was granted an accelerated approval by the FDA, so continued approval depends on additional data to confirm that increases in hemoglobin have clinical benefit.
With the new approvals, voxelotor is now available in 500-mg tablets and the 300-mg tablets for oral suspension. Dosing for ages 12 years and up is 1,500 mg once daily. Dosing for children 4 to up to 12 years old is weight based.
The most common side effects are headache, vomiting, diarrhea, abdominal pain, nausea, rash, and fever.
A version of this article first appeared on Medscape.com.
Telemedicine helps SCD patients survive COVID, but more need access
ATLANTA – , according to an investigator at the annual meeting of the American Society of Hematology.
During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.
Virtual visits, launched to deliver health care needs in the wake of a Georgia’s 2020 statewide shelter-in-place order, helped protect patients from COVID-19 infection, Dr. El Rassi said in a press conference at the meeting.
“The patients’ diligence and awareness to stay home during the pandemic have proven crucial to reducing morbidity and mortality in this vulnerable population,” he said. “The option of having virtual visits for health care delivery was key and should be utilized further in sickle cell care.”
However, virtual visits and other best practices to prevent and treat COVID-19 in patients with sickle cell disease can be challenging to implement outside of large, specialized centers such as Grady.
“The majority of sickle cell patients in major metropolitan areas are not plugged into dedicated sickle cell centers, and that’s a key issue,” said Dr. El Rassi.
“There’s a huge shortage of such clinics around major metropolitan areas, and that restricts things for the general population, unfortunately.”
COVID-19 prevention remains a challenge, no matter where patients are treated. Only about 50% of the center’s sickle cell disease patients are immunized, according to Dr. El Rassi, who added that assessment of vaccine response among those patients is ongoing.
Ifeyinwa (Ify) Osunkwo, MD, MPH, a sickle cell disease specialist, said long-term sustainability of virtual visits depends greatly on states’ continuation of laws or policies that facilitate access to telemedicine. A total of 22 states changed laws or policies during the pandemic to promote access to telemedicine, according to the Commonwealth Fund.
Virtual care is more challenging in states where expanded telemedicine coverage is not available or is ended, said Dr. Osunkwo, director of the Sickle Cell Enterprise at Levine Cancer Institute. The institute is part of Atrium Health, a large health system that operates in four states.
“We are no longer able to do virtual visits for our South Carolinian patients, even though across the border in North Carolina, you can still provide virtual care,” Dr. Osunkwo said in an interview.
“Sickle cell patients suffer from social determinants [of health], so getting to their doctor when they have a regular outpatient visit is kind of hard,” she added. “And having that virtual option actually makes them more adherent, and they have better access to care overall.”
In the study presented at the ASH meeting by Dr. El Rassi and colleagues, there were a total of 55 patients with COVID-19 among the 1,343 sickle cell disease patients they tracked. Of the 55 patients with COVID-19, 28 were female and 27 were male, and 35% were on hydroxyurea for disease modification.
Among these 55 patients with COVID-19, 44 (80%) were hospitalized, and the hospitalizations of 15 (27%) were deemed related to COVID-19 signs and symptoms, Dr. El Rassi said. Twelve of the 55 patients (22%) had emergency visits, including 5 (9%) because of COVID-19 symptoms, he added.
The two deaths from COVID-19 occurred in June and July 2020, said Dr. El Rassi, adding that those patients were among 20 total cases diagnosed from March to September of 2020.
Over the second reported wave of COVID-19, from October 2020 to March 2021, there were no deaths seen among 35 total COVID-19 cases, according to the report at the ASH meeting.
In an interview, Kaitlin Strumph, MD, a sickle cell disease specialist at the Children’s Hospital at Montefiore in New York, noted that patients with sickle cell disease who contract COVID-19 are considered at high risk for morbidity and mortality.
“Patients and providers should not let down their guard,” Dr. Strumph said in an interview. “The best way to protect people from COVID-19 right now is prevention, and vaccinations are the key to further improving outcomes.”
Virtual visits can help bridge gaps in care for patients with sickle cell disease, said Dr. Strumph, given that limited access to care is a large driver of health disparities in this population.
“Telemedicine allows patients to stay home and limit their exposure to COVID-19 out in the community and at the hospital,” she said. “I think most providers feel confident that virtual visits are a huge benefit for the community, and we hope they are here to stay.”
Dr. El Rassi reported disclosures related to Cyclerion, Novartis, Pfizer, Global Blood Therapeutics and bluebird bio.
ATLANTA – , according to an investigator at the annual meeting of the American Society of Hematology.
During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.
Virtual visits, launched to deliver health care needs in the wake of a Georgia’s 2020 statewide shelter-in-place order, helped protect patients from COVID-19 infection, Dr. El Rassi said in a press conference at the meeting.
“The patients’ diligence and awareness to stay home during the pandemic have proven crucial to reducing morbidity and mortality in this vulnerable population,” he said. “The option of having virtual visits for health care delivery was key and should be utilized further in sickle cell care.”
However, virtual visits and other best practices to prevent and treat COVID-19 in patients with sickle cell disease can be challenging to implement outside of large, specialized centers such as Grady.
“The majority of sickle cell patients in major metropolitan areas are not plugged into dedicated sickle cell centers, and that’s a key issue,” said Dr. El Rassi.
“There’s a huge shortage of such clinics around major metropolitan areas, and that restricts things for the general population, unfortunately.”
COVID-19 prevention remains a challenge, no matter where patients are treated. Only about 50% of the center’s sickle cell disease patients are immunized, according to Dr. El Rassi, who added that assessment of vaccine response among those patients is ongoing.
Ifeyinwa (Ify) Osunkwo, MD, MPH, a sickle cell disease specialist, said long-term sustainability of virtual visits depends greatly on states’ continuation of laws or policies that facilitate access to telemedicine. A total of 22 states changed laws or policies during the pandemic to promote access to telemedicine, according to the Commonwealth Fund.
Virtual care is more challenging in states where expanded telemedicine coverage is not available or is ended, said Dr. Osunkwo, director of the Sickle Cell Enterprise at Levine Cancer Institute. The institute is part of Atrium Health, a large health system that operates in four states.
“We are no longer able to do virtual visits for our South Carolinian patients, even though across the border in North Carolina, you can still provide virtual care,” Dr. Osunkwo said in an interview.
“Sickle cell patients suffer from social determinants [of health], so getting to their doctor when they have a regular outpatient visit is kind of hard,” she added. “And having that virtual option actually makes them more adherent, and they have better access to care overall.”
In the study presented at the ASH meeting by Dr. El Rassi and colleagues, there were a total of 55 patients with COVID-19 among the 1,343 sickle cell disease patients they tracked. Of the 55 patients with COVID-19, 28 were female and 27 were male, and 35% were on hydroxyurea for disease modification.
Among these 55 patients with COVID-19, 44 (80%) were hospitalized, and the hospitalizations of 15 (27%) were deemed related to COVID-19 signs and symptoms, Dr. El Rassi said. Twelve of the 55 patients (22%) had emergency visits, including 5 (9%) because of COVID-19 symptoms, he added.
The two deaths from COVID-19 occurred in June and July 2020, said Dr. El Rassi, adding that those patients were among 20 total cases diagnosed from March to September of 2020.
Over the second reported wave of COVID-19, from October 2020 to March 2021, there were no deaths seen among 35 total COVID-19 cases, according to the report at the ASH meeting.
In an interview, Kaitlin Strumph, MD, a sickle cell disease specialist at the Children’s Hospital at Montefiore in New York, noted that patients with sickle cell disease who contract COVID-19 are considered at high risk for morbidity and mortality.
“Patients and providers should not let down their guard,” Dr. Strumph said in an interview. “The best way to protect people from COVID-19 right now is prevention, and vaccinations are the key to further improving outcomes.”
Virtual visits can help bridge gaps in care for patients with sickle cell disease, said Dr. Strumph, given that limited access to care is a large driver of health disparities in this population.
“Telemedicine allows patients to stay home and limit their exposure to COVID-19 out in the community and at the hospital,” she said. “I think most providers feel confident that virtual visits are a huge benefit for the community, and we hope they are here to stay.”
Dr. El Rassi reported disclosures related to Cyclerion, Novartis, Pfizer, Global Blood Therapeutics and bluebird bio.
ATLANTA – , according to an investigator at the annual meeting of the American Society of Hematology.
During the first COVID-19 wave in the summer of 2020, Atlanta’s Grady Sickle Cell Center, the nation’s largest adult sickle cell center, recorded two deaths among the 20 COVID-19_infected patients seen there, said Fuad El Rassi, MD, of Emory University, Atlanta.
Virtual visits, launched to deliver health care needs in the wake of a Georgia’s 2020 statewide shelter-in-place order, helped protect patients from COVID-19 infection, Dr. El Rassi said in a press conference at the meeting.
“The patients’ diligence and awareness to stay home during the pandemic have proven crucial to reducing morbidity and mortality in this vulnerable population,” he said. “The option of having virtual visits for health care delivery was key and should be utilized further in sickle cell care.”
However, virtual visits and other best practices to prevent and treat COVID-19 in patients with sickle cell disease can be challenging to implement outside of large, specialized centers such as Grady.
“The majority of sickle cell patients in major metropolitan areas are not plugged into dedicated sickle cell centers, and that’s a key issue,” said Dr. El Rassi.
“There’s a huge shortage of such clinics around major metropolitan areas, and that restricts things for the general population, unfortunately.”
COVID-19 prevention remains a challenge, no matter where patients are treated. Only about 50% of the center’s sickle cell disease patients are immunized, according to Dr. El Rassi, who added that assessment of vaccine response among those patients is ongoing.
Ifeyinwa (Ify) Osunkwo, MD, MPH, a sickle cell disease specialist, said long-term sustainability of virtual visits depends greatly on states’ continuation of laws or policies that facilitate access to telemedicine. A total of 22 states changed laws or policies during the pandemic to promote access to telemedicine, according to the Commonwealth Fund.
Virtual care is more challenging in states where expanded telemedicine coverage is not available or is ended, said Dr. Osunkwo, director of the Sickle Cell Enterprise at Levine Cancer Institute. The institute is part of Atrium Health, a large health system that operates in four states.
“We are no longer able to do virtual visits for our South Carolinian patients, even though across the border in North Carolina, you can still provide virtual care,” Dr. Osunkwo said in an interview.
“Sickle cell patients suffer from social determinants [of health], so getting to their doctor when they have a regular outpatient visit is kind of hard,” she added. “And having that virtual option actually makes them more adherent, and they have better access to care overall.”
In the study presented at the ASH meeting by Dr. El Rassi and colleagues, there were a total of 55 patients with COVID-19 among the 1,343 sickle cell disease patients they tracked. Of the 55 patients with COVID-19, 28 were female and 27 were male, and 35% were on hydroxyurea for disease modification.
Among these 55 patients with COVID-19, 44 (80%) were hospitalized, and the hospitalizations of 15 (27%) were deemed related to COVID-19 signs and symptoms, Dr. El Rassi said. Twelve of the 55 patients (22%) had emergency visits, including 5 (9%) because of COVID-19 symptoms, he added.
The two deaths from COVID-19 occurred in June and July 2020, said Dr. El Rassi, adding that those patients were among 20 total cases diagnosed from March to September of 2020.
Over the second reported wave of COVID-19, from October 2020 to March 2021, there were no deaths seen among 35 total COVID-19 cases, according to the report at the ASH meeting.
In an interview, Kaitlin Strumph, MD, a sickle cell disease specialist at the Children’s Hospital at Montefiore in New York, noted that patients with sickle cell disease who contract COVID-19 are considered at high risk for morbidity and mortality.
“Patients and providers should not let down their guard,” Dr. Strumph said in an interview. “The best way to protect people from COVID-19 right now is prevention, and vaccinations are the key to further improving outcomes.”
Virtual visits can help bridge gaps in care for patients with sickle cell disease, said Dr. Strumph, given that limited access to care is a large driver of health disparities in this population.
“Telemedicine allows patients to stay home and limit their exposure to COVID-19 out in the community and at the hospital,” she said. “I think most providers feel confident that virtual visits are a huge benefit for the community, and we hope they are here to stay.”
Dr. El Rassi reported disclosures related to Cyclerion, Novartis, Pfizer, Global Blood Therapeutics and bluebird bio.
FROM ASH 2021
Beta-thalassemia gene therapy achieves lasting transfusion independence
, an investigator reported at the annual meeting of the American Society of Hematology.
Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.
In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.
Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.
“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.
This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.
“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.
Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.
“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.
Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.
With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.
Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.
At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.
A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.
Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.
“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.
Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.
Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.
The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.
Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.
Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.
“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.
Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
, an investigator reported at the annual meeting of the American Society of Hematology.
Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.
In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.
Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.
“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.
This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.
“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.
Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.
“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.
Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.
With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.
Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.
At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.
A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.
Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.
“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.
Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.
Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.
The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.
Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.
Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.
“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.
Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
, an investigator reported at the annual meeting of the American Society of Hematology.
Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.
In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.
Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.
“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.
This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.
“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.
Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.
“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.
Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.
With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.
Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.
At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.
A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.
Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.
“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.
Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.
Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.
The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.
Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.
Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.
“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.
Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
FROM ASH 2021
Does optimal iron absorption include vitamin C?
Her blood work shows a hematocrit level of 32, a mean corpuscular volume of 77, a platelet count of 390,000, and a ferritin level of 5.
What would you recommend for iron replacement?
A. FeSO4 325 mg three times a day with vitamin C
B. FeSO4 325 mg daily with vitamin C
C. FeSO4 325 mg every other day
Recommendations and supporting research
I think I would start with choice C, FeSO4 every other day.
Treatment of iron deficiency with oral iron has traditionally been done by giving 150-200 mg of elemental iron (which is equal to three 325 mg tablets of iron sulfate).1 This dosing regimen has considerable gastrointestinal side effects. Recent evidence has shown that iron absorption is diminished the more frequently it is given.
Stoffel and colleagues found that fractional iron absorption was higher in iron-deficient women who were given iron every other day, compared with those who received daily iron.2 They also found that the more frequently iron was administered, the higher the hepcidin levels were, and the lower the iron absorption.
Karacok and colleagues studied every other day iron versus daily iron for the treatment of iron-deficiency anemia of pregnancy.3 A total of 217 women completed randomization and participated in the study, with all women receiving 100 mg of elemental iron, either daily (111) or every other day (106). There was no significant difference in increase in ferritin levels, or hemoglobin increase between the groups. The daily iron group had more gastrointestinal symptoms (41.4%) than the every other day iron group (15.1%) (P < .0057).
Düzen Oflas and colleagues looked at the same question in nonpregnant women with iron deficiency anemia.4 Study patients either received 80 mg iron sulfate twice a day, 80 mg once a day, or 80 mg every other day. There was no statistically significant difference in hemoglobin improvement between groups, but the group that received twice a day dosing of iron had statistically significantly higher ferritin levels than the daily or every other day iron groups. This improvement in ferritin levels came at a cost, though, as 68% of patients in the twice daily iron group had gastrointestinal symptoms, compared with only 10% in the every other day iron group (P < .01).
Vitamin C is often recommended to be taken with iron to promote absorption. The evidence for this practice is scant, and dates back almost 50 years.5,6
Cook and Reddy found there was no significant difference in mean iron absorption among the three dietary periods studied in 12 patients despite a range of mean daily intakes of dietary vitamin C of 51-247 mg/d.7
Hunt and colleagues studied 25 non pregnant, healthy women with low ferritin levels.8 The women’s meals were supplemented with vitamin C (500 mg, three times a day) for 5 of the 10 weeks, in a double-blind, crossover design. Vitamin C supplementation did not lead to a difference in iron absorption, lab indices of iron deficiency, or the biological half-life of iron.
Li and colleagues looked at the effect of vitamin C supplementation on iron levels in women with iron deficiency anemia.9 A total of 440 women were recruited, with 432 completing the trial. Women were randomized to receive iron supplements plus vitamin C or iron supplements only. Their findings were that oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption.
Bottom line
Less frequent administration of iron supplements (every other day) is as effective as more frequent administration, with less GI symptoms. Also, adding vitamin C does not appear to improve absorption of iron supplements.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. 1. Fairbanks VF and Beutler E. Iron deficiency, in “Williams Textbook of Hematology, 6th ed.” (New York: McGraw-Hill, 2001).
2. Stoffel N et al. Lancet Haematology. 2017;4: e524-33.
3. Karakoc G et al. J Matern Fetal Neonatal Med. 2021 Apr 18:1-5
4. Düzen Oflas N et al. Intern Med J. 2020 Jul;50(7):854-8
5. Cook JD and Monsen ER. Am J Clin Nutr. 1977;30:235-41.
6. Hallberg L etal. Hum Nutr Appl Nutr. 1986;40: 97-113.
7. Cook JD and Reddy M. Am J Clin Nutr. 2001;73:93-8.
8. Hunt JR et al. Am J Clin Nutr. 1994 Jun;59(6):1381-5.
9. Li N et al. JAMA Netw Open. 2020 Nov 2;3(11):e2023644.
Her blood work shows a hematocrit level of 32, a mean corpuscular volume of 77, a platelet count of 390,000, and a ferritin level of 5.
What would you recommend for iron replacement?
A. FeSO4 325 mg three times a day with vitamin C
B. FeSO4 325 mg daily with vitamin C
C. FeSO4 325 mg every other day
Recommendations and supporting research
I think I would start with choice C, FeSO4 every other day.
Treatment of iron deficiency with oral iron has traditionally been done by giving 150-200 mg of elemental iron (which is equal to three 325 mg tablets of iron sulfate).1 This dosing regimen has considerable gastrointestinal side effects. Recent evidence has shown that iron absorption is diminished the more frequently it is given.
Stoffel and colleagues found that fractional iron absorption was higher in iron-deficient women who were given iron every other day, compared with those who received daily iron.2 They also found that the more frequently iron was administered, the higher the hepcidin levels were, and the lower the iron absorption.
Karacok and colleagues studied every other day iron versus daily iron for the treatment of iron-deficiency anemia of pregnancy.3 A total of 217 women completed randomization and participated in the study, with all women receiving 100 mg of elemental iron, either daily (111) or every other day (106). There was no significant difference in increase in ferritin levels, or hemoglobin increase between the groups. The daily iron group had more gastrointestinal symptoms (41.4%) than the every other day iron group (15.1%) (P < .0057).
Düzen Oflas and colleagues looked at the same question in nonpregnant women with iron deficiency anemia.4 Study patients either received 80 mg iron sulfate twice a day, 80 mg once a day, or 80 mg every other day. There was no statistically significant difference in hemoglobin improvement between groups, but the group that received twice a day dosing of iron had statistically significantly higher ferritin levels than the daily or every other day iron groups. This improvement in ferritin levels came at a cost, though, as 68% of patients in the twice daily iron group had gastrointestinal symptoms, compared with only 10% in the every other day iron group (P < .01).
Vitamin C is often recommended to be taken with iron to promote absorption. The evidence for this practice is scant, and dates back almost 50 years.5,6
Cook and Reddy found there was no significant difference in mean iron absorption among the three dietary periods studied in 12 patients despite a range of mean daily intakes of dietary vitamin C of 51-247 mg/d.7
Hunt and colleagues studied 25 non pregnant, healthy women with low ferritin levels.8 The women’s meals were supplemented with vitamin C (500 mg, three times a day) for 5 of the 10 weeks, in a double-blind, crossover design. Vitamin C supplementation did not lead to a difference in iron absorption, lab indices of iron deficiency, or the biological half-life of iron.
Li and colleagues looked at the effect of vitamin C supplementation on iron levels in women with iron deficiency anemia.9 A total of 440 women were recruited, with 432 completing the trial. Women were randomized to receive iron supplements plus vitamin C or iron supplements only. Their findings were that oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption.
Bottom line
Less frequent administration of iron supplements (every other day) is as effective as more frequent administration, with less GI symptoms. Also, adding vitamin C does not appear to improve absorption of iron supplements.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. 1. Fairbanks VF and Beutler E. Iron deficiency, in “Williams Textbook of Hematology, 6th ed.” (New York: McGraw-Hill, 2001).
2. Stoffel N et al. Lancet Haematology. 2017;4: e524-33.
3. Karakoc G et al. J Matern Fetal Neonatal Med. 2021 Apr 18:1-5
4. Düzen Oflas N et al. Intern Med J. 2020 Jul;50(7):854-8
5. Cook JD and Monsen ER. Am J Clin Nutr. 1977;30:235-41.
6. Hallberg L etal. Hum Nutr Appl Nutr. 1986;40: 97-113.
7. Cook JD and Reddy M. Am J Clin Nutr. 2001;73:93-8.
8. Hunt JR et al. Am J Clin Nutr. 1994 Jun;59(6):1381-5.
9. Li N et al. JAMA Netw Open. 2020 Nov 2;3(11):e2023644.
Her blood work shows a hematocrit level of 32, a mean corpuscular volume of 77, a platelet count of 390,000, and a ferritin level of 5.
What would you recommend for iron replacement?
A. FeSO4 325 mg three times a day with vitamin C
B. FeSO4 325 mg daily with vitamin C
C. FeSO4 325 mg every other day
Recommendations and supporting research
I think I would start with choice C, FeSO4 every other day.
Treatment of iron deficiency with oral iron has traditionally been done by giving 150-200 mg of elemental iron (which is equal to three 325 mg tablets of iron sulfate).1 This dosing regimen has considerable gastrointestinal side effects. Recent evidence has shown that iron absorption is diminished the more frequently it is given.
Stoffel and colleagues found that fractional iron absorption was higher in iron-deficient women who were given iron every other day, compared with those who received daily iron.2 They also found that the more frequently iron was administered, the higher the hepcidin levels were, and the lower the iron absorption.
Karacok and colleagues studied every other day iron versus daily iron for the treatment of iron-deficiency anemia of pregnancy.3 A total of 217 women completed randomization and participated in the study, with all women receiving 100 mg of elemental iron, either daily (111) or every other day (106). There was no significant difference in increase in ferritin levels, or hemoglobin increase between the groups. The daily iron group had more gastrointestinal symptoms (41.4%) than the every other day iron group (15.1%) (P < .0057).
Düzen Oflas and colleagues looked at the same question in nonpregnant women with iron deficiency anemia.4 Study patients either received 80 mg iron sulfate twice a day, 80 mg once a day, or 80 mg every other day. There was no statistically significant difference in hemoglobin improvement between groups, but the group that received twice a day dosing of iron had statistically significantly higher ferritin levels than the daily or every other day iron groups. This improvement in ferritin levels came at a cost, though, as 68% of patients in the twice daily iron group had gastrointestinal symptoms, compared with only 10% in the every other day iron group (P < .01).
Vitamin C is often recommended to be taken with iron to promote absorption. The evidence for this practice is scant, and dates back almost 50 years.5,6
Cook and Reddy found there was no significant difference in mean iron absorption among the three dietary periods studied in 12 patients despite a range of mean daily intakes of dietary vitamin C of 51-247 mg/d.7
Hunt and colleagues studied 25 non pregnant, healthy women with low ferritin levels.8 The women’s meals were supplemented with vitamin C (500 mg, three times a day) for 5 of the 10 weeks, in a double-blind, crossover design. Vitamin C supplementation did not lead to a difference in iron absorption, lab indices of iron deficiency, or the biological half-life of iron.
Li and colleagues looked at the effect of vitamin C supplementation on iron levels in women with iron deficiency anemia.9 A total of 440 women were recruited, with 432 completing the trial. Women were randomized to receive iron supplements plus vitamin C or iron supplements only. Their findings were that oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption.
Bottom line
Less frequent administration of iron supplements (every other day) is as effective as more frequent administration, with less GI symptoms. Also, adding vitamin C does not appear to improve absorption of iron supplements.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. 1. Fairbanks VF and Beutler E. Iron deficiency, in “Williams Textbook of Hematology, 6th ed.” (New York: McGraw-Hill, 2001).
2. Stoffel N et al. Lancet Haematology. 2017;4: e524-33.
3. Karakoc G et al. J Matern Fetal Neonatal Med. 2021 Apr 18:1-5
4. Düzen Oflas N et al. Intern Med J. 2020 Jul;50(7):854-8
5. Cook JD and Monsen ER. Am J Clin Nutr. 1977;30:235-41.
6. Hallberg L etal. Hum Nutr Appl Nutr. 1986;40: 97-113.
7. Cook JD and Reddy M. Am J Clin Nutr. 2001;73:93-8.
8. Hunt JR et al. Am J Clin Nutr. 1994 Jun;59(6):1381-5.
9. Li N et al. JAMA Netw Open. 2020 Nov 2;3(11):e2023644.
Infusion centers may best EDs for treating sickle cell crises
At infusion centers, patients received pain medication an average of 70 minutes faster compared with patients treated in EDs (62 vs. 132 minutes), according to a study published online in the Annals of Internal Medicine. In addition, patients at infusion centers were 3.8 times more likely to have their pain reassessed within 30 minutes of the first dose. And they were 4 times more likely to be discharged home, the researchers found.
“It’s not that the emergency room doctors don’t want to do the right thing,” study author Sophie Lanzkron, MD, said in an interview. “They do, but they aren’t experts in sickle cell disease. They work in an emergency room, which is an incredibly busy, stressful place where they see trauma and heart attacks and strokes and all of these things that need emergency care. And so it just is not the right setting to treat people with sickle cell disease.”
To assess whether care at specialty infusion centers or EDs leads to better outcomes for patients with sickle cell disease with uncomplicated vaso-occlusive crises, Dr. Lanzkron, director of the Sickle Cell Center for Adults at the Johns Hopkins Hospital, Baltimore, and colleagues conducted the ESCAPED (Examining Sickle Cell Acute Pain in the Emergency vs. Day Hospital) study.
The trial included 483 adults with sickle cell disease who lived within 60 miles of an infusion center in four U.S. cities: Baltimore, Maryland; Cleveland, Ohio; Milwaukee, Wisconsin; and Baton Rouge, Louisiana. Investigators recruited patients between April 2015 and December 2016 and followed them for 18 months after enrollment.
The present analysis focused on data from 269 participants who had infusion center visits or ED visits that occurred during weekdays when infusion centers were open. Two sites had infusion centers solely for adults with sickle cell disease (Baltimore and Milwaukee), and two infusion centers shared infusion space with other hematology-oncology patients. All four sites were in hospitals that also had EDs.
Although participants may have received comprehensive care at one of the sites with an infusion center, those who lived farther from an infusion center were likely to receive care for acute pain at an ED closer to home, the authors explain in the article.
The investigators used propensity score methodology to balance patient characteristics in the study groups.
Quick, effective pain reduction is beneficial
The results suggest that infusion centers “are more likely to provide guideline-based care than EDs,” and this care “can improve overall outcomes,” the authors write.
Although the specialty infusion centers the researchers studied used various models, similar outcomes were seen at all of them.
The study did not include patients who had complications of sickle cell disease in addition to vaso-occlusive crisis, the researchers note.
“[Because] the magnitude of the treatment effects estimated in our study is large and we have captured most of the important potential confounders, an unmeasured confounder that can nullify the treatment effect is unlikely to exist,” the authors write.
“Sickle cell disease is a complicated condition that affects multiple organs. Patients who present with acute pain will have better outcomes being treated under providers who know and understand the disease,” commented Julie Kanter, MD, director of the adult sickle cell disease program and codirector of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham. “Specialized infusion centers offer the opportunity to both improve outcomes and decrease the cost of care. Most importantly, it is better for the individual with sickle cell disease,” she said.
Dr. Kanter wrote an accompanying editorial about the ESCAPED findings. The editorialist notes that “opioid medications are the only option to reduce the pain caused by microvascular injury” in patients with sickle cell crisis, although these treatments do not reduce the underlying damage and have substantial side effects and risks. Nevertheless, “quick and effective reduction of pain can allow patients to more easily move, stretch, and breathe ... important to increase oxygenation and restore blood flow, which will eventually abate the crisis,” Dr. Kanter wrote.
The study shows that the infusion center treatment approach can benefit patients across different settings, commented John J. Strouse, MD, PhD, medical director of the adult sickle cell program at Duke University Sickle Cell Center, Durham, N.C., who was not involved in the study.
“They show that they can definitely get closer to the recommendations of guidelines for acute pain management and sickle cell disease” in a setting that is focused on one problem, he said. “The other piece that is really important is that people are much more likely to go home if you follow the guideline.”
Infusion centers are scarce
“These systems need to be built,” Dr. Lanzkron said. “In most places, patients don’t have access to the infusion center model for their care. And in some places, it is not going to be practical.” Still, there may be ways to establish infusion locations, such as at oncology centers. And while there are challenges to delivering sickle cell disease care in EDs, “emergency rooms need to try to meet the needs of this patient population as best as they can,” Dr. Lanzkron said.
“Structural racism has played a role in the quality of care delivered” to patients with sickle cell disease, Dr. Lanzkron said. “The big message is [that] there is a better way to do this.”
The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Lanzkron’s disclosures included grants or contracts with government agencies and companies that are paid to her institution, as well as consulting fees from Bluebird Bio, Novo Nordisk, and Pfizer. Coauthors have disclosed working with sickle cell organizations and various medical companies. Dr. Kanter and Dr. Strouse have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
At infusion centers, patients received pain medication an average of 70 minutes faster compared with patients treated in EDs (62 vs. 132 minutes), according to a study published online in the Annals of Internal Medicine. In addition, patients at infusion centers were 3.8 times more likely to have their pain reassessed within 30 minutes of the first dose. And they were 4 times more likely to be discharged home, the researchers found.
“It’s not that the emergency room doctors don’t want to do the right thing,” study author Sophie Lanzkron, MD, said in an interview. “They do, but they aren’t experts in sickle cell disease. They work in an emergency room, which is an incredibly busy, stressful place where they see trauma and heart attacks and strokes and all of these things that need emergency care. And so it just is not the right setting to treat people with sickle cell disease.”
To assess whether care at specialty infusion centers or EDs leads to better outcomes for patients with sickle cell disease with uncomplicated vaso-occlusive crises, Dr. Lanzkron, director of the Sickle Cell Center for Adults at the Johns Hopkins Hospital, Baltimore, and colleagues conducted the ESCAPED (Examining Sickle Cell Acute Pain in the Emergency vs. Day Hospital) study.
The trial included 483 adults with sickle cell disease who lived within 60 miles of an infusion center in four U.S. cities: Baltimore, Maryland; Cleveland, Ohio; Milwaukee, Wisconsin; and Baton Rouge, Louisiana. Investigators recruited patients between April 2015 and December 2016 and followed them for 18 months after enrollment.
The present analysis focused on data from 269 participants who had infusion center visits or ED visits that occurred during weekdays when infusion centers were open. Two sites had infusion centers solely for adults with sickle cell disease (Baltimore and Milwaukee), and two infusion centers shared infusion space with other hematology-oncology patients. All four sites were in hospitals that also had EDs.
Although participants may have received comprehensive care at one of the sites with an infusion center, those who lived farther from an infusion center were likely to receive care for acute pain at an ED closer to home, the authors explain in the article.
The investigators used propensity score methodology to balance patient characteristics in the study groups.
Quick, effective pain reduction is beneficial
The results suggest that infusion centers “are more likely to provide guideline-based care than EDs,” and this care “can improve overall outcomes,” the authors write.
Although the specialty infusion centers the researchers studied used various models, similar outcomes were seen at all of them.
The study did not include patients who had complications of sickle cell disease in addition to vaso-occlusive crisis, the researchers note.
“[Because] the magnitude of the treatment effects estimated in our study is large and we have captured most of the important potential confounders, an unmeasured confounder that can nullify the treatment effect is unlikely to exist,” the authors write.
“Sickle cell disease is a complicated condition that affects multiple organs. Patients who present with acute pain will have better outcomes being treated under providers who know and understand the disease,” commented Julie Kanter, MD, director of the adult sickle cell disease program and codirector of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham. “Specialized infusion centers offer the opportunity to both improve outcomes and decrease the cost of care. Most importantly, it is better for the individual with sickle cell disease,” she said.
Dr. Kanter wrote an accompanying editorial about the ESCAPED findings. The editorialist notes that “opioid medications are the only option to reduce the pain caused by microvascular injury” in patients with sickle cell crisis, although these treatments do not reduce the underlying damage and have substantial side effects and risks. Nevertheless, “quick and effective reduction of pain can allow patients to more easily move, stretch, and breathe ... important to increase oxygenation and restore blood flow, which will eventually abate the crisis,” Dr. Kanter wrote.
The study shows that the infusion center treatment approach can benefit patients across different settings, commented John J. Strouse, MD, PhD, medical director of the adult sickle cell program at Duke University Sickle Cell Center, Durham, N.C., who was not involved in the study.
“They show that they can definitely get closer to the recommendations of guidelines for acute pain management and sickle cell disease” in a setting that is focused on one problem, he said. “The other piece that is really important is that people are much more likely to go home if you follow the guideline.”
Infusion centers are scarce
“These systems need to be built,” Dr. Lanzkron said. “In most places, patients don’t have access to the infusion center model for their care. And in some places, it is not going to be practical.” Still, there may be ways to establish infusion locations, such as at oncology centers. And while there are challenges to delivering sickle cell disease care in EDs, “emergency rooms need to try to meet the needs of this patient population as best as they can,” Dr. Lanzkron said.
“Structural racism has played a role in the quality of care delivered” to patients with sickle cell disease, Dr. Lanzkron said. “The big message is [that] there is a better way to do this.”
The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Lanzkron’s disclosures included grants or contracts with government agencies and companies that are paid to her institution, as well as consulting fees from Bluebird Bio, Novo Nordisk, and Pfizer. Coauthors have disclosed working with sickle cell organizations and various medical companies. Dr. Kanter and Dr. Strouse have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
At infusion centers, patients received pain medication an average of 70 minutes faster compared with patients treated in EDs (62 vs. 132 minutes), according to a study published online in the Annals of Internal Medicine. In addition, patients at infusion centers were 3.8 times more likely to have their pain reassessed within 30 minutes of the first dose. And they were 4 times more likely to be discharged home, the researchers found.
“It’s not that the emergency room doctors don’t want to do the right thing,” study author Sophie Lanzkron, MD, said in an interview. “They do, but they aren’t experts in sickle cell disease. They work in an emergency room, which is an incredibly busy, stressful place where they see trauma and heart attacks and strokes and all of these things that need emergency care. And so it just is not the right setting to treat people with sickle cell disease.”
To assess whether care at specialty infusion centers or EDs leads to better outcomes for patients with sickle cell disease with uncomplicated vaso-occlusive crises, Dr. Lanzkron, director of the Sickle Cell Center for Adults at the Johns Hopkins Hospital, Baltimore, and colleagues conducted the ESCAPED (Examining Sickle Cell Acute Pain in the Emergency vs. Day Hospital) study.
The trial included 483 adults with sickle cell disease who lived within 60 miles of an infusion center in four U.S. cities: Baltimore, Maryland; Cleveland, Ohio; Milwaukee, Wisconsin; and Baton Rouge, Louisiana. Investigators recruited patients between April 2015 and December 2016 and followed them for 18 months after enrollment.
The present analysis focused on data from 269 participants who had infusion center visits or ED visits that occurred during weekdays when infusion centers were open. Two sites had infusion centers solely for adults with sickle cell disease (Baltimore and Milwaukee), and two infusion centers shared infusion space with other hematology-oncology patients. All four sites were in hospitals that also had EDs.
Although participants may have received comprehensive care at one of the sites with an infusion center, those who lived farther from an infusion center were likely to receive care for acute pain at an ED closer to home, the authors explain in the article.
The investigators used propensity score methodology to balance patient characteristics in the study groups.
Quick, effective pain reduction is beneficial
The results suggest that infusion centers “are more likely to provide guideline-based care than EDs,” and this care “can improve overall outcomes,” the authors write.
Although the specialty infusion centers the researchers studied used various models, similar outcomes were seen at all of them.
The study did not include patients who had complications of sickle cell disease in addition to vaso-occlusive crisis, the researchers note.
“[Because] the magnitude of the treatment effects estimated in our study is large and we have captured most of the important potential confounders, an unmeasured confounder that can nullify the treatment effect is unlikely to exist,” the authors write.
“Sickle cell disease is a complicated condition that affects multiple organs. Patients who present with acute pain will have better outcomes being treated under providers who know and understand the disease,” commented Julie Kanter, MD, director of the adult sickle cell disease program and codirector of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham. “Specialized infusion centers offer the opportunity to both improve outcomes and decrease the cost of care. Most importantly, it is better for the individual with sickle cell disease,” she said.
Dr. Kanter wrote an accompanying editorial about the ESCAPED findings. The editorialist notes that “opioid medications are the only option to reduce the pain caused by microvascular injury” in patients with sickle cell crisis, although these treatments do not reduce the underlying damage and have substantial side effects and risks. Nevertheless, “quick and effective reduction of pain can allow patients to more easily move, stretch, and breathe ... important to increase oxygenation and restore blood flow, which will eventually abate the crisis,” Dr. Kanter wrote.
The study shows that the infusion center treatment approach can benefit patients across different settings, commented John J. Strouse, MD, PhD, medical director of the adult sickle cell program at Duke University Sickle Cell Center, Durham, N.C., who was not involved in the study.
“They show that they can definitely get closer to the recommendations of guidelines for acute pain management and sickle cell disease” in a setting that is focused on one problem, he said. “The other piece that is really important is that people are much more likely to go home if you follow the guideline.”
Infusion centers are scarce
“These systems need to be built,” Dr. Lanzkron said. “In most places, patients don’t have access to the infusion center model for their care. And in some places, it is not going to be practical.” Still, there may be ways to establish infusion locations, such as at oncology centers. And while there are challenges to delivering sickle cell disease care in EDs, “emergency rooms need to try to meet the needs of this patient population as best as they can,” Dr. Lanzkron said.
“Structural racism has played a role in the quality of care delivered” to patients with sickle cell disease, Dr. Lanzkron said. “The big message is [that] there is a better way to do this.”
The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Lanzkron’s disclosures included grants or contracts with government agencies and companies that are paid to her institution, as well as consulting fees from Bluebird Bio, Novo Nordisk, and Pfizer. Coauthors have disclosed working with sickle cell organizations and various medical companies. Dr. Kanter and Dr. Strouse have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.