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COVID update: ASH experts discuss thrombosis, immunity
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
NEW ORLEANS –
In a presidential symposium at the annual meeting of the American Society of Hematology, La Jolla Institute of Immunology scientist Shane Crotty, PhD, explained that COVID-19 has a “superpower” that allows it to be “extraordinarily stealthy.”
The virus, he said, can sneak past the body’s innate immune system, which normally responds to viral invaders within minutes to hours. “This is why you have people with high viral loads who are presymptomatic. Their innate immune system hasn’t even recognized that these people are infected.”
The adaptive immune system kicks in later. As Dr. Crotty noted, adaptive immunity is composed of three branches: B cells (the source of antibodies), CD4 “helper” T cells, and CD8 “killer” T cells. In the first year of COVID-19, his team tracked 188 subjects post infection in what he said was the largest study of its kind ever for any viral infection.
“In 8 months, 95% of people who had been infected still had measurable immune memory. In fact, most of them had multiple different compartments of immune memory still detectable, and it was likely that these individuals would still have that memory years into the future. Based on that, we made the prediction that most people who have had COVID-19 would likely be protected from reinfection – at least by severe infections – for 3 years into the future. That prediction has widely held up even in the presence of variants which weren’t around at the time.”
How do vaccines fit into the immunity picture? Dr. Crotty’s lab has tracked subjects who received 4 vaccines – Moderna, Pfizer/BioNTech, Janssen/Johnson & Johnson, and Novavax. Researchers found that the mRNA vaccines, Moderna and Pfizer/BioNTech, “are fantastic at eliciting neutralizing antibodies quickly, but then they drop off rapidly at two doses and actually continue to drop for 10 months.”
Still, he said, “when we take a look at 6 months, actually the vaccines are doing pretty incredibly well. If we compare them to an average infected individual, the mRNA vaccines all have higher neutralizing antibody titers.”
What’s happening? According to Dr. Crotty, B cells are “making guesses about what other variants might look like.” But he said research suggests that an important component of this process – germinal centers – aren’t made in some vaccinated people who are immunocompromised. (Germinal centers have been described as “microbial boot camps” for B cells.)
The good news, Dr. Crotty noted, is that a greater understanding of how COVID-19 penetrates various layers of adaptive immune defenses will lead to better ways to protect the immunocompromised. “If you think about immunity in this layered defense way, there are various ways that it could be enhanced for individuals in different categories,” he said.
Hematologist Beverley J. Hunt, MD, OBE, of St. Thomas’ Hospital/King’s Healthcare Partners in London, spoke at the ASH presidential symposium about blood clots and COVID-19. As she noted, concern arose about vaccine-related blood clots. A British team “managed quickly to come up with a diagnostic criteria,” she said. “We looked at nearly 300 patients and essentially came up with a scoring system.”
The diagnostic criteria was based on an analysis of definite or probable cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) – all related to the AstraZeneca vaccine. The criteria appeared in a 2021 study in the New England Journal of Medicine.
The report’s data didn’t allow it to compare the efficacy of anticoagulants. However, Dr. Hunt noted that clinicians turned to plasma exchange in patients with low platelet counts and extensive thrombosis. The report stated “survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics.”
“Now we’re following up,” Dr. Hunt said. One question to answer: Is long-term anticoagulation helpful? “We have many patients,” she said, “who are taking an anti-platelet factor out of habit.”
Dr. Crotty and Dr. Hunt report no disclosures. This reporter is a paid participant in a COVID vaccine study run by Dr. Crotty’s lab.
AT ASH 2022
AAP offers new guidance on child exploitation and sex trafficking
In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.
“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”
The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.
As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.
Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”
Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”
Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?
Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.
- The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
- The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
- The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.
What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.
“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”
That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.
And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”
The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”
Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.
The study has no external funding. The authors report no disclosures.
In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.
“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”
The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.
As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.
Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”
Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”
Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?
Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.
- The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
- The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
- The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.
What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.
“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”
That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.
And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”
The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”
Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.
The study has no external funding. The authors report no disclosures.
In a new updated report, the American Academy of Pediatrics urges pediatricians to understand signs of exploitation and labor/sex trafficking and learn how to support children and adolescents who are targeted.
“It’s incredibly scary when you encounter someone you worry is a victim, and you don’t know how to help them, and they’re not saying what’s going on,” pediatrician and report coauthor Dana Kaplan, MD, of Staten Island (N.Y.) University Hospital, said in an interview. “Every case is so unique and different: There’s no algorithm of ‘If A, then B, then C.’ You have to approach each person as an individual, and it takes time to make sure you’re thinking things through about how to provide what’s needed.”
The AAP published the clinical report, which is intended to provide guidance to pediatricians, in the January 2023 issue of Pediatrics. The organization previously tackled this topic in a 2017 clinical report, and Dr. Kaplan said the new report includes updated recommendations.
As the new report notes, there aren’t reliable estimates of exploited children in the United States, although millions are thought to be trafficked and subjected to forced labor around the world. “By virtue of their young age, children and adolescents are vulnerable to manipulation and exploitation, because they have limited life experiences, a need for attachment and acceptance, an immature prefrontal cortex ... and limited options for action,” the report says.
Dr. Kaplan puts it this way: “By the nature of being a child, you’re vulnerable.”
Still, health care professionals often aren’t trained in regard to human trafficking, the report says, even though it’s clear that they “must remain alert for the possibility.”
Dr. Kaplan, who has special training in child abuse and often sees children at risk, cautioned that children usually don’t directly say that they need help. “That’s generally not the case. They don’t articulate what’s going on around them as unsafe, or concerning, or dangerous. If you go and see a doctor for 10 minutes, are you going to tell them everything?
Instead, clinicians must often rely on their own observations. The report lists multiple possible signs of exploitation.
- The patient is accompanied by a domineering adult who does not allow the child to answer questions or accompanied by an unrelated adult. Inconsistent information is provided by the patient or companion. There’s a delay in seeking medical care.
- The patient has multiple sexually transmitted infections, previous pregnancy or termination, and/or frequent visits for emergency contraception. There are signs of prior sexual abuse, assault, or other maltreatment.
- The patient is withdrawn, fearful, hostile, or has a suspicious demeanor. The patient is constantly checking his or her phone and appears anxious or afraid.
What should clinicians do if they suspect exploitation? The report recommends that health care organizations develop guidelines for workers to follow. For her part, Dr. Kaplan advises colleagues to let patients lead conversations and not dig too deeply into their lives.
“Don’t turn into an investigator. This is not [Law & Order] SVU,” she said. “Stay focused on what you’re trained to do – provide health care.”
That doesn’t mean clinicians should ignore signs of trouble. It’s crucial to develop trust with the patient over time, she said, and turn to a specialist in your community or institution if you have suspicions.
And be careful to not portray victims as perpetrators. The new report emphasizes that “it’s important for health care providers to emphasize to authorities that the patient is a victim of exploitation who needs services rather than a juvenile offender.”
The report also highlights the importance of creating an environment that supports clinicians themselves: “Self-care for the clinician is critical in preventing and addressing secondary traumatic stress. A work environment that fosters peer support, encourages open discussion of work-related stress, and implements reasonable work-life balance policies can help protect providers from secondary stress and its consequences.”
Resources for clinicians include the National Human Trafficking Hotline, the federal Office of Trafficking in Persons, and the Centers for Disease Control and Prevention’s domestic refugee screening guidelines.
The study has no external funding. The authors report no disclosures.
FROM PEDIATRICS
Immunotherapy drug boosts survival in newly diagnosed ALL
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
NEW ORLEANS – The immunotherapy drug blinatumomab improves survival as a first-line treatment in certain younger adult patients with B-lineage acute lymphoblastic leukemia, investigators have found. The extremely expensive drug is currently Food and Drug Administration approved for B-lineage ALL in relapsed/refractory cases.
“We feel that this represents a new standard of care for these patients and should be incorporated into their standard therapy,” said lead author and hematologist Mark R. Litzow, MD, of Mayo Clinic in Rochester, Minn., in a news briefing at the annual meeting of the American Society of Hematology.
B-lineage ALL, also known as B-cell ALL, represents 75% of cases of the blood cancer in adults according to the Leukemia & Lymphoma Society. It occurs when there’s an overgrowth of immature white blood cells known as B-cell lymphoblasts. “These are the blast cells that don’t function well and cause these patients to develop infections and bleeding,” Dr. Litzow said.
Treatments include chemotherapy and stem-cell transplants. Blinatumomab, a bispecific T-cell engager molecule, is FDA approved for patients with relapsed/refractory B-lineage ALL and those with morphologic complete remission who still have measurable residual disease (MRD).
As the new study notes, some patients who undergo chemotherapy and reach remission have poor survival outcomes even when there’s no sign of MRD. “Even though we can’t find leukemia in the patients’ bone marrow, it’s still hiding there,” Dr. Litzow said.
The new phase 3, randomized trial aims to determine if adding blinatumomab (Blincyto) to first-line chemotherapy improves outcomes. The drug “brings a normal T cell, part of the immune system, in proximity to a leukemia plasma cell and kills it.”
For the study, researchers from 2013 to 2019 recruited 488 patients aged 30-70 years with newly diagnosed BCR::ABL1 negative B-lineage ALL (median age = 51). The subjects underwent chemotherapy, and then were “randomized to receive an additional four cycles of consolidation chemo or two cycles of blin [blinatumomab] for 28 days each cycle followed by three cycles of consolidation chemo, another 4-week cycle of blinatumomab (third cycle of blinatumomab) followed by an additional cycle of chemo and then a fourth cycle of blinatumomab (step 3),” the researchers reported. “Following completion of consolidation chemo +/– blin, patients were given 2.5 years of POMP [prednisone, vincristine, 6-mercaptopurine, and methotrexate] maintenance therapy timed from the start of the intensification cycle (step 4).”
There were 112 patients in each group. Among MRD-negative patients, 56 patients died – 17 in the blinatumomab arm and 39 in the control arm at the third interim efficacy analysis. At a mean follow-up of 43 months, median overall survival for patients in the blinatumomab arm was not reached vs. 71.4 months in the control group (hazard ratio, 0.42, 95% confidence interval, 0.24-0.75; P = .003).
“The patients that got blinatumomab plus chemotherapy had an improved survival over those that got the standard chemotherapy,” Dr. Litzow said.
Dr. Litzow didn’t discuss the drug’s expense in his presentation. According to a 2019 report, when a daily vial of blinatumomab cost $3,464-$3,815, a treatment course of five month-long cycles could run to $535,000. According to drugs.com, the cost now is $4,740 per vial – more than $660,000 for five cycles.
In an interview, Cleveland Clinic hematologist/oncologist Anjali Advani, MD, said the study is “groundbreaking and one of the most exciting studies to come along in the acute lymphoblastic leukemia field.”
The trial “is one of the first studies to show improvement in outcome in a randomized manner with the addition of a novel agent,” she added. “This will change our standard of care for these patients.”
The National Cancer Institute funded the trial and drug manufacturer Amgen provided the medication and support through a cooperative research and development agreement.
Dr. Litzow discloses relationships with Actinium, Jazz, Syndax, Novartis, Astellas, Amgen, Abbvie, Pluristem and Biosight. Other authors have various disclosures with multiple drugmakers. Dr. Advani discloses relationships with Amgen, Jazz, Nkarta, Taiho, Beam, GMI, Kura, Pfizer, OBI, Incyte, Kite, ImmunoGen, GlycoMimetics, SGN, MacroGenics, and Servier.
AT ASH 2022
Antipsychotic shows benefit for Alzheimer’s agitation
SAN FRANCISCO – In a widely anticipated report,
Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.
“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”
Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.
In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.
Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
Three trials
All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.
Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.
The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”
The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).
In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).
In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.
The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.
The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.
Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.
University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”
But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”
What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.
Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – In a widely anticipated report,
Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.
“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”
Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.
In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.
Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
Three trials
All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.
Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.
The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”
The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).
In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).
In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.
The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.
The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.
Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.
University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”
But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”
What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.
Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – In a widely anticipated report,
Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.
“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”
Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.
In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.
Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
Three trials
All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.
Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.
The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”
The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).
In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).
In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.
The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.
The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.
Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.
University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”
But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”
What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.
Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
A version of this article first appeared on Medscape.com.
AT CTAD 2022
Study: Formula-fed extreme preemies need more iron
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
NEW ORLEANS –
“We were surprised that, despite actually receiving more iron in total each day on average, the formula-fed infants were significantly more iron deficient than breast-fed babies. This is the opposite of what one would expect,” study lead author Grace Power, a medical student at Dalhousie University, Halifax, N.S., said in an interview. She presented the results at the annual meeting of the American Society of Hematology.
According to Ms. Power, there’s limited research into how breastfeeding and formula feeding affect iron levels in preterm infants – especially those born extremely early, between 23 and 30 weeks’ gestation.
“This kind of research is important because preterm infants are highly susceptible to iron deficiency for a number of reasons,” she said. “Iron deficiency early in life is associated with developmental and behavioral problems later on in life. That association still stands, even if the iron deficiency is corrected, so prevention is key in this population. Knowing more about how feeding type affects iron status can help us learn about ways to prevent iron deficiency in these infants in the future.”
For the study, researchers retrospectively analyzed data about all preterm infants (< 31 weeks gestation) in Nova Scotia from 2005 to 2018. Of the 392 infants in this group (55.75% male; average age, about 5 months), 285 were fed with iron-rich formula (mean intake, 1.66 mg/kg per day), and 107 were fully or partially breast fed. The two groups were similar in terms of traits such as mean birth weight and gestational age.
The formula-fed infants were more likely to develop iron deficiency (ID, 36.8%) than the breast-fed infants (20.6%; P = .002). “Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born less than 1,100 g (P = .01). More babies in the ID group received at least one blood transfusion,” the researchers reported. “ID infants had a higher daily formula intake, daily iron intake from formula, and total daily iron intake combined from formula and supplements.”
Why is there such a gap between formula-fed infants and breast-fed infants? The researchers speculated that infants absorb less iron from formula versus breast milk, possibly because of the presence of lactoferrin in breast milk.
The researchers also wondered whether physicians may pull back on iron supplementation in infants who undergo blood transfusions out of fear of the risk of iron overload, which Ms. Power said can cause infection and poor growth. By doing so, they may inadvertently deprive the babies of their need for iron.
“We don’t want clinicians to assume an infant doesn’t need iron supplementation just because they’ve received a blood transfusion,” she said.
As for an overall message from the research, Ms. Power said clinicians “should be aware that formula feeding can put infants at risk for iron deficiency and consider this when making decisions about supplementation.” And she noted that guidelines from the American Academy of Pediatrics and Canadian Pediatric Society don’t highlight the importance of iron supplementation in formula-fed, very preterm infants.
In an interview, University of Michigan pediatrician Michael K. Georgieff, MD, who has studied iron supplementation, said the study’s primary findings are surprising, although it makes sense that infants with lower gestational age and birth weight would suffer from more ID. Blood transfusion can indeed raise iron levels, but it’s important to consider that these infants may already have low levels of iron.
Dr. Georgieff advised colleagues to understand the potential for various nutritional deficiencies in preterm infants well beyond the first few weeks. When the babies are handed off to other clinicians such as pediatricians, they should undergo nutritional screening at 6 months, not at a year.
Dalhousie University funded the study. The study authors and Dr. Georgieff have no disclosures.
AT ASH 2022
ITP: Biologic beat placebo, but few patients improved
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
NEW ORLEANS –
Nevertheless, “efgartigimod demonstrated a strong clinical benefit,” said hematologist/oncologist and study lead author Catherine M. Broome, MD, of Georgetown University, Washington, in an interview about the findings presented at the annual meeting of the American Society of Hematology.
“The data showed statistically significant and clinically meaningful improvement in platelet counts over placebo, a fast and robust platelet count improvement over placebo, and the confirmed ability for every-other-week dosing, as well as a favorable safety and tolerability profile, consistent with previous clinical trials,” she said.
In ITP, according to the National Organization for Rare Disorders, “the patient’s immune system tags their own platelets as ‘foreign,’ leading their B lymphocytes and plasma cells to produce self-reactive antiplatelet antibodies that attach to platelet surface.”
The prevalence of ITP among adults in the United States is 9.5 per 100,000, NORD says. Children are also affected, but they usually recover. An estimated 60% of adults recover within 3 years.
Treatment options include corticosteroids and intravenous immunoglobulin.
“There are a relatively large number of current treatments, and they tend to work well for most patients. However, there are a minority of patients who do not respond to or tolerate current therapies and would benefit from new treatment options,” said hematologist Adam C. Cuker, MD, MS, of Penn Medicine, Philadelphia, in an interview. He is chair of ASH’s Committee on Quality.
For the new industry-funded ADVANCE study, researchers recruited patients with long-standing, persistent/chronic ITP (an average of two platelet counts of < 30×109/L).
Subjects were randomized 2:1 to receive 10 mg/kg of efgartigimod weekly – or response-dependent doses after the first 4 weeks – or placebo for 24 weeks. There were 86 patients in the intervention group and 45 in the placebo group. Overall, 60 were male and 71 were female; 107 were under 65; 121 were White and 8 were Asian. Details about the others were not provided.
Subjects were allowed to take several other drugs such as oral corticosteroids, and oral thrombopoietin receptor agonists other than romiplostim.
Per the primary endpoint, 17/78 (21.8%) reached a sustained response, defined as platelet counts ≥ 50×109/L in ≥ four of six visits between weeks 19 and 24 without intercurrent events, such as rescue therapy at week 12 or later. In the placebo group, 2/40 reached this response (5.0%; P = .0316).
“The primary endpoint was a high bar to achieve,” Dr. Broome said. “This was a difficult-to-treat patient population heavily pretreated and refractory to other treatments: 68.6% of patients in the efgartigimod arm had received three or more prior ITP treatments.”
She added that “subgroup analyses – including prior ITP therapy, time since diagnosis, baseline platelet count and age/region demographics – of patients who achieved the primary endpoint all favored efgartigimod over placebo.”
Side effects were extremely common among both the drug and placebo groups, and serious adverse events were common in the placebo group. No deaths were reported.
Efgartigimod, a neonatal Fc receptor blocker, is an extremely expensive drug that is Food and Drug Administration approved for some cases of generalized myasthenia gravis. According to a report in Neurology earlier this year, company statements listed its price as $855,400 a year; the report questioned its cost-effectiveness.
In response to a query about price, Luc Truyen, MD, PhD, chief medical officer of drug manufacturer Argenx, declined to talk about cost – a sensitive topic for pharmaceutical companies. “It is too early to discuss pricing and access as no regulatory submission or discussion has occurred,” Dr. Truyen said.
Penn Medicine’s Dr. Cuker, who is familiar with the study findings, said the primary endpoint results are not very impressive. “That said, it should be borne in mind that the patients enrolled in the trial tended to be heavily pretreated and refractory patients,” he said.
As for adverse effects, he said the drug “appears to be safe and well tolerated. The biggest theoretical concern with this class of drugs is an increased risk of infection due to lowering of IgG levels.”
It would be helpful to have trials that directly compare second-line therapies in ITP, he added. “Unfortunately, no such trials exist, and pharmaceutical companies would not be motivated to conduct them.”
For now, he said, off-label use of efgartigimod “may be reasonable, but only in rare situations where other approved and better established ITP treatments have been exhausted.”
What’s next? According to Dr. Broome, another trial is currently evaluating efgartigimod for the treatment of primary ITP, with top-line data expected in the second half of 2023.
The study was funded by Argenx. Dr. Broome discloses honoraria from Alexion, Argenx, Apellis, and Sano. Dr. Truyen’s disclosures weren’t available. Dr. Cuker has no disclosures.
AT ASH 2022
MCL: Ibrutinib could become the ‘new standard’
First-line patients fared well on ibrutinib, a Bruton’s tyrosine kinase inhibitor, according to the findings.
“Based on the results so far ... at least for the majority of patients, ibrutinib early will become the new standard,” said study lead author Martin Dreyling, MD, associate professor of medicine at Ludwig Maximilian University (LMU) Munich. Dr. Dreyling spoke in a news briefing and at a separate presentation at the annual meeting of the American Society of Hematology. “It might well be that specific subsets of patients may benefit from autologous transplant.”
MCL is a rare form of non-Hodgkin’s lymphoma that strikes cells in the mantle zone of lymph nodes. It is usually diagnosed in older men and often presents at an advanced stage. Multiple available treatments include rituximab/bendamustine, CAR-T cell therapy, stem cell transplants, and Bruton’s tyrosine kinase inhibitors. Ibrutinib is approved by the Food and Drug Administration only for refractory/relapsed cases, however.
Dr. Dreyling was a pioneer in confirming benefit from stem-cell transplants for MCL. “However,” he said, “no one likes autologous transplant because it also has side effects.”
For the new open-label study, Dr. Dreyling and colleagues in the European MCL Network in 2016 began recruiting patients with newly diagnosed, advanced stage II-IV MCL. The patients were younger than 65.
The subjects were randomly assigned to three trial arms: Standard treatment (high-dose cytarabine followed by autologous stem cell transplant and rituximab maintenance, n = 288), the standard treatment plus ibrutinib (n = 292), and ibrutinib without stem cell transplant (n = 290). The median age was 57, and 76% of patients were male.
The primary endpoint was failure-free survival at 31 months. Standard therapy was not superior to the ibrutinib without transplant group (72% vs. 86%, respectively, P = .9979). However, standard therapy with ibrutinib was superior to the standard therapy group (88% vs. 72%, respectively, P = .0008). The researchers haven’t finished their analysis of standard therapy with ibrutinib vs. ibrutinib without transplant.
Subjects in the standard therapy plus ibrutinib arm had more grade 3-5 adverse events than did the standard therapy and ibrutinib without transplant groups: Neutropenia, 44%, 17%, and 23%, respectively; leukopenia, 4%, 2%, and 2%; febrile neutropenia, 6%, 3%, and 3%; infections and infestations, 25%, 13%, and 19%; and cardiac disorders, 3%, 1%, 4%. P values were not provided.
In an interview, Ohio State University hematologist Narendranath Epperla, MD, MS, who was not involved in the study, said that this research reflects efforts to understand how novel agents such as ibrutinib and cellular therapies fit into MCL treatment. “We are trying to incorporate them in the frontline setting with either chemo backbone or with other targeted agents to improve outcomes and minimize toxicity. We are also trying to understand in whom auto-HCT can be precluded.”
The results of the new study appear promising, Dr. Epperla said, but he questioned the primary endpoint (failure-free survival instead of progress-free survival) and the short duration of the trial.
“I would like to see how the patients with high-risk features such as TP53 mutation, complex cytogenetics, and blastoid/pleomorphic variants did on the three arms,” Dr. Epperla said. “And I would like to see longer follow-up data before adapting this – [addition] of ibrutinib to the chemotherapy backbone without auto-HCT – into clinical practice.”
What’s next? Dr. Dreyling said that upcoming data will provide further insight into ibrutinib vs. stem-cell transplantation. And “within the next half year or so,” he said, “there will be a next generation of studies challenging chemotherapy overall in mantle cell lymphoma and substituting targeted treatment, hopefully achieving much better tolerability.”
Funding information was not provided. Dr. Dreyling disclosed ties with Lilly/Loxo, AstraZeneca, Novartis, Amgen, Roche, Janssen, Gilead/Kite, BMS/Celgene, Bayer, Abbvie, and Beigene. The other study authors reported various disclosures. Dr. Epperla disclosed a relationship with Pharmacyclics.
First-line patients fared well on ibrutinib, a Bruton’s tyrosine kinase inhibitor, according to the findings.
“Based on the results so far ... at least for the majority of patients, ibrutinib early will become the new standard,” said study lead author Martin Dreyling, MD, associate professor of medicine at Ludwig Maximilian University (LMU) Munich. Dr. Dreyling spoke in a news briefing and at a separate presentation at the annual meeting of the American Society of Hematology. “It might well be that specific subsets of patients may benefit from autologous transplant.”
MCL is a rare form of non-Hodgkin’s lymphoma that strikes cells in the mantle zone of lymph nodes. It is usually diagnosed in older men and often presents at an advanced stage. Multiple available treatments include rituximab/bendamustine, CAR-T cell therapy, stem cell transplants, and Bruton’s tyrosine kinase inhibitors. Ibrutinib is approved by the Food and Drug Administration only for refractory/relapsed cases, however.
Dr. Dreyling was a pioneer in confirming benefit from stem-cell transplants for MCL. “However,” he said, “no one likes autologous transplant because it also has side effects.”
For the new open-label study, Dr. Dreyling and colleagues in the European MCL Network in 2016 began recruiting patients with newly diagnosed, advanced stage II-IV MCL. The patients were younger than 65.
The subjects were randomly assigned to three trial arms: Standard treatment (high-dose cytarabine followed by autologous stem cell transplant and rituximab maintenance, n = 288), the standard treatment plus ibrutinib (n = 292), and ibrutinib without stem cell transplant (n = 290). The median age was 57, and 76% of patients were male.
The primary endpoint was failure-free survival at 31 months. Standard therapy was not superior to the ibrutinib without transplant group (72% vs. 86%, respectively, P = .9979). However, standard therapy with ibrutinib was superior to the standard therapy group (88% vs. 72%, respectively, P = .0008). The researchers haven’t finished their analysis of standard therapy with ibrutinib vs. ibrutinib without transplant.
Subjects in the standard therapy plus ibrutinib arm had more grade 3-5 adverse events than did the standard therapy and ibrutinib without transplant groups: Neutropenia, 44%, 17%, and 23%, respectively; leukopenia, 4%, 2%, and 2%; febrile neutropenia, 6%, 3%, and 3%; infections and infestations, 25%, 13%, and 19%; and cardiac disorders, 3%, 1%, 4%. P values were not provided.
In an interview, Ohio State University hematologist Narendranath Epperla, MD, MS, who was not involved in the study, said that this research reflects efforts to understand how novel agents such as ibrutinib and cellular therapies fit into MCL treatment. “We are trying to incorporate them in the frontline setting with either chemo backbone or with other targeted agents to improve outcomes and minimize toxicity. We are also trying to understand in whom auto-HCT can be precluded.”
The results of the new study appear promising, Dr. Epperla said, but he questioned the primary endpoint (failure-free survival instead of progress-free survival) and the short duration of the trial.
“I would like to see how the patients with high-risk features such as TP53 mutation, complex cytogenetics, and blastoid/pleomorphic variants did on the three arms,” Dr. Epperla said. “And I would like to see longer follow-up data before adapting this – [addition] of ibrutinib to the chemotherapy backbone without auto-HCT – into clinical practice.”
What’s next? Dr. Dreyling said that upcoming data will provide further insight into ibrutinib vs. stem-cell transplantation. And “within the next half year or so,” he said, “there will be a next generation of studies challenging chemotherapy overall in mantle cell lymphoma and substituting targeted treatment, hopefully achieving much better tolerability.”
Funding information was not provided. Dr. Dreyling disclosed ties with Lilly/Loxo, AstraZeneca, Novartis, Amgen, Roche, Janssen, Gilead/Kite, BMS/Celgene, Bayer, Abbvie, and Beigene. The other study authors reported various disclosures. Dr. Epperla disclosed a relationship with Pharmacyclics.
First-line patients fared well on ibrutinib, a Bruton’s tyrosine kinase inhibitor, according to the findings.
“Based on the results so far ... at least for the majority of patients, ibrutinib early will become the new standard,” said study lead author Martin Dreyling, MD, associate professor of medicine at Ludwig Maximilian University (LMU) Munich. Dr. Dreyling spoke in a news briefing and at a separate presentation at the annual meeting of the American Society of Hematology. “It might well be that specific subsets of patients may benefit from autologous transplant.”
MCL is a rare form of non-Hodgkin’s lymphoma that strikes cells in the mantle zone of lymph nodes. It is usually diagnosed in older men and often presents at an advanced stage. Multiple available treatments include rituximab/bendamustine, CAR-T cell therapy, stem cell transplants, and Bruton’s tyrosine kinase inhibitors. Ibrutinib is approved by the Food and Drug Administration only for refractory/relapsed cases, however.
Dr. Dreyling was a pioneer in confirming benefit from stem-cell transplants for MCL. “However,” he said, “no one likes autologous transplant because it also has side effects.”
For the new open-label study, Dr. Dreyling and colleagues in the European MCL Network in 2016 began recruiting patients with newly diagnosed, advanced stage II-IV MCL. The patients were younger than 65.
The subjects were randomly assigned to three trial arms: Standard treatment (high-dose cytarabine followed by autologous stem cell transplant and rituximab maintenance, n = 288), the standard treatment plus ibrutinib (n = 292), and ibrutinib without stem cell transplant (n = 290). The median age was 57, and 76% of patients were male.
The primary endpoint was failure-free survival at 31 months. Standard therapy was not superior to the ibrutinib without transplant group (72% vs. 86%, respectively, P = .9979). However, standard therapy with ibrutinib was superior to the standard therapy group (88% vs. 72%, respectively, P = .0008). The researchers haven’t finished their analysis of standard therapy with ibrutinib vs. ibrutinib without transplant.
Subjects in the standard therapy plus ibrutinib arm had more grade 3-5 adverse events than did the standard therapy and ibrutinib without transplant groups: Neutropenia, 44%, 17%, and 23%, respectively; leukopenia, 4%, 2%, and 2%; febrile neutropenia, 6%, 3%, and 3%; infections and infestations, 25%, 13%, and 19%; and cardiac disorders, 3%, 1%, 4%. P values were not provided.
In an interview, Ohio State University hematologist Narendranath Epperla, MD, MS, who was not involved in the study, said that this research reflects efforts to understand how novel agents such as ibrutinib and cellular therapies fit into MCL treatment. “We are trying to incorporate them in the frontline setting with either chemo backbone or with other targeted agents to improve outcomes and minimize toxicity. We are also trying to understand in whom auto-HCT can be precluded.”
The results of the new study appear promising, Dr. Epperla said, but he questioned the primary endpoint (failure-free survival instead of progress-free survival) and the short duration of the trial.
“I would like to see how the patients with high-risk features such as TP53 mutation, complex cytogenetics, and blastoid/pleomorphic variants did on the three arms,” Dr. Epperla said. “And I would like to see longer follow-up data before adapting this – [addition] of ibrutinib to the chemotherapy backbone without auto-HCT – into clinical practice.”
What’s next? Dr. Dreyling said that upcoming data will provide further insight into ibrutinib vs. stem-cell transplantation. And “within the next half year or so,” he said, “there will be a next generation of studies challenging chemotherapy overall in mantle cell lymphoma and substituting targeted treatment, hopefully achieving much better tolerability.”
Funding information was not provided. Dr. Dreyling disclosed ties with Lilly/Loxo, AstraZeneca, Novartis, Amgen, Roche, Janssen, Gilead/Kite, BMS/Celgene, Bayer, Abbvie, and Beigene. The other study authors reported various disclosures. Dr. Epperla disclosed a relationship with Pharmacyclics.
AT ASH 2022
SSRI tied to improved cognition in comorbid depression, dementia
The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.
“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.
“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.
However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.
“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.
Potential neurotransmission modulator
Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”
The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.
Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.
The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.
In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.
“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.
“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.
More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.
For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”
A third of patients had drug-related treatment-emergent adverse events.
Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.
Small trial, open-label design
In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”
She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.
The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.
A version of this article first appeared on Medscape.com.
The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.
“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.
“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.
However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.
“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.
Potential neurotransmission modulator
Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”
The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.
Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.
The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.
In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.
“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.
“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.
More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.
For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”
A third of patients had drug-related treatment-emergent adverse events.
Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.
Small trial, open-label design
In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”
She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.
The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.
A version of this article first appeared on Medscape.com.
The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.
“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.
“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.
However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.
“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.
Potential neurotransmission modulator
Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”
The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.
Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.
The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.
In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.
“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.
“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.
More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.
For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”
A third of patients had drug-related treatment-emergent adverse events.
Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.
Small trial, open-label design
In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”
She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.
The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.
A version of this article first appeared on Medscape.com.
FROM CTAD 2022
Melanoma mortality rates fell in 2010s as new therapies took hold
, a new study finds, although the dip appeared to stabilize over the next 2 years.
“This data is very encouraging and represents the real-world effectiveness of these newer therapies, which include immunotherapies and targeted therapies,” hematologist/oncologist Navkirat Kahlon, MD, MPH, of Seacoast Cancer Center and Massachusetts General Brigham Wentworth-Douglass Hospital, Dover, N.H., one of the study authors, said in an interview. In clinical trials, these new treatments “have been very effective ... so the timing as well as magnitude of drop seen in melanoma-specific population mortality was not at all surprising. But it’s still very exciting.”
The report, published in JAMA Network Open, tracked mortality rates for the deadliest form of skin cancer from 1975 to 2019. The researchers launched the study to better understand outcomes in cutaneous melanoma following the rise of new therapies that now provide options in addition to chemotherapy. “With the use of novel therapies, the survival of these patients has increased from a few weeks or months to many years in clinical trials,” Dr. Kahlon said. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world U.S. population is deriving the same benefit.”
New drugs introduced in recent years include immunotherapy agents such as ipilimumab and targeted therapies such as vemurafenib.
The researchers analyzed age-adjusted melanoma outcome data from the Surveillance, Epidemiology, and End Results (SEER) database. In 1975, the long-term melanoma mortality rate for melanoma was 2.07 per 100,000 people (95% confidence interval [CI], 2.00-2.13). It rose to 2.65 (95% CI, 2.58-2.65) in 1988 and 2.67 (95% CI, 2.61-2.72) in 2013, then fell to 2.09 (95% CI, 2.05-2.14) in 2017 and 2.01 (95% CI, 1.97-2.06) in 2019.
Per the analysis, the rate grew at an annual percentage change (APC) of 1.65% (95% CI, 1.30%-2.00%, P < .001) from 1975 to 1988 and remained stable from 1988 to 2013 (P = .85). Then it fell by an APC of 6.28% (95% CI, –8.52% to –3.97%, P < .001) from 2013 to 2017. There was no statistically significant difference between 2017 and 2019, although “the trend was downward,” the authors noted.
“Our study didn’t study the parameters that can answer the question about how many more years of life patients are getting or how many lives aren’t lost,” Dr. Kahlon said in the interview. “But looking at other studies and clinical trial data, the prognosis of these patients with a historical median overall survival of a few weeks to months has improved to many months to years.”
But why do melanoma mortality rates remain roughly about the same as they were in 1975? “The incidence of melanoma has continued to rise,” she said. “Also, over time, we have become better at collecting more accurate information, so the [rate] in 1975 could potentially be an underestimated rate.”
In an interview, dermatologist Adewole “Ade” Adamson, MD, MPP, of the University of Texas at Austin, noted that a 2020 study examined melanoma death rates in Whites – who are most affected by melanoma – and found similar trends from 2013 to 2016. “Nothing about these [new] findings surprises me as they have been shown before. However, these confirmatory findings are reassuring because they show the powerful effect of novel treatments at a population level.”
Which treatments are making the biggest difference? “It is difficult to say, but it’s likely immunotherapy because some patients on these medications have durable responses for many years,” Dr. Adamson said. “Studies are ongoing to figure out just how much more life some patients may expect after treatment.”
He added that “while this study did not evaluate mortality trends by race or ethnicity, it is important to note that the sharp decline in melanoma mortality rates is exclusively among non-Hispanic White Americans.”
Dermatologist David Polsky, MD, PhD, professor of dermatologic oncology at New York (N.Y.) University, said in an interview that the findings reflect extraordinary progress in melanoma treatment. “Historically, only 10% of metastatic melanoma patients would live 5 years. And now 30% to 50% of metastatic patients are living 5 years. That’s amazing to me,” said Dr. Polsky, who coauthored the 2020 report cited by Dr. Adamson.
A few years ago, Dr. Polsky added, he talked to an oncologist about how life at her clinic had changed as a result of new melanoma treatments. “She said, ‘My clinic has gotten really crowded. It used to be that patients died in a span of about a year and a half, and I would turn over my patient population. Now all those patients are still alive, and I’m getting new patients.’”
The study was funded by the University of Toledo College of Medicine and Life Sciences. One author reported receiving honoraria from Boston Healthcare Associates and research funding from Bayer, ImmunoVaccine, and the Ludwig Institute for Cancer Research. Dr. Polsky disclosed relationships with Merck (advisory board) and Novartis and Bristol Myers Squibb (consulting). Dr. Adamson disclosed he is web editor and associate editor at JAMA Dermatology.
, a new study finds, although the dip appeared to stabilize over the next 2 years.
“This data is very encouraging and represents the real-world effectiveness of these newer therapies, which include immunotherapies and targeted therapies,” hematologist/oncologist Navkirat Kahlon, MD, MPH, of Seacoast Cancer Center and Massachusetts General Brigham Wentworth-Douglass Hospital, Dover, N.H., one of the study authors, said in an interview. In clinical trials, these new treatments “have been very effective ... so the timing as well as magnitude of drop seen in melanoma-specific population mortality was not at all surprising. But it’s still very exciting.”
The report, published in JAMA Network Open, tracked mortality rates for the deadliest form of skin cancer from 1975 to 2019. The researchers launched the study to better understand outcomes in cutaneous melanoma following the rise of new therapies that now provide options in addition to chemotherapy. “With the use of novel therapies, the survival of these patients has increased from a few weeks or months to many years in clinical trials,” Dr. Kahlon said. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world U.S. population is deriving the same benefit.”
New drugs introduced in recent years include immunotherapy agents such as ipilimumab and targeted therapies such as vemurafenib.
The researchers analyzed age-adjusted melanoma outcome data from the Surveillance, Epidemiology, and End Results (SEER) database. In 1975, the long-term melanoma mortality rate for melanoma was 2.07 per 100,000 people (95% confidence interval [CI], 2.00-2.13). It rose to 2.65 (95% CI, 2.58-2.65) in 1988 and 2.67 (95% CI, 2.61-2.72) in 2013, then fell to 2.09 (95% CI, 2.05-2.14) in 2017 and 2.01 (95% CI, 1.97-2.06) in 2019.
Per the analysis, the rate grew at an annual percentage change (APC) of 1.65% (95% CI, 1.30%-2.00%, P < .001) from 1975 to 1988 and remained stable from 1988 to 2013 (P = .85). Then it fell by an APC of 6.28% (95% CI, –8.52% to –3.97%, P < .001) from 2013 to 2017. There was no statistically significant difference between 2017 and 2019, although “the trend was downward,” the authors noted.
“Our study didn’t study the parameters that can answer the question about how many more years of life patients are getting or how many lives aren’t lost,” Dr. Kahlon said in the interview. “But looking at other studies and clinical trial data, the prognosis of these patients with a historical median overall survival of a few weeks to months has improved to many months to years.”
But why do melanoma mortality rates remain roughly about the same as they were in 1975? “The incidence of melanoma has continued to rise,” she said. “Also, over time, we have become better at collecting more accurate information, so the [rate] in 1975 could potentially be an underestimated rate.”
In an interview, dermatologist Adewole “Ade” Adamson, MD, MPP, of the University of Texas at Austin, noted that a 2020 study examined melanoma death rates in Whites – who are most affected by melanoma – and found similar trends from 2013 to 2016. “Nothing about these [new] findings surprises me as they have been shown before. However, these confirmatory findings are reassuring because they show the powerful effect of novel treatments at a population level.”
Which treatments are making the biggest difference? “It is difficult to say, but it’s likely immunotherapy because some patients on these medications have durable responses for many years,” Dr. Adamson said. “Studies are ongoing to figure out just how much more life some patients may expect after treatment.”
He added that “while this study did not evaluate mortality trends by race or ethnicity, it is important to note that the sharp decline in melanoma mortality rates is exclusively among non-Hispanic White Americans.”
Dermatologist David Polsky, MD, PhD, professor of dermatologic oncology at New York (N.Y.) University, said in an interview that the findings reflect extraordinary progress in melanoma treatment. “Historically, only 10% of metastatic melanoma patients would live 5 years. And now 30% to 50% of metastatic patients are living 5 years. That’s amazing to me,” said Dr. Polsky, who coauthored the 2020 report cited by Dr. Adamson.
A few years ago, Dr. Polsky added, he talked to an oncologist about how life at her clinic had changed as a result of new melanoma treatments. “She said, ‘My clinic has gotten really crowded. It used to be that patients died in a span of about a year and a half, and I would turn over my patient population. Now all those patients are still alive, and I’m getting new patients.’”
The study was funded by the University of Toledo College of Medicine and Life Sciences. One author reported receiving honoraria from Boston Healthcare Associates and research funding from Bayer, ImmunoVaccine, and the Ludwig Institute for Cancer Research. Dr. Polsky disclosed relationships with Merck (advisory board) and Novartis and Bristol Myers Squibb (consulting). Dr. Adamson disclosed he is web editor and associate editor at JAMA Dermatology.
, a new study finds, although the dip appeared to stabilize over the next 2 years.
“This data is very encouraging and represents the real-world effectiveness of these newer therapies, which include immunotherapies and targeted therapies,” hematologist/oncologist Navkirat Kahlon, MD, MPH, of Seacoast Cancer Center and Massachusetts General Brigham Wentworth-Douglass Hospital, Dover, N.H., one of the study authors, said in an interview. In clinical trials, these new treatments “have been very effective ... so the timing as well as magnitude of drop seen in melanoma-specific population mortality was not at all surprising. But it’s still very exciting.”
The report, published in JAMA Network Open, tracked mortality rates for the deadliest form of skin cancer from 1975 to 2019. The researchers launched the study to better understand outcomes in cutaneous melanoma following the rise of new therapies that now provide options in addition to chemotherapy. “With the use of novel therapies, the survival of these patients has increased from a few weeks or months to many years in clinical trials,” Dr. Kahlon said. “Given the magnitude of benefit compared to traditional chemotherapy in clinical trials, we decided to see if the real-world U.S. population is deriving the same benefit.”
New drugs introduced in recent years include immunotherapy agents such as ipilimumab and targeted therapies such as vemurafenib.
The researchers analyzed age-adjusted melanoma outcome data from the Surveillance, Epidemiology, and End Results (SEER) database. In 1975, the long-term melanoma mortality rate for melanoma was 2.07 per 100,000 people (95% confidence interval [CI], 2.00-2.13). It rose to 2.65 (95% CI, 2.58-2.65) in 1988 and 2.67 (95% CI, 2.61-2.72) in 2013, then fell to 2.09 (95% CI, 2.05-2.14) in 2017 and 2.01 (95% CI, 1.97-2.06) in 2019.
Per the analysis, the rate grew at an annual percentage change (APC) of 1.65% (95% CI, 1.30%-2.00%, P < .001) from 1975 to 1988 and remained stable from 1988 to 2013 (P = .85). Then it fell by an APC of 6.28% (95% CI, –8.52% to –3.97%, P < .001) from 2013 to 2017. There was no statistically significant difference between 2017 and 2019, although “the trend was downward,” the authors noted.
“Our study didn’t study the parameters that can answer the question about how many more years of life patients are getting or how many lives aren’t lost,” Dr. Kahlon said in the interview. “But looking at other studies and clinical trial data, the prognosis of these patients with a historical median overall survival of a few weeks to months has improved to many months to years.”
But why do melanoma mortality rates remain roughly about the same as they were in 1975? “The incidence of melanoma has continued to rise,” she said. “Also, over time, we have become better at collecting more accurate information, so the [rate] in 1975 could potentially be an underestimated rate.”
In an interview, dermatologist Adewole “Ade” Adamson, MD, MPP, of the University of Texas at Austin, noted that a 2020 study examined melanoma death rates in Whites – who are most affected by melanoma – and found similar trends from 2013 to 2016. “Nothing about these [new] findings surprises me as they have been shown before. However, these confirmatory findings are reassuring because they show the powerful effect of novel treatments at a population level.”
Which treatments are making the biggest difference? “It is difficult to say, but it’s likely immunotherapy because some patients on these medications have durable responses for many years,” Dr. Adamson said. “Studies are ongoing to figure out just how much more life some patients may expect after treatment.”
He added that “while this study did not evaluate mortality trends by race or ethnicity, it is important to note that the sharp decline in melanoma mortality rates is exclusively among non-Hispanic White Americans.”
Dermatologist David Polsky, MD, PhD, professor of dermatologic oncology at New York (N.Y.) University, said in an interview that the findings reflect extraordinary progress in melanoma treatment. “Historically, only 10% of metastatic melanoma patients would live 5 years. And now 30% to 50% of metastatic patients are living 5 years. That’s amazing to me,” said Dr. Polsky, who coauthored the 2020 report cited by Dr. Adamson.
A few years ago, Dr. Polsky added, he talked to an oncologist about how life at her clinic had changed as a result of new melanoma treatments. “She said, ‘My clinic has gotten really crowded. It used to be that patients died in a span of about a year and a half, and I would turn over my patient population. Now all those patients are still alive, and I’m getting new patients.’”
The study was funded by the University of Toledo College of Medicine and Life Sciences. One author reported receiving honoraria from Boston Healthcare Associates and research funding from Bayer, ImmunoVaccine, and the Ludwig Institute for Cancer Research. Dr. Polsky disclosed relationships with Merck (advisory board) and Novartis and Bristol Myers Squibb (consulting). Dr. Adamson disclosed he is web editor and associate editor at JAMA Dermatology.
FROM JAMA NETWORK OPEN
Post-transplant diet: Gruel no longer rules
NEW ORLEANS – A new Italian study yields more evidence that stem-cell transplant patients need not lose their appetites along with their immune systems. Low-bacterial, gruel-like diets, once the mainstay of immunity-lowering surgeries, don’t actually provide any protection against infections, researchers reported.
University of Miami hematologist Mikkael A. Sekeres, MD, MS, expressed delight to hear these findings.
“Around the world, we should eliminate these silly neutropenic diets, let people eat what they want, and give them a much better quality of life while they’re in the hospital,” said Dr. Sekeres, moderator of the news briefing where these research results were discussed at the annual meeting of the American Society of Hematology.
In recent decades, physicians and nutritionists have questioned the value of low-bacterial/neutropenic menus, designed to protect people with compromised immune systems from germs in food. These diets can be quite strict, outlawing food such as deli, processed, and cured meats; yogurt; hummus; strawberries and raspberries; lettuce; raw nuts; certain kinds of seafood; and herbs and spices such as pepper, unless they were cooked. Patients may be urged to avoid salad bars, buffets, and potlucks.
MD Anderson Cancer Center pediatrician Karen Moody, MD, MS, who has studied the diet, said in an interview that the diet has been around since the 1970s, despite a lack of evidence supporting it. “Cancer patients often suffer from treatment-related side effects that affect taste, appetite, and tolerance of food,” she said. “Further restricting food options in this population can be burdensome and reduce diet-related satisfaction.”
For the new multi-center, phase 3 study, researchers led by hematology resident Federico Stella, MD, of the University of Milan, randomly assigned consecutive adult patients undergoing hematopoietic stem cells transplantation or high-dose induction chemotherapy to either a low-bacterial diet (n = 224) or a non-restrictive diet (n = 224).
The low-bacterial diet emphasized food cooked to at least 176 degrees Fahrenheit and thick-skinned fruit. Raw fruits/vegetables, yogurt, honey, cold cuts and sausages, and raw fish and meat were forbidden.
The two groups were similar in age (median = 56 years), gender (about 57% male), and reason for admission (97% stem-cell transplants and 3% high-dose chemotherapy). The plan was to follow the patients for 100 days (stem-cell transplant recipients) or 30 days (high-dose chemotherapy patients).
No statistically significant differences between the group were found in the rates of infections of higher than Grade 2 (per CTCAE 4.0): These infections occurred in 38 (34%) of those on the low-bacterial diet and 44 (39%) of those on the non-restrictive diet (P = 0.5).
There were also no statistically significant differences in rates of fever of unknown origin (P = 0.2), sepsis (P = 0.5), and gastrointestinal infection (P = 0.7).
The findings show that the “use of a restrictive diet is an unnecessary burden for our patients’ quality of life,” said study lead author Dr. Stella at the news briefing.
Dr. Sekeres, the news briefing moderator, noted that the findings reflect his own suspicions about the worthlessness of the low-bacterial diet. “I’ve never seen a patient die of an infection that was foodborne. So years ago, when I was still in Cleveland, I eliminated the neutropenic diet on the leukemia floor. That did face a lot of resistance, as you can imagine. There were decades of people saying we should do this.”
Now, Dr. Sekeres said, he feels validated. “I love this study because it formalizes what I thought was true,” he said.
Dr. Moody said it’s difficult to evaluate the study since it’s in abstract form, and details are limited. “However,” she said, “the sample size, study design, and outcomes appear very appropriate, and I think most likely the full-length study will provide additional evidence to support abandonment of the low-microbial diet in transplant patients.”
Also, Dr. Moody said, the study “replicates the same findings of other prospective randomized trials of this diet that say it confers no protection from infection and has no identified health benefit whatsoever. Bottom line? This diet has burden without benefit.”
Moving forward, she said, “we need a lot more research on diet in general for cancer patients. Recently, there is a lot more interest in this topic. I think we are going to learn a lot in the next few decades about the relationship between diet, epigenetics, the microbiome, and various cancer-related health issues.”
No study funding was reported. Dr. Stella reports no disclosures, and other authors report various relationships with industry. Dr. Moody reports no disclosures, and disclosures for Dr. Sekeres were not available.
NEW ORLEANS – A new Italian study yields more evidence that stem-cell transplant patients need not lose their appetites along with their immune systems. Low-bacterial, gruel-like diets, once the mainstay of immunity-lowering surgeries, don’t actually provide any protection against infections, researchers reported.
University of Miami hematologist Mikkael A. Sekeres, MD, MS, expressed delight to hear these findings.
“Around the world, we should eliminate these silly neutropenic diets, let people eat what they want, and give them a much better quality of life while they’re in the hospital,” said Dr. Sekeres, moderator of the news briefing where these research results were discussed at the annual meeting of the American Society of Hematology.
In recent decades, physicians and nutritionists have questioned the value of low-bacterial/neutropenic menus, designed to protect people with compromised immune systems from germs in food. These diets can be quite strict, outlawing food such as deli, processed, and cured meats; yogurt; hummus; strawberries and raspberries; lettuce; raw nuts; certain kinds of seafood; and herbs and spices such as pepper, unless they were cooked. Patients may be urged to avoid salad bars, buffets, and potlucks.
MD Anderson Cancer Center pediatrician Karen Moody, MD, MS, who has studied the diet, said in an interview that the diet has been around since the 1970s, despite a lack of evidence supporting it. “Cancer patients often suffer from treatment-related side effects that affect taste, appetite, and tolerance of food,” she said. “Further restricting food options in this population can be burdensome and reduce diet-related satisfaction.”
For the new multi-center, phase 3 study, researchers led by hematology resident Federico Stella, MD, of the University of Milan, randomly assigned consecutive adult patients undergoing hematopoietic stem cells transplantation or high-dose induction chemotherapy to either a low-bacterial diet (n = 224) or a non-restrictive diet (n = 224).
The low-bacterial diet emphasized food cooked to at least 176 degrees Fahrenheit and thick-skinned fruit. Raw fruits/vegetables, yogurt, honey, cold cuts and sausages, and raw fish and meat were forbidden.
The two groups were similar in age (median = 56 years), gender (about 57% male), and reason for admission (97% stem-cell transplants and 3% high-dose chemotherapy). The plan was to follow the patients for 100 days (stem-cell transplant recipients) or 30 days (high-dose chemotherapy patients).
No statistically significant differences between the group were found in the rates of infections of higher than Grade 2 (per CTCAE 4.0): These infections occurred in 38 (34%) of those on the low-bacterial diet and 44 (39%) of those on the non-restrictive diet (P = 0.5).
There were also no statistically significant differences in rates of fever of unknown origin (P = 0.2), sepsis (P = 0.5), and gastrointestinal infection (P = 0.7).
The findings show that the “use of a restrictive diet is an unnecessary burden for our patients’ quality of life,” said study lead author Dr. Stella at the news briefing.
Dr. Sekeres, the news briefing moderator, noted that the findings reflect his own suspicions about the worthlessness of the low-bacterial diet. “I’ve never seen a patient die of an infection that was foodborne. So years ago, when I was still in Cleveland, I eliminated the neutropenic diet on the leukemia floor. That did face a lot of resistance, as you can imagine. There were decades of people saying we should do this.”
Now, Dr. Sekeres said, he feels validated. “I love this study because it formalizes what I thought was true,” he said.
Dr. Moody said it’s difficult to evaluate the study since it’s in abstract form, and details are limited. “However,” she said, “the sample size, study design, and outcomes appear very appropriate, and I think most likely the full-length study will provide additional evidence to support abandonment of the low-microbial diet in transplant patients.”
Also, Dr. Moody said, the study “replicates the same findings of other prospective randomized trials of this diet that say it confers no protection from infection and has no identified health benefit whatsoever. Bottom line? This diet has burden without benefit.”
Moving forward, she said, “we need a lot more research on diet in general for cancer patients. Recently, there is a lot more interest in this topic. I think we are going to learn a lot in the next few decades about the relationship between diet, epigenetics, the microbiome, and various cancer-related health issues.”
No study funding was reported. Dr. Stella reports no disclosures, and other authors report various relationships with industry. Dr. Moody reports no disclosures, and disclosures for Dr. Sekeres were not available.
NEW ORLEANS – A new Italian study yields more evidence that stem-cell transplant patients need not lose their appetites along with their immune systems. Low-bacterial, gruel-like diets, once the mainstay of immunity-lowering surgeries, don’t actually provide any protection against infections, researchers reported.
University of Miami hematologist Mikkael A. Sekeres, MD, MS, expressed delight to hear these findings.
“Around the world, we should eliminate these silly neutropenic diets, let people eat what they want, and give them a much better quality of life while they’re in the hospital,” said Dr. Sekeres, moderator of the news briefing where these research results were discussed at the annual meeting of the American Society of Hematology.
In recent decades, physicians and nutritionists have questioned the value of low-bacterial/neutropenic menus, designed to protect people with compromised immune systems from germs in food. These diets can be quite strict, outlawing food such as deli, processed, and cured meats; yogurt; hummus; strawberries and raspberries; lettuce; raw nuts; certain kinds of seafood; and herbs and spices such as pepper, unless they were cooked. Patients may be urged to avoid salad bars, buffets, and potlucks.
MD Anderson Cancer Center pediatrician Karen Moody, MD, MS, who has studied the diet, said in an interview that the diet has been around since the 1970s, despite a lack of evidence supporting it. “Cancer patients often suffer from treatment-related side effects that affect taste, appetite, and tolerance of food,” she said. “Further restricting food options in this population can be burdensome and reduce diet-related satisfaction.”
For the new multi-center, phase 3 study, researchers led by hematology resident Federico Stella, MD, of the University of Milan, randomly assigned consecutive adult patients undergoing hematopoietic stem cells transplantation or high-dose induction chemotherapy to either a low-bacterial diet (n = 224) or a non-restrictive diet (n = 224).
The low-bacterial diet emphasized food cooked to at least 176 degrees Fahrenheit and thick-skinned fruit. Raw fruits/vegetables, yogurt, honey, cold cuts and sausages, and raw fish and meat were forbidden.
The two groups were similar in age (median = 56 years), gender (about 57% male), and reason for admission (97% stem-cell transplants and 3% high-dose chemotherapy). The plan was to follow the patients for 100 days (stem-cell transplant recipients) or 30 days (high-dose chemotherapy patients).
No statistically significant differences between the group were found in the rates of infections of higher than Grade 2 (per CTCAE 4.0): These infections occurred in 38 (34%) of those on the low-bacterial diet and 44 (39%) of those on the non-restrictive diet (P = 0.5).
There were also no statistically significant differences in rates of fever of unknown origin (P = 0.2), sepsis (P = 0.5), and gastrointestinal infection (P = 0.7).
The findings show that the “use of a restrictive diet is an unnecessary burden for our patients’ quality of life,” said study lead author Dr. Stella at the news briefing.
Dr. Sekeres, the news briefing moderator, noted that the findings reflect his own suspicions about the worthlessness of the low-bacterial diet. “I’ve never seen a patient die of an infection that was foodborne. So years ago, when I was still in Cleveland, I eliminated the neutropenic diet on the leukemia floor. That did face a lot of resistance, as you can imagine. There were decades of people saying we should do this.”
Now, Dr. Sekeres said, he feels validated. “I love this study because it formalizes what I thought was true,” he said.
Dr. Moody said it’s difficult to evaluate the study since it’s in abstract form, and details are limited. “However,” she said, “the sample size, study design, and outcomes appear very appropriate, and I think most likely the full-length study will provide additional evidence to support abandonment of the low-microbial diet in transplant patients.”
Also, Dr. Moody said, the study “replicates the same findings of other prospective randomized trials of this diet that say it confers no protection from infection and has no identified health benefit whatsoever. Bottom line? This diet has burden without benefit.”
Moving forward, she said, “we need a lot more research on diet in general for cancer patients. Recently, there is a lot more interest in this topic. I think we are going to learn a lot in the next few decades about the relationship between diet, epigenetics, the microbiome, and various cancer-related health issues.”
No study funding was reported. Dr. Stella reports no disclosures, and other authors report various relationships with industry. Dr. Moody reports no disclosures, and disclosures for Dr. Sekeres were not available.
AT ASH 2022