Clinical Topics & News

In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.

When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.

When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.

The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”

The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.

It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
 

Oncologists’ ‘locker room talk’

I’ve noticed that “locker room talk” about death happens often. Phrases like “he’s definitely not going to do well” and “his life expectancy is poor” make their way into oncologists’ daily language. Thinking back on my own interactions, I realize I am also guilty of discussing death in this way.

And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.

This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.

But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.

The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
 

Making time for reflection

But taking time to reflect can be therapeutic.

I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.

I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”

When I checked in with the hospice, the patient had died.

I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.

It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
 

Abandoning locker room talk

So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.

We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.

We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.

And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.

Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
 

Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.

In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.

When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.

When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.

The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”

The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.

It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
 

Oncologists’ ‘locker room talk’

I’ve noticed that “locker room talk” about death happens often. Phrases like “he’s definitely not going to do well” and “his life expectancy is poor” make their way into oncologists’ daily language. Thinking back on my own interactions, I realize I am also guilty of discussing death in this way.

And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.

This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.

But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.

The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
 

Making time for reflection

But taking time to reflect can be therapeutic.

I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.

I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”

When I checked in with the hospice, the patient had died.

I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.

It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
 

Abandoning locker room talk

So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.

We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.

We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.

And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.

Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
 

Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.

In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.

When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.

When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.

The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”

The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.

It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
 

Oncologists’ ‘locker room talk’

I’ve noticed that “locker room talk” about death happens often. Phrases like “he’s definitely not going to do well” and “his life expectancy is poor” make their way into oncologists’ daily language. Thinking back on my own interactions, I realize I am also guilty of discussing death in this way.

And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.

This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.

But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.

The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
 

Making time for reflection

But taking time to reflect can be therapeutic.

I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.

I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”

When I checked in with the hospice, the patient had died.

I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.

It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
 

Abandoning locker room talk

So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.

We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.

We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.

And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.

Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
 

Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.

Background

We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.

Methods

We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.

Results

From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.

Implications

The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.

Background

We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.

Methods

We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.

Results

From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.

Implications

The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.

Background

We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.

Methods

We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.

Results

From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.

Implications

The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.

Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.

In a new study that examines umbilical cord blood from 36 deliveries, researchers provide additional evidence that vaccines – and not COVID-19 infections – elicited the antibodies detected in this cohort.

Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.

All neonates had antibodies to the spike protein at high titers, the researchers found.

Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.

The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.

“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”

Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.

The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.

Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.

Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.

When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.

“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”

The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.

“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.

As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.

Dr. Roman and Dr. Adhikari had no disclosures.

[email protected]

Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.

In a new study that examines umbilical cord blood from 36 deliveries, researchers provide additional evidence that vaccines – and not COVID-19 infections – elicited the antibodies detected in this cohort.

Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.

All neonates had antibodies to the spike protein at high titers, the researchers found.

Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.

The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.

“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”

Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.

The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.

Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.

Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.

When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.

“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”

The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.

“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.

As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.

Dr. Roman and Dr. Adhikari had no disclosures.

[email protected]

Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.

In a new study that examines umbilical cord blood from 36 deliveries, researchers provide additional evidence that vaccines – and not COVID-19 infections – elicited the antibodies detected in this cohort.

Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.

All neonates had antibodies to the spike protein at high titers, the researchers found.

Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.

The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.

“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”

Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.

The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.

Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.

Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.

When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.

“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”

The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.

“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.

As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.

Dr. Roman and Dr. Adhikari had no disclosures.

[email protected]

Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.

The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.

“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.

In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.

The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.

And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.

Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”

Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
 

Inside the Global Registry data

The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.  

Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.

The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.

Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).

In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).

Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).

Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm³ or less and an absolute neutrophil count of 500 cells per mm³ or more also had an elevated risk of severe illness from COVID-19.

Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.

Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.

Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).

The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.

In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.

“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.

Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
 

U.K. Monitoring Project

Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.

“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.

Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.

“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”

Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.

“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.

Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.

Data on COVID-19 vaccination in children with cancer are limited but promising so far.

As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”

The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.

The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.

“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.

In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.

The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.

And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.

Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”

Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
 

Inside the Global Registry data

The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.  

Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.

The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.

Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).

In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).

Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).

Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm³ or less and an absolute neutrophil count of 500 cells per mm³ or more also had an elevated risk of severe illness from COVID-19.

Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.

Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.

Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).

The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.

In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.

“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.

Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
 

U.K. Monitoring Project

Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.

“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.

Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.

“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”

Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.

“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.

Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.

Data on COVID-19 vaccination in children with cancer are limited but promising so far.

As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”

The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.

The findings, published online in Lancet Oncology, represent the first global registry data spanning different income groups to report COVID-19 outcomes in pediatric oncology patients.

“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, said in an interview.

In a cohort of 1,319 pediatric patients followed for 30 days, Dr. Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died – four times the mortality rate observed in published cohorts of general pediatric patients.

The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.

And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.

Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology and coauthor on the study, noted in a press release that, “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”

Dr. Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
 

Inside the Global Registry data

The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.  

Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.

The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.

Notably, more than 80% of either severe or critical infections occurred in patients with hematologic malignancies – with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia – followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).

In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).

Older age was associated with a higher likelihood of having severe disease – with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).

Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm³ or less and an absolute neutrophil count of 500 cells per mm³ or more also had an elevated risk of severe illness from COVID-19.

Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Dr. Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.

Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.

Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%), compared with patients in other income groups (23.9%).

The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries, compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.

In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.

“Treatment modifications were least common in patients from upper-middle–income countries, compared with other income groups,” the authors wrote.

Although an interesting observation, Dr. Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
 

U.K. Monitoring Project

Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the U.K. Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.

“[Given that] we had complete coverage of every center in the U.K. that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham (England), said in an interview.

Between March 2020 and July 2020, Dr. Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical – more in line with the incidence of severe illness reported in the general pediatric population.

“Thankfully, we had no children with cancer in the U.K. who died from COVID-19,” Dr. Millen noted. “Overall, in the U.K., we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”

Dr. Millen pointed out that the data in the U.K. study were “remarkably similar” to those from the high-income countries in the global St. Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease, compared with 7.4% of patients from their own U.K. cohort.

“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low- to middle-income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Dr. Millen said.

Both the U.K. and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.

Data on COVID-19 vaccination in children with cancer are limited but promising so far.

As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Dr. Mukkada could only speculate, but she noted that “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”

The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr. Millen disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Some women with the most-difficult-to-treat form of advanced breast cancer who have positively responded to atezolizumab (Tecentriq) are reporting panic and anxiety because oncologists have suddenly discontinued their prescriptions.

The discontinuance appears to be in reaction to an announcement by the manufacturer (Genentech) in late August that it has voluntarily withdrawn its application for accelerated approval of the drug for use in metastatic triple-negative breast cancer (mTNBC).

However, experts stress that discontinuing atezolizumab is not advised if a patient is responding to or is stable on the immune checkpoint inhibitor.

“I think the Genentech announcement has been misinterpreted,” Maryam Lustberg, MD, of Yale Cancer Center, New Haven, Conn., said in an interview. “The consensus opinion from all academic breast oncologists is that people should not be switching off atezolizumab if they are responding. They should not be changing their immunotherapy.”

Dr. Lustberg said the announcement had two major points: “don’t start a new patient on atezolizumab,” and the company is “committed” to supplying the drug to patients whose conditions are stable or responding.

Nevertheless, some patients with mTNBC were recently in a state of escalating emotional upset, said one patient advocate.

“The level of panic among those currently on & responding well to Atezo is growing quickly,” tweeted Janice Cowden on Sept. 5, a former nurse living with mTNBC in Bradenton, Fla.

Ms. Cowden explained that “at least 10-20 patients” were “pulled [off the drug by their oncologists] this past week who have been stable/no evidence of disease/no evidence of disease activity on Tecentriq.”

She estimated that as many as 50 patients in the 2,200-member Triple Negative BC Stage 4 Facebook group who have been responding to the drug were abruptly de-prescribed atezolizumab since the Aug. 27 announcement from Genentech.

Many women learned of the change via patient portals or text messaging, not directly from their physicians, Cowden told Medscape Medical News.

Some of the women had been taking atezolizumab for 2-3 years, including those with no evidence of disease, she said. “Finding out that their oncologist was discontinuing a treatment that was working for them has been driving so much anxiety and stress,” Ms. Cowden emphasized.

Most market withdrawals of drugs are related to safety, but that is not the case with atezolizumab, said Sara Horton, MD, of Howard University, Washington. She was speaking at the recent Facebook webinar on atezolizumab and mTNBC that was sponsored by the TNBC Foundation and the Young Survivors Coalition.

In the case of atezolizumab, it was a question about efficacy that prompted the withdrawal. After the indication was granted an accelerated approval on the basis of response data, a confirmatory trial set out to show clinical benefit. However, the confirmatory phase 3 IMpassion131 trial did not do so: it found that atezolizumab plus paclitaxel did not significantly reduce the risk for cancer progression and death in comparison with paclitaxel plus placebo among patients with TNBC with tumors that were positive for programmed cell death protein–1 (PD-L1), as reported by Medscape Medical News.

These results were discussed by the Food and Drug Administration on the first day of a historic 3-day meeting on accelerated approvals in April 2021. Despite the failure of confirmation of clinical benefit, the advisory panel voted 7-2 in favor of keeping the approval in place for atezolizumab in TNBC. At the same time, it urged Genentech to carry out more studies to show that the drug works in this patient population.

The company apparently decided not to do that and instead voluntarily withdrew the application for the indication some 4 months later.

During the recent TNBC Foundation webinar, Genentech official Lauren Davis said that the company sent letters about this decision to atezolizumab-prescribing physicians and included another letter that was to be shared with patients. Ms. Davis had not responded to this news organization’s request to review the communications at the time this article was published.

At the webinar, Ms. Davis did clarify that current atezolizumab patients (who are responding to the drug), who have commercial insurance, and who benefit from Genentech’s copay program will continue to receive the benefit until June 2022.

In its August announcement, Genentech said it decided to withdraw the atezolizumab approval on the basis of the FDA’s assessment of the “current mTNBC treatment landscape and in accordance with the requirements of the accelerated approval program.”

That landscape presumably includes pembrolizumab (Keytruda), which received a full approval for a TNBC indication similar to that of atezolizumab in July. That full approval was based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen in comparison with neoadjuvant chemotherapy alone for previously untreated stage II or III TNBC. Details of these clinical data will be presented at the upcoming annual meeting of the European Society of Medical Oncology.
 

Switching the immunotherapy?

Some U.S. oncologists have been telling patients with mTNBC that the atezolizumab withdrawal is “not an issue” because the new full approval of pembrolizumab in this setting will allow prescriptions to be switched, said patient advocate Ms. Cowden.

However, experts have said that no patient who is responding to or whose condition is stable with atezolizumab should switch immunotherapies. “This is a very aggressive disease,” reminded Dr. Lustberg.

Switching the immunotherapies is complicated by the difference in the respective drugs’ companion biomarker assays used to establish the presence of PD-L1.

Dr. Lustberg explained that patients who are not responding to atezolizumab and who now want to try pembrolizumab will have to be assessed with the CTS assay.

“About 22% of the patients who are positive for the atezolizumab biomarker assay SP-142 are not going to be positive for the CTS,” she said.

In other words, about one in four patients with mTNBC who are taking atezolizumab will not qualify for treatment with pembrolizumab.

Rebecca Shatsky, MD, of the University of California, San Diego, echoed those comments in an email to this news organization – and emphatically discouraged switching off atezolizumab (and going on pembrolizumab) if a patient is having success (i.e., stable disease or positive response).

“The two groups don’t always overlap, so it isn’t an easy switch. That’s why if they are already responding, I would NOT have them stop the drug,” she said.

Not every mTNBC patient receiving – and responding to – atezolizumab has had the unfortunate experience of having their prescription canceled.

Johanna Rauhala, of San Francisco, who is a former middle-school teacher and who writes the blog Pink Stinks, has been taking atezolizumab for 2 years. She has had a partial response and now, after taking the immunotherapy in combination with chemotherapy (gemcitabine and carboplatin), has stable disease. Currently, she is taking single-agent atezolizumab..

Ms. Rauhala has been living with mTNBC for 5 years. She said in an interview that she was “very surprised and concerned” to learn about Genentech’s withdrawal of its accelerated approval. She said that at her next treatment appointment, she was “probably going to ask the oncology nurse first [about the atezolizumab withdrawal] – because they are the front line, and I will then follow-up with my doctor. But I can’t imagine that they will take away something that is working.”

Dr. Shatsky, Dr. Horton, and Dr. Lunsberg report no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Some women with the most-difficult-to-treat form of advanced breast cancer who have positively responded to atezolizumab (Tecentriq) are reporting panic and anxiety because oncologists have suddenly discontinued their prescriptions.

The discontinuance appears to be in reaction to an announcement by the manufacturer (Genentech) in late August that it has voluntarily withdrawn its application for accelerated approval of the drug for use in metastatic triple-negative breast cancer (mTNBC).

However, experts stress that discontinuing atezolizumab is not advised if a patient is responding to or is stable on the immune checkpoint inhibitor.

“I think the Genentech announcement has been misinterpreted,” Maryam Lustberg, MD, of Yale Cancer Center, New Haven, Conn., said in an interview. “The consensus opinion from all academic breast oncologists is that people should not be switching off atezolizumab if they are responding. They should not be changing their immunotherapy.”

Dr. Lustberg said the announcement had two major points: “don’t start a new patient on atezolizumab,” and the company is “committed” to supplying the drug to patients whose conditions are stable or responding.

Nevertheless, some patients with mTNBC were recently in a state of escalating emotional upset, said one patient advocate.

“The level of panic among those currently on & responding well to Atezo is growing quickly,” tweeted Janice Cowden on Sept. 5, a former nurse living with mTNBC in Bradenton, Fla.

Ms. Cowden explained that “at least 10-20 patients” were “pulled [off the drug by their oncologists] this past week who have been stable/no evidence of disease/no evidence of disease activity on Tecentriq.”

She estimated that as many as 50 patients in the 2,200-member Triple Negative BC Stage 4 Facebook group who have been responding to the drug were abruptly de-prescribed atezolizumab since the Aug. 27 announcement from Genentech.

Many women learned of the change via patient portals or text messaging, not directly from their physicians, Cowden told Medscape Medical News.

Some of the women had been taking atezolizumab for 2-3 years, including those with no evidence of disease, she said. “Finding out that their oncologist was discontinuing a treatment that was working for them has been driving so much anxiety and stress,” Ms. Cowden emphasized.

Most market withdrawals of drugs are related to safety, but that is not the case with atezolizumab, said Sara Horton, MD, of Howard University, Washington. She was speaking at the recent Facebook webinar on atezolizumab and mTNBC that was sponsored by the TNBC Foundation and the Young Survivors Coalition.

In the case of atezolizumab, it was a question about efficacy that prompted the withdrawal. After the indication was granted an accelerated approval on the basis of response data, a confirmatory trial set out to show clinical benefit. However, the confirmatory phase 3 IMpassion131 trial did not do so: it found that atezolizumab plus paclitaxel did not significantly reduce the risk for cancer progression and death in comparison with paclitaxel plus placebo among patients with TNBC with tumors that were positive for programmed cell death protein–1 (PD-L1), as reported by Medscape Medical News.

These results were discussed by the Food and Drug Administration on the first day of a historic 3-day meeting on accelerated approvals in April 2021. Despite the failure of confirmation of clinical benefit, the advisory panel voted 7-2 in favor of keeping the approval in place for atezolizumab in TNBC. At the same time, it urged Genentech to carry out more studies to show that the drug works in this patient population.

The company apparently decided not to do that and instead voluntarily withdrew the application for the indication some 4 months later.

During the recent TNBC Foundation webinar, Genentech official Lauren Davis said that the company sent letters about this decision to atezolizumab-prescribing physicians and included another letter that was to be shared with patients. Ms. Davis had not responded to this news organization’s request to review the communications at the time this article was published.

At the webinar, Ms. Davis did clarify that current atezolizumab patients (who are responding to the drug), who have commercial insurance, and who benefit from Genentech’s copay program will continue to receive the benefit until June 2022.

In its August announcement, Genentech said it decided to withdraw the atezolizumab approval on the basis of the FDA’s assessment of the “current mTNBC treatment landscape and in accordance with the requirements of the accelerated approval program.”

That landscape presumably includes pembrolizumab (Keytruda), which received a full approval for a TNBC indication similar to that of atezolizumab in July. That full approval was based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen in comparison with neoadjuvant chemotherapy alone for previously untreated stage II or III TNBC. Details of these clinical data will be presented at the upcoming annual meeting of the European Society of Medical Oncology.
 

Switching the immunotherapy?

Some U.S. oncologists have been telling patients with mTNBC that the atezolizumab withdrawal is “not an issue” because the new full approval of pembrolizumab in this setting will allow prescriptions to be switched, said patient advocate Ms. Cowden.

However, experts have said that no patient who is responding to or whose condition is stable with atezolizumab should switch immunotherapies. “This is a very aggressive disease,” reminded Dr. Lustberg.

Switching the immunotherapies is complicated by the difference in the respective drugs’ companion biomarker assays used to establish the presence of PD-L1.

Dr. Lustberg explained that patients who are not responding to atezolizumab and who now want to try pembrolizumab will have to be assessed with the CTS assay.

“About 22% of the patients who are positive for the atezolizumab biomarker assay SP-142 are not going to be positive for the CTS,” she said.

In other words, about one in four patients with mTNBC who are taking atezolizumab will not qualify for treatment with pembrolizumab.

Rebecca Shatsky, MD, of the University of California, San Diego, echoed those comments in an email to this news organization – and emphatically discouraged switching off atezolizumab (and going on pembrolizumab) if a patient is having success (i.e., stable disease or positive response).

“The two groups don’t always overlap, so it isn’t an easy switch. That’s why if they are already responding, I would NOT have them stop the drug,” she said.

Not every mTNBC patient receiving – and responding to – atezolizumab has had the unfortunate experience of having their prescription canceled.

Johanna Rauhala, of San Francisco, who is a former middle-school teacher and who writes the blog Pink Stinks, has been taking atezolizumab for 2 years. She has had a partial response and now, after taking the immunotherapy in combination with chemotherapy (gemcitabine and carboplatin), has stable disease. Currently, she is taking single-agent atezolizumab..

Ms. Rauhala has been living with mTNBC for 5 years. She said in an interview that she was “very surprised and concerned” to learn about Genentech’s withdrawal of its accelerated approval. She said that at her next treatment appointment, she was “probably going to ask the oncology nurse first [about the atezolizumab withdrawal] – because they are the front line, and I will then follow-up with my doctor. But I can’t imagine that they will take away something that is working.”

Dr. Shatsky, Dr. Horton, and Dr. Lunsberg report no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Some women with the most-difficult-to-treat form of advanced breast cancer who have positively responded to atezolizumab (Tecentriq) are reporting panic and anxiety because oncologists have suddenly discontinued their prescriptions.

The discontinuance appears to be in reaction to an announcement by the manufacturer (Genentech) in late August that it has voluntarily withdrawn its application for accelerated approval of the drug for use in metastatic triple-negative breast cancer (mTNBC).

However, experts stress that discontinuing atezolizumab is not advised if a patient is responding to or is stable on the immune checkpoint inhibitor.

“I think the Genentech announcement has been misinterpreted,” Maryam Lustberg, MD, of Yale Cancer Center, New Haven, Conn., said in an interview. “The consensus opinion from all academic breast oncologists is that people should not be switching off atezolizumab if they are responding. They should not be changing their immunotherapy.”

Dr. Lustberg said the announcement had two major points: “don’t start a new patient on atezolizumab,” and the company is “committed” to supplying the drug to patients whose conditions are stable or responding.

Nevertheless, some patients with mTNBC were recently in a state of escalating emotional upset, said one patient advocate.

“The level of panic among those currently on & responding well to Atezo is growing quickly,” tweeted Janice Cowden on Sept. 5, a former nurse living with mTNBC in Bradenton, Fla.

Ms. Cowden explained that “at least 10-20 patients” were “pulled [off the drug by their oncologists] this past week who have been stable/no evidence of disease/no evidence of disease activity on Tecentriq.”

She estimated that as many as 50 patients in the 2,200-member Triple Negative BC Stage 4 Facebook group who have been responding to the drug were abruptly de-prescribed atezolizumab since the Aug. 27 announcement from Genentech.

Many women learned of the change via patient portals or text messaging, not directly from their physicians, Cowden told Medscape Medical News.

Some of the women had been taking atezolizumab for 2-3 years, including those with no evidence of disease, she said. “Finding out that their oncologist was discontinuing a treatment that was working for them has been driving so much anxiety and stress,” Ms. Cowden emphasized.

Most market withdrawals of drugs are related to safety, but that is not the case with atezolizumab, said Sara Horton, MD, of Howard University, Washington. She was speaking at the recent Facebook webinar on atezolizumab and mTNBC that was sponsored by the TNBC Foundation and the Young Survivors Coalition.

In the case of atezolizumab, it was a question about efficacy that prompted the withdrawal. After the indication was granted an accelerated approval on the basis of response data, a confirmatory trial set out to show clinical benefit. However, the confirmatory phase 3 IMpassion131 trial did not do so: it found that atezolizumab plus paclitaxel did not significantly reduce the risk for cancer progression and death in comparison with paclitaxel plus placebo among patients with TNBC with tumors that were positive for programmed cell death protein–1 (PD-L1), as reported by Medscape Medical News.

These results were discussed by the Food and Drug Administration on the first day of a historic 3-day meeting on accelerated approvals in April 2021. Despite the failure of confirmation of clinical benefit, the advisory panel voted 7-2 in favor of keeping the approval in place for atezolizumab in TNBC. At the same time, it urged Genentech to carry out more studies to show that the drug works in this patient population.

The company apparently decided not to do that and instead voluntarily withdrew the application for the indication some 4 months later.

During the recent TNBC Foundation webinar, Genentech official Lauren Davis said that the company sent letters about this decision to atezolizumab-prescribing physicians and included another letter that was to be shared with patients. Ms. Davis had not responded to this news organization’s request to review the communications at the time this article was published.

At the webinar, Ms. Davis did clarify that current atezolizumab patients (who are responding to the drug), who have commercial insurance, and who benefit from Genentech’s copay program will continue to receive the benefit until June 2022.

In its August announcement, Genentech said it decided to withdraw the atezolizumab approval on the basis of the FDA’s assessment of the “current mTNBC treatment landscape and in accordance with the requirements of the accelerated approval program.”

That landscape presumably includes pembrolizumab (Keytruda), which received a full approval for a TNBC indication similar to that of atezolizumab in July. That full approval was based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen in comparison with neoadjuvant chemotherapy alone for previously untreated stage II or III TNBC. Details of these clinical data will be presented at the upcoming annual meeting of the European Society of Medical Oncology.
 

Switching the immunotherapy?

Some U.S. oncologists have been telling patients with mTNBC that the atezolizumab withdrawal is “not an issue” because the new full approval of pembrolizumab in this setting will allow prescriptions to be switched, said patient advocate Ms. Cowden.

However, experts have said that no patient who is responding to or whose condition is stable with atezolizumab should switch immunotherapies. “This is a very aggressive disease,” reminded Dr. Lustberg.

Switching the immunotherapies is complicated by the difference in the respective drugs’ companion biomarker assays used to establish the presence of PD-L1.

Dr. Lustberg explained that patients who are not responding to atezolizumab and who now want to try pembrolizumab will have to be assessed with the CTS assay.

“About 22% of the patients who are positive for the atezolizumab biomarker assay SP-142 are not going to be positive for the CTS,” she said.

In other words, about one in four patients with mTNBC who are taking atezolizumab will not qualify for treatment with pembrolizumab.

Rebecca Shatsky, MD, of the University of California, San Diego, echoed those comments in an email to this news organization – and emphatically discouraged switching off atezolizumab (and going on pembrolizumab) if a patient is having success (i.e., stable disease or positive response).

“The two groups don’t always overlap, so it isn’t an easy switch. That’s why if they are already responding, I would NOT have them stop the drug,” she said.

Not every mTNBC patient receiving – and responding to – atezolizumab has had the unfortunate experience of having their prescription canceled.

Johanna Rauhala, of San Francisco, who is a former middle-school teacher and who writes the blog Pink Stinks, has been taking atezolizumab for 2 years. She has had a partial response and now, after taking the immunotherapy in combination with chemotherapy (gemcitabine and carboplatin), has stable disease. Currently, she is taking single-agent atezolizumab..

Ms. Rauhala has been living with mTNBC for 5 years. She said in an interview that she was “very surprised and concerned” to learn about Genentech’s withdrawal of its accelerated approval. She said that at her next treatment appointment, she was “probably going to ask the oncology nurse first [about the atezolizumab withdrawal] – because they are the front line, and I will then follow-up with my doctor. But I can’t imagine that they will take away something that is working.”

Dr. Shatsky, Dr. Horton, and Dr. Lunsberg report no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

[email protected]

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

[email protected]

Patients with chronic lymphocytic leukemia have similar outcomes following cardiac operations as patients without CLL, but commonly require more blood transfusions, according to the results of retrospective cohort study using the 2010-2017 Nationwide Readmissions Database (NRD).

The researchers assessed all adult patients undergoing elective coronary artery bypass grafting, valve repair, or valve replacement as identified using the NRD.

Patients were stratified by history of CLL and the incidence of in-hospital mortality, perioperative complications, blood transfusions, and readmission within 90 days were examined. A 3:1 nearest-neighbor matching was performed between patients with and without CLL for all primary and secondary outcomes of interest, according to the report, published online in Annals of Thoracic Surgery.
 

Comparable results

A total of 1,250,882 patients in the database were found who underwent cardiac operations. Of these, 0.23% had a diagnosis of CLL. Among 11,237 propensity-matched patients, those with CLL had similar rates of in-hospital mortality (3.8% vs. 2.6%, P = .08) and perioperative complications (33.4% vs. 33.6%, P = .92), compared with their non-CLL counterparts. However, the incidence of infection was comparable (8.5% vs. 9.4%, P = .38).

However, patients with CLL required blood transfusions more frequently (33.7% vs. 28.4%, P = .003) than did patients without CLL. In addition, patients with CLL were more likely to be readmitted within 90 days of discharge, compared with their counterparts, and “respiratory reasons, including pneumonia, contributed significantly to the readmission burden in this cohort,” the researchers, led by Josef Madrigal, BS, of the University of California, Los Angeles, stated.

“The inherent risk of transfusion and the possible benefits of blood conservation interventions must be considered in this patient population. Increased risk of rehospitalization in patients with CLL suggests the need for measures aimed at mitigating the risk of respiratory complications,” the researchers concluded.

There were no conflicts of interest reported in the article.

[email protected]

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.

The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.

The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.

“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.

Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.

Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.

Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.

“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”

KEYNOTE-826 details

This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.

The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.

Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).

PFS and OS results

The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.

After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).

The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.

In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).

OS rates were also significantly improved, he noted.

The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).

In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).

Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).

Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.

The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.

Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.

He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.

KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.


A version of this article was first published on Medscape.com.