B-Cell Lymphoma ICYMI

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

Patients with hematologic malignancies who are seronegative after full SARS-CoV-2 vaccination may benefit from a booster, but breakthrough infections will remain a risk, particularly in those with B-cell malignancies, an observational study suggests.

The findings, based on a review of COVID-19 booster vaccine recipients with B cell–derived hematologic malignancies from the prospective Leukemia & Lymphoma Society National Registry, provide valuable information about booster vaccinations in this vulnerable population, according to LLS chief medical officer and lead study author Gwen Nichols, MD.
 

The LLS Registry data

Of 49 patients included in the review, 38 failed to make antispike (anti-S) antibodies after full vaccination, and of those, 21 seroconverted after booster vaccination and 11 experienced seroelevation after the booster.

The patients who did not seroconvert were seronegative after initial vaccination and experienced no change in antibody level after the booster vaccination. In contrast, the 21 who seroconverted had a median 23.1 AU/ml increase in antibody level, Dr. Nichols, along with LLS chief scientific officer Lee M. Greenberger, PhD,and their colleagues reported online Sept. 6, 2021, in Cancer Cell.

Similar proportions of seroconverted patients had low-level responses between 2.2 and 23.1 AU/mL and robust response between 125 and 2,500 AU/mL, they noted. The 11 patients with seroelevation were seropositive after full vaccination and demonstrated a median increase of 2,128 AU/mL in antibody level after the booster vaccination.
 

Therapy effects on vaccine response

Outcomes of the current analysis also confirmed the authors’ previous finding, which suggested that “both disease and therapies can affect the serological response to vaccination,” they wrote, explaining that, among the 12 patients who received no malignancy-targeted treatments in the past 2 years, only 1 was a nonresponder, 7 demonstrated seroconversion, and 4 demonstrated seroelevation.

“In contrast, among the 21 patients who completed therapy with anti-CD20 antibodies either alone or in combination with other therapies, 12 patients were nonresponders, 7 patients demonstrated seroconversion, and 2 patients demonstrated seroelevation,” they added.

The authors also noted that five of seven patients who completed anti-CD20 antibody therapy alone or in combination with chemotherapy at least 7 months prior to the booster vaccination demonstrated seroconversion or seroelevation, whereas many of the patients with recent or maintenance anti-CD20 antibody therapy before the booster vaccination failed to seroconvert afterward.

In light of previous findings showing B-cell recovery begins 6-9 months after rituximab therapy, these data suggest that recent anti-CD20 antibody-containing treatment regimens may suppress booster vaccination response, the authors wrote.

The current data also support the group’s prior finding that use of a Bruton tyrosine kinase inhibitor may suppress vaccine response: Of the patients in the current study who experienced seroelevation and were treated with a BTKi, two discontinued BTKi therapy 7-23 months prior to booster vaccination, one maintained a low dose of ibrutinib before booster vaccination, one maintained BTKi therapy continuously before and after the booster, and the two who experienced marked seroconversion after booster vaccination stopped BTKi therapy at least 4 months prior.

Conversely, five patients with a very weak seroconversion and two patients with moderate seroconversion maintained BTKi therapy during booster vaccination.

“These data suggest that BTKi therapy can interfere with a response to booster vaccination,” they wrote, noting, however, that “it is encouraging that seven patients ... maintained on a BTKi seroconverted or experienced seroelevation after booster vaccination and [this] is consistent with a previous report on one patient.”
 

Study limitations and lessons

Although the findings of this study are limited by the small number of patients, the fact that treatment and disease were patient reported, and a lack of data on “antibody responses, particularly to the delta variant, B-cell memory, or T-cell responses,” they nevertheless provide encouraging news, Dr. Nichols told this news organization.

“Many blood cancer patients are getting boosters and a good number are able to make antibody with an additional dose. This is giving us much needed information about boosters,” she said. “Through the LLS National Patient Registry, we anticipate having data on hundreds of more patients over the course of the next few months.”

The information is needed because data suggest that up to 25% of patients with hematologic malignancies fail to make anti-S antibodies after full COVID-19 vaccination and that seronegative patients may be especially vulnerable to breakthrough infections, she and her colleagues noted.

Patients with B-cell malignancies are at the highest risk, and this is particularly concerning as some patients with blood cancer who contracted COVID-19 in the prevaccine period of the pandemic had “prolonged, severe infections; generated variant strains; and demonstrated significantly higher mortality rates compared to the general population,” they said.

However, a recently published placebo-controlled trial that demonstrated a booster vaccination–mediated increase in anti-S antibodies and neutralizing antibodies in immunosuppressed patients, and the current review, which focused on patients who obtained booster vaccinations prior to Aug. 12, 2021 (when the Food and Drug Administration granted emergency use authorization for booster doses in immunocompromised people), offer findings that suggest these patients may benefit from receiving COVID-19 boosters.

“We conclude that some patients with hematologic malignancies who are seronegative after a full course of vaccination may benefit from a booster,” the authors wrote. They added a warning: “Regulators, patients, and health care providers should be aware that a sizable subset of patients with blood cancer may remain at risk of breakthrough COVID-19 infections after full vaccination followed by booster vaccination.”

Dr. Nichols stressed that the findings “do not in any way suggest that blood cancer patients should stop therapy to get an antibody response to the vaccinations.”

“LLS is encouraging blood cancer patients to get vaccinated and to continue taking preventive measures such as wearing masks, social distancing, hand washing, and avoiding crowds and poorly ventilated indoor spaces,” she said.

Sergio Giralt, MD, professor and deputy head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center, New York, further emphasized the importance of preventive measures.

“I think the extra booster will go a long way to protect our patients at this time but should not be used as a replacement for masking indoors and continued social distancing in this vulnerable patient population,” he said.

This study was supported by the LLS.

[email protected]

Patients with hematologic malignancies who are seronegative after full SARS-CoV-2 vaccination may benefit from a booster, but breakthrough infections will remain a risk, particularly in those with B-cell malignancies, an observational study suggests.

The findings, based on a review of COVID-19 booster vaccine recipients with B cell–derived hematologic malignancies from the prospective Leukemia & Lymphoma Society National Registry, provide valuable information about booster vaccinations in this vulnerable population, according to LLS chief medical officer and lead study author Gwen Nichols, MD.
 

The LLS Registry data

Of 49 patients included in the review, 38 failed to make antispike (anti-S) antibodies after full vaccination, and of those, 21 seroconverted after booster vaccination and 11 experienced seroelevation after the booster.

The patients who did not seroconvert were seronegative after initial vaccination and experienced no change in antibody level after the booster vaccination. In contrast, the 21 who seroconverted had a median 23.1 AU/ml increase in antibody level, Dr. Nichols, along with LLS chief scientific officer Lee M. Greenberger, PhD,and their colleagues reported online Sept. 6, 2021, in Cancer Cell.

Similar proportions of seroconverted patients had low-level responses between 2.2 and 23.1 AU/mL and robust response between 125 and 2,500 AU/mL, they noted. The 11 patients with seroelevation were seropositive after full vaccination and demonstrated a median increase of 2,128 AU/mL in antibody level after the booster vaccination.
 

Therapy effects on vaccine response

Outcomes of the current analysis also confirmed the authors’ previous finding, which suggested that “both disease and therapies can affect the serological response to vaccination,” they wrote, explaining that, among the 12 patients who received no malignancy-targeted treatments in the past 2 years, only 1 was a nonresponder, 7 demonstrated seroconversion, and 4 demonstrated seroelevation.

“In contrast, among the 21 patients who completed therapy with anti-CD20 antibodies either alone or in combination with other therapies, 12 patients were nonresponders, 7 patients demonstrated seroconversion, and 2 patients demonstrated seroelevation,” they added.

The authors also noted that five of seven patients who completed anti-CD20 antibody therapy alone or in combination with chemotherapy at least 7 months prior to the booster vaccination demonstrated seroconversion or seroelevation, whereas many of the patients with recent or maintenance anti-CD20 antibody therapy before the booster vaccination failed to seroconvert afterward.

In light of previous findings showing B-cell recovery begins 6-9 months after rituximab therapy, these data suggest that recent anti-CD20 antibody-containing treatment regimens may suppress booster vaccination response, the authors wrote.

The current data also support the group’s prior finding that use of a Bruton tyrosine kinase inhibitor may suppress vaccine response: Of the patients in the current study who experienced seroelevation and were treated with a BTKi, two discontinued BTKi therapy 7-23 months prior to booster vaccination, one maintained a low dose of ibrutinib before booster vaccination, one maintained BTKi therapy continuously before and after the booster, and the two who experienced marked seroconversion after booster vaccination stopped BTKi therapy at least 4 months prior.

Conversely, five patients with a very weak seroconversion and two patients with moderate seroconversion maintained BTKi therapy during booster vaccination.

“These data suggest that BTKi therapy can interfere with a response to booster vaccination,” they wrote, noting, however, that “it is encouraging that seven patients ... maintained on a BTKi seroconverted or experienced seroelevation after booster vaccination and [this] is consistent with a previous report on one patient.”
 

Study limitations and lessons

Although the findings of this study are limited by the small number of patients, the fact that treatment and disease were patient reported, and a lack of data on “antibody responses, particularly to the delta variant, B-cell memory, or T-cell responses,” they nevertheless provide encouraging news, Dr. Nichols told this news organization.

“Many blood cancer patients are getting boosters and a good number are able to make antibody with an additional dose. This is giving us much needed information about boosters,” she said. “Through the LLS National Patient Registry, we anticipate having data on hundreds of more patients over the course of the next few months.”

The information is needed because data suggest that up to 25% of patients with hematologic malignancies fail to make anti-S antibodies after full COVID-19 vaccination and that seronegative patients may be especially vulnerable to breakthrough infections, she and her colleagues noted.

Patients with B-cell malignancies are at the highest risk, and this is particularly concerning as some patients with blood cancer who contracted COVID-19 in the prevaccine period of the pandemic had “prolonged, severe infections; generated variant strains; and demonstrated significantly higher mortality rates compared to the general population,” they said.

However, a recently published placebo-controlled trial that demonstrated a booster vaccination–mediated increase in anti-S antibodies and neutralizing antibodies in immunosuppressed patients, and the current review, which focused on patients who obtained booster vaccinations prior to Aug. 12, 2021 (when the Food and Drug Administration granted emergency use authorization for booster doses in immunocompromised people), offer findings that suggest these patients may benefit from receiving COVID-19 boosters.

“We conclude that some patients with hematologic malignancies who are seronegative after a full course of vaccination may benefit from a booster,” the authors wrote. They added a warning: “Regulators, patients, and health care providers should be aware that a sizable subset of patients with blood cancer may remain at risk of breakthrough COVID-19 infections after full vaccination followed by booster vaccination.”

Dr. Nichols stressed that the findings “do not in any way suggest that blood cancer patients should stop therapy to get an antibody response to the vaccinations.”

“LLS is encouraging blood cancer patients to get vaccinated and to continue taking preventive measures such as wearing masks, social distancing, hand washing, and avoiding crowds and poorly ventilated indoor spaces,” she said.

Sergio Giralt, MD, professor and deputy head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center, New York, further emphasized the importance of preventive measures.

“I think the extra booster will go a long way to protect our patients at this time but should not be used as a replacement for masking indoors and continued social distancing in this vulnerable patient population,” he said.

This study was supported by the LLS.

[email protected]

Patients with hematologic malignancies who are seronegative after full SARS-CoV-2 vaccination may benefit from a booster, but breakthrough infections will remain a risk, particularly in those with B-cell malignancies, an observational study suggests.

The findings, based on a review of COVID-19 booster vaccine recipients with B cell–derived hematologic malignancies from the prospective Leukemia & Lymphoma Society National Registry, provide valuable information about booster vaccinations in this vulnerable population, according to LLS chief medical officer and lead study author Gwen Nichols, MD.
 

The LLS Registry data

Of 49 patients included in the review, 38 failed to make antispike (anti-S) antibodies after full vaccination, and of those, 21 seroconverted after booster vaccination and 11 experienced seroelevation after the booster.

The patients who did not seroconvert were seronegative after initial vaccination and experienced no change in antibody level after the booster vaccination. In contrast, the 21 who seroconverted had a median 23.1 AU/ml increase in antibody level, Dr. Nichols, along with LLS chief scientific officer Lee M. Greenberger, PhD,and their colleagues reported online Sept. 6, 2021, in Cancer Cell.

Similar proportions of seroconverted patients had low-level responses between 2.2 and 23.1 AU/mL and robust response between 125 and 2,500 AU/mL, they noted. The 11 patients with seroelevation were seropositive after full vaccination and demonstrated a median increase of 2,128 AU/mL in antibody level after the booster vaccination.
 

Therapy effects on vaccine response

Outcomes of the current analysis also confirmed the authors’ previous finding, which suggested that “both disease and therapies can affect the serological response to vaccination,” they wrote, explaining that, among the 12 patients who received no malignancy-targeted treatments in the past 2 years, only 1 was a nonresponder, 7 demonstrated seroconversion, and 4 demonstrated seroelevation.

“In contrast, among the 21 patients who completed therapy with anti-CD20 antibodies either alone or in combination with other therapies, 12 patients were nonresponders, 7 patients demonstrated seroconversion, and 2 patients demonstrated seroelevation,” they added.

The authors also noted that five of seven patients who completed anti-CD20 antibody therapy alone or in combination with chemotherapy at least 7 months prior to the booster vaccination demonstrated seroconversion or seroelevation, whereas many of the patients with recent or maintenance anti-CD20 antibody therapy before the booster vaccination failed to seroconvert afterward.

In light of previous findings showing B-cell recovery begins 6-9 months after rituximab therapy, these data suggest that recent anti-CD20 antibody-containing treatment regimens may suppress booster vaccination response, the authors wrote.

The current data also support the group’s prior finding that use of a Bruton tyrosine kinase inhibitor may suppress vaccine response: Of the patients in the current study who experienced seroelevation and were treated with a BTKi, two discontinued BTKi therapy 7-23 months prior to booster vaccination, one maintained a low dose of ibrutinib before booster vaccination, one maintained BTKi therapy continuously before and after the booster, and the two who experienced marked seroconversion after booster vaccination stopped BTKi therapy at least 4 months prior.

Conversely, five patients with a very weak seroconversion and two patients with moderate seroconversion maintained BTKi therapy during booster vaccination.

“These data suggest that BTKi therapy can interfere with a response to booster vaccination,” they wrote, noting, however, that “it is encouraging that seven patients ... maintained on a BTKi seroconverted or experienced seroelevation after booster vaccination and [this] is consistent with a previous report on one patient.”
 

Study limitations and lessons

Although the findings of this study are limited by the small number of patients, the fact that treatment and disease were patient reported, and a lack of data on “antibody responses, particularly to the delta variant, B-cell memory, or T-cell responses,” they nevertheless provide encouraging news, Dr. Nichols told this news organization.

“Many blood cancer patients are getting boosters and a good number are able to make antibody with an additional dose. This is giving us much needed information about boosters,” she said. “Through the LLS National Patient Registry, we anticipate having data on hundreds of more patients over the course of the next few months.”

The information is needed because data suggest that up to 25% of patients with hematologic malignancies fail to make anti-S antibodies after full COVID-19 vaccination and that seronegative patients may be especially vulnerable to breakthrough infections, she and her colleagues noted.

Patients with B-cell malignancies are at the highest risk, and this is particularly concerning as some patients with blood cancer who contracted COVID-19 in the prevaccine period of the pandemic had “prolonged, severe infections; generated variant strains; and demonstrated significantly higher mortality rates compared to the general population,” they said.

However, a recently published placebo-controlled trial that demonstrated a booster vaccination–mediated increase in anti-S antibodies and neutralizing antibodies in immunosuppressed patients, and the current review, which focused on patients who obtained booster vaccinations prior to Aug. 12, 2021 (when the Food and Drug Administration granted emergency use authorization for booster doses in immunocompromised people), offer findings that suggest these patients may benefit from receiving COVID-19 boosters.

“We conclude that some patients with hematologic malignancies who are seronegative after a full course of vaccination may benefit from a booster,” the authors wrote. They added a warning: “Regulators, patients, and health care providers should be aware that a sizable subset of patients with blood cancer may remain at risk of breakthrough COVID-19 infections after full vaccination followed by booster vaccination.”

Dr. Nichols stressed that the findings “do not in any way suggest that blood cancer patients should stop therapy to get an antibody response to the vaccinations.”

“LLS is encouraging blood cancer patients to get vaccinated and to continue taking preventive measures such as wearing masks, social distancing, hand washing, and avoiding crowds and poorly ventilated indoor spaces,” she said.

Sergio Giralt, MD, professor and deputy head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center, New York, further emphasized the importance of preventive measures.

“I think the extra booster will go a long way to protect our patients at this time but should not be used as a replacement for masking indoors and continued social distancing in this vulnerable patient population,” he said.

This study was supported by the LLS.

[email protected]

The Food and Drug Administration has approved atogepant (Qulipta), a novel calcitonin gene-related peptide (CGRP) receptor antagonist, for the prevention of episodic migraine, the manufacturer announced in a release.

The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.

“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.

Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.

As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.

With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.

“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.

“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
 

Practice changing?

In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.

In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.

The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.

Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.

“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.

Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.

How the approval will affect clinical practice is also unclear, he noted.

“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
 

Not a ‘breakthrough’ treatment

Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”

Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.

“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.

“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.

These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.

Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.

The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”

It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.

“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.

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

The Food and Drug Administration has approved atogepant (Qulipta), a novel calcitonin gene-related peptide (CGRP) receptor antagonist, for the prevention of episodic migraine, the manufacturer announced in a release.

The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.

“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.

Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.

As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.

With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.

“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.

“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
 

Practice changing?

In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.

In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.

The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.

Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.

“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.

Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.

How the approval will affect clinical practice is also unclear, he noted.

“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
 

Not a ‘breakthrough’ treatment

Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”

Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.

“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.

“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.

These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.

Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.

The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”

It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.

“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.

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

The Food and Drug Administration has approved atogepant (Qulipta), a novel calcitonin gene-related peptide (CGRP) receptor antagonist, for the prevention of episodic migraine, the manufacturer announced in a release.

The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.

“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.

Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.

As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.

With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.

“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.

“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
 

Practice changing?

In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.

In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.

The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.

Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.

“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.

Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.

How the approval will affect clinical practice is also unclear, he noted.

“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
 

Not a ‘breakthrough’ treatment

Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”

Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.

“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.

“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.

These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.

Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.

The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”

It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.

“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.

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.

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.